The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys

PubMed Central

Petry, Nicolai; Olofin, Ibironke; Hurrell, Richard F.; Boy, Erick; Wirth, James P.; Moursi, Mourad; Donahue Angel, Moira; Rohner, Fabian

2016-01-01

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia. PMID:27827838

The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys.

PubMed

Petry, Nicolai; Olofin, Ibironke; Hurrell, Richard F; Boy, Erick; Wirth, James P; Moursi, Mourad; Donahue Angel, Moira; Rohner, Fabian

2016-11-02

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia.

Iron biofortification of maize grain

USDA-ARS?s Scientific Manuscript database

Mineral nutrient deficiencies are a worldwide problem that is directly correlated with poverty and food insecurity. The most common of these is iron deficiency; more than one-third of the world’s population suffers from iron deficiency-induced anemia, 80% of which are in developing countries. The de...

Iron biofortification of maize grain

USDA-ARS?s Scientific Manuscript database

Mineral nutrient deficiencies are a worldwide problem that is directly correlated with poverty and food insecurity. The most common of these is iron deficiency; more than one-third of the world’s population suffers from iron deficiency-induced anemia, 80% of which are in developing countries. The co...

Iron deficiency anemia: adverse effects on infant psychomotor development.

PubMed

Walter, T; De Andraca, I; Chadud, P; Perales, C G

1989-07-01

In a double-blind, placebo-control prospective cohort study of 196 infants from birth to 15 months of age, assessment was made at 12 months of age of the relationship between iron status and psychomotor development, the effect of a short-term (10-day) trial of oral iron vs placebo, and the effect of long-term (3 months) oral iron therapy. Development was assessed with the mental and psychomotor indices and the infant behavior record of the Bayley Scales of Infant Development in 39 anemic, 30 control, and 127 nonanemic iron-deficient children. Anemic infants had significantly lower Mental and Psychomotor Developmental Index scores than control infants or nonanemic iron-deficient infants (one-way analysis of variance, P less than .0001). Control infants and nonanemic iron-deficient infants performed comparably. No difference was noted between the effect of oral administration of iron or placebo after 10 days or after 3 months of iron therapy. Among anemic infants a hemoglobin concentration less than 10.5 g/dL and duration of anemia of greater than 3 months were correlated with significantly lower motor and mental scores (P less than .05). Anemic infants failed specifically in language capabilities and body balance-coordination skills when compared with controls. These results, in a design in which intervening variables were closely controlled, suggest that when iron deficiency progresses to anemia, but not before, adverse influences in the performance of developmental tests appear and persist for at least 3 months despite correction of anemia with iron therapy. If these impairments prove to be long standing, prevention of iron deficiency anemia in early infancy becomes the only way to avoid them.

Screening for iron deficiency and iron deficiency anaemia in pregnancy: a structured review and gap analysis against UK national screening criteria.

PubMed

Rukuni, Ruramayi; Knight, Marian; Murphy, Michael F; Roberts, David; Stanworth, Simon J

2015-10-20

Iron deficiency anaemia is a common problem in pregnancy despite national recommendations and guidelines for treatment. The aim of this study was to appraise the evidence against the UK National Screening Committee (UKNSC) criteria as to whether a national screening programme could reduce the prevalence of iron deficiency anaemia and/or iron deficiency in pregnancy and improve maternal and fetal outcomes. Search strategies were developed for the Cochrane library, Medline and Embase to identify evidence relevant to UK National Screening Committee (UKNSC) appraisal criteria which cover the natural history of iron deficiency and iron deficiency anaemia, the tests for screening, clinical management and evidence of cost effectiveness. Many studies evaluated haematological outcomes of anaemia, but few analysed clinical consequences. Haemoglobin and ferritin appeared the most suitable screening tests, although future options may follow recent advances in understanding iron homeostasis. The clinical consequences of iron deficiency without anaemia are unknown. Oral and intravenous iron are effective in improving haemoglobin and iron parameters. There have been no trials or economic evaluations of a national screening programme for iron deficiency anaemia in pregnancy. Iron deficiency in pregnancy remains an important problem although effective tests and treatment exist. A national screening programme could be of value for early detection and intervention. However, high quality studies are required to confirm whether this would reduce maternal and infant morbidity and be cost effective.

Maternal iron deficiency alters circulating thyroid hormone levels in developing neonatal rats

EPA Science Inventory

Thyroid hormone insufficiency and iron deficiency (FeD) during fetal and neonatal life are both similarly deleterious to mammalian development suggesting a possible linkage between iron and thyroid hormone insufficiencies. Recent published data from our laboratory demonstrate a r...

A question mark on iron deficiency in 185 million people of Pakistan: its outcomes and prevention.

PubMed

Ahmed, Anwaar; Ahmad, Asif; Khalid, Nauman; David, Angel; Sandhu, Mansoor Abdullah; Randhawa, Muhammad Atif; Suleria, Hafiz Ansar Rasul

2014-01-01

Micronutrient deficiency especially the iron deficiency is the bane of our lives, affecting all strata of society. Unfortunately, the women during pregnancy, adolescence, and children are under this curse particularly in developing countries like Pakistan. It is one of the biggest reasons of complications during pregnancy and malnourished children under five years of age. Maternal death, still-births, and underweight births are most common consequences of iron deficiency and these outbreaks as iron-deficiency anemia in Pakistan. Disastrous nature of iron deficiency requires an urgent call to eradicate it. Hence, the solution should not be frail comparing with the huge economic loss and other incompatibilities. Flour fortification, supplementation, dietary diversification, and especially maternal education are possible solutions for combating this micronutrient deficiency.

Retention of iron by infants.

PubMed

Fomon, S J; Nelson, S E; Ziegler, E E

2000-01-01

Throughout the world, the most common nutritional deficiency disorder of infants is iron deficiency. Developing effective strategies for preventing iron deficiency requires detailed knowledge of iron retention under ordinary living conditions. For the adult population, such knowledge is at an advanced stage, but relatively little is known about infants. Many reports of iron retention by infants have been based on the assumption that, as in normal and iron-deficient adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating erythrocytes, but this assumption is not supported by available data. This communication presents a review of iron retention by term and preterm infants, as determined by metabolic balance studies or (59)Fe whole-body counting studies, and it explores the relationship between iron retention and postnatal age, iron nutritional status, iron intake (or dose), and type of feeding.

Intravenous iron treatments for iron deficiency anemia in inflammatory bowel disease: a budget impact analysis of iron isomaltoside 1000 (Monofer) in the UK.

PubMed

Pollock, R F; Muduma, G

2017-12-01

Iron deficiency is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment for clinically active IBD or previous oral iron intolerance. The aim of the present study was to develop a comparative model of iron deficiency and delivery for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency anemia associated with IBD. Areas covered: A model was developed to evaluate iron delivery characteristics, resource use and costs associated with IIM, FCM, LMWID and IS. Iron deficiency was modeled using dosing tables and retreatments were modeled based on a pooled retrospective analysis. The analyses were conducted over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin levels of 10.77 g/dL based on observational data. Expert opinion: The modeling analysis showed that using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS, respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

Calculation of Haem Iron Intake and Its Role in the Development of Iron Deficiency in Young Women from the Australian Longitudinal Study on Women's Health.

PubMed

Reeves, Angela J; McEvoy, Mark A; MacDonald-Wicks, Lesley K; Barker, Daniel; Attia, John; Hodge, Allison M; Patterson, Amanda J

2017-05-19

Total iron intake is not strongly associated with iron stores, but haem iron intake may be more predictive. Haem iron is not available in most nutrient databases, so experimentally determined haem contents were applied to an Australian Food Frequency Questionnaire (FFQ) to estimate haem iron intake in a representative sample of young women (25-30 years). The association between dietary haem iron intakes and incident self-reported diagnosed iron deficiency over six years of follow-up was examined. Haem iron contents for Australian red meats, fish, and poultry were applied to haem-containing foods in the Dietary Questionnaire for Epidemiological Studies V2 (DQESv2) FFQ. Haem iron intakes were calculated for 9076 women from the Australian Longitudinal Study on Women's Health (ALSWH) using the DQESv2 dietary data from 2003. Logistic regression was used to examine the association between haem iron intake (2003) and the incidence of iron deficiency in 2006 and 2009. Multiple logistic regression showed baseline haem iron intake was a statistically significant predictor of iron deficiency in 2006 (Odds Ratio (OR): 0.91; 95% Confidence Interval (CI): 0.84-0.99; p -value: 0.020) and 2009 (OR: 0.89; 95% CI: 0.82-0.99; p -value: 0.007). Using the energy-adjusted haem intake made little difference to the associations. Higher haem iron intake is associated with reduced odds of iron deficiency developing in young adult Australian women.

Iron Overload and Heart Fibrosis in Mice Deficient for Both β2-Microglobulin and Rag1

PubMed Central

Santos, Manuela M.; de Sousa, Maria; Rademakers, Luke H. P. M.; Clevers, Hans; Marx, J. J. M.; Schilham, Marco W.

2000-01-01

Genetic causes of hereditary hemochromatosis (HH) include mutations in the HFE gene, a β2-microglobulin (β2m)-associated major histocompatibility complex class I-like protein. Accordingly, mutant β2m−/− mice have increased intestinal iron absorption and develop parenchymal iron overload in the liver. In humans, other genetic and environmental factors have been suggested to influence the pathology and severity of HH. Previously, an association has been reported between low numbers of lymphocytes and the severity of clinical expression of the iron overload in HH. In the present study, the effect of a total absence of lymphocytes on iron overload was investigated by crossing β2m−/− mice (which develop iron overload resembling human disease) with mice deficient in recombinase activator gene 1 (Rag1), which is required for normal B and T lymphocyte development. Iron overload was more severe in β2mRag1 double-deficient mice than in each of the single deficient mice, with iron accumulation in parenchymal cells of the liver, in acinar cells of the pancreas, and in heart myocytes. With increasing age β2mRag1−/− mice develop extensive heart fibrosis, which could be prevented by reconstitution with normal hematopoietic cells. Thus, the development of iron-mediated cellular damage is substantially enhanced when a Rag1 mutation, which causes a lack of mature lymphocytes, is introduced into β2m−/− mice. Mice deficient in β2m and Rag1 thus offer a new experimental model of iron-related cardiomyopathy. PMID:11106561

Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

PubMed Central

Shaw, Julia G.; Friedman, Jennifer F.

2011-01-01

Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

Identification of quantitative trait loci associated with seed iron in the legumes Lotus japonicus and Medicago truncatula

USDA-ARS?s Scientific Manuscript database

Iron deficiency is one of the leading micronuntrient deficiencies in humans, and increasing the amount of bioavailable iron in commonly consumed plant foods has been proposed as a means to ameliorate this deficiency. This approach seems especially beneficial in developing countries where plant food...

Iron-Deficiency Anemia After Partial Gastrectomy

PubMed Central

Geokas, M. C.; McKenna, R. D.

1967-01-01

Although the mechanism for its development is not well understood, iron-deficiency anemia is a well-recognized consequence of partial gastrectomy. The reported incidence varies considerably, depending upon the criteria used to define anemia, and other factors. Rapid emptying of the gastric remnant, intestinal “hurry”, and borderline dietary-iron intake, with or without concomitant blood loss, produce malabsorption of some forms of iron that appears to be responsible for development of the deficiency. The diagnosis rests on hematological findings in the peripheral blood, the evaluation of iron stores, epithelial changes, and the response to adequate treatment. Oral iron therapy can be both effective and inexpensive and should form the mainstay of treatment. PMID:6019057

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency

PubMed Central

Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-01-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. PMID:26208645

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency.

PubMed

Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-11-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Anaemia, iron deficiency and iron deficiency anaemia among blood donors in Port Harcourt, Nigeria.

PubMed

Jeremiah, Zaccheaus Awortu; Koate, Baribefe Banavule

2010-04-01

There is paucity of information on the effect of blood donation on iron stores in Port Harcourt, Nigeria. The present study was, therefore, designed to assess, using a combination of haemoglobin and iron status parameters, the development of anaemia and prevalence of iron deficiency anaemia in this area of Nigeria. Three hundred and forty-eight unselected consecutive whole blood donors, comprising 96 regular donors, 156 relatives of patients and 96 voluntary donors, constituted the study population. Three haematological parameters (haemoglobin, packed cell volume, and mean cell haemoglobin concentration) and four biochemical iron parameters (serum ferritin, serum iron, total iron binding capacity and transferrin saturation) were assessed using standard colorimetric and ELISA techniques. The prevalence of anaemia alone (haemoglobin <11.0 g/dL) was 13.7%. The prevalence of isolated iron deficiency (serum ferritin <12 ng/mL) was 20.6% while that of iron-deficiency anaemia (haemoglobin <11.0 g/dL + serum ferritin <12.0 ng/mL) was 12.0%. Among the three categories of the donors, the regular donors were found to be most adversely affected as shown by the reduction in mean values of both haematological and biochemical iron parameters. Interestingly, anaemia, iron deficiency and iron-deficiency anaemia were present almost exclusively among regular blood donors, all of whom were over 35 years old. Anaemia, iron deficiency and iron-deficiency anaemia are highly prevalent among blood donors in Port Harcourt, Nigeria. It will be necessary to review the screening tests for the selection of blood donors and also include serum ferritin measurement for the routine assessment of blood donors, especially among regular blood donors.

Iron Deficiency Anemia: A Common and Curable Disease

PubMed Central

Miller, Jeffery L.

2013-01-01

Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations. PMID:23613366

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

PubMed Central

Mihaila, Camelia; Schramm, Jordan; Strathmann, Frederick G.; Lee, Dawn L.; Gelein, Robert M.

2011-01-01

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring. Our data may have significant relevance for understanding the impact of suboptimal iron levels during pregnancy not only on the mother but also on the developing fetus and hence might lead to a more informed timing of iron supplementation during pregnancy. PMID:21423661

Iron Deficiency's Long-Term Effects: An Interview with Pediatrician Betsy Lozoff

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

Betsy Lozoff is among the world's leading experts on iron deficiency and its effects on infant brain development and behavior. Iron deficiency is the most common single nutrient disorder in the world, affecting more than half of the world's infants and young children. Research by Lozoff and others has shown that there are long-lasting…

Calculation of Haem Iron Intake and Its Role in the Development of Iron Deficiency in Young Women from the Australian Longitudinal Study on Women’s Health

PubMed Central

Reeves, Angela J.; McEvoy, Mark A.; MacDonald-Wicks, Lesley K.; Barker, Daniel; Attia, John; Hodge, Allison M.; Patterson, Amanda J.

2017-01-01

Total iron intake is not strongly associated with iron stores, but haem iron intake may be more predictive. Haem iron is not available in most nutrient databases, so experimentally determined haem contents were applied to an Australian Food Frequency Questionnaire (FFQ) to estimate haem iron intake in a representative sample of young women (25–30 years). The association between dietary haem iron intakes and incident self-reported diagnosed iron deficiency over six years of follow-up was examined. Haem iron contents for Australian red meats, fish, and poultry were applied to haem-containing foods in the Dietary Questionnaire for Epidemiological Studies V2 (DQESv2) FFQ. Haem iron intakes were calculated for 9076 women from the Australian Longitudinal Study on Women’s Health (ALSWH) using the DQESv2 dietary data from 2003. Logistic regression was used to examine the association between haem iron intake (2003) and the incidence of iron deficiency in 2006 and 2009. Multiple logistic regression showed baseline haem iron intake was a statistically significant predictor of iron deficiency in 2006 (Odds Ratio (OR): 0.91; 95% Confidence Interval (CI): 0.84–0.99; p-value: 0.020) and 2009 (OR: 0.89; 95% CI: 0.82–0.99; p-value: 0.007). Using the energy-adjusted haem intake made little difference to the associations. Higher haem iron intake is associated with reduced odds of iron deficiency developing in young adult Australian women. PMID:28534830

Sleep and Neurofunctions Throughout Child Development: Lasting Effects of Early Iron Deficiency

PubMed Central

Peirano, Patricio D.; Algarín, Cecilia R.; Chamorro, Rodrigo; Garrido, Marcelo I.; Lozoff, Betsy

2013-01-01

Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. Infants are at particular risk due to rapid growth and limited dietary sources of iron. An estimated 20–25% of the world’s infants have IDA, with at least as many having iron deficiency without anemia. High prevalence is found primarily in developing countries, but also among poor, minority, and immigrant groups in developed ones. Infants with IDA test lower in mental and motor development assessments and show affective differences. After iron therapy, follow-up studies point to long-lasting differences in several domains. Neurofunctional studies showed slower neural transmission in the auditory system despite 1 year of iron therapy in IDA infants; they still had slower transmission in both the auditory and visual systems at preschool age. Different motor activity patterning in all sleep-waking states and several differences in sleep states organization were reported. Persistant sleep and neurofunctional effects could contribute to reduced potential for optimal behavioral and cognitive outcomes in children with a history of IDA. PMID:19214058

Blood and hair lead in children with different extents of iron deficiency in Karachi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ataur Rahman, Muhammad; Rahman, Bushra; Saeed Ahmad, Muhammad

Childhood iron deficiency has a high incidence in Pakistan. Some but not all studies have shown that dietary iron deficiency may cause increased absorption of lead as both compete for the same transporters in the small intestine. Therefore, children in Pakistan, residing in heavily polluted cities like Karachi may be prone to lead poisoning. This hypothesis was tested by investigating blood and hair lead concentrations in children from Karachi who were divided into four groups of iron status; normal, borderline iron deficiency, iron deficiency and iron deficiency anaemia. A prospective observational study was conducted where 269 children were categorized intomore » four groups of iron status using the World Health Organization criteria and one based on soluble transferrin receptor measurements. Blood iron status was determined using a full blood count, serum iron, ferritin, transferrin saturation and soluble transferrin receptor measurements. Blood lead was determined by graphite atomic absorption spectroscopy, whereas hair lead was assessed using an inductively coupled plasma atomic emission spectroscopy technique. Blood lead concentrations were significantly higher in children with iron deficiency anaemia (mean [95% confidence intervals] were 24.9 [22.6-27.2] {mu}g/dL) compared to those with normal iron status (19.1 [16.8-21.4] {mu}g/dL) using WHO criteria. In contrast, hair lead content was not significantly different in children of different iron status. Our findings reinforce the importance of not only reducing environmental lead pollution but also the development of national health strategies to reduce childhood iron deficiency in Pakistan.« less

Relationship of vitamin A deficiency, iron deficiency, and inflammation to anemia among preschool children in the Republic of the Marshall Islands.

PubMed

Gamble, M V; Palafox, N A; Dancheck, B; Ricks, M O; Briand, K; Semba, R D

2004-10-01

Although vitamin A deficiency, iron deficiency, and inflammation may contribute to anemia, their relative contribution to anemia has not been well characterized in preschool children in developing countries. To characterize the contributions of vitamin A and iron deficiencies and inflammation to anemia among preschool children in the Republic of the Marshall Islands. A community-based survey, the Republic of the Marshall Islands Vitamin A Deficiency Study, was conducted among 919 preschool children. The relationship of vitamin A and iron status and markers of inflammation, tumor necrosis factor-alpha, alpha1-acid glycoprotein, and interleukin-10, to anemia were studied in a subsample of 367 children. Among the 367 children, the prevalence of anemia was 42.5%. The prevalence of severe vitamin A deficiency (serum vitamin A < 0.35 micromol/l) and iron deficiency (serum ferritin < 12 microg/dl) were 10.9 and 51.7%, respectively. The respective prevalence of iron deficiency anemia (hemoglobin < 110 g/l and iron deficiency), anemia with inflammation (anemia with TNF-alpha > 2 pg/ml and/or AGP > 1000 mg/l), and severe vitamin A deficiency combined with anemia was 26.7, 35.6, and 7.6%. In multivariate linear regression models that adjusted for age, sex, and inflammation, both iron deficiency (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.08-2.83, P = 0.023) and severe vitamin A deficiency (OR 4.85, 95% CI 2.14-10.9, P < 0.0001) were significantly associated with anemia. Both iron and vitamin A deficiencies were independent risk factors for anemia, but inflammation was not a significant risk factor for anemia among these preschool children.

Prevention of iron deficiency in preterm neonates during infancy.

PubMed

Heese, H D; Smith, S; Watermeyer, S; Dempster, W S; Jakubiec, L

1990-04-07

The preterm infant inevitably develops iron deficiency unless supplementary iron is given. Oral iron supplementation is preferred in ideal social circumstances but, where compliance with such therapy is uncertain, intramuscular iron dextran may be a more effective treatment. A study was conducted to compare the effectiveness of two methods of preventing iron deficiency of prematurity. One group of healthy premature infants was given oral iron 2 mg/kg/d until the age of 6 months. The second similar group was given 100 mg as intramuscular iron dextran (Imferon; Fisons) between the ages of 6 and 8 weeks. Both kinds of supplementary iron appeared to have benefited the majority of infants in this trial.

Iron supplementation in early childhood: health benefits and risks123

PubMed Central

Iannotti, Lora L; Tielsch, James M; Black, Maureen M; Black, Robert E

2012-01-01

The prevalence of iron deficiency among infants and young children living in developing countries is high. Because of its chemical properties—namely, its oxidative potential—iron functions in several biological systems that are crucial to human health. Iron, which is not easily eliminated from the body, can also cause harm through oxidative stress, interference with the absorption or metabolism of other nutrients, and suppression of critical enzymatic activities. We reviewed 26 randomized controlled trials of preventive, oral iron supplementation in young children (aged 0–59 mo) living in developing countries to ascertain the associated health benefits and risks. The outcomes investigated were anemia, development, growth, morbidity, and mortality. Initial hemoglobin concentrations and iron status were considered as effect modifiers, although few studies included such subgroup analyses. Among iron-deficient or anemic children, hemoglobin concentrations were improved with iron supplementation. Reductions in cognitive and motor development deficits were observed in iron-deficient or anemic children, particularly with longer-duration, lower-dose regimens. With iron supplementation, weight gains were adversely affected in iron-replete children; the effects on height were inconclusive. Most studies found no effect on morbidity, although few had sample sizes or study designs that were adequate for drawing conclusions. In a malaria-endemic population of Zanzibar, significant increases in serious adverse events were associated with iron supplementation, whereas, in Nepal, no effects on mortality in young children were found. More research is needed in populations affected by HIV and tuberculosis. Iron supplementation in preventive programs may need to be targeted through identification of iron-deficient children. PMID:17158406

Micronutrient supplementation adherence and influence on the prevalences of anemia and iron, zinc and vitamin A deficiencies in preemies with a corrected age of six months

PubMed Central

de Freitas, Brunnella Alcantara Chagas; Lima, Luciana Moreira; Moreira, Maria Elisabeth Lopes; Priore, Silvia Eloiza; Henriques, Bruno David; Carlos, Carla Fernanda Lisboa Valente; Sabino, Jusceli Souza Nogueira; do Carmo Castro Franceschini, Sylvia

2016-01-01

OBJECTIVE: To analyze adherence to the recommended iron, zinc and multivitamin supplementation guidelines for preemies, the factors associated with this adherence, and the influence of adherence on the occurrence of anemia and iron, zinc and vitamin A deficiencies. METHODS: This prospective cohort study followed 58 preemies born in 2014 until they reached six months corrected age. The preemies were followed at a referral secondary health service and represented 63.7% of the preterm infants born that year. Outcomes of interest included high or low adherence to iron, zinc and multivitamin supplementation guidelines; prevalence of anemia; and prevalences of iron, zinc, and vitamin A deficiencies. The prevalence ratios were calculated by Poisson regression. RESULTS: Thirty-eight (65.5%) preemies presented high adherence to micronutrient supplementation guidelines. At six months of corrected age, no preemie had vitamin A deficiency. The prevalences of anemia, iron deficiency and zinc deficiency were higher in the low-adherence group but also concerning in the high-adherence group. Preemies with low adherence to micronutrient supplementation guidelines were 2.5 times more likely to develop anemia and 3.1 times more likely to develop zinc deficiency. Low maternal education level increased the likelihood of nonadherence to all three supplements by 2.2 times. CONCLUSIONS: Low maternal education level was independently associated with low adherence to iron, zinc and vitamin A supplementation guidelines in preemies, which impacted the prevalences of anemia and iron and zinc deficiencies at six months of corrected age. PMID:27626474

Pregnancy and maternal iron deficiency stimulate hepatic CRBPII expression in rats.

PubMed

Cottin, Sarah C; Gambling, Lorraine; Hayes, Helen E; Stevens, Valerie J; McArdle, Harry J

2016-06-01

Iron deficiency impairs vitamin A (VA) metabolism in the rat but the mechanisms involved are unknown and the effect during development has not been investigated. We investigated the effect of pregnancy and maternal iron deficiency on VA metabolism in the mother and fetus. 54 rats were fed either a control or iron deficient diet for 2weeks prior to mating and throughout pregnancy. Another 15 female rats followed the same diet and were used as non-pregnant controls. Maternal liver, placenta and fetal liver were collected at d21 for total VA, retinol and retinyl ester (RE) measurement and VA metabolic gene expression analysis. Iron deficiency increased maternal hepatic RE (P<.05) and total VA (P<.0001), fetal liver RE (P<.05), and decreased placenta total VA (P<.05). Pregnancy increased Cellular Retinol Binding Protein (CRBP)-II gene expression by 7 fold (P=.001), decreased VA levels (P=.0004) and VA metabolic gene expression (P<.0001) in the liver. Iron deficiency increased hepatic CRBPII expression by a further 2 fold (P=.044) and RBP4 by~20% (P=.005), increased RBPR2 and decreased CRBPII, LRAT, and TTR in fetal liver, while it had no effect on VA metabolic gene expression in the placenta. Hepatic CRBPII expression is increased by pregnancy and further increased by iron deficiency, which may play an important role in VA metabolism and homeostasis. Maternal iron deficiency also alters VA metabolism in the fetus, which is likely to have consequences for development. Copyright © 2016 Elsevier Inc. All rights reserved.

IRON DEFICIENCY AND INFANT MOTOR DEVELOPMENT

PubMed Central

Shafir, Tal; Angulo-Barroso, Rosa; Jing, Yuezhou; Lu Angelilli, Mary; Jacobson, Sandra W.; Lozoff, Betsy

2011-01-01

Background Iron deficiency (ID) during early development impairs myelination and basal ganglia function in animal models. Aims To examine the effects of iron deficiency anemia (IDA) and iron deficiency (ID) without anemia on infant motor skills that are likely related to myelination and basal ganglia function. Study design Observational study. Subjects Full-term inner-city African-American 9- to 10-month-old infants who were free of acute or chronic health problems with iron status indicators ranging from IDA to iron sufficiency (n = 106). Criteria for final iron status classification were met by 77 of these infants: 28 IDA, 28 non-anemic iron-deficient (NA ID), and 21 iron-sufficient (IS). Outcome measures Gross motor developmental milestones, Peabody Developmental Motor Scale, Infant Neurological International Battery (INFANIB), motor quality factor of the Bayley Behavioral Rating Scale, and a sequential/bi-manual coordination toy retrieval task. General linear model analyses tested for linear effects of iron status group and thresholds for effects. Results There were linear effects of iron status on developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, motor quality, and toy retrieval. The threshold for effects was ID with or without anemia for developmental milestones, INFANIB standing item, and motor quality and IDA for toy retrieval. Conclusions Using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. Poorer motor function among non-anemic ID infants is particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA. PMID:18272298

The influence of maternal smoking on transferrin sialylation and fetal biometric parameters.

PubMed

Wrześniak, Marta; Królik, Małgorzata; Kepinska, Marta; Milnerowicz, Halina

2016-10-01

Transferrin is a glycosylated protein responsible for transporting iron, an essential metal responsible for proper fetal development. Tobacco is a heavily used xenobiotic having a negative impact on the human body and pregnancy outcomes. Aims of this study was to examine the influence of tobacco smoking on transferrin sialic acid residues and their connection with fetal biometric parameters in women with iron-deficiency. The study involved 173 samples from pregnant women, smokers and non-smokers, iron deficient and not. Transferrin sialylation was determined by capillary electrophoresis. The cadmium (Cd) level was measured by atomic absorption and the sialic acid concentration by the resorcinol method. Women with iron deficiencies who smoked gave birth earlier than non-smoking, non-iron-deficient women. The Cd level, but not the cotinine level, was positively correlated with transferrin sialylation in the blood of iron-deficient women who smoked; 3-, 4-, 5- and 6-sialoTf correlated negatively with fetal biometric parameters in the same group. It has been shown the relationship between Cd from tobacco smoking and fetal biometric parameters observed only in the iron deficient group suggests an additive effect of these two factors, and indicate that mothers with anemia may be more susceptible to Cd toxicity and disturbed fetal development. Copyright © 2016 Elsevier B.V. All rights reserved.

Perinatal iron deficiency predisposes the developing rat hippocampus to greater injury from mild to moderate hypoxia–ischemia

PubMed Central

Rao, Raghavendra; Tkac, Ivan; Townsend, Elise L; Ennis, Kathleen; Gruetter, Rolf; Georgieff, Michael K

2008-01-01

The hippocampus is injured in both hypoxia–ischemia (HI) and perinatal iron deficiency that are comorbidities in infants of diabetic mothers and intrauterine growth restricted infants. We hypothesized that preexisting perinatal iron deficiency predisposes the hippocampus to greater injury when exposed to a relatively mild HI injury. Iron-sufficient and iron-deficient rats (hematocrit 40% lower and brain iron concentration 55% lower) were subjected to unilateral HI injury of 15, 30, or 45 mins (n = 12 to 13/HI duration) on postnatal day 14. Sixteen metabolite concentrations were measured from an 11 μL volume on the ipsilateral (HI) and contralateral (control) hippocampi 1 week later using in vivo 1H NMR spectroscopy. The concentrations of creatine, glutamate, myo-inositol, and N-acetylaspartate were lower on the control side in the iron-deficient group (P < 0.02, each). Magnetic resonance imaging showed hippocampal injury in the majority of the iron-deficient rats (58% versus 11%, P < 0.0001) with worsening severity with increasing durations of HI (P = 0.0001). Glucose, glutamate, N-acetylaspartate, and taurine concentrations were decreased and glutamine, lactate and myo-inositol concentrations, and glutamate/glutamine ratio were increased on the HI side in the iron-deficient group (P < 0.01, each), mainly in the 30 and 45 mins HI subgroups (P < 0.02, each). These neurochemical changes likely reflect the histochemically detected neuronal injury and reactive astrocytosis in the iron-deficient group and suggest that perinatal iron deficiency predisposes the hippocampus to greater injury from exposure to a relatively mild HI insult. PMID:16868555

[Effect of anemia on child development: long-term consequences].

PubMed

Zavaleta, Nelly; Astete-Robilliard, Laura

2017-01-01

Anemia in children younger than 3 years is a public health problem in Peru and worldwide. It is believed that one of the primary causes of anemia is iron deficiency. Numerous studies and reviews have reported that iron deficiency limited psychomotor development in children and that, despite the correction of anemia, children with iron deficiency experienced poorer long-term performance in cognitive, social, and emotional functioning. These outcomes were reported in observational studies, follow-up studies, and experimental studies with a control group. Anemia can decrease school performance, productivity in adult life, quality of life, and the general income of affected individuals. Here we describe possible mechanisms underlying the effect of iron deficiency, with or without anemia, on childhood development. The high rate of anemia in this age group is a cause for concern. Moreover, anemia should be prevented in the first year of life to avoid long-term negative effects on individual development.

Iron Deficiency and the Cognitive and Psychomotor Development of Children: A Pilot Study with Institutionalized Children.

ERIC Educational Resources Information Center

Driva, A.; And Others

1985-01-01

Describes a pilot study, involving 48 institutionalized infants and toddlers, which aimed to treat iron deficiency anemia and to discover other factors contributing to the problem. Results indicate improvement in cognitive development after the administration of iron among three groups, while no significant differences were observed in psychomotor…

Iron deficiency anaemia: with the conclusion of a need for iron reader

NASA Astrophysics Data System (ADS)

Lim, Wai Feng; Yap, Boon Kar; Lai, Mei I.; Talik, Noorazrina; Nasser, Ammar Ahmed; Al-Haiqi, Ahmed Mubarak Ahmed; Sankar Krishnan, Prajindra

2017-10-01

In our bloodstream, there are plenty of red blood cells (RBC), which function as an important oxygen carrier in our bodies. Each RBC consists of millions of haemoglobin (Hb), which is made up from globin and iron. If any deficiency/malfunction of any globin, it will lead to anaemia as indicated in low Hb level while iron deficiency anaemia (IDA) is anaemic due to the lacking of iron as indicated in low Hb and ferritin levels. IDA affects almost two billion people globally while anaemia without iron deficiency, such as thalassaemia, affects almost 4.5% in Malaysian population. These anaemic conditions have similar clinical symptoms like fatigue, dizziness, in which disturb their cognitive development and productivity in workplace. In areas without proper medical access, many anaemic individuals were misdiagnosed and treated with iron tablets because they were thought to have iron deficiency anaemia due to low Hb content. But, excess iron is toxic to the body. Misdiagnosis can be avoided by iron status assessment. We hereby review the currently available iron status parameters in laboratory and field study with the conclusion of demonstrating the importance of a need for iron reader, in the effort to reduce the prevalence of IDA globally.

Iron Status of Vegetarian Children: A Review of Literature.

PubMed

Pawlak, Roman; Bell, Kami

2017-01-01

Iron is considered a nutrient of concern for vegetarians. In children, inadequate iron status may lead to anemia and poor growth. Thirteen original manuscripts met the inclusion criteria. Various biochemical markers of iron status, such as hemoglobin (Hb) and serum ferritin, were used. Seven of the 13 studies reported the prevalence of iron deficiency separately for vegetarians and non-vegetarians. Five out of 7 showed a higher prevalence of iron deficiency among the vegetarian participants, while the other 2 showed a higher prevalence of iron deficiency among non-vegetarians. A wide range of iron deficiency prevalence, from 4.3% of vegetarian participants in one study to 73% having ferritin <10 µg/L in another study, was found. Hb data showed almost as wide variations from 0% of children having Hb values lower than 11 g/dL to 47.5% having Hb values below 3rd percentile. Key Messages: The prevalence of iron deficiency among vegetarian children varies considerably from one study to another. The wide variation in the prevalence of inadequate iron status was consistent for studies from industrial and developing countries. The physiological significance of low iron status among vegetarians reported in some studies is unknown. © 2017 S. Karger AG, Basel.

Dietary Determinants of and Possible Solutions to Iron Deficiency for Young Women Living in Industrialized Countries: A Review

PubMed Central

Beck, Kathryn L.; Conlon, Cathryn A.; Kruger, Rozanne; Coad, Jane

2014-01-01

Iron deficiency is a concern in both developing and developed (industrialized) countries; and young women are particularly vulnerable. This review investigates dietary determinants of and possible solutions to iron deficiency in young women living in industrialized countries. Dietary factors including ascorbic acid and an elusive factor in animal protein foods (meat; fish and poultry) enhance iron absorption; while phytic acid; soy protein; calcium and polyphenols inhibit iron absorption. However; the effects of these dietary factors on iron absorption do not necessarily translate into an association with iron status and iron stores (serum ferritin concentration). In cross-sectional studies; only meat intake has consistently (positively) been associated with higher serum ferritin concentrations. The enhancing effects of ascorbic acid and meat on iron absorption may be negated by the simultaneous consumption of foods and nutrients which are inhibitory. Recent cross-sectional studies have considered the combination and timing of foods consumed; with mixed results. Dietary interventions using a range of focused dietary measures to improve iron status appear to be more effective than dietary approaches that focus on single nutrients or foods. Further research is needed to determine optimal dietary recommendations for both the prevention and treatment of iron deficiency. PMID:25244367

Serum ferritin thresholds for the diagnosis of iron deficiency in pregnancy: a systematic review.

PubMed

Daru, J; Allotey, J; Peña-Rosas, J P; Khan, K S

2017-06-01

The aim of this review was to understand the landscape of serum ferritin in diagnosing iron deficiency in the aetiology of anaemia in pregnancy. Iron deficiency in pregnancy is a major public health problem leading to the development of anaemia. Reducing the global prevalence of anaemia in women of reproductive age is a 2025 global nutrition target. Bone marrow aspiration is the gold standard test for iron deficiency but requires an invasive procedure; therefore, serum ferritin is the most clinically useful test. We undertook a systematic search of electronic databases and trial registers from inception to January 2016. Studies of iron or micronutrient supplementation in pregnancy with pre-defined serum ferritin thresholds were included. Two independent reviewers selected studies, extracted data and assessed quality. There were 76 relevant studies mainly of observational study design (57%). The most commonly used thresholds of serum ferritin for the diagnosis of iron deficiency were <12 and <15 ng mL -1 (68%). Most primary studies provided no justification for the choice of serum ferritin threshold used, but 25 studies (33%) used thresholds defined by expert consensus in a guideline development process. There were five studies (7%) using a serum ferritin threshold defining iron deficiency derived from primary studies of bone marrow aspiration. Unified international thresholds of iron deficiency for women throughout pregnancy are required for accurate assessments of the global disease burden and for evaluating effectiveness of interventions addressing this problem. © 2017 World Health Organization licensed by Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.

Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential.

PubMed

Black, Maureen M; Quigg, Anna M; Hurley, Kristen M; Pepper, Margery Reese

2011-11-01

This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non-responsive mother-child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non-responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother-child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron-rich complementary foods, and ensure access to postnatal interventions that promote responsive mother-infant interaction patterns and early learning opportunities for infants. © 2011 International Life Sciences Institute.

Current misconceptions in diagnosis and management of iron deficiency

PubMed Central

Muñoz, Manuel; Gómez-Ramírez, Susana; Besser, Martin; Pavía, José; Gomollón, Fernando; Liumbruno, Giancarlo M.; Bhandari, Sunil; Cladellas, Mercé; Shander, Aryeh; Auerbach, Michael

2017-01-01

The prevention and treatment of iron deficiency is a major public health goal. Challenges in the treatment of iron deficiency include finding and addressing the underlying cause and the selection of an iron replacement product which meets the needs of the patient. However, there are a number of non-evidence-based misconceptions regarding the diagnosis and management of iron deficiency, with or without anaemia, as well as inconsistency of terminology and lack of clear guidance on clinical pathways. In particular, the pathogenesis of iron deficiency is still frequently not addressed and iron not replaced, with indiscriminate red cell transfusion used as a default therapy. In our experience, this imprudent practice continues to be endorsed by non-evidence-based misconceptions. The intent of the authors is to provide a consensus that effectively challenges these misconceptions, and to highlight evidence-based alternatives for appropriate management (referred to as key points). We believe that this approach to the management of iron deficiency may be beneficial for both patients and healthcare systems. We stress that this paper solely presents the Authors’ independent opinions. No pharmaceutical company funded or influenced the conception, development or writing of the manuscript. PMID:28880842

Current misconceptions in diagnosis and management of iron deficiency.

PubMed

Muñoz, Manuel; Gómez-Ramírez, Susana; Besser, Martin; Pavía, José; Gomollón, Fernando; Liumbruno, Giancarlo M; Bhandari, Sunil; Cladellas, Mercé; Shander, Aryeh; Auerbach, Michael

2017-09-01

The prevention and treatment of iron deficiency is a major public health goal. Challenges in the treatment of iron deficiency include finding and addressing the underlying cause and the selection of an iron replacement product which meets the needs of the patient. However, there are a number of non-evidence-based misconceptions regarding the diagnosis and management of iron deficiency, with or without anaemia, as well as inconsistency of terminology and lack of clear guidance on clinical pathways. In particular, the pathogenesis of iron deficiency is still frequently not addressed and iron not replaced, with indiscriminate red cell transfusion used as a default therapy. In our experience, this imprudent practice continues to be endorsed by non-evidence-based misconceptions. The intent of the authors is to provide a consensus that effectively challenges these misconceptions, and to highlight evidence-based alternatives for appropriate management (referred to as key points). We believe that this approach to the management of iron deficiency may be beneficial for both patients and healthcare systems. We stress that this paper solely presents the Authors' independent opinions. No pharmaceutical company funded or influenced the conception, development or writing of the manuscript.

A pilot iron substitution programme in female blood donors with iron deficiency without anaemia.

PubMed

Pittori, C; Buser, A; Gasser, U E; Sigle, J; Job, S; Rüesch, M; Tichelli, A; Infanti, L

2011-04-01

Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non-anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain. Women aged≤50 with haemoglobin levels adequate for donation and serum ferritin≤10 ng/ml were offered iron supplementation. Substitution lasted 16 weeks and the donation interval was extended. History collection including iron deficiency-related symptoms, whole blood count and serum ferritin determination was performed at baseline and after 2 and 6 months. Data were recorded prospectively and compared with those of 108 female controls with iron deficiency not receiving iron substitution (retrospective data). Of the 116 participating subjects, 60% completed the programme. Significant results were serum ferritin increase (from a mean value of 7.12 to 25.2 ng/ml), resolution of prostration, fatigue, sleep disturbances, tension in the neck, hair loss and nail breakage. No case of anaemia occurred. Sixty per cent of the women completed the programme and donated blood again. Targeted iron substitution prevents the development of anaemia and enhances donation return in premenopausal female blood donors with iron deficiency. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Severe hypophosphataemia after intravenous iron administration.

PubMed

Anand, Gurpreet; Schmid, Christoph

2017-03-13

Iron deficiency is common and can be effectively treated with parenteral iron infusion. We report a case of an iron-deficient and vitamin D-deficient woman who developed severe symptomatic hypophosphataemia following intravenous ferric carboxymaltose administration. We stress the need of increased awareness of this potential complication among physicians. Patients should be informed of this complication and instructed to report for follow-up if they experience new musculoskeletal symptoms or worsening of tiredness. As severe hypophosphataemia is usually symptomatic, we recommend screening symptomatic patients for this complication. Recognising and treating the possible exacerbating factors, especially vitamin D deficiency, might be a simple measure to mitigate this complication. 2017 BMJ Publishing Group Ltd.

Severe hypophosphataemia after intravenous iron administration

PubMed Central

Anand, Gurpreet; Schmid, Christoph

2017-01-01

Iron deficiency is common and can be effectively treated with parenteral iron infusion. We report a case of an iron-deficient and vitamin D-deficient woman who developed severe symptomatic hypophosphataemia following intravenous ferric carboxymaltose administration. We stress the need of increased awareness of this potential complication among physicians. Patients should be informed of this complication and instructed to report for follow-up if they experience new musculoskeletal symptoms or worsening of tiredness. As severe hypophosphataemia is usually symptomatic, we recommend screening symptomatic patients for this complication. Recognising and treating the possible exacerbating factors, especially vitamin D deficiency, might be a simple measure to mitigate this complication. PMID:28289000

Artificial intelligence models for predicting iron deficiency anemia and iron serum level based on accessible laboratory data.

PubMed

Azarkhish, Iman; Raoufy, Mohammad Reza; Gharibzadeh, Shahriar

2012-06-01

Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide. Measuring serum iron is time consuming, expensive and not available in most hospitals. In this study, based on four accessible laboratory data (MCV, MCH, MCHC, Hb/RBC), we developed an artificial neural network (ANN) and an adaptive neuro-fuzzy inference system (ANFIS) to diagnose the IDA and to predict serum iron level. Our results represent that the neural network analysis is superior to ANFIS and logistic regression models in diagnosing IDA. Moreover, the results show that the ANN is likely to provide an accurate test for predicting serum iron levels with high accuracy and acceptable precision.

Iron-deficient erythropoiesis in blood donors and red blood cell recovery after transfusion: initial studies with a mouse model

PubMed Central

Bandyopadhyay, Sheila; Brittenham, Gary M.; Francis, Richard O.; Zimring, James C.; Hod, Eldad A.; Spitalnik, Steven L.

2017-01-01

Background Most frequent red cell (RBC) donors and many first-time donors are iron deficient, but meet haemoglobin standards. However, the effects of donation-induced iron deficiency on RBC storage quality are unknown. Thus, we used a mouse model to determine if donor iron deficiency reduced post-transfusion RBC recovery. Methods Weanling mice received a control diet or an iron-deficient diet. A third group receiving the iron-deficient diet was also phlebotomised weekly. This provided 3 groups of mice with different iron status: (1) iron replete, (2) mild iron deficiency with iron-deficient erythropoiesis, and (3) iron-deficiency anaemia. At ten weeks of age, blood was collected, leucoreduced, and stored at 4 ºC. After 12 days of storage, 24-hour (h) post-transfusion RBC recovery was quantified in recipients by flow cytometry. Results Before blood collection, mean haemoglobin concentrations in the iron-replete, iron-deficient, and iron-deficiency anaemia donor mice were 16.5±0.4, 11.5±0.4, and 7.0±1.4 [g/dL± 1 standard deviation (SD)], respectively (p<0.01 for all comparisons between groups). The 24-h post-transfusion RBC recoveries in recipients receiving transfusions from these three cohorts were 77.1±13.2, 66.5±10.9, and 46.7±15.9 (% ±1 SD), respectively (p<0.05 for all comparisons between groups). Discussion In summary, donor iron deficiency significantly reduced 24-h post-transfusion RBC recovery in recipient mice. RBCs from mice with mild iron deficiency and iron-deficient erythropoiesis, with haemoglobin levels similar to those used for human autologous blood donation, had intermediate post-transfusion RBC recovery, as compared to iron-replete donors and those with iron-deficiency anaemia. This suggests that, in addition to the effects of iron deficiency on donor health, frequent blood donation, leading to iron-deficient erythropoiesis, may also have adverse effects for transfusion recipients. PMID:28263174

Patterns and determinants of functional and absolute iron deficiency in patients undergoing cardiac rehabilitation following heart surgery.

PubMed

Tramarin, Roberto; Pistuddi, Valeria; Maresca, Luigi; Pavesi, Marco; Castelvecchio, Serenella; Menicanti, Lorenzo; de Vincentiis, Carlo; Ranucci, Marco

2017-05-01

Background Anaemia and iron deficiency are frequent following major surgery. The present study aims to identify the iron deficiency patterns in cardiac surgery patients at their admission to a cardiac rehabilitation programme, and to determine which perioperative risk factor(s) may be associated with functional and absolute iron deficiency. Design This was a retrospective study on prospectively collected data. Methods The patient population included 339 patients. Functional iron deficiency was defined in the presence of transferrin saturation <20% and serum ferritin ≥100 µg/l. Absolute iron deficiency was defined in the presence of serum ferritin values <100 µg/l. Results Functional iron deficiency was found in 62.9% of patients and absolute iron deficiency in 10% of the patients. At a multivariable analysis, absolute iron deficiency was significantly ( p = 0.001) associated with mechanical prosthesis mitral valve replacement (odds ratio 5.4, 95% confidence interval 1.9-15) and tissue valve aortic valve replacement (odds ratio 4.5, 95% confidence interval 1.9-11). In mitral valve surgery, mitral repair carried a significant ( p = 0.013) lower risk of absolute iron deficiency (4.4%) than mitral valve replacement with tissue valves (8.3%) or mechanical prostheses (22.5%). Postoperative outcome did not differ between patients with functional iron deficiency and patients without iron deficiency; patients with absolute iron deficiency had a significantly ( p = 0.017) longer postoperative hospital stay (median 11 days) than patients without iron deficiency (median nine days) or with functional iron deficiency (median eight days). Conclusions Absolute iron deficiency following cardiac surgery is more frequent in heart valve surgery and is associated with a prolonged hospital stay. Routine screening for iron deficiency at admission in the cardiac rehabilitation unit is suggested.

Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.

PubMed

Naito, Yoshiro; Hosokawa, Manami; Sawada, Hisashi; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Hirotani, Shinichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

2016-12-01

Several recent observations provide the association of iron deficiency with pulmonary hypertension (PH) in human and animal studies. However, it remains completely unknown whether PH leads to iron deficiency or iron deficiency enhances the development of PH. In addition, it is obscure whether iron is associated with the development of pulmonary vascular remodeling in PH. In this study, we investigate the impacts of dietary iron restriction on the development of hypoxia-induced pulmonary vascular remodeling in mice. Eight- to ten-week-old male C57BL/6J mice were exposed to chronic hypoxia for 4 weeks. Mice exposed to hypoxia were randomly divided into two groups and were given a normal diet or an iron-restricted diet. Mice maintained in room air served as normoxic controls. Chronic hypoxia induced pulmonary vascular remodeling, while iron restriction led a modest attenuation of this change. In addition, chronic hypoxia exhibited increased RV systolic pressure, which was attenuated by iron restriction. Moreover, the increase in RV cardiomyocyte cross-sectional area and RV interstitial fibrosis was observed in mice exposed to chronic hypoxia. In contrast, iron restriction suppressed these changes. Consistent with these changes, RV weight to left ventricular + interventricular septum weight ratio was increased in mice exposed to chronic hypoxia, while this increment was inhibited by iron restriction. Taken together, these results suggest that iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.

Iron Deficiency in Long-Term Parenteral Nutrition Therapy.

PubMed

Hwa, Yi L; Rashtak, Shahrooz; Kelly, Darlene G; Murray, Joseph A

2016-08-01

Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from 11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P = .007). Patients receiving HPN are susceptible to IDA. Iron supplementation should be addressed for patients who rely on PN. © 2015 American Society for Parenteral and Enteral Nutrition.

Beyond Stimulus Deprivation: Iron Deficiency and Cognitive Deficits in Postinstitutionalized Children

ERIC Educational Resources Information Center

Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.; Carlson, Stephanie M.

2014-01-01

Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on…

Iron and Folate-Deficiency Anaemias.

ERIC Educational Resources Information Center

Hercberg, Serge

1990-01-01

Nutritional anemia is believed to be the most widespread nutritional disorder in the world. While it generally affects developing countries, developed countries are also affected to an extent sufficient to justify the implementation of preventive measures at a national level. This report focuses on iron and folate deficiencies, which are by far…

Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis

PubMed Central

Ramos, Emilio; Ruchala, Piotr; Goodnough, Julia B.; Kautz, Léon; Preza, Gloria C.; Nemeth, Elizabeta

2012-01-01

The deficiency of hepcidin, the hormone that controls iron absorption and its tissue distribution, is the cause of iron overload in nearly all forms of hereditary hemochromatosis and in untransfused iron-loading anemias. In a recent study, we reported the development of minihepcidins, small drug-like hepcidin agonists. Here we explore the feasibility of using minihepcidins for the prevention and treatment of iron overload in hepcidin-deficient mice. An optimized minihepcidin (PR65) was developed that had superior potency and duration of action compared with natural hepcidin or other minihepcidins, and favorable cost of synthesis. PR65 was administered by subcutaneous injection daily for 2 weeks to iron-depleted or iron-loaded hepcidin knockout mice. PR65 administration to iron-depleted mice prevented liver iron loading, decreased heart iron levels, and caused the expected iron retention in the spleen and duodenum. At high doses, PR65 treatment also caused anemia because of profound iron restriction. PR65 administration to hepcidin knockout mice with pre-existing iron overload had a more moderate effect and caused partial redistribution of iron from the liver to the spleen. Our study demonstrates that minihepcidins could be beneficial in iron overload disorders either used alone for prevention or possibly as adjunctive therapy with phlebotomy or chelation. PMID:22990014

Iron deficiency associated with higher blood lead in children living in contaminated environments.

PubMed Central

Bradman, A; Eskenazi, B; Sutton, P; Athanasoulis, M; Goldman, L R

2001-01-01

The evidence that iron deficiency increases lead child exposure is based primarily on animal data and limited human studies, and some of this evidence is contradictory. No studies of iron status and blood lead levels in children have accounted for environmental lead contamination and, therefore, the source of their exposure. Thus, no studies have directly determined whether iron deficiency modifies the relationship of environmental lead and blood lead. In this study, we compared blood lead levels of iron-deficient and iron-replete children living in low, medium, or highly contaminated environments. Measurements of lead in paint, soil, dust, and blood, age of housing, and iron status were collected from 319 children ages 1-5. We developed two lead exposure factors to summarize the correlated exposure variables: Factor 1 summarized all environmental measures, and Factor 2 was weighted for lead loading of house dust. The geometric mean blood lead level was 4.9 microg/dL; 14% exceeded 10 microg/dL. Many of the children were iron deficient (24% with ferritin < 12 ng/dL). Seventeen percent of soil leads exceeded 500 microg/g, and 23% and 63% of interior and exterior paint samples exceeded 5,000 microg/g. The unadjusted geometric mean blood lead level for iron-deficient children was higher by 1 microg/dL; this difference was greater (1.8 microg/dL) after excluding Asians. Blood lead levels were higher for iron-deficient children for each tertile of exposure as estimated by Factors 1 and 2 for non-Asian children. Elevated blood lead among iron-deficient children persisted after adjusting for potential confounders by multivariate regression; the largest difference in blood lead levels between iron-deficient and -replete children, approximately 3 microg/dL, was among those living in the most contaminated environments. Asian children had a paradoxical association of sufficient iron status and higher blood lead level, which warrants further investigation. Improving iron status, along with reducing exposures, may help reduce blood lead levels among most children, especially those living in the most contaminated environments. PMID:11675273

Prevalence of anaemia, deficiencies of iron and folic acid and their determinants in Ethiopian women.

PubMed

Haidar, Jemal

2010-08-01

A cross-sectional community-based study with analytic component was conducted among Ethiopian women during June-July 2005 to assess the magnitude of anaemia and deficiencies of iron and folic acid and to compare the factors responsible for anaemia among anaemic and non-anaemic cases. In total, 970 women, aged 15-19 years, were selected systematically for haematological and other important parameters. The overall prevalence of anaemia, iron deficiency, iron-deficiency anaemia, deficiency of folic acid, and parasitic infestations was 30.4%, 50.1%, 18.1%, 31.3%, and 13.7% respectively. Women who had more children aged less than five years but above two years, open-field toilet habits, chronic illnesses, and having intestinal parasites were positively associated with anaemia. Women who had no formal education and who did not use contraceptives were negatively associated with anaemia. The major determinants identified for anaemia were chronic illnesses [adjusted odds ratio (AOR) = 1.1, 95% confidence interval (CI) 1.15-1.55), deficiency of iron (AOR = 0.4, 95% CI 0.35-0.64), and deficiency of folic acid (AOR = 0.5, 95% CI 0.50-0.90). The odds for developing anaemia was 1.1 times more likely among women with chronic illnesses, 60% more likely in the iron-deficient and 40% more likely in the folic acid-deficient than their counterparts. One in every three women had anaemia and deficiency of folic acid while one in every two had iron deficiency, suggesting that deficiencies of both folic acid and iron constitute the major micronutrient deficiencies in Ethiopian women. The risk imposed by anaemia to the health of women ranging from impediment of daily activities and poor pregnancy outcome calls for effective public-health measures, such as improved nutrient supplementation, health education, and timely treatment of illnesses.

Iron in pregnancy: How do we secure an appropriate iron status in the mother and child?

PubMed

Milman, Nils

2011-01-01

Iron deficiency and iron deficiency anemia (IDA) during pregnancy are risk factors for preterm delivery, prematurity, and small for gestational age birth weight. Iron deficiency has a negative effect on intelligence and behavioral development in the infant. It is essential to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. The requirements for absorbed iron increase during pregnancy from ∼1.0 mg/day in the first trimester to 7.5 mg/day in the third trimester. More than 90% of Scandinavian women of reproductive age have a dietary iron intake below the recommended 15 mg/day. Among nonpregnant women of reproductive age, ∼40% have plasma ferritin ≤30 μg/l, i.e. an unfavorable iron status with respect to pregnancy. An adequate iron status during pregnancy implies body iron reserves ≥500 mg at conception, but only 15-20% of women have iron reserves of such a magnitude. Iron supplements during pregnancy reduce the prevalence of IDA. In Europe, IDA can be prevented by a general low-dose iron prophylaxis of 30-40 mg ferrous iron taken between meals from early pregnancy to delivery. In affluent societies, individual iron prophylaxis tailored by the ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are: ferritin >70 μg/l, no iron supplements; ferritin 31-70 μg/l, 30-40 mg ferrous iron per day, and ferritin ≤30 μg/l, 60-80 mg ferrous iron per day. In women with ferritin <15 μg/l, i.e. depleted iron reserves and possible IDA, therapeutic doses of 100 mg ferrous iron per day should be advised. Copyright © 2011 S. Karger AG, Basel.

Young Zanzibari children with iron deficiency, iron deficiency anemia, stunting, or malaria have lower motor activity scores and spend less time in locomotion.

PubMed

Olney, Deanna K; Pollitt, Ernesto; Kariger, Patricia K; Khalfan, Sabra S; Ali, Nadra S; Tielsch, James M; Sazawal, Sunil; Black, Robert; Mast, Darrell; Allen, Lindsay H; Stoltzfus, Rebecca J

2007-12-01

Motor activity improves cognitive and social-emotional development through a child's exploration of his or her physical and social environment. This study assessed anemia, iron deficiency, hemoglobin (Hb), length-for-age Z-score (LAZ), and malaria infection as predictors of motor activity in 771 children aged 5-19 mo. Trained observers conducted 2- to 4-h observations of children's motor activity in and around their homes. Binary logistic regression assessed the predictors of any locomotion. Children who did not locomote during the observation (nonmovers) were excluded from further analyses. Linear regression evaluated the predictors of total motor activity (TMA) and time spent in locomotion for all children who locomoted during the observation combined (movers) and then separately for crawlers and walkers. Iron deficiency (77.0%), anemia (58.9%), malaria infection (33.9%), and stunting (34.6%) were prevalent. Iron deficiency with and without anemia, Hb, LAZ, and malaria infection significantly predicted TMA and locomotion in all movers. Malaria infection significantly predicted less TMA and locomotion in crawlers. In walkers, iron deficiency anemia predicted less activity and locomotion, whereas higher Hb and LAZ significantly predicted more activity and locomotion, even after controlling for attained milestone. Improvements in iron status and growth and prevention or effective treatment of malaria may improve children's motor, cognitive, and social-emotional development either directly or through improvements in motor activity. However, the relative importance of these factors is dependent on motor development, with malaria being important for the younger, less developmentally advanced children and Hb and LAZ becoming important as children begin to attain walking skills.

Iron deficiency and anemia: a common problem in female elite soccer players.

PubMed

Landahl, Göran; Adolfsson, Peter; Börjesson, Mats; Mannheimer, Clas; Rödjer, Stig

2005-12-01

The objective of the study was to determine the prevalence of iron deficiency and iron deficiency anemia among elite women soccer players. Hemoglobin, serum iron, serum total iron binding capacity, and ferritin were determined in 28 female soccer players called up for the national team. Of the investigated female soccer players, 57% had iron deficiency and 29% iron deficiency anemia 6 months before the FIFA Women's World Cup. It is concluded that iron deficiency and iron deficiency anemia is common in female soccer players at the top international level. Some might suffer from relative anemia and measurement of hemoglobin alone is not sufficient to reveal relative anemia. Regular monitoring of hemoglobin concentration and iron status is necessary to institute iron supplementation when indicated.

Investigation and treatment for iron deficiency in heart failure: the unmet need in Lower and Middle Income Countries.

PubMed

Makubi, Abel; Roberts, David J

2017-06-01

Frank iron deficiency has been associated with a wide range of cardiac and pulmonary abnormalities including non-ischaemic cardiomyopathy. Iron deficiency anaemia and isolated iron deficiency are well-defined adverse prognostic factors in non-ischaemic cardiac failure. Furthermore, iron-deficient patients in chronic heart failure with a serum ferritin of <100 μg/l or <300 μg/l with reduced transferrin saturation of <20%, who were given intravenous iron showed improved clinical outcomes. Iron deficiency with or without anaemia affects over a quarter of the world's population, but the impact of iron deficiency in heart failure and the effective management of iron deficiency in heart failure in Lower and Middle Income Countries (LMICs) is not well described. Heart failure in African cohorts occurs at a younger age than in North America and Europe and is more likely to be due to hypertension. Recent studies suggest that iron deficiency anaemia, which is very common in heart failure patients in Africa, and iron deficiency are independently associated with a poor prognosis in heart failure. Preliminary data suggest that iron deficiency in patients with heart failure can be treated with oral iron, with significant beneficial effects on haematological and physiological variables. Cost may prohibit the use of intravenous iron on a large scale in LMICs and optimal regimes to treat iron deficiency in heart failure patients with oral iron therapy remain to be defined. © 2017 John Wiley & Sons Ltd.

Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants.

PubMed

Lozoff, Betsy; De Andraca, Isidora; Castillo, Marcela; Smith, Julia B; Walter, Tomas; Pino, Paulina

2003-10-01

To determine the behavioral and developmental effects of preventing iron-deficiency anemia in infancy. Healthy full-term Chilean infants who were free of iron-deficiency anemia at 6 months were assigned to high- or low-iron groups or to high- or no-added-iron groups. Behavioral/developmental outcomes at 12 months of age included overall mental and motor test scores and specific measures of motor functioning, cognitive processing, and behavior. There were no differences between high- and low-iron groups in the prevalence of iron-deficiency anemia or behavioral/developmental outcome, and they were combined to form an iron-supplemented group (n = 1123) for comparison with the no-added-iron group (n = 534). At 12 months, iron-deficiency anemia was present in 3.1% and 22.6% of the supplemented and unsupplemented groups, respectively. The groups differed in specific behavioral/developmental outcomes but not on global test scores. Infants who did not receive supplemental iron processed information slower. They were less likely to show positive affect, interact socially, or check their caregivers' reactions. A smaller proportion of them resisted giving up toys and test materials, and more could not be soothed by words or objects when upset. They crawled somewhat later and were more likely to be tremulous. The results suggest that unsupplemented infants responded less positively to the physical and social environment. The observed differences seem to be congruent with current understanding of the effects of iron deficiency on the developing brain. The study shows that healthy full-term infants may receive developmental and behavioral benefits from iron supplementation in the first year of life.

Advantages and disadvantages of an iron-rich diet.

PubMed

Hallberg, L

2002-03-01

A review by invitation about advantages and disadvantages of an iron-rich diet by analyzing physiological iron requirements, dietary factors influencing iron absorption and the regulatory systems available to control iron absorption according to needs. The control to prevent iron deficiency is good but not perfect, as observed in previously described studies on relationships between individual iron requirements and the probability of iron deficiency developing in relation to diet. The control to prevent iron overload seems to be perfect except in the few subjects being homozygotes for hereditary hemochromatosis. A diet rich in easily available iron is important for covering basal iron losses, menstrual iron losses and the high iron requirements for growth from infancy to adolescence and for pregnancy.

Controversy on iron needs, intake levels, deficiency stigmata and benefits from iron supplementation

PubMed Central

Walker, Alexander R. P.

1969-01-01

At present there is considerable controversy over many aspects of iron nutrition, including: (1) iron needs and intake levels; (2) the bearing of iron intake on haematological levels; (3) iron deficiency anaemia and deficiency stigmata; and (4) iron therapy, prophylaxis, and the haematological and clinical benefits accruing. Differences of opinion prevail because of inadequacies of knowledge of the level of haemoglobin (or other parameter of iron status) below which unequivocal signs and symptoms of ill-health become manifest in the major proportion of those affected. Difficulties arise equally from lack of knowledge of the level of haemoglobin above which no clinical benefit, short-term or long-term, can be detected from iron supplementation. Clarification of the situation can be obtained only by carrying out the same meticulous and time-consuming procedures that have been used in respect of requirements and deficiency stigmata of other nutrients. Comprehensive iron depletion studies, real and simulated, and repletion studies, including the use of placebos, will be required. Epidemiological investigations bearing on haematological status and morbidity will also need to be undertaken, and include groups of subjects in both Western, and developing countries. PMID:4905446

Results of the First American Prospective Study of Intravenous Iron in Oral Iron-Intolerant Iron-Deficient Gravidas.

PubMed

Auerbach, Michael; James, Stephanie E; Nicoletti, Melissa; Lenowitz, Steven; London, Nicola; Bahrain, Huzefa F; Derman, Richard; Smith, Samuel

2017-12-01

Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes. Seventy-four oral iron-intolerant, second- and third-trimester iron-deficient gravidas were questioned for oral iron intolerance and treated with intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in 250 mL normal saline. Fifteen minutes after a test dose, the remainder was infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin levels and iron parameters were measured. Paired t test was used for hemoglobin and iron; 58/73 women were questioned about interval growth and development of their babies. Seventy-three of 74 enrolled subjects completed treatment. Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin concentrations were 9.7 and 10.8 g/dL (P < .00001), transferrin saturations 11.7% and 22.6% (P = .0003), and ferritins 14.5 and 126.3 ng/mL, respectively (P < .000001). Six experienced minor infusion reactions. All resolved. Data for 58 infants were available; one was low on its growth charts for 11 months. The remaining 57 were normal. None were diagnosed with iron deficiency anemia. Intravenous iron has less toxicity and is more effective, supporting moving it closer to frontline therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Ferritin and iron levels in children with autistic disorder.

PubMed

Hergüner, Sabri; Keleşoğlu, Fatih Mehmet; Tanıdır, Cansaran; Cöpür, Mazlum

2012-01-01

Iron has an important role on cognitive, behavioral, and motor development. High prevalence of iron deficiency has been reported in autism. The aim of this study was to investigate iron status in a group of children with autistic disorder. The sample was composed of 116 children between 3 and 16 years with a diagnosis of autistic disorder according to DSM-IV criteria. Serum ferritin, iron, hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width values were measured. We found that 24.1% of subjects had iron deficiency, and 15.5% had anemia. There was a significant positive correlation between age and ferritin and hematological measures. Results of this study confirmed that iron deficiency and anemia are common in children with autistic disorder. These findings suggest that ferritin levels should be measured in subjects with autism as a part of routine investigation.

Iron Status Predicts Malaria Risk in Malawian Preschool Children

PubMed Central

Jonker, Femkje A. M.; Calis, Job C. J.; van Hensbroek, Michael Boele; Phiri, Kamija; Geskus, Ronald B.; Brabin, Bernard J.; Leenstra, Tjalling

2012-01-01

Introduction Iron deficiency is highly prevalent in pre-school children in developing countries and an important health problem in sub-Saharan Africa. A debate exists on the possible protective effect of iron deficiency against malaria and other infections; yet consensus is lacking due to limited data. Recent studies have focused on the risks of iron supplementation but the effect of an individual's iron status on malaria risk remains unclear. Studies of iron status in areas with a high burden of infections often are exposed to bias. The aim of this study was to assess the predictive value of baseline iron status for malaria risk explicitly taking potential biases into account. Methods and materials We prospectively assessed the relationship between baseline iron deficiency (serum ferritin <30 µg/L) and malaria risk in a cohort of 727 Malawian preschool children during a year of follow-up. Data were analyzed using marginal structural Cox regression models and confounders were selected using causal graph theory. Sensitivity of results to bias resulting from misclassification of iron status by concurrent inflammation and to bias from unmeasured confounding were assessed using modern causal inference methods. Results and Conclusions The overall incidence of malaria parasitemia and clinical malaria was 1.9 (95% CI 1.8–2.0) and 0.7 (95% CI 0.6–0.8) events per person-year, respectively. Children with iron deficiency at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratio's 0.55 (95%-CI:0.41–0.74) and 0.49 (95%-CI:0.33–0.73), respectively. Our results suggest that iron deficiency protects against malaria parasitemia and clinical malaria in young children. Therefore the clinical importance of treating iron deficiency in a pre-school child should be weighed carefully against potential harms. In malaria endemic areas treatment of iron deficiency in children requires sustained prevention of malaria. PMID:22916146

Iron Homeostasis and Nutritional Iron Deficiency123

PubMed Central

Theil, Elizabeth C.

2011-01-01

Nonheme food ferritin (FTN) iron minerals, nonheme iron complexes, and heme iron contribute to the balance between food iron absorption and body iron homeostasis. Iron absorption depends on membrane transporter proteins DMT1, PCP/HCP1, ferroportin (FPN), TRF2, and matriptase 2. Mutations in DMT1 and matriptase-2 cause iron deficiency; mutations in FPN, HFE, and TRF2 cause iron excess. Intracellular iron homeostasis depends on coordinated regulation of iron trafficking and storage proteins encoded in iron responsive element (IRE)-mRNA. The noncoding IRE-mRNA structures bind protein repressors, IRP1 or 2, during iron deficiency. Integration of the IRE-RNA in translation regulators (near the cap) or turnover elements (after the coding region) increases iron uptake (DMT1/TRF1) or decreases iron storage/efflux (FTN/FPN) when IRP binds. An antioxidant response element in FTN DNA binds Bach1, a heme-sensitive transcription factor that coordinates expression among antioxidant response proteins like FTN, thioredoxin reductase, and quinone reductase. FTN, an antioxidant because Fe2+ and O2 (reactive oxygen species generators) are consumed to make iron mineral, is also a nutritional iron concentrate that is an efficiently absorbed, nonheme source of iron from whole legumes. FTN protein cages contain thousands of mineralized iron atoms and enter cells by receptor-mediated endocytosis, an absorption mechanism distinct from transport of nonheme iron salts (ferrous sulfate), iron chelators (ferric-EDTA), or heme. Recognition of 2 nutritional nonheme iron sources, small and large (FTN), will aid the solution of iron deficiency, a major public health problem, and the development of new policies on iron nutrition. PMID:21346101

Iron

MedlinePlus

... too little iron, you may develop iron deficiency anemia. Causes of low iron levels include blood loss, poor diet, or an inability to absorb enough iron from foods. People at higher risk of having too little iron are young children and women who are pregnant or have periods. ...

Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats

PubMed Central

Walter, Patrick B.; Knutson, Mitchell D.; Paler-Martinez, Andres; Lee, Sonia; Xu, Yu; Viteri, Fernando E.; Ames, Bruce N.

2002-01-01

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (≤5 μg/day) and iron-normal (800 μg/day) rats and in both groups after daily high-iron supplementation (8,000 μg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 μg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 × nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake. PMID:11854522

Iron deficiency and new insights into therapy.

PubMed

Low, Michael Sy; Grigoriadis, George

2017-07-17

Iron deficiency and iron deficiency anaemia remain prevalent in Australia. The groups at highest risk are pre-menopausal women, socially disadvantaged people and those of Indigenous background. Diagnosing iron deficiency using a full blood examination and iron studies can be difficult and can be further complicated by concomitant inflammation. Results of iron studies should always be interpreted as an overall picture rather than focusing on individual parameters. In difficult clinical scenarios, soluble transferrin receptor assays can be useful. Management of iron deficiency involves identification and treatment of the cause of iron deficiency, as well as effective iron replacement. Clinicians should always take a detailed history and perform a comprehensive physical examination of a patient with iron deficiency. Patients should be monitored even if a likely cause of iron deficiency is identified. Patients who fail to respond to iron replacement or maintain iron status should be referred for further investigation, including endoscopy to exclude internal bleeding. Both enteral and parenteral iron are effective at replacing iron. For most adult patients, we recommend trialling daily oral iron (30-100 mg of elemental iron) as the first-line therapy. Safety and efficacy of intravenous iron infusions have improved with the availability of a newer formulation, ferric carboxymaltose. Patients who fail to respond to oral iron replacement can be safely managed with intravenous iron. Blood transfusion for iron deficiency anaemia should be reserved for life-threatening situations and should always be followed by appropriate iron replacement.

Iron-Deficiency Anemia (For Parents)

MedlinePlus

... Videos for Educators Search English Español Iron-Deficiency Anemia KidsHealth / For Parents / Iron-Deficiency Anemia What's in ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

The treatment of iron deficiency without anaemia (in otherwise healthy persons).

PubMed

Clénin, German E

2017-06-21

Iron deficiency is the most widespread and frequent nutritional disorder in the world. It affects a high proportion of children and women in developing countries and is also significantly prevalent in the industrialised world, with a clear predominance in adolescents and menstruating females. Iron is essential for optimal cognitive function and physical performance, not only as a binding site of oxygen but also as a critical constituent of many enzymes. Therefore iron deficiency at all its levels - nonanaemic iron deficiency, iron deficiency with microcytosis or hypochromia and iron deficiency anaemia - should be treated. In the presence of normal stores, however, preventative iron administration is inefficient, has side effects and seems to be harmful. In symptomatic patients with fatigue or in a population at risk for iron deficiency (adolescence, heavy or prolonged menstruation, high performance sport, vegetarian or vegan diet, eating disorder, underweight), a baseline set of blood tests including haemoglobin concentration, haematocrit, mean cellular volume, mean cellular haemoglobin, percentage of hypochromic erythrocytes and serum ferritin levels are important to monitor iron deficiency. To avoid false negative results (high ferritin levels in spite of iron deficiency), an acute phase reaction should be excluded by history and measurement of C-reactive protein. An algorithm leads through this diagnostic process and the decision making for a possible treatment. For healthy males and females aged >15 years, a ferritin cut-off of 30 µg/l is appropriate. For children from 6-12 years and younger adolescents from 12-15 years, cut-offs of 15 and 20 µg/l, respectively, are recommended. As a first step in treatment, counselling and oral iron therapy are usually combined. Integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial. In order to prevent reduced compliance, mainly as a result of gastrointestinal side effects of oral treatment, the use of preparations with reasonable but not excessive elemental iron content (28-50 mg) seems appropriate. Only in exceptional cases will an intravenous injection be necessary (e.g., concomitant disease needing urgent treatment, repeated failure of first-step therapy).To measure the success of treatment, the basic blood tests should be repeated after 8 to 10 weeks. Patients with repeatedly low ferritin will benefit from intermittent oral substitution to preserve iron stores and from long term follow-up, with the basic blood tests repeated every 6 or 12 months to monitor iron stores. Long-term daily oral or intravenous iron supplementation in the presence of normal or even high ferritin values is, however, not recommended and is potentially harmful.

Impact of neonatal iron deficiency on hippocampal DNA methylation and gene transcription in a porcine biomedical model of cognitive development.

PubMed

Schachtschneider, Kyle M; Liu, Yingkai; Rund, Laurie A; Madsen, Ole; Johnson, Rodney W; Groenen, Martien A M; Schook, Lawrence B

2016-11-03

Iron deficiency is a common childhood micronutrient deficiency that results in altered hippocampal function and cognitive disorders. However, little is known about the mechanisms through which neonatal iron deficiency results in long lasting alterations in hippocampal gene expression and function. DNA methylation is an epigenetic mark involved in gene regulation and altered by environmental factors. In this study, hippocampal DNA methylation and gene expression were assessed via reduced representation bisulfite sequencing and RNA-seq on samples from a previous study reporting reduced hippocampal-based learning and memory in a porcine biomedical model of neonatal iron deficiency. In total 192 differentially expressed genes (DEGs) were identified between the iron deficient and control groups. GO term and pathway enrichment analysis identified DEGs associated with hypoxia, angiogenesis, increased blood brain barrier (BBB) permeability, and altered neurodevelopment and function. Of particular interest are genes previously implicated in cognitive deficits and behavioral disorders in humans and mice, including HTR2A, HTR2C, PAK3, PRSS12, and NETO1. Altered genome-wide DNA methylation was observed across 0.5 million CpG and 2.4 million non-CpG sites. In total 853 differentially methylated (DM) CpG and 99 DM non-CpG sites were identified between groups. Samples clustered by group when comparing DM non-CpG sites, suggesting high conservation of non-CpG methylation in response to neonatal environment. In total 12 DM sites were associated with 9 DEGs, including genes involved in angiogenesis, neurodevelopment, and neuronal function. Neonatal iron deficiency leads to altered hippocampal DNA methylation and gene regulation involved in hypoxia, angiogenesis, increased BBB permeability, and altered neurodevelopment and function. Together, these results provide new insights into the mechanisms through which neonatal iron deficiency results in long lasting reductions in cognitive development in humans.

Iron deficiency anaemia among apparently healthy pre-school children in Lagos, Nigeria.

PubMed

Akodu, Olufemi S; Disu, Elizabeth A; Njokanma, Olisamedua F; Kehinde, Omolara A

2016-03-01

Iron deficiency, and specifically iron deficiency anaemia, remains one of the most severe and important nutritional deficiencies in the world today. To estimate the prevalence and associated factors for iron deficiency anaemia among pre-school children in Lagos. The study was conducted from December 2009 to February 2010 at the outpatient clinics of Lagos State University Teaching Hospital, Lagos. Serum iron, total iron binding capacity, transferrin saturation and serum ferritin were assayed in subjects. The primary outcome measured was iron deficiency anaemia established based on the following criteria: hemoglobin <11.0 g/dl1 plus 2 or more of the following: MCV <70fl, transferrin saturation <10% or serum ferritin <15ng/dL. Statistical analysis included Pearson Chi square analysis and logistic regression analysis. A total of 87 apparently healthy subjects were recruited. Only one subject had iron depletion and this child belonged to the ≤ 2 years age category. None of the recruited subjects had iron deficiency without anaemia. Nine of the study subjects (10.11%) had iron deficiency anaemia. The prevalence of iron deficiency anaemia was significantly higher among younger age group than in the older age group (19.1% Vs 2.1%, p = 0.022). The prevalence of iron deficiency anaemia was significantly higher among subjects with weight-for-age, and weight-for-height Z scores below two standard scores (83.3% and 75.0% respectively, p = <0.001 and 0.001 respectively). The overall prevalence of iron deficiency anaemia among study subjects was 10.11%. Iron deficiency anaemia was more common in children aged two years and below. Weight-for-age and weight-for-height Z scores below minus two standard scores were strongly associated with iron deficiency anaemia.

Ethylene response factor AtERF72 negatively regulates Arabidopsis thaliana response to iron deficiency.

PubMed

Liu, Wei; Li, Qiwei; Wang, Yi; Wu, Ting; Yang, Yafei; Zhang, Xinzhong; Han, Zhenhai; Xu, Xuefeng

2017-09-23

Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H + velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H + -ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

PubMed

Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

2016-07-01

Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

Iron Deficiency in Patients with Nonalcoholic Fatty Liver Disease is Associated with Obesity, Female Sex, and Low Serum Hepcidin

PubMed Central

Siddique, Asma; Nelson, James E.; Aouizerat, Bradley; Yeh, Matthew M.; Kowdley, Kris V.

2014-01-01

Background & Aims Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines IL6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin and IL6 and IL1β, and other risk factors in patients with non-alcoholic fatty liver disease (NAFLD) with iron deficiency. Methods We collected data on 675 adult subjects (>18 y old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, as well as serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results One third of patients (231/675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P<.01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61±45 vs 81±51 ng/mL; P<.0001). Iron deficiency was significantly associated with female sex, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, Black or American Indian/Alaska Native race (P≤.018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal; P≤.0001 and 0.45 vs 0.32 for iron normal; P≤.005). Conclusion Iron deficiency is prevalent in patients with NAFLD and associated with female sex, increased body mass index, and non-white race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiological response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD. PMID:24269922

Vitamin A deficiency, iron deficiency, and anemia among preschool children in the Republic of the Marshall Islands.

PubMed

Palafox, Neal A; Gamble, Mary V; Dancheck, Barbara; Ricks, Michelle O; Briand, Kennar; Semba, Richard D

2003-05-01

We investigated the co-occurrence of vitamin A deficiency, iron deficiency, and anemia among young children in the Republic of the Marshall Islands. Hemoglobin, serum retinol, and serum ferritin were assessed in the Republic of the Marshall Islands Vitamin A Deficiency Study, a community-based survey that involved 919 children ages 1 to 5 y. The proportion of children with vitamin A deficiency (serum retinol concentrations < 0.70 microM/L) was 59.9%. The prevalences of anemia (hemoglobin < 110 g/L), iron deficiency (serum ferritin < 12 microg/L), and iron deficiency anemia (iron deficiency and anemia) were 36.4%, 53.5%, and 23.8%, respectively. The proportion of children who had co-occurrence of vitamin A and iron deficiencies was 33.2%. The mean ages of children with and without vitamin A deficiency were 3.2 +/- 1.4 and 2.9 +/- 1.5 y, respectively (P = 0.01), and the mean ages of those with and without iron deficiency were 2.7 +/- 1.3 and 3.5 +/- 1.4 y, respectively (P < 0.0001). Children in the Republic of the Marshall Islands, ages 1 to 5 y, are at high risk of anemia, vitamin A deficiency, and iron deficiency, and one-third of these children had the co-occurrence of vitamin A and iron deficiencies. Further investigation is needed to identify risk factors and evaluate interventions to address vitamin A and iron deficiencies among children.

Motor development in 9-month-old infants in relation to cultural differences and iron status.

PubMed

Angulo-Barroso, Rosa M; Schapiro, Lauren; Liang, Weilang; Rodrigues, Onike; Shafir, Tal; Kaciroti, Niko; Jacobson, Sandra W; Lozoff, Betsy

2011-03-01

Motor development, which allows infants to explore their environment, promoting cognitive, social, and perceptual development, can be influenced by cultural practices and nutritional factors, such as iron deficiency. This study compared fine and gross motor development in 209 9-month-old infants from urban areas of China, Ghana, and USA (African-Americans) and considered effects of iron status. Iron deficiency anemia was most common in the Ghana sample (55%) followed by USA and China samples. Controlling for iron status, Ghanaian infants displayed precocity in gross motor development and most fine-motor reach-and-grasp tasks. US African-Americans performed the poorest in all tasks except bimanual coordination and the large ball. Controlling for cultural site, iron status showed linear trends for gross motor milestones and fine motor skills with small objects. Our findings add to the sparse literature on infant fine motor development across cultures. The results also indicate the need to consider nutritional factors when examining cultural differences in infant development. Copyright © 2010 Wiley Periodicals, Inc.

Motor Development in 9-Month-Old Infants in Relation to Cultural Differences and Iron Status

PubMed Central

Schapiro, Lauren; Liang, Weilang; Rodrigues, Onike; Shafir, Tal; Kaciroti, Niko; Jacobson, Sandra W.; Lozoff, Betsy

2011-01-01

Motor development, which allows infants to explore their environment, promoting cognitive, social, and perceptual development, can be influenced by cultural practices and nutritional factors, such as iron deficiency. This study compared fine and gross motor development in 209 9-month-old infants from urban areas of China, Ghana, and USA (African-Americans) and considered effects of iron status. Iron deficiency anemia was most common in the Ghana sample (55%) followed by USA and China samples. Controlling for iron status, Ghanaian infants displayed precocity in gross motor development and most fine-motor reach-and-grasp tasks. US African-Americans performed the poorest in all tasks except bimanual coordination and the large ball. Controlling for cultural site, iron status showed linear trends for gross motor milestones and fine motor skills with small objects. Our findings add to the sparse literature on infant fine motor development across cultures. The results also indicate the need to consider nutritional factors when examining cultural differences in infant development. PMID:21298634

The Pseudomonas fluorescens Siderophore Pyoverdine Weakens Arabidopsis thaliana Defense in Favor of Growth in Iron-Deficient Conditions1

PubMed Central

Trapet, Pauline; Avoscan, Laure; Klinguer, Agnès; Pateyron, Stéphanie; Chervin, Christian; Mazurier, Sylvie; Lemanceau, Philippe; Wendehenne, David; Besson-Bard, Angélique

2016-01-01

Pyoverdines are siderophores synthesized by fluorescent Pseudomonas spp. Under iron-limiting conditions, these high-affinity ferric iron chelators are excreted by bacteria in the soil to acquire iron. Pyoverdines produced by beneficial Pseudomonas spp. ameliorate plant growth. Here, we investigate the physiological incidence and mode of action of pyoverdine from Pseudomonas fluorescens C7R12 on Arabidopsis (Arabidopsis thaliana) plants grown under iron-sufficient or iron-deficient conditions. Pyoverdine was provided to the medium in its iron-free structure (apo-pyoverdine), thus mimicking a situation in which it is produced by bacteria. Remarkably, apo-pyoverdine abolished the iron-deficiency phenotype and restored the growth of plants maintained in the iron-deprived medium. In contrast to a P. fluorescens C7R12 strain impaired in apo-pyoverdine production, the wild-type C7R12 reduced the accumulation of anthocyanins in plants grown in iron-deficient conditions. Under this condition, apo-pyoverdine modulated the expression of around 2,000 genes. Notably, apo-pyoverdine positively regulated the expression of genes related to development and iron acquisition/redistribution while it repressed the expression of defense-related genes. Accordingly, the growth-promoting effect of apo-pyoverdine in plants grown under iron-deficient conditions was impaired in iron-regulated transporter1 and ferric chelate reductase2 knockout mutants and was prioritized over immunity, as highlighted by an increased susceptibility to Botrytis cinerea. This process was accompanied by an overexpression of the transcription factor HBI1, a key node for the cross talk between growth and immunity. This study reveals an unprecedented mode of action of pyoverdine in Arabidopsis and demonstrates that its incidence on physiological traits depends on the plant iron status. PMID:26956666

Influence of iron deficiency on the growth rate and physiological state of Prorocentrum micans Ehrenberg

NASA Astrophysics Data System (ADS)

Huan-Xin, W.; Xiang-Wei, S.; Jing-Ke, W.; Ya-Chao, Q.

2004-12-01

Previous researches had shown that iron is an important limiting element to marine primary production. However, the mechanism of how iron affects marine algae is not well understood. Prorocentrum micans Ehrenberg is an armoured marine planktonic dinoflagellate, which causes harmful red tide when blooming. In this research, we discussed the mechanism of iron deficiency affecting the growth rate and physiological state of P. micans Ehrenberg, based on the observation of the growth of P. micans Ehrenberg under iron deficiency. The results showed that the growth rate of P. micans Ehrenberg decreased under iron deficiency, as the time to reach the peak of cell numbers was delayed 3-4 days compared to the control group. Meanwhile, the maximal cell number and the concentration of chlorophyll a dropped slightly. Examination of cell morphology by transmission electron microscope showed that the arrangement of P. micans Ehrenberg chloroplast granum was disturbed under iron deficiency. The thylakoids exhibited twisted structure with larger interstices among the thylakoid layers. Chloroplast membrane system folded abnormally and fewer starch particles were synthesized and accumulated compared to the control group. In addition, many cavities appeared in mitochondria, and a few cells developed incomplete nuclear envelop. The energy spectrogram of the algal cells showed that the relative ratio of the contents of the elements in cell also changed as the degree of iron deficiency changed. The iron deficiency-induced morphological changes of P. micans Ehrenberg cell organelles may be due to the misfolding of some core proteins that originally require iron ion as folding center. The structural abnormality of the major cell organelles further led to the functional retardation or loss in photosynthesis, electron transport, and metabolism, which blocks normal growth of P. micans Ehrenberg. Taken together, the research helped to improve our understanding on the limiting effects of iron on marine algae growth and proposed a potential way to control red tides caused by algae blooming.

Two MATE Proteins Play a Role in Iron Efficiency in Soybean

USDA-ARS?s Scientific Manuscript database

Iron is a necessary but often limiting nutrient for plant growth and development. Soybeans grown on the high-pH calcareous soils are especially prone to developing iron deficiency chlorosis and suffering the resultant yield losses. Once iron is transported into the root, it must be translocated from...

Nutritional and Micronutrient Status of Female Workers in a Garment Factory in Cambodia.

PubMed

Makurat, Jan; Friedrich, Hanna; Kuong, Khov; Wieringa, Frank T; Chamnan, Chhoun; Krawinkel, Michael B

2016-11-02

Concerns about the nutritional status of Cambodian garment workers were raised years ago but data are still scarce. The objectives of this study are to examine the nutritional, hemoglobin and micronutrient status of female workers in a garment factory in Phnom Penh, Cambodia, and to assess if body mass index is associated with hemoglobin and/or micronutrient status. A cross-sectional survey was conducted among 223 female workers (nulliparous, non-pregnant) at a garment factory in Phnom Penh. Anthropometric measurements were performed and blood samples were taken to obtain results on hemoglobin, iron, vitamin A, vitamin B12 and inflammation status (hemoglobinopathies not determined). Bivariate correlations were used to assess associations. Overall, 31.4% of workers were underweight, 26.9% showed anemia, 22.1% showed iron deficiency, while 46.5% had marginal iron stores. No evidence of vitamin A or vitamin B12 deficiency was found. Body mass index was associated with serum ferritin (negative) and serum retinol-binding protein (positive) concentrations, but not strongly. A comparison between underweight and not underweight workers resulted in distinctions for iron deficiency and iron deficiency anemia, with a higher prevalence among not underweight. The prevalence of underweight, anemia and poor iron status was high. Young and nulliparous female garment workers in Cambodia might constitute a group with elevated risk for nutritional deficiencies. Strategies need to be developed for improving their nutritional, micronutrient and health status. The poor iron status seems to contribute to the overall prevalence of anemia. Low hemoglobin and iron deficiency affected both underweight and those not underweight. Despite the fact that body mass index was negatively associated with iron stores, true differences in iron status between underweight and not underweight participants cannot be confirmed.

Nutritional and Micronutrient Status of Female Workers in a Garment Factory in Cambodia

PubMed Central

Makurat, Jan; Friedrich, Hanna; Kuong, Khov; Wieringa, Frank T.; Chamnan, Chhoun; Krawinkel, Michael B.

2016-01-01

Background: Concerns about the nutritional status of Cambodian garment workers were raised years ago but data are still scarce. The objectives of this study are to examine the nutritional, hemoglobin and micronutrient status of female workers in a garment factory in Phnom Penh, Cambodia, and to assess if body mass index is associated with hemoglobin and/or micronutrient status. Methods: A cross-sectional survey was conducted among 223 female workers (nulliparous, non-pregnant) at a garment factory in Phnom Penh. Anthropometric measurements were performed and blood samples were taken to obtain results on hemoglobin, iron, vitamin A, vitamin B12 and inflammation status (hemoglobinopathies not determined). Bivariate correlations were used to assess associations. Results: Overall, 31.4% of workers were underweight, 26.9% showed anemia, 22.1% showed iron deficiency, while 46.5% had marginal iron stores. No evidence of vitamin A or vitamin B12 deficiency was found. Body mass index was associated with serum ferritin (negative) and serum retinol-binding protein (positive) concentrations, but not strongly. A comparison between underweight and not underweight workers resulted in distinctions for iron deficiency and iron deficiency anemia, with a higher prevalence among not underweight. Conclusions: The prevalence of underweight, anemia and poor iron status was high. Young and nulliparous female garment workers in Cambodia might constitute a group with elevated risk for nutritional deficiencies. Strategies need to be developed for improving their nutritional, micronutrient and health status. The poor iron status seems to contribute to the overall prevalence of anemia. Low hemoglobin and iron deficiency affected both underweight and those not underweight. Despite the fact that body mass index was negatively associated with iron stores, true differences in iron status between underweight and not underweight participants cannot be confirmed. PMID:27827854

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

PubMed

Evstatiev, Rayko; Bukaty, Adam; Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Surman, Lidia; Schmid, Werner; Eferl, Robert; Lippert, Kathrin; Scheiber-Mojdehkar, Barbara; Kvasnicka, Hans Michael; Khare, Vineeta; Gasche, Christoph

2014-05-01

Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Copyright © 2014 Wiley Periodicals, Inc.

Treatment of Iron Deficiency in Women

PubMed Central

Breymann, C.; Römer, T.; Dudenhausen, J. W.

2013-01-01

Iron deficiency with and without anaemia is a common cause of morbidity, particularly in women. Iron deficiency is generally the result of an imbalance between iron loss and iron absorption. In women with symptoms suspicious for iron deficiency, it is important to confirm or exclude the suspicion using proper tests. The use of serum ferritin levels is considered the gold standard for diagnosis. Although the ideal ferritin levels are not unknown the current consent is that levels < 40 ng/ml indicate iron deficiency, which needs to be treated in symptomatic patients. However, symptoms can already occur at ferritin levels of < 100 ng/ml and treatment must be adapted to the individual patient. Iron supplementation is only indicated in symptomatic patients diagnosed with iron deficiency whose quality of life is affected. It is important to treat iron deficiency together with its causes or risk factors. For example, blood loss from hypermenorrhea should be reduced. Women also need to receive information about the benefits of an iron-rich diet. If oral treatment with iron supplements is ineffective, parenteral iron administration is recommended. PMID:26633902

Recovering from iron deficiency chlorosis in near-isogenic soybeans: a microarray study.

PubMed

O'Rourke, Jamie A; Graham, Michelle A; Vodkin, Lila; Gonzalez, Delkin Orlando; Cianzio, Silvia R; Shoemaker, Randy C

2007-05-01

Iron deficiency chlorosis (IDC) in soybeans has proven to be a perennial problem in the calcareous soils of the U.S. upper Midwest. A historically difficult trait to study in fields, the use of hydroponics in a controlled greenhouse environment has provided a mechanism to study genetic variation while limiting environmental complications. IDC susceptible plants growing in calcareous soils and in iron-controlled hydroponic experiments often exhibit a characteristic chlorotic phenotype early in the growing season but are able to re-green later in the season. To examine the changes in gene expression of these plants, near-isogenic lines, iron efficient PI548553 (Clark) and iron inefficient PI547430 (IsoClark), developed for their response to iron deficiency stress [USDA, ARS, National Genetic Resources Program, Germplasm Resources Information Network - GRIN. (Online Database) National Germplasm Resources Laboratory, Beltsville, MD, 2004. Available: http://www.ars.grin.gov/cgi-bin/npgs/html/acc_search.pl?accid=PI+547430. [22] were grown in iron-deficient hydroponic conditions for one week, then transferred to iron sufficient conditions for another week. This induced a phenotypic response mimicking the growth of the plants in the field; initial chlorosis followed by re-greening. RNA was isolated from root tissue and transcript profiles were examined between the two near-isogenic lines using publicly available cDNA microarrays. By alleviating the iron deficiency stress our expectation was that plants would return to baseline expression levels. However, the microarray comparison identified four cDNAs that were under-expressed by a two-fold or greater difference in the iron inefficient plant compared to the iron efficient plant. This differential expression was re-examined and confirmed by real time PCR experimentation. Control experiments showed that these genes are not differentially expressed in plants grown continually under iron rich hydroponic conditions. The expression differences suggest potential residual effects of iron deficiency on plant health.

Association between functional iron deficiency and reactive thrombocytosis in hospitalised patients: a case-control study.

PubMed

Nicola, H; Ho, K M; Cordingley, F

2016-11-01

The association of deficiency in total body iron with an increased risk of reactive thrombocytosis is well known, but whether 'functional iron deficiency' is also associated with reactive thrombocytosis is unknown. This retrospective case-control study assessed the relationships between functional iron deficiency, reactive thrombocytosis and risk of thromboembolism. A total of 150 patients with reactive thrombocytosis (platelet count >400 x 10 9 /l) and 343 controls (platelet count <400 x 10 9 /l) were selected from the hospital laboratory database system. Patients with haematological disease or recent chemotherapy were excluded. Reactive thrombocytosis, infection, and an elevated C-reactive protein (CRP) concentration were all significantly more common in patients with functional iron deficiency than in those without functional iron deficiency (all P <0.01). After adjusting for infection and CRP concentration, functional iron deficiency was the only marker of iron status significantly associated with reactive thrombocytosis (odds ratio 1.66, 95% confidence interval 1.10-2.75; P =0.048). Thromboembolic events occurred in 32 patients (6.6%). This was not significantly associated with functional iron deficiency. Our results suggest that in patients without haematological malignancy or recent chemotherapy there might be a link between functional iron deficiency and reactive thrombocytosis. Whether treating patients with functional iron deficiency with intravenous iron corrects reactive thrombocytosis without inducing infection remains uncertain, but merits further investigation.

The Deterioration Seen in Myelin Related Morphophysiology in Vanadium Exposed Rats is Partially Protected by Concurrent Iron Deficiency.

PubMed

Usende, Ifukibot Levi; Leitner, Dominque F; Neely, Elizabeth; Connor, James R; Olopade, James O

2016-08-30

Oligodendrocyte development and myelination occurs vigorously during the early post natal period which coincides with the period of peak mobilization of iron. Oligodendrocyte progenitor cells (OPCs) are easily disturbed by any agent that affects iron homeostasis and its assimilation into these cells. Environmental exposure to vanadium, a transition metal can disrupt this iron homeostasis. We investigated the interaction of iron deficiency and vanadium exposure on the myelination infrastructure and its related neurobehavioural phenotypes, and neurocellular profiles in developing rat brains. Control group (C) dams were fed normal diet while Group 2 (V) dams were fed normal diet and pups were injected with 3mg/kg body weight of sodium metavanadate daily from postnatal day (PND) 1-21. Group 3 (I+V) dams were fed iron deficient diet after delivery and pups injected with 3mg/kg body weight sodium metavanadate from PND1-21. Body and brain weights deteriorated in I+V relative to C and V while neurobehavioral deficit occurred more in V. Whereas immunohistochemical staining shows more astrogliosis and microgliosis indicative of neuroinflammation in I+V, more intense OPCs depletion and hypomyelination were seen in the V, and this was partially protected in I+V. In in vitro studies, vanadium induced glial cells toxicity was partially protected only at the LD 50 dose with the iron chelator, desferroxamine. The data indicate that vanadium promotes myelin damage and iron deficiency in combination with vanadium partially protects this neurotoxicological effects of vanadium.

Maternal iron – infection interactions and neonatal mortality, with an emphasis on developing countries

PubMed Central

Brabin, Loretta; Brabin, Bernard J.; Gies, Sabine

2013-01-01

Infection is a major cause of neonatal death in developing countries. We address the question whether host iron status affects maternal and/or neonatal infection risk, potentially contributing to neonatal death. We summarize the iron acquisition mechanisms described for pathogens causing stillbirth, preterm birth, and congenital infection. There is in vitro evidence that iron availability influences severity and chronicity of infections that cause these outcomes. The risk in vivo is unknown as relevant studies of maternal iron supplementation have not assessed infection risk. Reducing iron deficiency anemia among women is beneficial and should improve the iron stores of babies, but there is evidence that iron status in young children predicts malaria risk and possibly invasive bacterial diseases. Caution with maternal iron supplementation is indicated in iron-replete women who have high infection exposure, although distinguishing iron-replete and iron-deficient women is currently difficult. Further research is indicated to investigate infection risk in relation to iron status in mothers and babies in order to avoid iron intervention strategies that result in detrimental birth outcomes for some groups of women. PMID:23865798

The impact of anaemia and iron deficiency in chronic obstructive pulmonary disease: A clinical overview.

PubMed

Robalo Nunes, A; Tátá, M

Anaemia is increasingly recognised as an important comorbidity in the context of chronic obstructive pulmonary disease (COPD), but remains undervalued in clinical practice. This review aims to characterise the impact of anaemia and iron deficiency in COPD. Literature review of studies exploring the relationship between anaemia/iron deficiency and COPD, based on targeted MEDLINE and Google Scholar queries. The reported prevalence of anaemia in COPD patients, ranging from 4.9% to 38.0%, has been highly variable, due to different characteristics of study populations and lack of a consensus on the definition of anaemia. Inflammatory processes seem to play an important role in the development of anaemia, but other causes (including nutritional deficiencies) should not be excluded from consideration. Anaemia in COPD has been associated with increased morbidity, mortality, and overall reduced quality of life. The impact of iron deficiency, irrespective of anaemia, is not as well studied, but it might have important implications, since it impacts production of red blood cells and respiratory enzymes. Treatment of anaemia/iron deficiency in COPD remains poorly studied, but it appears reasonable to assume that COPD patients should at least receive the same type of treatment as other patients. Anaemia and iron deficiency continue to be undervalued in most COPD clinical settings, despite affecting up to one-third of patients and having negative impact on prognosis. Special efforts should be made to improve clinical management of anaemia and iron deficiency in COPD patients as a means of achieving better patient care. Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

An overview of methods for assessment of iron bioavailability from foods nutritionally enhanced through biotechnology.

PubMed

Cockell, Kevin A

2007-01-01

Iron deficiency and iron deficiency anemia continue to be significant public health problems worldwide. While supplementation and fortification have been viable means to improve iron nutriture of the population in developed countries, they may be less successful in developing regions for a number of reasons, including complexities in distribution and consumer compliance. Biofortification of staple crops, through conventional plant breeding strategies or modern methods of biotechnology, provides an alternative approach that may be more sustainable once initial investments have been made. Three types of biofortification strategies are being essayed, singly or in combination: increasing the total iron content of edible portions of the plant, decreasing the levels of inhibitors of iron absorption, and increasing the levels of factors that enhance iron absorption. Bioavailability is a key concept in iron nutrition, particularly for nonheme iron such as is found in these biofortified foods. An overview is presented of methods for evaluation of iron bioavailability from foods nutritionally enhanced through biotechnology.

Correction of iron-deficiency anaemia in colorectal surgery reduces perioperative transfusion rates: A before and after study.

PubMed

Quinn, Edel M; Meland, Ellen; McGinn, Stacy; Anderson, John H

2017-02-01

Preoperative anaemia is a risk factor for poorer postoperative outcomes and many colorectal cancer patients have iron-deficiency anaemia. The aim of this study was to assess if a preoperative iron-deficiency anaemia management protocol for elective colorectal surgery patients helps improve detection and treatment of iron-deficiency, and improve patient outcomes. Retrospective data was collected from 95 consecutive patients undergoing colorectal cancer surgery to establish baseline anaemia correction rates and perioperative transfusion rates. A new pathway for early detection of iron-deficiency anaemia, and treatment with intravenous iron replacement, for colorectal cancer patients was then developed and implemented. Data from 81 patients was collected prospectively post-implementation to assess the impact of the pathway. Pre-intervention data showed anaemic patients were seventeen times more likely to require perioperative transfusion than non-anaemic patients (95% CI 1.9-151.0, p = 0.011). Post-intervention, fifteen patients with iron-deficiency were treated with either intravenous (n = 8) or oral iron (n = 7). Mean Day 3 postoperative haemoglobin levels were significantly lower in patients with uncorrected anaemia (9.5 g/dL, p = 0.004); those patients whose anaemia was corrected by iron replacement therapy preoperatively had similar postoperative results to non-anaemic patients (10.93 g/dL vs 11.4 g/dL, p = 0.781). Postoperative transfusion rates remained high at 38% in patients with uncorrected anaemia, compared to 0% in corrected anaemia and 3.5% in non-anaemic patients. Introduction of an iron-deficiency anaemia management pathway has resulted in improved perioperative haemoglobin levels, with a reduction in perioperative transfusion, in elective colorectal patients. Implementation of this pathway could result in similar outcomes across other categories of surgical patients. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Nitric Oxide Improves Internal Iron Availability in Plants1

PubMed Central

Graziano, Magdalena; Beligni, María Verónica; Lamattina, Lorenzo

2002-01-01

Iron deficiency impairs chlorophyll biosynthesis and chloroplast development. In leaves, most of the iron must cross several biological membranes to reach the chloroplast. The components involved in the complex internal iron transport are largely unknown. Nitric oxide (NO), a bioactive free radical, can react with transition metals to form metal-nitrosyl complexes. Sodium nitroprusside, an NO donor, completely prevented leaf interveinal chlorosis in maize (Zea mays) plants growing with an iron concentration as low as 10 μm Fe-EDTA in the nutrient solution. S-Nitroso-N-acetylpenicillamine, another NO donor, as well as gaseous NO supply in a translucent chamber were also able to revert the iron deficiency symptoms. A specific NO scavenger, 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, blocked the effect of the NO donors. The effect of NO treatment on the photosynthetic apparatus of iron-deficient plants was also studied. Electron micrographs of mesophyll cells from iron-deficient maize plants revealed plastids with few photosynthetic lamellae and rudimentary grana. In contrast, in NO-treated maize plants, mesophyll chloroplast appeared completely developed. NO treatment did not increase iron content in plant organs, when expressed in a fresh matter basis, suggesting that root iron uptake was not enhanced. NO scavengers 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and methylene blue promoted interveinal chlorosis in iron-replete maize plants (growing in 250 μm Fe-EDTA). Even though results support a role for endogenous NO in iron nutrition, experiments did not establish an essential role. NO was also able to revert the chlorotic phenotype of the iron-inefficient maize mutants yellow stripe1 and yellow stripe3, both impaired in the iron uptake mechanisms. All together, these results support a biological action of NO on the availability and/or delivery of metabolically active iron within the plant. PMID:12481068

Prevalence of anemia and micronutrient deficiencies in early pregnancy in rural Bangladesh, the MINIMat trial.

PubMed

Lindström, Emma; Hossain, Mohammad B; Lönnerdal, Bo; Raqib, Rubhana; El Arifeen, Shams; Ekström, Eva-Charlotte

2011-01-01

To describe the prevalence of anemia and micronutrient deficiencies as well as their determinants in early pregnancy. Baseline data from a population-based randomized intervention trial. The study was conducted in Matlab, a sub-district in rural Bangladesh from 1 January to 31 December 2002. Pregnant women (n= 740) were enrolled in approximately week 14 in pregnancy. Data were collected using questionnaires, physical examinations and laboratory analyses of blood samples for concentrations of hemoglobin, ferritin, zinc, folate and vitamin B-12. Covariates associated with anemia and micronutrient deficiencies in bivariate analyses were evaluated in multivariate logistic regression models adjusting for potential confounders. Anemia was present in 28% of the women, 55% were zinc deficient, 46% were vitamin B-12 deficient and 18% were folate deficient. Anemia was not associated with iron deficiency but rather with vitamin B-12 deficiency. Infestation with Ascaris was highly prevalent (67%) and associated with both folate and vitamin B-12 deficiency. Anemia and micronutrient deficiencies all varied significantly with season. The high prevalences of zinc and vitamin B-12 deficiencies in early pregnancy are a concern, as it could lead to adverse pregnancy outcomes and increased health risks for both mother and child. The prevalence of iron deficiency was low, but as this was during early pregnancy, the women might develop iron deficiency and consequently iron deficiency anemia as the pregnancy progresses. © 2010 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2010 Nordic Federation of Societies of Obstetrics and Gynecology.

The iron-chelate transporter OsYSL9 plays a role in iron distribution in developing rice grains.

PubMed

Senoura, Takeshi; Sakashita, Emi; Kobayashi, Takanori; Takahashi, Michiko; Aung, May Sann; Masuda, Hiroshi; Nakanishi, Hiromi; Nishizawa, Naoko K

2017-11-01

Rice OsYSL9 is a novel transporter for Fe(II)-nicotianamine and Fe(III)-deoxymugineic acid that is responsible for internal iron transport, especially from endosperm to embryo in developing seeds. Metal chelators are essential for safe and efficient metal translocation in plants. Graminaceous plants utilize specific ferric iron chelators, mugineic acid family phytosiderophores, to take up sparingly soluble iron from the soil. Yellow Stripe 1-Like (YSL) family transporters are responsible for transport of metal-phytosiderophores and structurally similar metal-nicotianamine complexes. Among the rice YSL family members (OsYSL) whose functions have not yet been clarified, OsYSL9 belongs to an uncharacterized subgroup containing highly conserved homologs in graminaceous species. In the present report, we showed that OsYSL9 localizes mainly to the plasma membrane and transports both iron(II)-nicotianamine and iron(III)-deoxymugineic acid into the cell. Expression of OsYSL9 was induced in the roots but repressed in the nonjuvenile leaves in response to iron deficiency. In iron-deficient roots, OsYSL9 was induced in the vascular cylinder but not in epidermal cells. Although OsYSL9-knockdown plants did not show a growth defect under iron-sufficient conditions, these plants were more sensitive to iron deficiency in the nonjuvenile stage compared with non-transgenic plants. At the grain-filling stage, OsYSL9 expression was strongly and transiently induced in the scutellum of the embryo and in endosperm cells surrounding the embryo. The iron concentration was decreased in embryos of OsYSL9-knockdown plants but was increased in residual parts of brown seeds. These results suggested that OsYSL9 is involved in iron translocation within plant parts and particularly iron translocation from endosperm to embryo in developing seeds.

Iron Deficiency and Iron-deficiency Anemia in Toddlers Ages 18 to 36 Months: A Prospective Study.

PubMed

Levin, Carina; Harpaz, Shira; Muklashi, Isam; Lumelsky, Nadia; Komisarchik, Ina; Katzap, Ilia; Abu Hanna, Manhal; Koren, Ariel

2016-04-01

In young children, iron deficiency (ID)-the most common cause of anemia-may adversely affect long-term neurodevelopment and behavior. We prospectively evaluated the prevalence of ID and iron deficiency anemia (IDA) in 256 healthy 18- to 36-month-old children in Northern Israel. Complete blood count and ferritin evaluation were performed, and risk factors were assessed. Hemoglobin (Hgb) was compared with first-year routine screening. Complete data were obtained from 208 children: 56.2% were boys; the mean age was 26.1±5.27 months. A prevalence of 5.8% IDA, 16.3% ID without anemia, 9.6% anemia with normal ferritin, and 68.3% normal Hgb and ferritin was found. In nonanemic infants at 1 year of age (n=156), ID/IDA was found in 19.9%, and 12.8% became anemic at study evaluation. Despite iron supplementation in the first year, and normal Hgb at first-year screening, ID and IDA were still prevalent, and might develop during the second year of life. Recognition of this child subset and consideration of iron supplementation are mandatory.

Abnormal Brain Iron Metabolism in Irp2 Deficient Mice Is Associated with Mild Neurological and Behavioral Impairments

PubMed Central

Zumbrennen-Bullough, Kimberly B.; Becker, Lore; Garrett, Lillian; Hölter, Sabine M.; Calzada-Wack, Julia; Mossbrugger, Ilona; Quintanilla-Fend, Leticia; Racz, Ildiko; Rathkolb, Birgit; Klopstock, Thomas; Wurst, Wolfgang; Zimmer, Andreas; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valerie; de Angelis, Martin Hrabě; Romney, Steven J.; Leibold, Elizabeth A.

2014-01-01

Iron Regulatory Protein 2 (Irp2, Ireb2) is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2−/− mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc), expression are increased and decreased, respectively, in the brain from Irp2−/− mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments. PMID:24896637

Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome.

PubMed

Quiroz, César; Gulyani, Seema; Ruiqian, Wan; Bonaventura, Jordi; Cutler, Roy; Pearson, Virginia; Allen, Richard P; Earley, Christopher J; Mattson, Mark P; Ferré, Sergi

2016-12-01

Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyperarousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances. Nevertheless, they develop the main neurochemical dopaminergic changes found in RLS, such as decrease in striatal dopamine D 2 receptor density. On the other hand, brain iron deficient mice exhibit the characteristic pattern of hyperarousal in RLS, providing a tool to find the link between brain iron deficiency and sleep disturbances in RLS. The present study provides evidence for a role of the endogenous sleep-promoting factor adenosine. Three different experimental preparations, long-term (22 weeks) severe or moderate iron-deficient (ID) diets (3- or 7-ppm iron diet) in mice and short-term (3 weeks) severe ID diet (3-ppm iron diet) in rats, demonstrated a significant downregulation (Western blotting in mouse and radioligand binding saturation experiments in rat brain tissue) of adenosine A 1 receptors (A1R) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A 2A receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for A1R downregulation in the PLMS and hyperarousal in RLS. Published by Elsevier Ltd.

Obesity and iron deficiency: a quantitative meta-analysis.

PubMed

Zhao, L; Zhang, X; Shen, Y; Fang, X; Wang, Y; Wang, F

2015-12-01

Hypoferraemia (i.e. iron deficiency) was initially reported among obese individuals several decades ago; however, whether obesity and iron deficiency are correlated remains unclear. Here, we evaluated the putative association between obesity and iron deficiency by assessing the concentration of haematological iron markers and the risks associated with iron deficiency in both obese (including overweight) subjects and non-overweight participants. We performed a systematic search in the databases PubMed and Embase for relevant research articles published through December 2014. A total of 26 cross-sectional and case-control studies were analysed, comprising 13,393 overweight/obese individuals and 26,621 non-overweight participants. Weighted or standardized mean differences of blood iron markers and odds ratio (OR) of iron deficiency were compared between the overweight/obese participants and the non-overweight participants using a random-effects model. Compared with the non-overweight participants, the overweight/obese participants had lower serum iron concentrations (weighted mean difference [WMD]: -8.37 μg dL(-1) ; 95% confidence interval [CI]: -11.38 to -5.36 μg dL(-1) ) and lower transferrin saturation percentages (WMD: 2.34%, 95% CI: -3.29% to -1.40%). Consistent with this finding, the overweight/obese participants had a significantly increased risk of iron deficiency (OR: 1.31; 95% CI: 1.01-1.68). Moreover, subgroup analyses revealed that the method used to diagnose iron deficiency can have a critical effect on the results of the association test; specifically, we found a significant correlation between iron deficiency and obesity in studies without a ferritin-based diagnosis, but not in studies that used a ferritin-based diagnosis. Based upon these findings, we concluded that obesity is significantly associated with iron deficiency, and we recommend early monitoring and treatment of iron deficiency in overweight and obese individuals. Future longitudinal studies will help to test whether causal relationship exists between obesity and iron deficiency. © 2015 World Obesity.

How I treat anemia in pregnancy: iron, cobalamin, and folate.

PubMed

Achebe, Maureen M; Gafter-Gvili, Anat

2017-02-23

Anemia of pregnancy, an important risk factor for fetal and maternal morbidity, is considered a global health problem, affecting almost 50% of pregnant women. In this article, diagnosis and management of iron, cobalamin, and folate deficiencies, the most frequent causes of anemia in pregnancy, are discussed. Three clinical cases are considered. Iron deficiency is the most common cause. Laboratory tests defining iron deficiency, the recognition of developmental delays and cognitive abnormalities in iron-deficient neonates, and literature addressing the efficacy and safety of IV iron in pregnancy are reviewed. An algorithm is proposed to help clinicians diagnose and treat iron deficiency, recommending oral iron in the first trimester and IV iron later. Association of folate deficiency with neural tube defects and impact of fortification programs are discussed. With increased obesity and bariatric surgery rates, prevalence of cobalamin deficiency in pregnancy is rising. Low maternal cobalamin may be associated with fetal growth retardation, fetal insulin resistance, and excess adiposity. The importance of treating cobalamin deficiency in pregnancy is considered. A case of malarial anemia emphasizes the complex relationship between iron deficiency, iron treatment, and malaria infection in endemic areas; the heightened impact of combined etiologies on anemia severity is highlighted. © 2017 by The American Society of Hematology.

Behavior and Monoamine Deficits in Prenatal and Perinatal Iron Deficiency Are Not Corrected by Early Postnatal Moderate-Iron or High-Iron Diets in Rats12

PubMed Central

Unger, Erica L.; Hurst, Amy R.; Georgieff, Michael K.; Schallert, Tim; Rao, Raghavendra; Connor, James R.; Kaciroti, Niko; Lozoff, Betsy; Felt, Barbara

2012-01-01

Developmental iron deficiency anemia (IDA) causes brain and behavioral deficits in rodent models, which cannot be reversed when treated at periods equivalent to later infancy in humans. This study sought to determine whether earlier iron treatment can normalize deficits of IDA in rats and what iron dose is optimal. The offspring of dams with IDA during gestation were cross-fostered at postnatal d (P) 8 to dams receiving diets with 1 of 3 iron concentrations until weaning (P21): 0.003–0.01 g/kg [totally iron deficient (TID)]; 0.04 g/kg [formerly iron deficient (FID-40)]; or 0.4 g/kg (FID-400). Always iron-sufficient control dams (CN-40) received a 0.04-g/kg iron diet. At P21, TID pups received a 0.01 g iron/kg diet; all others received a 0.04 g iron/kg diet. Hematocrit and brain iron and monoamine concentrations were assessed at P21 and P100. Pup growth, development, activity, object recognition, hesitancy, and watermaze performance were evaluated. Regional brain iron was restored by iron treatment. Regional monoamine and metabolite concentrations were elevated in FID-40 rats and reduced in FID-400 and TID rats compared with CN-40 rats. FID-40 offspring had motor delays similar to TID during lactation and FID-400 rats had elevated thigmotaxis similar to TID rats at P25 and P100 in the spatial watermaze. In conclusion, iron treatment at P8 in rats did not normalize all monoamine or behavioral measures after early IDA. Moderate iron treatment improved adult behavior, but higher iron treatment caused brain and behavioral patterns similar to TID in the short and long term. PMID:22990465

Anaemia control and the interpretation of biochemical tests for iron status in children.

PubMed

Gwetu, Thando P; Chhagan, Meera K; Taylor, Myra; Kauchali, Shuaib; Craib, Murray

2017-04-26

Anaemia is one of the world's most prevalent child health problems. Its control in Africa and other developing nations has been hindered by uncertainty regarding its cause. Anaemia control has been particularly problematic in regions where the non-iron deficiency causes of anaemia, are projected to be substantial. The implementation of effective interventions to reduce the anaemia prevalence, requires improved documentation on iron status and other causes of anaemia for target populations. This cross-sectional study enrolled n = 184 children, aged 6-8 years from Kwazulu-Natal, South Africa. Tests of haemoglobin, serum ferritin, soluble transferrin receptor and C-reactive protein were performed. These conventional measures of iron status were used to calculate body iron and to categorize the children into different groups of anaemia profiles. Anaemia prevalence was high, 43/184 (23.4%). Iron deficiency anaemia contributed 7/43 (16.3%) to the anaemia prevalence compared to non-iron deficiency anaemia 34/43 (79.1%) and mixed anaemia 2/43 (4.7%). In total 47/184 (25.5%) of the sampled children had either iron deficiency or anaemia. Information about the presence of inflammation was used to adjust serum ferritin concentrations, resulting in improved diagnosis of iron deficiency. Appropriate investigations for iron status and inflammation/infection screening, need to be integral in the evaluation of anaemia and its causes before anaemia control interventions are implemented. Interventions that target the multifactorial nature of anaemia in school-aged children need to be strengthened. Additionally, regular screening of anaemia in school-aged children from disadvantaged communities is recommended.

Iron deficiency intravenous substitution in a Swiss academic primary care division: analysis of practices

PubMed Central

Varcher, Monica; Zisimopoulou, Sofia; Braillard, Olivia; Favrat, Bernard; Junod Perron, Noëlle

2016-01-01

Background Iron deficiency is a common problem in primary care and is usually treated with oral iron substitution. With the recent simplification of intravenous (IV) iron administration (ferric carboxymaltose) and its approval in many countries for iron deficiency, physicians may be inclined to overutilize it as a first-line substitution. Objective The aim of this study was to evaluate iron deficiency management and substitution practices in an academic primary care division 5 years after ferric carboxymaltose was approved for treatment of iron deficiency in Switzerland. Methods All patients treated for iron deficiency during March and April 2012 at the Geneva University Division of Primary Care were identified. Their medical files were analyzed for information, including initial ferritin value, reasons for the investigation of iron levels, suspected etiology, type of treatment initiated, and clinical and biological follow-up. Findings were assessed using an algorithm for iron deficiency management based on a literature review. Results Out of 1,671 patients, 93 were treated for iron deficiency. Median patients’ age was 40 years and 92.5% (n=86) were female. The average ferritin value was 17.2 μg/L (standard deviation 13.3 μg/L). The reasons for the investigation of iron levels were documented in 82% and the suspected etiology for iron deficiency was reported in 67%. Seventy percent of the patients received oral treatment, 14% IV treatment, and 16% both. The reasons for IV treatment as first- and second-line treatment were reported in 57% and 95%, respectively. Clinical and biological follow-up was planned in less than two-thirds of the cases. Conclusion There was no clear overutilization of IV iron substitution. However, several steps of the iron deficiency management were not optimally documented, suggesting shortcuts in clinical reasoning. PMID:27445502

Nitric oxide ameliorates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

PubMed

Kaushik, Manish Singh; Srivastava, Meenakshi; Srivastava, Alka; Singh, Anumeha; Mishra, Arun Kumar

2016-11-01

In cyanobacterium Anabaena 7120, iron deficiency leads to oxidative stress with unavoidable consequences. Nitric oxide reduces pigment damage and supported the growth of Anabaena 7120 in iron-deficient conditions. Elevation in nitric oxide accumulation and reduced superoxide radical production justified the role of nitric oxide in alleviating oxidative stress in iron deficiency. Increased activities of antioxidative enzymes and higher levels of ROS scavengers (ascorbate, glutathione and thiol) in iron deficiency were also observed in the presence of nitric oxide. Nitric oxide also supported the membrane integrity of Anabaena cells and reduces protein and DNA damage caused by oxidative stress induced by iron deficiency. Results suggested that nitric oxide alleviates the damaging effects of oxidative stress induced by iron deficiency in cyanobacterium Anabaena 7120.

Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency.

PubMed

Kobayashi, Masahiro; Kato, Hiroki; Hada, Hiroshi; Itoh-Nakadai, Ari; Fujiwara, Tohru; Muto, Akihiko; Inoguchi, Yukihiro; Ichiyanagi, Kenji; Hojo, Wataru; Tomosugi, Naohisa; Sasaki, Hiroyuki; Harigae, Hideo; Igarashi, Kazuhiko

2017-03-01

Iron plays the central role in oxygen transport by erythrocytes as a constituent of heme and hemoglobin. The importance of iron and heme is also to be found in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is deactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 -/- mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1 -/- mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin. Copyright© Ferrata Storti Foundation.

Iron deficiency and anemia are associated with low retinol levels in children aged 1 to 5 years.

PubMed

Saraiva, Bárbara C A; Soares, Michele C C; Santos, Luana C dos; Pereira, Simone C L; Horta, Paula M

2014-01-01

To analyze the occurrence of anemia and iron deficiency in children aged 1 to 5 years and the association of these events and retinol deficiency. This was an observational analytic cross-sectional study conducted in Vitoria, ES, Brazil, between April and August of 2008, with healthy children aged 1 to 5 years (n=692) that lived in areas covered by primary healthcare services. Sociodemographic and economic conditions, dietary intake (energy, protein, iron, and vitamin A ingestion), anthropometric data (body mass index-for-age and height-for-age), and biochemical parameters (ferritin, hemoglobin, and retinol serum) were collected. The prevalence of anemia, iron deficiency, and retinol deficiency was 15.7%, 28.1%, and 24.7%, respectively. Univariate analysis showed a higher prevalence of anemia (PR: 4.62, 95% CI: 3.36, 6.34, p<0.001) and iron deficiency (PR: 4.51, 95% CI: 3.30, 6.17, p<0.001) among children with retinol deficiency. The same results were obtained after adjusting for socioeconomic and demographic conditions, dietary intake, and anthropometric variables. There was a positive association between ferritin vs. retinol serum (r=0.597; p<0.001) and hemoglobin vs. retinol serum (r=0.770; p<0.001). Anemia and iron deficiency were associated with low levels of serum retinol in children aged 1 to 5 years, and a positive correlation was verified between serum retinol and serum ferritin and hemoglobin levels. These results indicate the importance of initiatives encouraging the development of new treatments and further research regarding retinol deficiency. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans

PubMed Central

Pereira, Dora I.A.; Bruggraber, Sylvaine F.A.; Faria, Nuno; Poots, Lynsey K.; Tagmount, Mani A.; Aslam, Mohamad F.; Frazer, David M.; Vulpe, Chris D.; Anderson, Gregory J.; Powell, Jonathan J.

2014-01-01

Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase (P < 0.0001) and direct in vitro cellular uptake (P = 0.001), but not with gastric solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia. From the Clinical Editor This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition. PMID:24983890

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease.

PubMed

Łukaszyk, Ewelina; Łukaszyk, Mateusz; Koc-Żórawska, Ewa; Tobolczyk, Jolanta; Bodzenta-Łukaszyk, Anna; Małyszko, Jolanta

2015-01-01

One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency. © 2015 S. Karger AG, Basel.

Iron Deficiency in Preschool Children with Autistic Spectrum Disorders

ERIC Educational Resources Information Center

Bilgic, Ayhan; Gurkan, Kagan; Turkoglu, Serhat; Akca, Omer Faruk; Kilic, Birim Gunay; Uslu, Runa

2010-01-01

Iron deficiency (ID) causes negative outcomes on psychomotor and behavioral development of infants and young children. Children with autistic spectrum disorders (ASD) are under risk for ID and this condition may increase the severity of psychomotor and behavioral problems, some of which already inherently exist in these children. In the present…

[Prevalence of iron and iodine deficiency, and parasitosis among children from Arandas, Jalisco, Mexico].

PubMed

Vásquez-Garibay, Edgar Manuel; Romero-Velarde, Enrique; Nápoles-Rodríguez, Francisco; Nuño-Cosío, María Eugenia; Trujillo-Contreras, Francisco; Sánchez-Mercado, Oscar

2002-01-01

To estimate the prevalence of iron deficiency, iodine deficiency and parasitosis in children attending the Instituto Alteño para el Desarrollo de Jalisco (Highlands Institute for Development of Jalisco State, INADEJ), Arandas, Jalisco, Mexico. A cross-sectional study was conducted between 1997 and 1999, among 432 children aged 12 to 120 months attending the INADEJ. Measurements included hematological values, urine iodine concentration, and presence of parasites. Student's t test chi square tests were used for parametric and nonparametric analysis. The prevalence figures of anemia (20 vs 7.4%, p = 0.007) and iron deficiency (60.9 vs 44.4%, p = 0.02) were higher in preschool than in school children. Iodine deficiency was found in 29% (10.5% moderate or severe) and parasitosis in 47.2% of children, mainly E. histolytica (30.2%) and G. lamblia (28.9%). Low income, male gender and lack of social security policy holding were associated to parasitosis. The high prevalence rates of iron deficiency, iodine deficiency, and parasitosis, should be addressed by state health services with effective interventions to restrain these preventable diseases. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Iron deficiency anemia in patients with inflammatory bowel disease

PubMed Central

Goldberg, Neil D

2013-01-01

Iron deficiency anemia is the most common form of anemia worldwide, caused by poor iron intake, chronic blood loss, or impaired absorption. Patients with inflammatory bowel disease (IBD) are increasingly likely to have iron deficiency anemia, with an estimated prevalence of 36%–76%. Detection of iron deficiency is problematic as outward signs and symptoms are not always present. Iron deficiency can have a significant impact on a patient’s quality of life, necessitating prompt management and treatment. Effective treatment includes identifying and treating the underlying cause and initiating iron replacement therapy with either oral or intravenous iron. Numerous formulations for oral iron are available, with ferrous fumarate, sulfate, and gluconate being the most commonly prescribed. Available intravenous formulations include iron dextran, iron sucrose, ferric gluconate, and ferumoxytol. Low-molecular weight iron dextran and iron sucrose have been shown to be safe, efficacious, and effective in a host of gastrointestinal disorders. Ferumoxytol is the newest US Food and Drug Administration-approved intravenous iron therapy, indicated for iron deficiency anemia in adults with chronic kidney disease. Ferumoxytol is also being investigated in Phase 3 studies for the treatment of iron deficiency anemia in patients without chronic kidney disease, including subgroups with IBD. A review of the efficacy and safety of iron replacement in IBD, therapeutic considerations, and recommendations for the practicing gastroenterologist are presented. PMID:23766655

Iron homeostasis and its disruption in mouse lung in iron deficiency and overload.

PubMed

Giorgi, Gisela; D'Anna, María Cecilia; Roque, Marta Elena

2015-10-01

What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co-ordinated action of iron proteins, such as divalent metal transporter 1, ZRT-IRE-like-protein 14, transferrin receptor, ferritin, haemochromatosis-associated protein and ferroportin. Iron dyshomeostasis is associated with several forms of chronic lung disease, but its mechanisms of action remain to be elucidated. The aim of the present study was to determine the role of the lung in whole-animal models with iron deficiency and iron overload, studying the divalent metal transporter 1 (DMT1), ZRT-IRE-like protein 14 (ZIP14), transferrin receptor (TfR), haemochromatosis-associated protein (HFE), hepcidin, ferritin and ferroportin (FPN) expression. In each model, adult CF1 mice were divided into the following groups (six mice per group): (i) iron-overload model, iron saccharate i.p. and control group (iron adequate), 0.9% NaCl i.p.; and (ii) iron-deficiency model, induced by repeated bleeding, and control group (sham operated). Proteins were assessed by immunohistochemistry and Western blot. In control mice, DMT1 was localized in the cytoplasm of airway cells, and in iron deficiency and overload it was in the apical membrane. Divalent metal transporter 1 and TfR increased in iron deficiency, without changes in iron overload. ZRT-IRE-like protein 14 decreased in airway cells in iron deficiency and increased in iron overload. In iron deficiency, HFE and FPN were immunolocalized close to the apical membrane. Ferroportin increased in iron overload. Prohepcidin was present in control groups, with no changes in iron deficiency and iron overload. In iron overload, ferritin showed intracytoplasmic localization close to the apical membrane of airway cells and intense immunostaining in macrophage-like cells. The results show that pulmonary hepcidin does not appear to modify cellular iron mobilization in the lung. We propose the following two novel pathways in the lung: (i) for supplying iron in iron deficiency, mediated principally by DMT1 and TfR and regulated by the action of FPN and HFE; and (ii) for iron detoxification in order to protect the lung against iron overload, facilitated by the action of DMT1, ZIP14, FPN and ferritin. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Iron balance in the red blood cell donor.

PubMed

Brittenham, G M

2005-01-01

Phlebotomy of a unit of blood produces a loss of 200 to 250 mg of iron in haemoglobin. Because of physiological differences in iron balance between women of childbearing age and men, the loss of similar amounts of iron at donation has divergent consequences for committed donors. Women of childbearing age have an increased risk of iron deficiency if they donate more than one unit per year while men are usually able to maintain iron balance while donating four or more units of blood per year. Lack of iron is the most important medical reason for deferral from repeat donation and primarily affects women of childbearing age. Deferral of these women discourages them from further donation and may lead to their loss as donors. Provisions for blood donation should protect those who give blood from adverse consequences of their altruism. Safe and effective approaches to iron replacement after donation have been developed that can prevent iron deficiency in women who give blood repeatedly. Blood centres should consider incorporating programmes of iron replacement for women of childbearing age who give blood repeatedly to protect these donors against iron deficiency and to enhance their retention and commitment as dedicated donors.

Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study.

PubMed

Cable, Ritchard G; Glynn, Simone A; Kiss, Joseph E; Mast, Alan E; Steele, Whitney R; Murphy, Edward L; Wright, David J; Sacher, Ronald A; Gottschall, Jerry L; Tobler, Leslie H; Simon, Toby L

2012-04-01

Blood donors are at risk of iron deficiency. We evaluated the effects of blood donation intensity on iron and hemoglobin (Hb) in a prospective study. Four cohorts of frequent and first-time or reactivated (FT/RA) blood donors (no donation in 2 years), female and male, totaling 2425, were characterized and followed as they donated blood frequently. At enrollment and the final visit, ferritin, soluble transferrin receptor (sTfR), and Hb were determined. Models to predict iron deficiency and Hb deferral were developed. Iron depletion was defined at two levels: iron deficiency erythropoiesis (IDE) [log(sTfR/ferritin) ≥ 2.07] and absent iron stores (AIS; ferritin < 12 ng/mL). Among returning female FT and RA donors, 20 and 51% had AIS and IDE at their final visit, respectively; corresponding proportions for males were 8 and 20%. Among female frequent donors who returned, 27 and 62% had AIS and IDE, respectively, while corresponding proportions for males were 18 and 47%. Predictors of IDE and/or AIS included a higher frequency of blood donation in the past 2 years, a shorter interdonation interval, and being female and young; conversely, taking iron supplements reduced the risk of iron depletion. Predictors of Hb deferral included female sex, black race, and a shorter interdonation interval. There is a high prevalence of iron depletion in frequent blood donors. Increasing the interdonation interval would reduce the prevalence of iron depletion and Hb deferral. Alternatively, replacement with iron supplements may allow frequent donation without the adverse outcome of iron depletion. © 2011 American Association of Blood Banks.

Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management

PubMed Central

Comin‐Colet, Josep; de Francisco, Angel; Dignass, Axel; Doehner, Wolfram; S. P. Lam, Carolyn; Macdougall, Iain C.; Rogler, Gerhard; Camaschella, Clara; Kadir, Rezan; Kassebaum, Nicholas J.; Spahn, Donat R.; Taher, Ali T.; Musallam, Khaled M.

2017-01-01

Abstract Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease‐specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. PMID:28612425

Targeting, Monitoring and Effect of Oral Iron Therapy on Haemoglobin Levels in Older Patients Discharged to Primary Care from Inpatient Rehabilitation: A Cohort Study Using Routinely Collected Data.

PubMed

Thomson, Zach; Hands, Katherine J; Witham, Miles D

2016-08-01

Oral iron is commonly prescribed to older patients with suspected or confirmed iron-deficiency anaemia; however, few studies have examined the effectiveness of oral iron therapy in the real world in this population. We therefore determined the prevalence of iron deficiency in older people prescribed oral iron, examined the response mounted to therapy and ascertained predictors of response to oral iron. We analysed a routinely collected, linked dataset from older patients who had undergone inpatient rehabilitation between 1999 and 2011. An initial analysis examined patients within this cohort who were prescribed iron after rehabilitation and derived three groups based upon their ferritin and transferrin indices: probably, possibly and not iron deficient. A second analysis compared pre- and post-treatment haemoglobin to determine the degree of response to iron therapy across each category of deficiency. Finally, patient demographics, linked biochemistry data and comorbid disease based on International Classification of Disease (ICD-10) codes from previous hospital admissions were used in regression modelling to evaluate factors affecting response to therapy. A total of 490 patients were prescribed oral iron within 90 days of rehabilitation discharge. Of these, 413 (84 %) had iron indices performed; 94 (23 %) were possibly deficient, 224 (54 %) were probably deficient, and 95 (23 %) were not deficient. Of the 490 patients, 360 had both pre- and post-treatment haemoglobin data and iron indices; probably deficient patients mounted a slightly greater response to oral iron (17 vs. 12 g/L for not deficient; p < 0.05). Only pre-treatment haemoglobin, mean cell volume and lower gastrointestinal pathology were significant predictors of a response to oral iron therapy. Notably, acid-suppressant use was not a predictor of response. We conclude that many older patients are exposed to oral iron without good evidence of either iron deficiency or a significant response to therapy.

Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

PubMed

Bahrainwala, Jehan; Berns, Jeffrey S

2016-03-01

Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship of Iron Deficiency and Serum Ferritin Levels with Pulmonary Hypertension: The Jackson Heart Study.

PubMed

Jankowich, Matthew; Elston, Beth; Evans, Samuel K; Wu, Wen-Chih; Choudhary, Gaurav

2016-01-01

Iron deficiency is prevalent in idiopathic pulmonary arterial hypertension (IPAH), but whether iron deficiency or ferritin levels are associated with pulmonary hypertension (PH) in the general population is unknown. We performed a cross-sectional analysis of data on iron deficiency (exposure), and PH (pulmonary artery systolic pressure>40mmHg on echocardiogram) (outcome) on subjects with complete data on exposures and outcomes as well as covariates (n = 2,800) enrolled in the Jackson Heart Study, a longitudinal prospective observational cohort study of heart disease in African-Americans from Jackson, Mississippi. Iron deficiency was defined as a serum ferritin level < 15ng/mL (females); < 30ng/mL (males). We determined crude prevalence ratios (PRs) for PH in iron deficient versus non-iron deficient groups using modified Poisson regression modeling. We also analyzed the prevalence of PH by sex-specific quartiles of ferritin (Females ≤ 47ng/mL; > 47ng/mL- 95ng/mL; > 95ng/mL- 171ng/mL; > 171ng/mL; Males ≤ 110ng/mL; > 110ng/mL- 182ng/mL; > 182ng/mL- 294ng/mL; > 294ng/mL), using the same modeling technique with the lowest quartile as the referent. Median pulmonary artery systolic pressure was 27mmHg (interquartile range 23-31mmHg) in the study cohort. 147 subjects (5.2%) had PH and 140 (5.0%) had iron deficiency. However, of the 147 subjects with PH, only 4 were also iron deficient. The crude PH PR was 0.5 (95% CI 0.2-1.4) in iron-deficiency compared to non-deficient. In analysis by quartiles of ferritin, adjusting for age and sex, there was no evidence of association with PH in quartiles 2 (PR 1.1, 95% CI 0.7-1.6), 3 (PR 0.8, 95% CI 0.5-1.3), or 4 (PR 0.8, 95% CI 0.5-1.2) compared with quartile 1 (referent group, PR 1). Further analyses of the relationship between PH and ferritin as a log-transformed continuous variable or by quartiles of serum iron showed similar results. In the Jackson Heart Study, the prevalence of PH was similar in iron-deficient and non-iron deficient subjects. There was no evidence of association between ferritin (or serum iron) levels and PH. Iron deficiency has been associated with IPAH, a rare disorder. However, in a large community-based sample of African-Americans, there was no evidence that iron deficiency or low iron levels were associated with PH.

Association between oral contraceptive use and markers of iron deficiency in a cross-sectional study of Tanzanian women.

PubMed

Haile, Zelalem T; Teweldeberhan, Asli K; Chertok, Ilana R A

2016-01-01

To analyze the associations between oral contraceptive (OC) use and markers of iron deficiency, objectively measured using hemoglobin and soluble transferrin receptor. A secondary data analysis was performed of a population-based cross-sectional study using data from the 2010 Tanzania Demographic and Health Survey. Weighted percentages were calculated. Multivariable logistic regression was used to examine the associations between OC use and iron deficiency, anemia, and iron deficiency anemia. Of the 4336 participants, only 7.3% reported a history of OC use. The prevalence rates of iron deficiency, anemia, and iron deficiency anemia were 30.3%, 40.9%, and 15.1%, respectively. Use of OCs was negatively associated with anemia and iron deficiency anemia, independent of potential confounders. Compared with OC nonusers, the multivariable-adjusted odds ratio among OC users was 0.44 (95% confidence interval 0.32-0.59; P<0.001) for anemia and 0.43 (95% confidence interval 0.27-0.68; P<0.001) for iron deficiency anemia. A longer duration of OC use was negatively associated with iron deficiency (P=0.003 for trend), anemia (P<0.001 for trend), and iron deficiency anemia (P<0.001 for trend). The significant association between OC use and iron status has important implications for educating healthcare providers and women about additional nutritional benefits of the use of OCs. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

A link between premenopausal iron deficiency and breast cancer malignancy

PubMed Central

2013-01-01

Background Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. Methods One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. Results We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). Conclusions Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients. PMID:23800380

Low Prevalence of Iron and Vitamin A Deficiency among Cambodian Women of Reproductive Age

PubMed Central

Wieringa, Frank T.; Sophonneary, Prak; Whitney, Sophie; Mao, Bunsoth; Berger, Jacques; Conkle, Joel; Dijkhuizen, Marjoleine A.; Laillou, Arnaud

2016-01-01

Nearly half of women of reproductive age (WRA) in Cambodia are anemic. To guide interventions, national data on nutritional causes of anemia, including iron deficiency and vitamin A deficiency, are needed. In 2012, a national household survey in WRA on antibodies to routine vaccine-preventable disease immunity was performed. We used serum samples from this survey to estimate the prevalence of iron and vitamin A deficiency in 2112 Cambodian WRA, aged 15 to 39 years. Iron deficiency was classified as low or marginal iron stores (ferritin concentrations corrected for inflammation <15 μg/L and <50 μg/L respectively; Fer), iron deficient erythropoiesis (soluble transferrin receptor concentrations >8.3 mg/L; sTfR), or low total body iron (TBI) derived from Fer and sTfR concentrations (<0 mg/kg). Vitamin A status was classified using retinol binding protein (RBP) concentrations corrected for inflammation as deficient (<0.70 μmol/L) or marginal (<1.05 μmol/L. Overall, the prevalence of low iron stores, low TBI and iron deficient erythropoiesis was 8.1%, 5.0% and 9.3% respectively. Almost 40% of the women had marginal iron stores. Iron status was better in women living in urban areas compared to rural areas (p < 0.05 for TBI and sTfR). The prevalence of vitamin A deficiency was <1%. These findings suggest that the contribution of iron and vitamin A deficiency to the high prevalence of anemia in Cambodian WRA may be limited. The etiology of anemia in Cambodia needs to be elucidated further to guide current policies on anemia. PMID:27043624

The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention.

PubMed

Bialkowski, W; Bryant, B J; Schlumpf, K S; Wright, D J; Birch, R; Kiss, J E; D'Andrea, P; Cable, R G; Spencer, B R; Vij, V; Mast, A E

2015-02-01

Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. 'Strategies To Reduce Iron Deficiency' (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. Iron deficient erythropoiesis was present in 52·7% of males and 74·6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0·002), but not more common in those receiving iron than placebo (P = 0·68). The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo. © 2014 International Society of Blood Transfusion.

Possibilities in Anaemia Prevention during Pregnancy through the Basic Health Care System

ERIC Educational Resources Information Center

Karácsony, Ilona; Albrecht, Hanna; Brantmüller, Éva

2015-01-01

In case of pregnancies, one of the most common pathological conditions in internal medicine is aneamia with iron-deficiency. Furthermore, iron deficiency may also affect the mother and the fetus negatively. We wanted to find out which group of expectant mothers are mostly affected, which factors influence the development of aneamia. It was also…

Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

PubMed

Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

2016-05-01

Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

Differential iron distribution in seeds of two closely related legume species

USDA-ARS?s Scientific Manuscript database

The World Health Organization states that the lack of micronutrients such as zinc and iron represents a major threat to the health and development of populations around the world. Iron deficiency affects over 2 billion people, in particular children and pregnant women in developing countries. A comm...

Infant motor development in rural Vietnam and intrauterine exposures to anaemia, iron deficiency and common mental disorders: a prospective community-based study.

PubMed

Tran, Thach D; Tran, Tuan; Simpson, Julie A; Tran, Ha T; Nguyen, Trang T; Hanieh, Sarah; Dwyer, Terence; Biggs, Beverley-Ann; Fisher, Jane

2014-01-08

Antenatal anaemia, iron deficiency and common mental disorders (CMD) are prevalent in low- and middle-income countries. The aim of this study was to examine the direct and indirect effects of antenatal exposures to these risks and infant motor development. A cohort of women who were pregnant with a single foetus and between 12 and 20 weeks pregnant in 50 randomly-selected rural communes in Ha Nam province was recruited. Participants provided data twice during pregnancy (early and late gestation) and twice after giving birth (8 weeks and 6 months postpartum). The Edinburgh Postnatal Depression Scale was used at all four data collection waves to detect CMD (score ≥ 4). Maternal anaemia (Hb < 11 g/dL) and iron deficiency (ferritin < 15 ng/mL) were evaluated at early and late gestation. Infants' motor development was assessed by the Bayley of Infant and Toddler Development Motor Scales (BSID-M) at the age of six months. Direct and indirect effects of the exposures on the outcome were examined with Path analysis. In total, 497 of 523 (97%) eligible pregnant women were recruited and 418 mother-infant pairs provided complete data and were included in the analyses. The prevalence of anaemia was 21.5% in early pregnancy and 24.4% in late pregnancy. There was 4.1% iron deficiency at early pregnancy and 48.2% at late pregnancy. Clinically significant symptoms of CMD were apparent among 40% women in early pregnancy and 28% in late pregnancy. There were direct adverse effects on infant BSID-M scores at 6 months of age due to antenatal anaemia in late pregnancy (an estimated mean reduction of 2.61 points, 95% Confidence Interval, CI, 0.57 to 4.65) and CMD in early pregnancy (7.13 points, 95% CI 3.13 to 11.13). Iron deficiency and anaemia in early pregnancy were indirectly related to the outcome via anaemia during late pregnancy. Antenatal anaemia, iron deficiency, and CMD have a negative impact on subsequent infant motor development. These findings highlight the need to improve the quality of antenatal care when developing interventions for pregnant women that aim to optimise early childhood development in low- and middle-income countries.

Solemnity: A Clinical Risk Index for Iron Deficient Infants.

ERIC Educational Resources Information Center

Honig, Alice Sterling; Oski, Frank A.

1984-01-01

Studies four groups of infants with iron deficiency but without anemia in an attempt to discover behavioral signs that can be used to index high-risk probability for iron deficiency. Solemnity in well-attached infants is suggested as a clinical sign to indicate the need for biochemical screening for iron deficiency. (AS)

Iron Deficiency in Autism and Asperger Syndrome.

ERIC Educational Resources Information Center

Latif, A.; Heinz, P.; Cook, R.

2002-01-01

Retrospective analysis of the full blood count and, when available, serum ferritin measurements of 96 children (52 with autism and 44 with Asperger syndrome) found six autistic children had iron deficiency and 12 of the 23 autistic children with serum ferritin measures were iron deficient. Far fewer Asperger children were iron deficient. Results…

Iron-deficiency anemia as a subclinical celiac disease presentation in an Argentinian population.

PubMed

Lasa, J S; Olivera, P; Soifer, L; Moore, R

There is a wide heterogeneity in the reports of celiac disease prevalence in iron-deficiency anemia patients. To determine the prevalence of celiac disease in patients with iron-deficiency anemia. Adult patients with a diagnosis of iron-deficiency anemia were enrolled for upper endoscopy with duodenal biopsies. Healthy volunteers that underwent upper endoscopy were enrolled as controls. A total of 135 patients with iron-deficiency anemia and 133 controls were enrolled. Celiac disease prevalence was higher in the iron-deficiency anemia group [11.11 vs. 1.51%, OR: 8.18 (1.83-36.55), P=.001). Of the celiac disease patients in the iron-deficiency anemia group, 73.3% had at least one endoscopic sign suggesting villous atrophy, whereas 100% of the celiac disease patients in the control group presented with at least one endoscopic sign. Patients with iron-deficiency anemia have an increased risk for celiac disease. Up to 25% of these patients may not present any endoscopic sign suggesting villous atrophy. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Effect of Iron Deficiency on the Phenotype of β-Thalassaemia Trait.

PubMed

Arshad, Maham; Ahmed, Suhaib; Ali, Nadir

2016-03-01

The objective of this study was to determine the effect of iron deficiency on Hb-A2 level in β-thalassaemia trait and to determine the frequency of individuals with β-thalassaemia trait who could be missed due to concomitant iron deficiency. A total of 120 patients were studied, out of which 23 were iron deficient (serum ferritin < 20 ng/ml). Mean Hb-A2 in the iron deficient individuals was 4.1 ± 0.47% as compared to 5.1 ± 0.58% in the remaining 97 individuals without iron deficiency (p < 0.001). In the 120 individuals with β-thalassaemia trait, mean Hb-A2 was 5.8% with range 3 - 6.8% and confidence interval was 95%. In 2 individuals with β-thalassaemia trait, Iron deficiency was observed and showed Hb-A2 less than 3.5%. These could have been missed while screening by Hb-A2 estimation alone. Co-existence of Iron deficiency and β-thalassaemia trait may mask the diagnosis of beta thalassaemia trait and such individuals can be missed during screening by Hb-A2 estimation alone.

Insights into the diagnosis and management of iron deficiency in inflammatory bowel disease.

PubMed

Bou-Fakhredin, Rayan; Halawi, Racha; Roumi, Joseph; Taher, Ali

2017-09-01

Iron deficiency is a frequent comorbidity of chronic diseases such as inflammatory bowel disease that can severely impact the health and quality of life of affected individuals. It can exist as a silent condition and manifest in non-specific symptoms even in the absence of anemia. Even though iron deficiency anemia is the most common complication and extra-intestinal manifestation of inflammatory bowel disease, the majority of inflammatory bowel disease patients who are diagnosed with iron deficiency anemia are not treated. Areas covered: In this review, we discuss iron deficiency and iron deficiency anemia in patients with inflammatory bowel disease, and review diagnostic and therapeutic options. Expert commentary: We invite international gastroenterological societies and associations to refine the practice guidelines and include iron deficiency as a potential morbidity associated with IBD in analogy to arthritis, uveitis or any other extra intestinal manifestations. There should a more unanimous agreement among different societies on the specific diagnostic cutoff values for C-reactive protein levels, serum ferritin, and transferrin saturation in order to differentiate iron deficiency anemia from anemia of chronic disease.

Breastfeeding, Mixed, or Formula Feeding at 9 Months of Age and the Prevalence of Iron Deficiency and Iron Deficiency Anemia in Two Cohorts of Infants in China.

PubMed

Clark, Katy M; Li, Ming; Zhu, Bingquan; Liang, Furong; Shao, Jie; Zhang, Yueyang; Ji, Chai; Zhao, Zhengyan; Kaciroti, Niko; Lozoff, Betsy

2017-02-01

To assess associations between breastfeeding and iron status at 9 months of age in 2 samples of Chinese infants. Associations between feeding at 9 months of age (breastfed as sole milk source, mixed fed, or formula fed) and iron deficiency anemia (IDA), iron deficiency, and iron sufficiency were determined in infants from Zhejiang (n = 142) and Hebei (n= 813) provinces. Iron deficiency was defined as body iron < 0 mg/kg, and IDA as iron deficiency + hemoglobin < 110 g/L. Multiple logistic regression assessed associations between feeding pattern and iron status. Breastfeeding was associated with iron status (P < .001). In Zhejiang, 27.5% of breastfed infants had IDA compared with 0% of formula-fed infants. The odds of iron deficiency/IDA were increased in breastfed and mixed-fed infants compared with formula-fed infants: breastfed vs formula-fed OR, 28.8 (95% CI, 3.7-226.4) and mixed-fed vs formula-fed OR, 11.0 (95% CI, 1.2-103.2). In Hebei, 44.0% of breastfed infants had IDA compared with 2.8% of formula-fed infants. With covariable adjustment, odds of IDA were increased in breastfed and mixed-fed groups: breastfed vs formula-fed OR, 78.8 (95% CI, 27.2-228.1) and mixed-fed vs formula-fed OR, 21.0 (95% CI, 7.3-60.9). In both cohorts, the odds of iron deficiency/IDA at 9 months of age were increased in breastfed and mixed-fed infants, and iron deficiency/IDA was common. Although the benefits of breastfeeding are indisputable, these findings add to the evidence that breastfeeding in later infancy identifies infants at risk for iron deficiency/IDA in many settings. Protocols for detecting and preventing iron deficiency/IDA in breastfed infants are needed. ClinicalTrials.gov: NCT00642863 and NCT00613717. Copyright © 2016 Elsevier Inc. All rights reserved.

Excess adiposity, inflammation, and iron-deficiency in female adolescents.

PubMed

Tussing-Humphreys, Lisa M; Liang, Huifang; Nemeth, Elizabeta; Freels, Sally; Braunschweig, Carol A

2009-02-01

Iron deficiency is more prevalent in overweight children and adolescents but the mechanisms that underlie this condition remain unclear. The purpose of this cross-sectional study was to assess the relationship between iron status and excess adiposity, inflammation, menarche, diet, physical activity, and poverty status in female adolescents included in the National Health and Nutrition Examination Survey 2003-2004 dataset. Descriptive and simple comparative statistics (t test, chi(2)) were used to assess differences between normal-weight (5th < or = body mass index [BMI] percentile <85th) and heavier-weight girls (< or = 85th percentile for BMI) for demographic, biochemical, dietary, and physical activity variables. In addition, logistic regression analyses predicting iron deficiency and linear regression predicting serum iron levels were performed. Heavier-weight girls had an increased prevalence of iron deficiency compared to those with normal weight. Dietary iron, age of and time since first menarche, poverty status, and physical activity were similar between the two groups and were not independent predictors of iron deficiency or log serum iron levels. Logistic modeling predicting iron deficiency revealed having a BMI > or = 85th percentile and for each 1 mg/dL increase in C-reactive protein the odds ratio for iron deficiency more than doubled. The best-fit linear model to predict serum iron levels included both serum transferrin receptor and C-reactive protein following log-transformation for normalization of these variables. Findings indicate that heavier-weight female adolescents are at greater risk for iron deficiency and that inflammation stemming from excess adipose tissue contributes to this phenomenon. Food and nutrition professionals should consider elevated BMI as an additional risk factor for iron deficiency in female adolescents.

In Vitro Iron Bioavailability of Brazilian Food-Based by-Products.

PubMed

Chiocchetti, Gabriela M; De Nadai Fernandes, Elisabete A; Wawer, Anna A; Fairweather-Tait, Susan; Christides, Tatiana

2018-05-16

Background : Iron deficiency is a public health problem in many low- and middle-income countries. Introduction of agro-industrial food by-products, as additional source of nutrients, could help alleviate this micronutrient deficiency, provide alternative sources of nutrients and calories in developed countries, and be a partial solution for disposal of agro-industry by-products. Methods : The aim of this study was to determine iron bioavailability of 5 by-products from Brazilian agro-industry (peels from cucumber, pumpkin, and jackfruit, cupuaçu seed peel, and rice bran), using the in vitro digestion/ Caco-2 cell model; with Caco-2 cell ferritin formation as a surrogate marker of iron bioavailability. Total and dialyzable Fe, macronutrients, the concentrations of iron-uptake inhibitors (phytic acid, tannins, fiber) and their correlation with iron bioavailability were also evaluated. Results : The iron content of all by-products was high, but the concentration of iron and predicted bioavailability were not related. Rice bran and cupuaçu seed peel had the highest amount of phytic acid and tannins, and lowest iron bioavailability. Cucumber peels alone, and with added extrinsic Fe, and pumpkin peels with extrinsic added iron, had the highest iron bioavailability. Conclusion : The results suggest that cucumber and pumpkin peel could be valuable alternative sources of bioavailable Fe to reduce iron deficiency in at-risk populations.

Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

PubMed

Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

2008-02-22

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

Rethinking iron regulation and assessment in iron deficiency, the anemia of chronic disease, and obesity: introducing Hepcidin

USDA-ARS?s Scientific Manuscript database

Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins; a vital player in cellular metabolism, and essential to cell growth and differentiation. Tight regulation of iron at the systemic and cytosolic level is necessary bec...

Iron status and anaemia in Sri Lankan secondary school children: A cross-sectional survey.

PubMed

Allen, Angela; Allen, Stephen; Rodrigo, Rexan; Perera, Lakshman; Shao, Wei; Li, Chao; Wang, Duolao; Olivieri, Nancy; Weatherall, David J; Premawardhena, Anuja

2017-01-01

Iron deficiency, the most common micronutrient disorder and cause of anaemia globally, impairs growth, cognition, behaviour and resistance to infection. As part of a national survey of inherited haemoglobin variants in 7526 students from 72 secondary schools purposefully selected from the 25 districts of Sri Lanka, we studied 5912 students with a normal haemoglobin genotype. Median age was 16.0 (IQR 15.0-17.0) years and 3189 (53.9%) students were males. Most students were Sinhalese (65.7%), with fewer Tamils (23.1%) and Muslims (11.2%). Anaemia occurred in 470 students and was more common in females (11.1%) than males (5.6%). Haemoglobin, serum ferritin, transferrin receptor and iron were determined in 1196 students with low red cell indices and a structured sample of those with normal red cell indices (n = 513). The findings were weighted to estimate the frequencies of iron deficiency and iron deficiency anaemia classified according to WHO criteria. Iron depletion (serum ferritin <15ug/ml) occurred in 19.2% and cellular iron deficiency (low serum ferritin and transferrin receptor >28.1 nmol/l) in 11.6% students. Iron deficiency anaemia (cellular iron deficiency with low haemoglobin) occurred in only 130/2794 (4.6%) females and 28/2789 (1.0%) males. Iron biomarkers were normal in 83/470 (14.6%) students with anaemia. In multiple regression analysis, the odds for iron depletion and cellular iron deficiency were about one-third in males compared with females, and the odds for iron deficiency anaemia were about one fifth in males compared to females. Tamil ethnicity and age <16 years increased the risk of all three stages of iron deficiency and living at high altitude significantly reduced the risk of iron depletion. Low iron status and anaemia remain common problems in Sri Lankan secondary school students especially females, younger students and the socioeconomically disadvantaged Tamil population. More research is needed to identify factors other than low iron status that contribute to anaemia in adolescents.

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia.

PubMed

Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A; Muñoz, Manuel

2016-03-01

Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500-1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000-2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1-3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.

Induction of root Fe(lll) reductase activity and proton extrusion by iron deficiency is mediated by auxin-based systemic signalling in Malus xiaojinensis.

PubMed

Wu, Ting; Zhang, Heng-Tao; Wang, Yi; Jia, Wen-Suo; Xu, Xue-Feng; Zhang, Xin-Zhong; Han, Zhen Hai

2012-01-01

Iron is a critical cofactor for a number of metalloenzymes involved in respiration and photosynthesis, but plants often suffer from iron deficiency due to limited supplies of soluble iron in the soil. Iron deficiency induces a series of adaptive responses in various plant species, but the mechanisms by which they are triggered remain largely unknown. Using pH imaging and hormone localization techniques, it has been demonstrated here that root Fe(III) reductase activity and proton extrusion upon iron deficiency are up-regulated by systemic auxin signalling in a Fe-efficient woody plant, Malus xiaojinensis. Split-root experiments demonstrated that Fe-deprivation in a portion of the root system induced a dramatic increase in Fe(III) reductase activity and proton extrusion in the Fe-supplied portion, suggesting that the iron deficiency responses were mediated by a systemic signalling. Reciprocal grafting experiments of M. xiaojinensis with Malus baccata, a plant with no capability to produce the corresponding responses, indicate that the initiation of the systemic signalling is likely to be determined by roots rather than shoots. Iron deficiency induced a substantial increase in the IAA content in the shoot apex and supplying exogenous IAA analogues (NAA) to the shoot apex could mimic the iron deficiency to trigger the corresponding responses. Conversely, preventing IAA transport from shoot to roots blocked the iron deficiency responses. These results strongly indicate that the iron deficiency-induced physiological responses are mediated by systemic auxin signalling.

Diagnosis and treatment of iron-deficiency anaemia in pregnancy and postpartum.

PubMed

Breymann, C; Honegger, C; Hösli, I; Surbek, D

2017-12-01

Iron deficiency occurs frequently in pregnancy and can be diagnosed by serum ferritin-level measurement (threshold value < 30 μg/L). Screening for iron-deficiency anemia is recommended in every pregnant women, and should be done by serum ferritin-level screening in the first trimester and regular hemoglobin checks at least once per trimester. In the case of iron deficiency with or without anaemia in pregnancy, oral iron therapy should be given as first-line treatment. In the case of severe iron-deficiency anemia, intolerance of oral iron, lack of response to oral iron, or in the case of a clinical need for rapid and efficient treatment of anaemia (e.g., advanced pregnancy), intravenous iron therapy should be administered. In the postpartum period, oral iron therapy should be administered for mild iron-deficiency anemia (haemorrhagic anemia), and intravenous iron therapy for moderately severe-to-severe anemia (Hb < 95 g/L). If there is an indication for intravenous iron therapy in pregnancy or postpartum, iron-containing drugs which have been studied in well-controlled clinical trials in pregnancy and postpartum such as ferric carboxymaltose must be preferred for safety reasons. While anaphylactic reactions are extremely are with non-dextrane products, close surveillance during administration is recommended for all intravenous iron products.

Changes in the concentrations of biochemical indicators of diet and nutritional status of pregnant women across pregnancy trimesters in Trujillo, Peru, 2004-2005.

PubMed

Horton, D Kevin; Adetona, Olorunfemi; Aguilar-Villalobos, Manuel; Cassidy, Brandon E; Pfeiffer, Christine M; Schleicher, Rosemary L; Caldwell, Kathleen L; Needham, Larry L; Rathbun, Stephen L; Vena, John E; Naeher, Luke P

2013-06-11

In developing countries, deficiencies in essential micronutrients are common, particularly in pregnant women. Although, biochemical indicators of diet and nutrition are useful to assess nutritional status, few studies have examined such indicators throughout pregnancy in women in developing countries. The primary objective of this study was to assess the nutritional status of 78 Peruvian women throughout pregnancy for 16 different nutritional indicators including fat-soluble vitamins and carotenoids, iron-status indicators, and selenium. Venous blood samples from which serum was prepared were collected during trimesters one (n = 78), two (n = 65), three (n = 62), and at term via the umbilical cord (n = 52). Questionnaires were completed to determine the demographic characteristics of subjects. Linear mixed effects models were used to study the associations between each maternal indicator and the demographic characteristics. None of the women were vitamin A and E deficient at any stage of pregnancy and only 1/62 women (1.6%) was selenium deficient during the third trimester. However, 6.4%, 44% and 64% of women had ferritin levels indicative of iron deficiency during the first, second and third trimester, respectively. Statistically significant changes (p ≤ 0.05) throughout pregnancy were noted for 15/16 nutritional indicators for this Peruvian cohort, with little-to-no association with demographic characteristics. Three carotenoids (beta-carotene, beta-cryptoxanthin and trans-lycopene) were significantly associated with education status, while trans-lycopene was associated with age and beta-cryptoxanthin with SES (p < 0.05). Concentrations of retinol, tocopherol, beta-cryptoxanthin, lutein + zeaxanthin and selenium were lower in cord serum compared with maternal serum (p < 0.05). Conversely, levels of iron status indicators (ferritin, transferrin saturation and iron) were higher in cord serum (p < 0.05). The increasing prevalence of iron deficiency throughout pregnancy in these Peruvian women was expected. It was surprising though not to find deficiencies in other nutrients. The results highlight the importance of continual monitoring of women throughout pregnancy for iron deficiency which could be caused by increasing fetal needs and/or inadequate iron intake as pregnancy progresses.

Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans.

PubMed

Pereira, Dora I A; Bruggraber, Sylvaine F A; Faria, Nuno; Poots, Lynsey K; Tagmount, Mani A; Aslam, Mohamad F; Frazer, David M; Vulpe, Chris D; Anderson, Gregory J; Powell, Jonathan J

2014-11-01

Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase (P < 0.0001) and direct in vitro cellular uptake (P = 0.001), but not with gastric solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia. This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Cardiac remodeling in response to chronic iron deficiency: role of the erythropoietin receptor.

PubMed

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Hirotani, Shinichi; Mano, Toshiaki; Tsujino, Takeshi; Masuyama, Tohru

2015-06-01

Anemia is a common comorbidity of patients with heart failure, and iron deficiency is known as one of the causes of anemia in heart failure. Recent studies have shown that iron deficiency alone, without overt anemia, is associated with poor outcomes in patients with heart failure. Thus, to minimize the mortality in patients with heart failure, it is important to understand the link between iron deficiency and cardiac function. Chronic untreated iron deficiency results in cardiac remodeling, and we have previously reported that erythropoietin (Epo) and cardiac Epo receptor (EpoR) signaling may be associated with its remodeling. However, the link between EpoR signaling and its remodeling remains to be elucidated. Herein, we investigated the role of EpoR signaling on cardiac remodeling in response to chronic iron deficiency. Wild-type mice and transgene-rescued EpoR-null mutant mice, which express EpoR only in the hematopoietic lineage (EpoR-restricted mice), were fed with either a normal or an iron-restricted diet, and the molecular mechanisms were investigated. Dietary iron restriction gradually induced anemia, Epo secretion, and cardiac hypertrophy in wild-type mice. In contrast, EpoR-restricted mice fed with an iron-restricted diet exhibited anemia, left ventricular dilatation, and cardiac dysfunction compared with wild-type mice. Interestingly, altered cardiac mitochondrial biogenesis was observed in EpoR-restricted mice following iron deficiency. Moreover, cardiac p53 expression was increased in EpoR-restricted mice compared with wild-type mice following iron deficiency. These data indicate that EpoR signaling is associated with cardiac remodeling following chronic iron deficiency.

Use of Reticulocyte Hemoglobin Content in the Assessment of Iron Deficiency in Children with Inflammatory Bowel Disease

PubMed Central

Syed, Sana; Kugathasan, Subra; Kumar, Archana; Prince, Jarod; Schoen, Bess T.; McCracken, Courtney; Ziegler, Thomas R.; Suchdev, Parminder S.

2016-01-01

BACKGROUND Iron deficiency and anemia affect up to 50–75% of inflammatory bowel disease (IBD) patients. Iron deficiency in IBD may be difficult to diagnose because of the effect of inflammation on iron status biomarkers. Thus, there is a need for better methods to accurately determine iron status in IBD. OBJECTIVE To investigate the association of inflammation with hemoglobin content of reticulocytes (CHr) and the utility of CHr in comparison to standard iron biomarkers. DESIGN/METHODS We conducted a cross-sectional study of children with IBD. Iron biomarkers [CHr, ferritin, soluble transferrin receptor (sTfR), hepcidin, hemoglobin] were measured along with systemic biomarkers of inflammation [C-reactive protein (CRP), α1-acid glycoprotein (AGP)]. Spearman correlations were used to evaluate the relationship of inflammation and iron biomarkers. The gold standard for iron deficiency was defined as inflammation-corrected ferritin < 15 μg/L or sTfR > 8.3mg/L. Receiver operating characteristic (ROC) curves were used to estimate the prognostic values of all iron biomarkers to identify patients with iron deficiency. RESULTS We analyzed data in 62 children aged 5 to < 19 years. Sixty-nine % of our subjects had Crohn’s disease and 31% had ulcerative colitis, of which 42% were females and 53% African American. The prevalence of anemia was 32%, of iron deficiency was 52% using ferritin < 15 μg/L or sTfR > 8.3mg/L, 39% using RDW>14.5%, 26% using BIS<0mg/kg body weight, 25% using CHr <28 pg and 11% using MCV <75fL/cell. After correcting ferritin and sTfR levels for inflammation, the prevalence of iron deficiency was 68%. CHr was correlated with CRP (rs −0.44, p < 0.001) and AGP (rs −0.37, p < 0.05). The optimal prognostic value for inflammation-adjusted CHr to predict iron deficiency was 34 pg (area under the ROC of 0.70), with 88% sensitivity and 30% specificity. CONCLUSIONS Iron deficiency and anemia are very common in this pediatric IBD cohort. All explored iron biomarkers, including CHr, were affected by inflammation and should be adjusted. A single iron biomarker is unlikely to best predict iron deficiency in pediatric IBD. Iron intervention studies are needed to examine the response of iron biomarkers to iron supplementation in the setting of inflammation. PMID:27429427

[Biological diagnosis of iron deficiency in children].

PubMed

Thuret, I

2017-05-01

Measurement of serum ferritin (SF) is currently the laboratory test recommended for diagnosing iron deficiency. In the absence of an associated disease, a low SF value is an early and highly specific indicator of iron deficiency. The WHO criteria proposed to define depleted storage iron are 12μg/L for children under 5 years and 15μg/L for those over 5 years. A higher threshold of 30μg/L is used in the presence of infection or inflammation. Iron deficiency anemia, with typical low mean corpuscular volume and mean corpuscular hemoglobin, is only present at the end stage of iron deficiency. Other diagnostic tests for iron deficiency including iron parameters (low serum iron, increased total iron-binding capacity, low transferrin saturation) and erythrocyte traits (low mean corpuscular volume, increased zinc protoporphyrin) provide little additional diagnostic value over SF. In children, serum soluble transferrin receptor (sTfR) has been reported to be a sensitive indicator of iron deficiency and is relatively unaffected by inflammation. On the other hand, sTfR is directly related to extent of erythroid activity and not commonly used in clinical practice. In population surveys, approaches based on combinations of markers have been explored to improve the specificity and sensitivity of diagnostic. In addition to Hb value determination, a combination of parameters (among transferrin saturation, zinc protoporphyrin, mean corpuscular volume or serum ferritin) was generally used to assess iron deficiency. More recently sTfR/ ferritin index were evaluated, sTfR in conjunction with SF allowing to better distinguishing iron deficiency from inflammatory anemia. Also, hepcidin measurements appeared an interesting marker for diagnosing iron deficiency and identifying individuals in need of iron supplementation in populations where inflammatory or infectious diseases are frequently encountered. Reticulocyte Hb content (CHr) determination is an early parameter of iron deficiency erythropoiesis. CHr can be measured with several automated hematology analyzers and so, used for individual's iron status assessment. In addition to Hb concentration determination, individual's iron status is commonly assessed in the pediatric clinical practice by the SF measurement accompanied by the determination of C-reactive protein for detection of a simultaneous acute infection and/or inflammation. © 2017 Elsevier Masson SAS. Tous droits réservés.

Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy.

PubMed

Verstovsek, Srdan; Harrison, Claire N; Kiladjian, Jean-Jacques; Miller, Carole; Naim, Ahmad B; Paranagama, Dilan C; Habr, Dany; Vannucchi, Alessandro M

2017-05-01

Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effects of a Tripeptide Iron on Iron-Deficiency Anemia in Rats.

PubMed

Xiao, Chen; Lei, Xingen; Wang, Qingyu; Du, Zhongyao; Jiang, Lu; Chen, Silu; Zhang, Mingjie; Zhang, Hao; Ren, Fazheng

2016-02-01

This study aims to investigate the effects of a tripeptide iron (REE-Fe) on iron-deficiency anemia rats. Sprague-Dawley rats were randomly divided into seven groups: a normal control group, an iron-deficiency control group, and iron-deficiency groups treated with ferrous sulfate (FeSO4), ferrous glycinate (Fe-Gly), or REE-Fe at low-, medium-, or high-dose groups. The rats in the iron-deficiency groups were fed on an iron-deficient diet to establish iron-deficiency anemia (IDA) model. After the model established, different iron supplements were given to the rats once a day by intragastric administration for 21 days. The results showed that REE-Fe had effective restorative action returning body weight, organ coefficients, and hematological parameters in IDA rats to normal level. In addition, comparing with FeSO4 or Fe-Gly, high-dose REE-Fe was more effective on improving the levels of renal coefficient, total iron-binding capacity, and transferrin. Furthermore, the liver hepcidin messenger RNA (mRNA) expression in the high-dose group was significantly higher (p < 0.05) than that in the FeSO4 or Fe-Gly group and showed no significant difference (p > 0.05) with the normal control group. The findings suggest that REE-Fe is an effective source of iron supplement for IDA rats and might be exploited as a new iron fortifier.

Lead Toxicity and Iron Deficiency in Utah Migrant Children.

ERIC Educational Resources Information Center

Ratcliffe, Stephen D.; And Others

1989-01-01

Determines the frequency of presumptive iron deficiency and lead toxicity in 198 Utah migrant children, aged 9-72 months. There were no confirmed cases of lead toxicity. Thirteen percent of all children tested, and 30 percent of those aged 9-23 months, were iron deficient. Hematocrit determination is an insensitive screen for iron deficiency.…

The Evidence-Based Evaluation of Iron Deficiency Anemia.

PubMed

Hempel, Eliana V; Bollard, Edward R

2016-09-01

Anemia is a prevalent disease with multiple possible etiologies and resultant complications. Iron deficiency anemia is a common cause of anemia and is typically due to insufficient intake, poor absorption, or overt or occult blood loss. Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment. In addition, identifying the underlying cause of iron deficiency is also necessary to help guide management of these patients. We review the key components to an evidence-based, cost-conscious evaluation of suspected iron deficiency anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management.

PubMed

Cappellini, Maria Domenica; Comin-Colet, Josep; de Francisco, Angel; Dignass, Axel; Doehner, Wolfram; Lam, Carolyn S; Macdougall, Iain C; Rogler, Gerhard; Camaschella, Clara; Kadir, Rezan; Kassebaum, Nicholas J; Spahn, Donat R; Taher, Ali T; Musallam, Khaled M

2017-10-01

Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease-specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

Iron deficiency and anemia in heart failure.

PubMed

Çavuşoğlu, Yüksel; Altay, Hakan; Çetiner, Mustafa; Güvenç, Tolga Sinan; Temizhan, Ahmet; Ural, Dilek; Yeşilbursa, Dilek; Yıldırım, Nesligül; Yılmaz, Mehmet Birhan

2017-03-01

Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

Two iron-regulated transporter (IRT) genes showed differential expression in poplar trees under iron or zinc deficiency.

PubMed

Huang, Danqiong; Dai, Wenhao

2015-08-15

Two iron-regulated transporter (IRT) genes were cloned from the iron chlorosis resistant (PtG) and susceptible (PtY) Populus tremula 'Erecta' lines. Nucleotide sequence analysis showed no significant difference between PtG and PtY. The predicted proteins contain a conserved ZIP domain with 8 transmembrane (TM) regions. A ZIP signature sequence was found in the fourth TM domain. Phylogenetic analysis revealed that PtIRT1 was clustered with tomato and tobacco IRT genes that are highly responsible to iron deficiency. The PtIRT3 gene was clustered with the AtIRT3 gene that was related to zinc and iron transport in plants. Tissue specific expression indicated that PtIRT1 only expressed in the root, while PtIRT3 constitutively expressed in all tested tissues. Under iron deficiency, the expression of PtIRT1 was dramatically increased and a significantly higher transcript level was detected in PtG than in PtY. Iron deficiency also enhanced the expression of PtIRT3 in PtG. On the other hand, zinc deficiency down-regulated the expression of PtIRT1 and PtIRT3 in both PtG and PtY. Zinc accumulated significantly under iron-deficient conditions, whereas the zinc deficiency showed no significant effect on iron accumulation. A yeast complementation test revealed that the PtIRT1 and PtIRT3 genes could restore the iron uptake ability under the iron uptake-deficiency condition. The results will help understand the mechanisms of iron deficiency response in poplar trees and other woody species. Copyright © 2015 Elsevier GmbH. All rights reserved.

Iron deficiency stress can induce MxNRAMP1 protein endocytosis in M. xiaojinensis.

PubMed

Pan, Haifa; Wang, Yi; Zha, Qian; Yuan, Mudan; Yin, Lili; Wu, Ting; Zhang, Xinzhong; Xu, Xuefeng; Han, Zhenhai

2015-08-10

Iron deficiency is one of the most common nutritional disorders in plants, especially in fruit trees grown in calcareous soil. Iron deficiency stress can induce a series of adaptive responses in plants, the cellular and molecular mechanisms of which remain unclear. NRAMPs (natural resistance-associated macrophage proteins) play an important role in divalent metal ion transportation. In this study, we cloned MxNRAMP1, an NRAMP family gene from a highly iron-efficient apple genotype, Malus xiaojinensis. Further research showed that iron deficiency stress could induce MxNRAMP1 expression in roots and leaves. A protoplast transient expression system and immune electron microscopy localization techniques were used to prove that MxNRAMP1 mainly exists in the plasma membrane and vesicles. Interestingly, iron deficiency stress could induce the MxNRAMP protein to transport iron ions to specific organelles (lysosome and chloroplast) through vesicle endocytosis. Stable transgenic tobacco showed that MxNRAMP1 over-expression could promote iron absorption and accumulation in plants, and increase the plant's resistance against iron deficiency stress. These results showed that, in M. xiaojinensis, MxNRAMP1 not only plays an important role in iron absorption and transportation, it can also produce adaptive responses against iron deficiency through endocytosis. Copyright © 2015 Elsevier B.V. All rights reserved.

[Iron from soil to plant products].

PubMed

Briat, Jean-François

2005-11-01

As an essential mineral, iron plays an important role in fundamental biological processes such as photosynthesis, respiration, nitrogen fixation and assimilation, and DNA synthesis. Iron is also a co-factor of many enzymes involved in the synthesis of plant hormones. The latter are involved in many pathways controling plant development or adaptative responses to environmental conditions. Iron reactivity with oxygen leads to its insolubility (responsible for deficiency) and potential toxicity, and complicates iron use by aerobic organisms. If plants lacked an active root system with which to acquire iron from the soil, most would experience iron deficiency and show physiological changes. In contrast, an excess of soluble iron, which can occur in flooded acidic soils, can lead to ferrous iron toxicity due to iron reactivity with reduced forms of oxygen and subsequent free radical production. An optimal iron concentration is thus required for a plant to grow and develop normally. This concentration depends on multiple regulatory mechanisms controlling iron uptake from soil by the roots, as well as iron transport and distribution to the various plant organs. Optimized seed iron content is a major biotechnological challenge identified by the World Health Organization, and it is therefore crucial to understand the underlying mechanisms. Iron delivery to seeds is tightly controlled, and depends on the nature of iron speciation in specific chelates, and their transport.

Iron deficiency or anemia of inflammation? : Differential diagnosis and mechanisms of anemia of inflammation.

PubMed

Nairz, Manfred; Theurl, Igor; Wolf, Dominik; Weiss, Günter

2016-10-01

Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body's iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear phagocytes system in liver and spleen. This results in iron-limited erythropoiesis and anemia. This review summarizes current diagnostic and pathophysiological concepts of iron deficiency anemia and anemia of inflammation, as well as combined conditions, and provides a brief outlook on novel therapeutic options.

Endogenous Siderophore 2,5-Dihydroxybenzoic Acid Deficiency Promotes Anemia and Splenic Iron Overload in Mice

PubMed Central

Liu, Zhuoming; Ciocea, Alieta

2014-01-01

Eukaryotes produce a siderophore-like molecule via a remarkably conserved biosynthetic pathway. 3-OH butyrate dehydrogenase (BDH2), a member of the short-chain dehydrogenase (SDR) family of reductases, catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA). Depletion of the mammalian siderophore by inhibiting expression of bdh2 results in abnormal accumulation of intracellular iron and mitochondrial iron deficiency in cultured mammalian cells, as well as in yeast cells and zebrafish embryos We disrupted murine bdh2 by homologous recombination to analyze the effect of bdh2 deletion on erythropoiesis and iron metabolism. bdh2 null mice developed microcytic anemia and tissue iron overload, especially in the spleen. Exogenous supplementation with 2,5-DHBA alleviates splenic iron overload in bdh2 null mice. Additionally, bdh2 null mice exhibit reduced serum iron. Although BDH2 has been proposed to oxidize ketone bodies, we found that BDH2 deficiency did not alter ketone body metabolism in vivo. In sum, our findings demonstrate a key role for BDH2 in erythropoiesis. PMID:24777603

The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention

PubMed Central

Bialkowski, W.; Bryant, B. J.; Schlumpf, K. S.; Wright, D. J.; Birch, R.; Kiss, J. E.; D’Andrea, P.; Cable, R. G.; Spencer, B. R.; Vij, V.; Mast, A. E.

2014-01-01

Background and Objectives Repeated blood donation produces iron deficiency. Changes in dietary iron intake do not prevent donation-induced iron deficiency. Prolonging the interdonation interval or using oral iron supplements can mitigate donation-induced iron deficiency. The most effective operational methods for reducing iron deficiency in donors are unknown. Materials and Methods ‘Strategies To Reduce Iron Deficiency’ (STRIDE) was a two-year, randomized, placebo-controlled study in blood donors. 692 donors were randomized into one of two educational groups or one of three interventional groups. Donors randomized to educational groups either received letters thanking them for donating, or, suggesting iron supplements or delayed donation if they had low ferritin. Donors randomized to interventional groups either received placebo, 19-mg or 38-mg iron pills. Results Iron deficient erythropoiesis was present in 52.7% of males and 74.6% of females at enrolment. Adverse events within 60 days of enrolment were primarily mild gastrointestinal symptoms (64%). The incidence of de-enrolment within 60 days was more common in the interventional groups than in the educational groups (P = 0.002), but not more common in those receiving iron than placebo (P = 0.68). Conclusion The prevalence of iron deficient erythropoiesis in donors enrolled in the STRIDE study is comparable to previously described cohorts of regular blood donors. De-enrolment within 60 days was higher for donors receiving tablets, although no more common in donors receiving iron than placebo. PMID:25469720

Plant Ferritin—A Source of Iron to Prevent Its Deficiency

PubMed Central

Zielińska-Dawidziak, Magdalena

2015-01-01

Iron deficiency anemia affects a significant part of the human population. Due to the unique properties of plant ferritin, food enrichment with ferritin iron seems to be a promising strategy to prevent this malnutrition problem. This protein captures huge amounts of iron ions inside the apoferritin shell and isolates them from the environment. Thus, this iron form does not induce oxidative change in food and reduces the risk of gastric problems in consumers. Bioavailability of ferritin in human and animal studies is high and the mechanism of absorption via endocytosis has been confirmed in cultured cells. Legume seeds are a traditional source of plant ferritin. However, even if the percentage of ferritin iron in these seeds is high, its concentration is not sufficient for food fortification. Thus, edible plants have been biofortified in iron for many years. Plants overexpressing ferritin may find applications in the development of bioactive food. A crucial achievement would be to develop technologies warranting stability of ferritin in food and the digestive tract. PMID:25685985

Investigation of iron deficiency in patients with congestive heart failure: A medical practice that requires greater attention.

PubMed

Belmar Vega, Lara; de Francisco, Alm; Albines Fiestas, Zoila; Serrano Soto, Mara; Kislikova, María; Seras Mozas, Miguel; Unzueta, Mayte García; Arias Rodríguez, Manuel

2016-01-01

Iron deficiency in congestive heart failure (CHF), with or without concomitant anaemia, is associated with health-related quality of life, NYHA functional class, and exercise capacity. Prospective, randomised studies have demonstrated that correcting iron deficiency improves the quality of life and functional status of patients with CHF, including those who do not have anaemia. The aim of this study was to analyse how frequently these iron parameters are tested and thus determine the extent to which this quality improvement tool has been implemented in patients admitted with CHF. Retrospective observational study of patients from a university hospital diagnosed with CHF on admission between 01/01/2012 and 11/06/2013. Iron parameters were tested in 39% (324) of the 824 patients analysed. There was no significant difference in age between the patients whose iron was tested and those whose iron was not tested, but the difference in terms of gender was significant (P=.007). Glomerular filtration rate and haemoglobin, were significantly lower in the group of patients whose iron was tested (P<.001). The proportion of patients with anaemia, renal failure or both was significantly higher in the group of patients who had iron tests (P<.001). Of the 324 patients whose iron parameters were tested, 164 (51%) had iron deficiency. There were no differences between patients with and without iron deficiency in terms of age or gender. The iron parameters in both groups, ferritin and transferrin saturation index were significantly lower among the patients with iron deficiency (P<.001). The glomerular filtration rate values were significantly lower in patients with no iron deficiency (P<.001). Significant differences were also observed between those with and without iron deficiency in the proportion of patients with renal failure (79 vs. 66%, respectively, P=.013), but not in terms of haemoglobin concentration. Congestive heart failure is very frequently associated with anaemia, iron deficiency and renal failure. Despite the fact that correcting iron deficiency is known to improve symptoms, testing of iron parameters in patients admitted with CHF is not performed as often as it should be. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Quantitative Proteomic Analysis Reveals Populus cathayana Females Are More Sensitive and Respond More Sophisticatedly to Iron Deficiency than Males.

PubMed

Zhang, Sheng; Zhang, Yunxiang; Cao, Yanchun; Lei, Yanbao; Jiang, Hao

2016-03-04

Previous studies have shown that there are significant sexual differences in the morphological and physiological responses of Populus cathayana Rehder to nitrogen and phosphorus deficiencies, but little is known about the sex-specific differences in responses to iron deficiency. In this study, the effects of iron deficiency on the morphology, physiology, and proteome of P. cathayana males and females were investigated. The results showed that iron deficiency (25 days) significantly decreased height growth, photosynthetic rate, chlorophyll content, and tissue iron concentration in both sexes. A comparison between the sexes indicated that iron-deficient males had less height inhibition and photosynthesis system II or chloroplast ultrastructural damage than iron-deficient females. iTRAQ-based quantitative proteomic analysis revealed that 144 and 68 proteins were decreased in abundance (e.g., proteins involved in photosynthesis, carbohydrate and energy metabolism, and gene expression regulation) and 78 and 39 proteins were increased in abundance (e.g., proteins involved in amino acid metabolism and stress response) according to the criterion of ratio ≥1.5 in females and males, respectively. A comparison between the sexes indicated that iron-deficient females exhibited a greater change in the proteins involved in photosynthesis, carbon and energy metabolism, the redox system, and stress responsive proteins. This study reveals females are more sensitive and have a more sophisticated response to iron deficiency compared with males and provides new insights into differential sexual responses to nutrient deficiency.

Nitric oxide maintains cell survival of Trichomonas vaginalis upon iron depletion.

PubMed

Cheng, Wei-Hung; Huang, Kuo-Yang; Huang, Po-Jung; Hsu, Jo-Hsuan; Fang, Yi-Kai; Chiu, Cheng-Hsun; Tang, Petrus

2015-07-25

Iron plays a pivotal role in the pathogenesis of Trichomonas vaginalis, the causative agent of highly prevalent human trichomoniasis. T. vaginalis resides in the vaginal region, where the iron concentration is constantly changing. Hence, T. vaginalis must adapt to variations in iron availability to establish and maintain an infection. The free radical signaling molecules reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been proven to participate in iron deficiency in eukaryotes. However, little is known about the roles of these molecules in iron-deficient T. vaginalis. T. vaginalis cultured in iron-rich and -deficient conditions were collected for all experiments in this study. Next generation RNA sequencing was conducted to investigate the impact of iron on transcriptome of T. vaginalis. The cell viabilities were monitored after the trophozoites treated with the inhibitors of nitric oxide (NO) synthase (L-NG-monomethyl arginine, L-NMMA) and proteasome (MG132). Hydrogenosomal membrane potential was measured using JC-1 staining. We demonstrated that NO rather than ROS accumulates in iron-deficient T. vaginalis. The level of NO was blocked by MG132 and L-NMMA, indicating that NO production is through a proteasome and arginine dependent pathway. We found that the inhibition of proteasome activity shortened the survival of iron-deficient cells compared with untreated iron-deficient cells. Surprisingly, the addition of arginine restored both NO level and the survival of proteasome-inhibited cells, suggesting that proteasome-derived NO is crucial for cell survival under iron-limited conditions. Additionally, NO maintains the hydrogenosomal membrane potential, a determinant for cell survival, emphasizing the cytoprotective effect of NO on iron-deficient T. vaginalis. Collectively, we determined that NO produced by the proteasome prolonged the survival of iron-deficient T. vaginalis via maintenance of the hydrogenosomal functions. The findings in this study provide a novel role of NO in adaptation to iron-deficient stress in T. vaginalis and shed light on a potential therapeutic strategy for trichomoniasis.

Development of a fortified juice beverage: assessment of iron bioavailability using an established caco-2 cell bioassay

USDA-ARS?s Scientific Manuscript database

Poor iron bioavailability is a contributing factor to the high prevalence of iron deficiency anemia in India, and food fortification with bioavailable iron is one strategy to help address the problem. Validated in vitro methods to measure iron (Fe) bioavailability are useful tools that can be levera...

Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

PubMed

Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

2018-06-01

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

Anaemia and iron deficiency in children with inflammatory bowel disease.

PubMed

Wiskin, Anthony E; Fleming, Ben J; Wootton, Stephen A; Beattie, R Mark

2012-07-01

Anaemia and iron deficiency are common in children with Inflammatory Bowel Disease (IBD) however it is not known if the prevalence of anaemia and iron deficiency alters following diagnosis. Laboratory results from diagnosis, and at follow up one and two years later were recorded retrospectively in children with IBD recruited from a tertiary centre. Anaemia was defined using WHO standards and iron deficiency defined using published guidelines. 46 children (16 girls) with Crohn's disease and 34 children (18 girls) with UC were studied. 75% of children with IBD were anaemic at diagnosis, 30% were anaemic at follow up two years later. 90% of children with Crohn's and 95% of children with Ulcerative Colitis (UC) were iron deficient at diagnosis. At follow up two years later 70% of children with Crohn's and 65% of children with UC were iron deficient. Persistent anaemia and iron deficiency are common in childhood IBD, prevalence alters with duration of time from diagnosis. Copyright © 2011. Published by Elsevier B.V.

Influence of diet, menstruation and genetic factors on iron status: a cross-sectional study in Spanish women of childbearing age.

PubMed

Blanco-Rojo, Ruth; Toxqui, Laura; López-Parra, Ana M; Baeza-Richer, Carlos; Pérez-Granados, Ana M; Arroyo-Pardo, Eduardo; Vaquero, M Pilar

2014-03-06

The aim of this study was to investigate the combined influence of diet, menstruation and genetic factors on iron status in Spanish menstruating women (n = 142). Dietary intake was assessed by a 72-h detailed dietary report and menstrual blood loss by a questionnaire, to determine a Menstrual Blood Loss Coefficient (MBLC). Five selected SNPs were genotyped: rs3811647, rs1799852 (Tf gene); rs1375515 (CACNA2D3 gene); and rs1800562 and rs1799945 (HFE gene, mutations C282Y and H63D, respectively). Iron biomarkers were determined and cluster analysis was performed. Differences among clusters in dietary intake, menstrual blood loss parameters and genotype frequencies distribution were studied. A categorical regression was performed to identify factors associated with cluster belonging. Three clusters were identified: women with poor iron status close to developing iron deficiency anemia (Cluster 1, n = 26); women with mild iron deficiency (Cluster 2, n = 59) and women with normal iron status (Cluster 3, n = 57). Three independent factors, red meat consumption, MBLC and mutation C282Y, were included in the model that better explained cluster belonging (R2 = 0.142, p < 0.001). In conclusion, the combination of high red meat consumption, low menstrual blood loss and the HFE C282Y mutation may protect from iron deficiency in women of childbearing age. These findings could be useful to implement adequate strategies to prevent iron deficiency anemia.

Underestimation of the coexistence of iron deficiencies and thalassemia minors: a single institution experience in Taiwan.

PubMed

Lin, Chung-King; Chen, Ling-Ping; Chang, Hsiu-Lin; Sung, Yung-Chuan

2014-08-01

Some physicians neglect the possible coexistence of an iron deficiency with a thalassemia minor and do not treat the iron deficiency accordingly. This motivated us to conduct this study. We retrospectively reviewed the records of 3892 patients who visited our clinics and had hemoglobin (Hb) electrophoreses performed in our hematologic laboratory from August 1, 2007 to December 31, 2012. The thalassemia minors were identified by characteristic complete blood count (CBC) parameters obtained from an autoanalyzer and Hb electrophoresis, and some cases were confirmed with molecular tests. Then, we checked iron studies [ferritin and/or serum iron with total iron-binding capacity (TIBC)] to determine the coexistence of an iron deficiency with a thalassemia minor and a response to iron, if such treatments were given. We found 792 cases with thalassemia minors, and excluded those without iron studies, with 661 cases as our sample. A total of 202/661 cases (31%) also had iron deficiencies. They had lower red blood cell (RBC) counts, Hb, and ferritin levels as compared to those thalassemia minor cases without coexistence of iron deficiencies. We concluded that the thalassemia minor patients did not have iron overload complications in our population. On the contrary, iron deficiencies commonly coexist in the clinical visits. We propose that if Hb < 11.5 g/dL in a case of thalassemia minor, one should screen for iron deficiency simultaneously. The sensitivity is 79.8% and the specificity is 82.6%. Therefore, physicians should be aware of this coexisting condition, and know how to recognize and treat it accordingly. Copyright © 2014. Published by Elsevier B.V.

Response of the iron-deficient erythrocyte in the rat to hyperoxia

NASA Technical Reports Server (NTRS)

Larkin, E. C.; Kimzey, S. L.; Siler, K.

1978-01-01

Normal and iron-deficient rats were exposed to 90% O2 at 760 Torr for 24 or 48 h. Erythrocyte response to hyperoxia was monitored by potassium (rubidium) influx studies, by storage stress, and by ultrastructural studies. Normal rat erythrocytes exhibited morphological changes and decrease of ouabain-sensitive potassium influx compared to unexposed controls. Both components of erythrocyte potassium influx were affected by iron deficiency. Erythrocytes from unexposed iron-deficient rats showed a 50% increase in ouabain-sensitive potassium influx compared to controls. Iron-deficient rats exposed to hyperoxia for 24 or 48 h, had erythrocytes with morphological changes. Erythrocytes of iron-deficient rats exposed for 24 h showned no influx change; those exposed for 48 h showed a decrease of ouabain-sensitive influx compared to erythrocytes of controls.

[Iron deficiency and pica].

PubMed

Muñoz, J A; Marcos, J; Risueño, C E; de Cos, C; López, R; Capote, F J; Martín, M V; Gil, J L

1998-02-01

To study the relationship between pica and iron-lack anaemia in a series of iron-deficiency patients in order to establish the pathogenesis of such relationship. Four-hundred and thirty-three patients were analysed. Pica was studied by introducing certain diet queries into the clinical history. All patients received oral iron and were periodically controlled with the usual clinico-haematological procedures. Pica was present in 23 patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate, ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and paper) substances were involved. A second episode of pica appeared in 9 cases upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic and substitutive therapy in all instances. No clear correlation was found with either socio-economic status or pathogenetic causes of iron deficiency and pica, and no haematological differences were seen between patients with pica and those without this alteration. (1) The pathogenesis of pica is unclear, although it appears unrelated to the degree of iron deficiency. (2) According to the findings in this series, pica seems a consequence of iron deficiency rather than its cause. (3) Adequate therapy can cure both conditions, although pica may reappear upon relapse of iron deficiency.

Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip

PubMed Central

Hennig, Georg; Homann, Christian; Teksan, Ilknur; Hasbargen, Uwe; Hasmüller, Stephan; Holdt, Lesca M.; Khaled, Nadia; Sroka, Ronald; Stauch, Thomas; Stepp, Herbert; Vogeser, Michael; Brittenham, Gary M.

2016-01-01

Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non-invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ∼1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non-invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of-care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure. PMID:26883939

Vegetarian diets and children.

PubMed

Sanders, T A

1995-08-01

Although the general health and development of vegan and vegetarian children seem to be normal, there may be subtle differences compared with omnivores. They are at increased risk of iron deficiency, and impaired psychomotor development associated with iron deficiency has been reported in macrobiotic infants. Fortunately, this impairment is not permanent, and follow-up studies have reported higher-than-average intelligence quotients among older macrobiotic children. Several other hazards of vegetarian diets have been identified, including vitamin B12 deficiency, rickets, and a bulky diet that can restrict energy intake in the first few years of life; however, these pitfalls can be avoided easily, and children can be successfully reared on vegetarian diets.

Iron status and anaemia in Sri Lankan secondary school children: A cross-sectional survey

PubMed Central

Allen, Stephen; Rodrigo, Rexan; Perera, Lakshman; Shao, Wei; Li, Chao; Wang, Duolao; Olivieri, Nancy; Weatherall, David J.; Premawardhena, Anuja

2017-01-01

Background Iron deficiency, the most common micronutrient disorder and cause of anaemia globally, impairs growth, cognition, behaviour and resistance to infection. Methods/Results As part of a national survey of inherited haemoglobin variants in 7526 students from 72 secondary schools purposefully selected from the 25 districts of Sri Lanka, we studied 5912 students with a normal haemoglobin genotype. Median age was 16.0 (IQR 15.0–17.0) years and 3189 (53.9%) students were males. Most students were Sinhalese (65.7%), with fewer Tamils (23.1%) and Muslims (11.2%). Anaemia occurred in 470 students and was more common in females (11.1%) than males (5.6%). Haemoglobin, serum ferritin, transferrin receptor and iron were determined in 1196 students with low red cell indices and a structured sample of those with normal red cell indices (n = 513). The findings were weighted to estimate the frequencies of iron deficiency and iron deficiency anaemia classified according to WHO criteria. Iron depletion (serum ferritin <15ug/ml) occurred in 19.2% and cellular iron deficiency (low serum ferritin and transferrin receptor >28.1 nmol/l) in 11.6% students. Iron deficiency anaemia (cellular iron deficiency with low haemoglobin) occurred in only 130/2794 (4.6%) females and 28/2789 (1.0%) males. Iron biomarkers were normal in 83/470 (14.6%) students with anaemia. In multiple regression analysis, the odds for iron depletion and cellular iron deficiency were about one-third in males compared with females, and the odds for iron deficiency anaemia were about one fifth in males compared to females. Tamil ethnicity and age <16 years increased the risk of all three stages of iron deficiency and living at high altitude significantly reduced the risk of iron depletion. Conclusions Low iron status and anaemia remain common problems in Sri Lankan secondary school students especially females, younger students and the socioeconomically disadvantaged Tamil population. More research is needed to identify factors other than low iron status that contribute to anaemia in adolescents. PMID:29155855

[Is iron important in heart failure?].

PubMed

Murín, Ján; Pernický, Miroslav

2015-01-01

Iron deficiency is a frequent comorbidity in a patient with chronic heart failure, and it associates with a worse pro-gnosis of that patient. Mainly worse quality of life and more rehospitalizations are in these iron deficient patients. Iron metabolism is rather complex and there is some new information concerning this complexity in heart failure. We distinquish an absolute and a functional iron deficiency in heart failure. It is this deficit which is important and not as much is anemia important here. Prevalence of anaemia in heart failure is about 30-50 %, higher it is in patients suffering more frequently heart failure decompensations. Treatment of iron deficiency is important and it improves prognosis of these patients. Most experiences there are with i.v. iron treatment (FERRIC HF, FAIR HF and CONFIRM HF studies), less so with per oral treatment. There are no clinical trials which analysed mortality influences. heart failure - iron metabolism in heart failure - prevalence of iron deficit - treatment of iron deficiency in heart failure.

Obesity as an emerging risk factor for iron deficiency.

PubMed

Aigner, Elmar; Feldman, Alexandra; Datz, Christian

2014-09-11

Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the "dysmetabolic iron overload syndrome (DIOS)". Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

Iron deficiency thrombocytopenia: a case report.

PubMed

Shah, Binay Kumar; Shah, Tara

2011-01-01

To describe a rare case of thrombocytopenia secondary to iron deficiency. A 34-year-old woman presented with severe microcytic hypochromic anemia and thrombocytopenia. Her ferritin was 1 ng/dl. A diagnosis of iron deficiency anemia and thrombocytopenia was made and the patient was treated with packed red blood cell transfusion and intravenous iron. Thrombocytopenia rapidly improved to normal. This case showed that iron deficiency should be considered as a cause of thrombocytopenia in the appropriate setting after ruling out common causes. Copyright © 2011 S. Karger AG, Basel.

Variation and inheritance of iron reductase activity in the roots of common vean (Phaseolus vulgaris L.) and association with seed iron accumulation QTL

USDA-ARS?s Scientific Manuscript database

Iron deficiency anemia is a global problem, which often affects women and children of developing countries and is based on diets that are low in iron. Strategy I plants, such as common bean (Phaseolus vulgaris L.) take up iron through a process that involves an iron reduction mechanism in their root...

Novel approaches and application of contemporary sensory evaluation practices in iron fortification programs

NASA Technical Reports Server (NTRS)

Bovell-Benjamin, Adelia C.; Guinard, Jean-Xavier

2003-01-01

Iron deficiency is the leading nutritional deficiency in the U.S. and the rest of the world, with its highest prevalences in the developing world. Iron fortification of food has been proposed as a strategy to reduce the high prevalence of iron deficiency. Poor consumer acceptance, unacceptable taste, and discoloration of the iron-fortified foods have been frequently listed as causes of unsuccessful iron fortification programs. An excellent prospect for improving consumer acceptance of iron-fortified foods is the incorporation of a thorough, organized, and unified approach to sensory evaluation practices into iron fortification programs for product optimization. The information gained from systematic sensory evaluation allows for the manipulation of the sensory attributes, and thus improvement of the sensory properties of the fortified food. However, iron fortification programs have not systematically measured the effect of fortification on the sensory quality of the food. Because sensory evaluation is an important criterion in successful iron fortification, an integrated approach is necessary. Therefore, nutritionists and sensory scientists should work closely with each other to select the most suitable sensory tests and methods. The objectives of this article are to: (1) critically review and discuss some traditional and contemporary approaches and applications of sensory evaluation practices in iron fortification programs, and (2) demonstrate the importance of incorporating a multidisciplinary, systematic sensory evaluation approach in iron fortification programs.

Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)

PubMed Central

Finberg, Karin E; Heeney, Matthew M; Campagna, Dean R; Aydınok, Yeşim; Pearson, Howard A; Hartman, Kip R; Mayo, Mary M; Samuel, Stewart M; Strouse, John J; Markianos, Kyriacos; Andrews, Nancy C; Fleming, Mark D

2011-01-01

Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans. PMID:18408718

Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia

PubMed Central

Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

2015-01-01

Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15 mg/kg; maximum of 1000 mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID:26670403

Iron balance and iron supplementation for the female athlete: A practical approach.

PubMed

Pedlar, Charles R; Brugnara, Carlo; Bruinvels, Georgie; Burden, Richard

2018-03-01

Maintaining a positive iron balance is essential for female athletes to avoid the effects of iron deficiency and anaemia and to maintain or improve performance. A major function of iron is in the production of the oxygen and carbon dioxide carrying molecule, haemoglobin, via erythropoiesis. Iron balance is under the control of a number of factors including the peptide hormone hepcidin, dietary iron intake and absorption, environmental stressors (e.g. altitude), exercise, menstrual blood loss and genetics. Menstruating females, particularly those with heavy menstrual bleeding are at an elevated risk of iron deficiency. Haemoglobin concentration [Hb] and serum ferritin (sFer) are traditionally used to identify iron deficiency, however, in isolation these may have limited value in athletes due to: (1) the effects of fluctuations in plasma volume in response to training or the environment on [Hb], (2) the influence of inflammation on sFer and (3) the absence of sport, gender and individually specific normative data. A more detailed and longitudinal examination of haematology, menstrual cycle pattern, biochemistry, exercise physiology, environmental factors and training load can offer a superior characterisation of iron status and help to direct appropriate interventions that will avoid iron deficiency or iron overload. Supplementation is often required in iron deficiency; however, nutritional strategies to increase iron intake, rest and descent from altitude can also be effective and will help to prevent future iron deficient episodes. In severe cases or where there is a time-critical need, such as major championships, iron injections may be appropriate.

Iron, zinc and iodide status in Mexican children under 12 years and women 12-49 years of age. A probabilistic national survey.

PubMed

Villalpando, Salvador; García-Guerra, Armando; Ramírez-Silva, Claudia Ivonne; Mejía-Rodríguez, Fabiola; Matute, Guadalupe; Shamah-Levy, Teresa; Rivera, Juan A

2003-01-01

To describe the epidemiology of iron, zinc and iodide deficiencies in a probabilistic sample of Mexican women and children and explore its association with some dietary and socio-demographic variables. We carried out in 1999 an epidemiological description of iron (percent transferrin saturation, PTS, < 16%), serum zinc (< 65 ug/dl) and iodide (< 50 ug/l urine) deficiencies in a probabilistic sample of 1,363 Mexican children under 12 years and of 731 women of child-bearing age. Serum iron, Total Iron Binding Capacity (TIBC) and zinc were measured by atomic absorption spectrometry, and urinary iodide by a colorimetric method. Logistic regression models explored determinants for such micromineral deficiencies. Iron deficiency was higher (67%) in infants < 2 years of age. Prevalence declined (34-39%) at school age. The prevalence for iron deficiency in women was 40%. Zinc deficiency was higher in infants < 2 years of age (34%) than in school-age children (19-24%). Prevalence in women was 30%, with no rural/urban difference. In women the likelihood of iron deficiency decreased as SEL improved (p = 0.04) and increased with the intake of cereals (p = 0.01). The likelihood of low serum zinc levels was greater in women and children of low socioeconomic level (SEL) (p < 0.02 and p = 0.001) iodide deficiency was negligible in both children and women. The data shows high prevalence of iron deficiency-specially in infants 12 to 24 months of age. It is suggested that in older children and women 12 to 49 years of age that iron bioavailability is low. The prevalence of zinc deficiency was also very high. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

Iron deficiency anaemia in pregnancy: The role of parenteral iron.

PubMed

Esen, Umo I

2017-01-01

Maternal and perinatal morbidity and mortality remain major challenges in the delivery of safe maternity care worldwide. Anaemia in pregnancy is an important contributor to this dismal picture, especially where blood transfusion services are poorly developed. An early diagnosis and treatment of iron deficiency anaemia in pregnancy using the new generation dextran-free parenteral iron preparations can save lives and reduce morbidity in selected pregnancies. It is time to cast aside the fears associated with the use of the old parenteral iron preparations which were associated a high incidence of anaphylaxis, and embrace the use of new parenteral iron products which have better side effect profiles and can deliver total dose infusions without the need for test dosing. In selected women, the benefits of this treatment far outweigh any disadvantages.

Anemia and iron deficiency before and after bariatric surgery.

PubMed

Salgado, Wilson; Modotti, Caue; Nonino, Carla Barbosa; Ceneviva, Reginaldo

2014-01-01

Iron deficiency and anemia are changes often associated with obesity. Bariatric surgery is responsible for increasing the iron loss and reducing its absorption. The objective of this study was to evaluate anemia and iron deficiency before and after bariatric surgery and to relate them to possible predisposing factors. A retrospective study was conducted on obese patients submitted to open Roux-en-Y gastric bypass, in which clinical and laboratory data were obtained up to 48 months postoperatively. Patients were divided into groups according to the presence or absence of anemia and to the presence or absence of iron deficiency (even without anemia), and all data were compared between these groups. Preoperatively, 21.5% of patients had anemia and 20% had iron deficiency. The number of patients with anemia did not vary through the 4 years of the study, but ferritin levels significantly decreased with time (P<.01). Younger patients and patients with greater weight loss had a higher incidence of anemia. Female gender was a variable associated with a greater incidence of iron deficiency. Anemia and iron deficiency are frequent in obese patients and must be treated before surgery. Medical and nutritional surveillance is important in the postoperative period of bariatric surgery. Management of each condition must be directed at correcting the 2 major sources of iron deficiency and anemia: food intolerance (mostly meat intolerance) and losses (frequently due to menstruation). These are the factors more related to iron deficient anemia. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Early Iron Deficiency Has Brain and Behavior Effects Consistent with Dopaminergic Dysfunction123

PubMed Central

Lozoff, Betsy

2011-01-01

To honor the late John Beard’s many contributions regarding iron and dopamine biology, this review focuses on recent human studies that test specific hypotheses about effects of early iron deficiency on dopamine system functioning. Short- and long-term alterations associated with iron deficiency in infancy can be related to major dopamine pathways (mesocortical, mesolimbic, nigrostriatal, tuberohypophyseal). Children and young adults who had iron deficiency anemia in infancy show poorer inhibitory control and executive functioning as assessed by neurocognitive tasks where pharmacologic and neuroimaging studies implicate frontal-striatal circuits and the mesocortical dopamine pathway. Alterations in the mesolimbic pathway, where dopamine plays a major role in behavioral activation and inhibition, positive affect, and inherent reward, may help explain altered social-emotional behavior in iron-deficient infants, specifically wariness and hesitance, lack of positive affect, diminished social engagement, etc. Poorer motor sequencing and bimanual coordination and lower spontaneous eye blink rate in iron-deficient anemic infants are consistent with impaired function in the nigrostriatal pathway. Short- and long-term changes in serum prolactin point to dopamine dysfunction in the tuberohypophyseal pathway. These hypothesis-driven findings support the adverse effects of early iron deficiency on dopamine biology. Iron deficiency also has other effects, specifically on other neurotransmitters, myelination, dendritogenesis, neurometabolism in hippocampus and striatum, gene and protein profiles, and associated behaviors. The persistence of poorer cognitive, motor, affective, and sensory system functioning highlights the need to prevent iron deficiency in infancy and to find interventions that lessen the long-term effects of this widespread nutrient disorder. PMID:21346104

Copper Deficiency Leads to Anemia, Duodenal Hypoxia, Upregulation of HIF-2α and Altered Expression of Iron Absorption Genes in Mice

PubMed Central

Matak, Pavle; Zumerle, Sara; Mastrogiannaki, Maria; El Balkhi, Souleiman; Delga, Stephanie; Mathieu, Jacques R. R.; Canonne-Hergaux, François; Poupon, Joel; Sharp, Paul A.; Vaulont, Sophie; Peyssonnaux, Carole

2013-01-01

Iron and copper are essential trace metals, actively absorbed from the proximal gut in a regulated fashion. Depletion of either metal can lead to anemia. In the gut, copper deficiency can affect iron absorption through modulating the activity of hephaestin - a multi-copper oxidase required for optimal iron export from enterocytes. How systemic copper status regulates iron absorption is unknown. Mice were subjected to a nutritional copper deficiency-induced anemia regime from birth and injected with copper sulphate intraperitoneally to correct the anemia. Copper deficiency resulted in anemia, increased duodenal hypoxia and Hypoxia inducible factor 2α (HIF-2α) levels, a regulator of iron absorption. HIF-2α upregulation in copper deficiency appeared to be independent of duodenal iron or copper levels and correlated with the expression of iron transporters (Ferroportin - Fpn, Divalent Metal transporter – Dmt1) and ferric reductase – Dcytb. Alleviation of copper-dependent anemia with intraperitoneal copper injection resulted in down regulation of HIF-2α-regulated iron absorption genes in the gut. Our work identifies HIF-2α as an important regulator of iron transport machinery in copper deficiency. PMID:23555700

Anemia, Iron Deficiency and Iodine Deficiency among Nepalese School Children.

PubMed

Khatiwada, Saroj; Lamsal, Madhab; Gelal, Basanta; Gautam, Sharad; Nepal, Ashwini Kumar; Brodie, David; Baral, Nirmal

2016-07-01

To assess iodine and iron nutritional status among Nepalese school children. A cross-sectional, community based study was conducted in the two districts, Ilam (hilly region) and Udayapur (plain region) of eastern Nepal. A total of 759 school children aged 6-13 y from different schools within the study areas were randomly enrolled. A total of 759 urine samples and 316 blood samples were collected. Blood hemoglobin level, serum iron, total iron binding capacity and urinary iodine concentration was measured. Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values. The mean level of hemoglobin, serum iron, total iron binding capacity, transferrin saturation and median urinary iodine excretion were 12.29 ± 1.85 g/dl, 70.45 ± 34.46 μg/dl, 386.48 ± 62.48 μg/dl, 19.94 ± 12.07 % and 274.67 μg/L respectively. Anemia, iron deficiency and iodine deficiency (urinary iodine excretion <100 μg/L) were present in 34.5 %, 43.4 % and 12.6 % children respectively. Insufficient urinary iodine excretion (urinary iodine excretion <100 μg/L) was common in anemic and iron deficient children. Iron deficiency and anemia are common in Nepalese children, whereas, iodine nutrition is more than adequate. Low urinary iodine excretion was common in iron deficiency and anemia.

The Effect of Low Dose Iron and Zinc Intake on Child Micronutrient Status and Development during the First 1000 Days of Life: A Systematic Review and Meta-Analysis.

PubMed

Petry, Nicolai; Olofin, Ibironke; Boy, Erick; Donahue Angel, Moira; Rohner, Fabian

2016-11-30

Adequate supply of micronutrients during the first 1000 days is essential for normal development and healthy life. We aimed to investigate if interventions administering dietary doses up to the recommended nutrient intake (RNI) of iron and zinc within the window from conception to age 2 years have the potential to influence nutritional status and development of children. To address this objective, a systematic review and meta-analysis of randomized and quasi-randomized fortification, biofortification, and supplementation trials in women (pregnant and lactating) and children (6-23 months) delivering iron or zinc in doses up to the recommended nutrient intake (RNI) levels was conducted. Supplying iron or zinc during pregnancy had no effects on birth outcomes. There were limited or no data on the effects of iron/zinc during pregnancy and lactation on child iron/zinc status, growth, morbidity, and psychomotor and mental development. Delivering up to 15 mg iron/day during infancy increased mean hemoglobin by 4 g/L ( p < 0.001) and mean serum ferritin concentration by 17.6 µg/L ( p < 0.001) and reduced the risk for anemia by 41% ( p < 0.001), iron deficiency by 78% (ID; p < 0.001) and iron deficiency anemia by 80% (IDA; p < 0.001), but had no effect on growth or psychomotor development. Providing up to 10 mg of additional zinc during infancy increased plasma zinc concentration by 2.03 µmol/L ( p < 0.001) and reduced the risk of zinc deficiency by 47% ( p < 0.001). Further, we observed positive effects on child weight for age z -score (WAZ) ( p < 0.05), weight for height z -score (WHZ) ( p < 0.05), but not on height for age z -score (HAZ) or the risk for stunting, wasting, and underweight. There are no studies covering the full 1000 days window and the effects of iron and zinc delivered during pregnancy and lactation on child outcomes are ambiguous, but low dose daily iron and zinc use during 6-23 months of age has a positive effect on child iron and zinc status.

The Effect of Low Dose Iron and Zinc Intake on Child Micronutrient Status and Development during the First 1000 Days of Life: A Systematic Review and Meta-Analysis

PubMed Central

Petry, Nicolai; Olofin, Ibironke; Boy, Erick; Donahue Angel, Moira; Rohner, Fabian

2016-01-01

Adequate supply of micronutrients during the first 1000 days is essential for normal development and healthy life. We aimed to investigate if interventions administering dietary doses up to the recommended nutrient intake (RNI) of iron and zinc within the window from conception to age 2 years have the potential to influence nutritional status and development of children. To address this objective, a systematic review and meta-analysis of randomized and quasi-randomized fortification, biofortification, and supplementation trials in women (pregnant and lactating) and children (6–23 months) delivering iron or zinc in doses up to the recommended nutrient intake (RNI) levels was conducted. Supplying iron or zinc during pregnancy had no effects on birth outcomes. There were limited or no data on the effects of iron/zinc during pregnancy and lactation on child iron/zinc status, growth, morbidity, and psychomotor and mental development. Delivering up to 15 mg iron/day during infancy increased mean hemoglobin by 4 g/L (p < 0.001) and mean serum ferritin concentration by 17.6 µg/L (p < 0.001) and reduced the risk for anemia by 41% (p < 0.001), iron deficiency by 78% (ID; p < 0.001) and iron deficiency anemia by 80% (IDA; p < 0.001), but had no effect on growth or psychomotor development. Providing up to 10 mg of additional zinc during infancy increased plasma zinc concentration by 2.03 µmol/L (p < 0.001) and reduced the risk of zinc deficiency by 47% (p < 0.001). Further, we observed positive effects on child weight for age z-score (WAZ) (p < 0.05), weight for height z-score (WHZ) (p < 0.05), but not on height for age z-score (HAZ) or the risk for stunting, wasting, and underweight. There are no studies covering the full 1000 days window and the effects of iron and zinc delivered during pregnancy and lactation on child outcomes are ambiguous, but low dose daily iron and zinc use during 6–23 months of age has a positive effect on child iron and zinc status. PMID:27916873

Is Higher Consumption of Animal Flesh Foods Associated with Better Iron Status among Adults in Developed Countries? A Systematic Review

PubMed Central

Jackson, Jacklyn; Williams, Rebecca; McEvoy, Mark; MacDonald-Wicks, Lesley; Patterson, Amanda

2016-01-01

Iron deficiency (ID) is the most prevalent nutrient deficiency within the developed world. This is of concern as ID has been shown to affect immunity, thermoregulation, work performance and cognition. Animal flesh foods provide the richest and most bioavailable source of dietary (haem) iron, however, it is unclear whether low animal flesh diets contribute to ID. This systematic review aimed to investigate whether a higher consumption of animal flesh foods is associated with better iron status in adults. CINAHL, Cochrane, EMBASE and MEDLINE were searched for published studies that included adults (≥18 years) from developed countries and measured flesh intakes in relation to iron status indices. Eight experimental and 41 observational studies met the inclusion criteria. Generally, studies varied in population and study designs and results were conflicting. Of the seven high quality studies, five showed a positive association between animal flesh intake (85–300 g/day) and iron status. However, the optimum quantity or frequency of flesh intake required to maintain or achieve a healthy iron status remains unclear. Results show a promising relationship between animal flesh intake and iron status, however, additional longitudinal and experimental studies are required to confirm this relationship and determine optimal intakes to reduce ID development. PMID:26891320

Iron deficiency in infancy is associated with altered neural correlates of recognition memory at 10 years

PubMed Central

Congdon, Eliza L.; Westerlund, Alissa; Algarin, Cecilia R.; Peirano, Patricio D.; Gregas, Matthew; Lozoff, Betsy; Nelson, Charles A.

2012-01-01

Objective To determine the long-term effects of iron deficiency on the neural correlates of recognition memory. Study design Non-anemic control participants (n=93) and 116 otherwise healthy formerly iron-deficient anemic (FIDA) Chilean children were selected from a larger longitudinal study. Participants were identified at 6, 12, or 18 months as iron-deficient anemic or non-anemic and subsequently received oral iron treatment. This follow-up was conducted when participants were 10 years old. Behavioral measures and event-related potentials from 28 scalp electrodes were measured during an old/new word recognition memory task. Results The new/old effect of the FN400 amplitude, where new words are associated with greater amplitude than old words, was present within the control group only. The control group also showed faster FN400 latency than the FIDA group and larger mean amplitude for the P300 component. Conclusions Although overall behavioral performance is comparable between groups, the results show that group differences in cognitive function have not been resolved ten years after iron treatment. Long-lasting changes in myelination and energy metabolism, perhaps especially in the hippocampus, may account for these long-term effects on an important aspect of human cognitive development. PMID:22244466

Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

PubMed

Toki, Yasumichi; Ikuta, Katsuya; Kawahara, Yoshie; Niizeki, Noriyasu; Kon, Masayuki; Enomoto, Motoki; Tada, Yuko; Hatayama, Mayumi; Yamamoto, Masayo; Ito, Satoshi; Shindo, Motohiro; Kikuchi, Yoko; Inoue, Mitsutaka; Sato, Kazuya; Fujiya, Mikihiro; Okumura, Toshikatsu

2017-07-01

Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives

PubMed Central

Jankowska, Ewa A.; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr

2013-01-01

Iron is a micronutrient essential for cellular energy and metabolism, necessary for maintaining body homoeostasis. Iron deficiency is an important co-morbidity in patients with heart failure (HF). A major factor in the pathogenesis of anaemia, it is also a separate condition with serious clinical consequences (e.g. impaired exercise capacity) and poor prognosis in HF patients. Experimental evidence suggests that iron therapy in iron-deficient animals may activate molecular pathways that can be cardio-protective. Clinical studies have demonstrated favourable effects of i.v. iron on the functional status, quality of life, and exercise capacity in HF patients. It is hypothesized that i.v. iron supplementation may become a novel therapy in HF patients with iron deficiency. PMID:23100285

Working memory impairment and recovery in iron deficient children.

PubMed

Otero, Gloria A; Pliego-Rivero, F Bernardo; Porcayo-Mercado, Rosario; Mendieta-Alcántara, Gustavo

2008-08-01

Iron is an important oligoelement participating in multiple metabolic processes, including the synthesis of catecholamines, and its deficiency (ID) throughout development is particularly insidious on brain maturation and the emergence of cognitive functions during school age. A working memory (WM) study in 8-10-year-old ID children is presented. It is hypothesized that an impairment in WM exists in ID school-age children and a substantial restoration of this mental ability should occur after iron supplementation. Event-related potentials (ERPs) were recorded during the completion of a Sternberg-type task in control, ID and ID-iron supplemented children. ID children showed less correct answers and diminished ERP amplitude in frontal, central, parietal and temporal regions compared to control children. After iron supplementation and normalizing bodily iron stores, behavioral and ERP differences disappeared between ID and control children. Considering that WM is fundamentally related to attention ability, the results presented here confirm and reinforce previous observations: ID severely diminishes attention [Otero GA, Pliego-Rivero FB, Contreras G, Ricardo J, Fernandez T. Iron supplementation brings up a lacking P300 in iron deficient children. Clin Neurophysiol 2004;115:2259-66] and WM while iron supplementation substantially restores the cognitive capabilities tested. This is one of very few reports using ERP showing a diminished WM capability in ID school-age children.

Iron deficiency--facts and fallacies.

PubMed

Oski, F A

1985-04-01

Iron deficiency occurs in all strata of society, is primarily a result of postnatal feeding practices and not due to congenital deficiencies of iron, can be prevented by appropriate dietary guidance, and, when present, produces important nonhematologic manifestations.

Dietary Supplements for Toddlers

MedlinePlus

... about which supplements are needed and the amounts. Iron Deficiency Iron deficiency does occur among some young children and can ... Drinking large quantities of milk may lead to iron deficiency anemia, as the child will be less interested ...

An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

PubMed

Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

2015-01-01

A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

Iron deficiency anaemia.

PubMed

Lopez, Anthony; Cacoub, Patrice; Macdougall, Iain C; Peyrin-Biroulet, Laurent

2016-02-27

Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anaemia and iron deficiency in cardiac patients: what do nurses and allied professionals know?

PubMed

Verheijden Klompstra, Leonie; Jaarsma, Tiny; Moons, Philip; Norekvål, Tone M; Smith, Karen; Martensson, Jan; Thompson, David R; De Geest, Sabina; Lenzen, Mattie; Strömberg, Anna

2012-03-01

Cardiac nurses and allied professionals often take care of patients who also have anaemia or iron deficiency. To deliver optimal care, professionals should be knowledgeable about the prevalence, diagnosis, pathophysiology, and therapeutic management of these conditions. We therefore set out a survey to get a first impression on the current knowledge of nurses and allied professionals on anaemia and iron deficiency. A questionnaire was designed for this study by the Undertaking Nursing Interventions Throughout Europe (UNITE) Study Group. Data were collected from 125 cardiovascular nurses and allied professionals visiting the 11th Annual Spring Meeting of the Council on Cardiovascular Nursing and Allied Professionals of the European Society of Cardiology. Most respondents had general knowledge on the definition of anaemia and iron deficiency and 54% of the respondents rated anaemia and iron deficiency as important when evaluating a cardiac patient. Specific knowledge regarding anaemia and more prominently of iron deficiency was not optimal. Although cardiac nurses and allied professionals have basic knowledge of anaemia and iron deficiency, they would benefit from additional knowledge and skills to optimally deliver patient care.

Absolute and Functional Iron Deficiency Is a Common Finding in Patients With Heart Failure and After Heart Transplantation.

PubMed

Przybylowski, P; Wasilewski, G; Golabek, K; Bachorzewska-Gajewska, H; Dobrzycki, S; Koc-Zorawska, E; Malyszko, J

2016-01-01

Anemia is relatively common in patients with heart failure and heart transplant recipients. Both absolute and functional iron deficiency may contribute to the anemia in these populations. Functional iron deficiency (defined as ferritin greater than 200 ng/mL with TSAT (Transferrin saturation) less than 20%) is characterized by the presence of adequate iron stores as defined by conventional criteria, but with insufficient iron mobilization to adequately support. The aim of this study was to determine prevalence of absolute and functional iron deficiency in patients with heart failure (n = 269) and after heart transplantation (n = 130) and their relation to parameters of iron status and inflammation. Iron status, complete blood count, and creatinine levels were assessed using standard laboratory methods. C-reactive protein, hepcidin and hemojuvelin were measured using commercially available kits. Absolute iron deficiency was present in 15% of patients with heart failure and 30% in heart transplant recipients, whereas functional iron deficiency was present in 18% of patients with heart failure and 17% in heart transplant recipients. Functional iron deficiency was associated with significantly higher C-reactive protein and hepcidin levels in heart failure patients, and higher hepcidin and lower estimate glomerular filtration rates in heart transplant recipients. Prevalence of anemia (according to the World Health Organization) was significantly higher in heart transplant recipients (40% vs 22%, P < .001), they were also younger, but with worse kidney function than patients with heart failure. Both absolute and functional iron deficiency were present in a considerable group of patients. This population should be carefully screened for possible reversible causes of inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron intakes and status of 2-year-old children in the Cork BASELINE Birth Cohort Study.

PubMed

McCarthy, Elaine K; Ní Chaoimh, Carol; Hourihane, Jonathan O'B; Kenny, Louise C; Irvine, Alan D; Murray, Deirdre M; Kiely, Mairead

2017-07-01

Young children are at risk of iron deficiency and subsequent anaemia, resulting in long-term consequences for cognitive, motor and behavioural development. This study aimed to describe the iron intakes, status and determinants of status in 2-year-old children. Data were collected prospectively in the mother-child Cork BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood. At the 24-month assessment, serum ferritin, haemoglobin and mean corpuscular volume were measured, and food/nutrient intake data were collected using a 2-day weighed food diary. Iron status was assessed in 729 children (median [IQR] age: 2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean (SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%). Following an iron series workup, five more children were diagnosed with iron deficiency anaemia. Twenty-one per cent had ferritin concentrations <15 µg/L. Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows' milk intakes ≥ 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron status. Iron-fortified formula consumption was associated with decreased risk (0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a lower prevalence of low iron status was observed than in previous reports. Compliance with dietary recommendations to limit cows' milk intakes in young children and consumption of iron-fortified products appears to have contributed to improved iron status at two years. © 2016 John Wiley & Sons Ltd.

Effects of Iron Deficiency on Iron Binding and Internalization into Acidic Vacuoles in Dunaliella salina1[W][OA

PubMed Central

Paz, Yakov; Shimoni, Eyal; Weiss, Meira; Pick, Uri

2007-01-01

Uptake of iron in the halotolerant alga Dunaliella salina is mediated by a transferrin-like protein (TTf), which binds and internalizes Fe3+ ions. Recently, we found that iron deficiency induces a large enhancement of iron binding, which is associated with accumulation of three other plasma membrane proteins that associate with TTf. In this study, we characterized the kinetic properties of iron binding and internalization and identified the site of iron internalization. Iron deficiency induces a 4-fold increase in Fe binding, but only 50% enhancement in the rate of iron uptake and also increases the affinity for iron and bicarbonate, a coligand for iron binding. These results indicate that iron deprivation leads to accumulation and modification of iron-binding sites. Iron uptake in iron-sufficient cells is preceded by an apparent time lag, resulting from prebound iron, which can be eliminated by unloading iron-binding sites. Iron is tightly bound to surface-exposed sites and hardly exchanges with medium iron. All bound iron is subsequently internalized. Accumulation of iron inhibits further iron binding and internalization. The vacuolar inhibitor bafilomycin inhibits iron uptake and internalization. Internalized iron was localized by electron microscopy within vacuolar structures that were identified as acidic vacuoles. Iron internalization is accompanied by endocytosis of surface proteins into these acidic vacuoles. A novel kinetic mechanism for iron uptake is proposed, which includes two pools of bound/compartmentalized iron separated by a rate-limiting internalization stage. The major parameter that is modulated by iron deficiency is the iron-binding capacity. We propose that excessive iron binding in iron-deficient cells serves as a temporary reservoir for iron that is subsequently internalized. This mechanism is particularly suitable for organisms that are exposed to large fluctuations in iron availability. PMID:17513481

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

PubMed Central

Quintana-Díaz, Manuel; Fabra-Cadenas, Sara; Gómez-Ramírez, Susana; Martínez-Virto, Ana; García-Erce, José A.; Muñoz, Manuel

2016-01-01

Background Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. Materials and methods From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500–1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. Results Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000–2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1–3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. Discussion Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED. PMID:26674819

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach.

PubMed

Bhardwaj, Divya; Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-12-01

Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli's method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. There was a statistically significant difference in serum iron and haemoglobin level in all three groups (p<0.05). The serum iron level was lowest in OSMF group and haemoglobin was lowest in iron deficiency anaemia group. A progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF was also observed. The iron deficiency anaemia group was not found to be suffering from OSMF in the absence of areca-nut or tobacco chewing habits, but OSMF patients with chewing habits were found to be suffering from iron deficiency anaemia. There is a progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF so it can be used as an auxillary test in assessment of prognosis of the disease.

Determinants of iron status in Malaysian adolescents from a rural community.

PubMed

Foo, Leng Huat; Khor, Geok Lin; Tee, E-Siong; Dhanaraj, Prabakaran

2004-09-01

Iron deficiency anaemia is the most common micronutrient deficiency worldwide. The prevalence of anaemia in the developing countries is three to four times higher than that in the developed countries. The iron status was assessed in 199 apparently healthy male and female adolescents aged 12-19 years living in a fishing community in Sabah, Malaysia. Data on socio-economic characteristics, lifestyles, anthropometry measurements, iron status, and dietary intake were gathered. Dietary intake of energy, iron, and most nutrients (with the exception of protein and vitamin C) were below the recommended levels for Malaysian adolescents. Three-quarters of the iron was derived from plant foods. The mean haemoglobin value for the male was 13.9 +/- 1.3 g/dl with 9.5% having less than 12 g/dl, while the respective figures for the female were 12.4 +/- 1.6 g/dl and 28.6%. The mean serum ferritin concentrations for male and female adolescents were 21.5 and 15.4 microg/l, respectively; with 25.7% of the males and 49.5% of the females having deficient levels of ferritin. Dietary intake of total energy and iron, and gender were found to be independent determinants of serum ferritin and haemoglobin levels, accounting for over 40% of the variations for each of these iron indicators. In males, but not in females, the intake of dietary protein and iron, and physical activity were also found to be significant determinants of serum ferritin. The age of subjects and household size were significant determinants of haemoglobin levels for male subjects, but not for female subjects. The findings indicate the importance of adequate intake of energy and dietary iron for improving the iron status of adolescents.

Behavior of Infants with Iron-Deficiency Anemia.

ERIC Educational Resources Information Center

Lozoff, Betsy; And Others

1998-01-01

Compared behavior of 52 Costa Rican 12- to 23-month-olds with iron-deficiency anemia to that of 139 infants with better iron status. Found that iron-deficient infants maintained closer contact with caregivers; showed less pleasure and playfulness; were more wary, hesitant, and easily tired; made fewer attempts at test items; and attended less to…

Activation of Nrf2/Keap1 signaling and autophagy induction against oxidative stress in heart in iron deficiency.

PubMed

Inoue, Hirofumi; Kobayashi, Ken-Ichi; Ndong, Moussa; Yamamoto, Yuji; Katsumata, Shin-Ichi; Suzuki, Kazuharu; Uehara, Mariko

2015-01-01

We investigated the effects of dietary iron deficiency on the redox system in the heart. Dietary iron deficiency increased heart weight and accumulation of carbonylated proteins. However, expression levels of heme oxygenase-1 and LC3-II, an antioxidant enzyme and an autophagic marker, respectively, in iron-deficient mice were upregulated compared to the control group, resulting in a surrogate phenomenon against oxidative stress.

Effects of a large-scale micronutrient powder and young child feeding education program on the micronutrient status of children 6-24 months of age in the Kyrgyz Republic.

PubMed

Serdula, M K; Lundeen, E; Nichols, E K; Imanalieva, C; Minbaev, M; Mamyrbaeva, T; Timmer, A; Aburto, N J

2013-07-01

To combat iron and other micronutrient deficiencies, the Ministry of Health of the Kyrgyz Republic launched a regional Infant and Young Child Nutrition (IYCN) program in 2009, which included promotion of home fortification with micronutrient powder (MNP) containing iron (12.5 mg elemental iron), vitamin A (300 μg) and other micronutrients. Every 2 months children aged 6-24 months were provided 30 sachets to be taken on a flexible schedule. The objective was to assess biochemical indicators of iron and vitamin A status among children aged 6-24 months at the baseline and follow-up surveys. Cross-sectional representative cluster surveys were conducted in 2008 (n=571 children) and 2010 (n=541). Data collected included measurement of hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), retinol-binding protein, C-reactive protein (CRP) and α1-glycoprotein acid (AGP). Among all children, declines were observed in the prevalence of: anemia, 50.6% versus 43.8% (P=0.05); total iron deficiency (either low ferritin or high sTfR), 77.3% versus 63.7% (P<0.01); and iron deficiency anemia, 45.5% versus 33.4% (P<0.01). Among children without inflammation as measured by CRP and AGP, similar declines were observed, but only declines in total iron deficiency and iron deficiency anemia reached statistical significance. Among all children and those without inflammation, the prevalence of vitamin A deficiency remained the same. One year after the introduction of home fortification with MNP, within a larger IYCN program, the prevalence of anemia, iron deficiency and iron deficiency anemia declined, but vitamin A deficiency remained unchanged.

The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat.

PubMed

Hay, Susan M; McArdle, Harry J; Hayes, Helen E; Stevens, Valerie J; Rees, William D

2016-11-01

Iron is essential for the oxidative metabolism of lipids. Lipid metabolism changes during gestation to meet the requirements of the growing fetus and to prepare for lactation. The temporal effects of iron deficiency during gestation were studied in female rats fed complete or iron-deficient diets. Plasma triglycerides were elevated in the iron-deficient group throughout gestation. There were time-dependent changes in the triglyceride content of the maternal liver, falling at the midpoint of gestation and then increasing on d21.5. Compared to the control, triglycerides in the maternal liver were not different in the iron-deficient group prior to pregnancy and on d12.5, but were markedly reduced by d21.5. The abundance of mRNAs in the maternal liver suggests that lipogenesis is unchanged and beta-oxidation is reduced on d21.5 by iron deficiency. On d21.5 of gestation, the expression of placental lipase was unchanged by iron deficiency, however, the abundance of mRNAs for SREBP-1c, FABP4 were reduced, suggesting that there were changes in fatty acid handling. In the fetal liver, iron deficiency produced a marked decrease in the abundance of the L-CPT-1 mRNA, suggesting that beta-oxidation is reduced. This study shows that the major effect of iron deficiency on maternal lipid metabolism occurs late in gestation and that perturbed lipid metabolism may be a common feature of models of fetal programming. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

[Prevalence of iron deficiency].

PubMed

Dupont, C

2017-05-01

Studies of prévalence in iron deficiency separate iron depletion (defined as decreased blood ferritin) and iron deficiency anemia (defined as blood decrease in both ferritin and hemoglobin). In Europe, most studies are outdated. Prevalence of iron depletion varies from 7 to 18 % and 24 to 36% in toddlers and adolescents, respectively. Prevalence of iron deficiency anemia varies from 2 to 8.5% and 7 to 10% in toddlers and adolescents. In French speaking African countries, Demography Health Surveys show that 80% of children aged 0 to 2 years are anemic, severely for 5 to 9% of them. © 2017 Elsevier Masson SAS. Tous droits réservés.

Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice.

PubMed

Clinkenbeard, Erica L; Farrow, Emily G; Summers, Lelia J; Cass, Taryn A; Roberts, Jessica L; Bayt, Christine A; Lahm, Tim; Albrecht, Marjorie; Allen, Matthew R; Peacock, Munro; White, Kenneth E

2014-02-01

Fibroblast growth factor 23 (FGF23) gain of function mutations can lead to autosomal dominant hypophosphatemic rickets (ADHR) disease onset at birth, or delayed onset following puberty or pregnancy. We previously demonstrated that the combination of iron deficiency and a knock-in R176Q FGF23 mutation in mature mice induced FGF23 expression and hypophosphatemia that paralleled the late-onset ADHR phenotype. Because anemia in pregnancy and in premature infants is common, the goal of this study was to test whether iron deficiency alters phosphate handling in neonatal life. Wild-type (WT) and ADHR female breeder mice were provided control or iron-deficient diets during pregnancy and nursing. Iron-deficient breeders were also made iron replete. Iron-deficient WT and ADHR pups were hypophosphatemic, with ADHR pups having significantly lower serum phosphate (p < 0.01) and widened growth plates. Both genotypes increased bone FGF23 mRNA (>50 fold; p < 0.01). WT and ADHR pups receiving low iron had elevated intact serum FGF23; ADHR mice were affected to a greater degree (p < 0.01). Iron-deficient mice also showed increased Cyp24a1 and reduced Cyp27b1, and low serum 1,25-dihydroxyvitamin D (1,25D). Iron repletion normalized most abnormalities. Because iron deficiency can induce tissue hypoxia, oxygen deprivation was tested as a regulator of FGF23, and was shown to stimulate FGF23 mRNA in vitro and serum C-terminal FGF23 in normal rats in vivo. These studies demonstrate that FGF23 is modulated by iron status in young WT and ADHR mice and that hypoxia independently controls FGF23 expression in situations of normal iron. Therefore, disturbed iron and oxygen metabolism in neonatal life may have important effects on skeletal function and structure through FGF23 activity on phosphate regulation. © 2014 American Society for Bone and Mineral Research.

Obesity as an Emerging Risk Factor for Iron Deficiency

PubMed Central

Aigner, Elmar; Feldman, Alexandra; Datz, Christian

2014-01-01

Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the “dysmetabolic iron overload syndrome (DIOS)”. Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity. PMID:25215659

Iron deficiency anemia and megaloblastic anemia in obese patients.

PubMed

Arshad, Mahmoud; Jaberian, Sara; Pazouki, Abdolreza; Riazi, Sajedeh; Rangraz, Maryam Aghababa; Mokhber, Somayyeh

2017-03-01

The association between obesity and different types of anemia remained uncertain. The present study aimed to assess the relation between obesity parameters and the occurrence of iron deficiency anemia and also megaloblastic anemia among Iranian population. This cross-sectional study was performed on 1252 patients with morbid obesity that randomly selected from all patients referred to Clinic of obesity at Rasoul-e-Akram Hospital in 2014. The morbid obesity was defined according to the guideline as body mass index (BMI) equal to or higher than 40 kg/m2. Various laboratory parameters including serum levels of hemoglobin, iron, ferritin, folic acid, and vitamin B12 were assessed using the standard laboratory techniques. BMI was adversely associated with serum vitamin B12, but not associated with other hematologic parameters. The overall prevalence of iron deficiency anemia was 9.8%. The prevalence of iron deficiency anemia was independent to patients' age and also to body mass index. The prevalence of vitamin B12 deficiency was totally 20.9%. According to the multivariable logistic regression model, no association was revealed between BMI and the occurrence of iron deficiency anemia adjusting gender and age. A similar regression model showed that higher BMI could predict occurrence of vitamin B12 deficiency in morbid obese patients. Although iron deficiency is a common finding among obese patients, vitamin B12 deficiency is more frequent so about one-fifth of these patients suffer vitamin B12 deficiency. In fact, the exacerbation of obesity can result in exacerbation of vitamin B12 deficiency.

Potential of common bean to enhance dietary iron availability in humans: Germplasm diversity and QTL analysis

USDA-ARS?s Scientific Manuscript database

We are interested in the improvement of iron nutritional status of humans living in developing world countries where iron deficiency anemia is quite severe. We also wish to promote the use of plant-based food sources to improve human iron status, and thus are focusing on staple food crops like comm...

A local equation for differential diagnosis of β-thalassemia trait and iron deficiency anemia by logistic regression analysis in Southeast Iran.

PubMed

Sargolzaie, Narjes; Miri-Moghaddam, Ebrahim

2014-01-01

The most common differential diagnosis of β-thalassemia (β-thal) trait is iron deficiency anemia. Several red blood cell equations were introduced during different studies for differential diagnosis between β-thal trait and iron deficiency anemia. Due to genetic variations in different regions, these equations cannot be useful in all population. The aim of this study was to determine a native equation with high accuracy for differential diagnosis of β-thal trait and iron deficiency anemia for the Sistan and Baluchestan population by logistic regression analysis. We selected 77 iron deficiency anemia and 100 β-thal trait cases. We used binary logistic regression analysis and determined best equations for probability prediction of β-thal trait against iron deficiency anemia in our population. We compared diagnostic values and receiver operative characteristic (ROC) curve related to this equation and another 10 published equations in discriminating β-thal trait and iron deficiency anemia. The binary logistic regression analysis determined the best equation for best probability prediction of β-thal trait against iron deficiency anemia with area under curve (AUC) 0.998. Based on ROC curves and AUC, Green & King, England & Frazer, and then Sirdah indices, respectively, had the most accuracy after our equation. We suggest that to get the best equation and cut-off in each region, one needs to evaluate specific information of each region, specifically in areas where populations are homogeneous, to provide a specific formula for differentiating between β-thal trait and iron deficiency anemia.

[Intravenous ferric carboxymaltose-associated hypophosphatemia in patients with iron deficiency anemia. A common side effect].

PubMed

Sánchez González, Rebeca; Ternavasio-de la Vega, Hugo Guillermo; Moralejo Alonso, Leticia; Inés Revuelta, Sandra; Fuertes Martín, Aurelio

2015-08-07

To determine the frequency, severity, time of onset and factors associated with the development of hypophosphatemia (HF) in patients with iron deficiency anemia treated with intravenous ferric carboxymatose (ivFCM). Retrospective cohort study in patients iron deficiency anemia who received ivFCM and had an a prior and subsequent determination of serum phosphate. We carried out a comparative analysis between baseline and post-ivFCM levels of serum phosphate. In order to identify variables independently associated with HF a logistic regression analysis was also performed. One hundred twenty-five patients were included. HF frequency was 58%. The median time to onset of HF was 18 days. Age, baseline ferritin levels and baseline phosphate levels were independently associated with the development of HF. The risk of HF in patients with baseline phosphate levels ≤ 3.1mg/dl was 67% higher than patients with ≥ 3.7 mg/dl. ivFCM-associated HF is a frequent, early and, sometimes, prolonged effect in patients with iron deficiency anemia. Serum phosphate levels should be monitored after ivFCM administration, especially in older patients and in those with lower baseline phosphate or ferritin levels. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Enterobactin-mediated iron transport in Pseudomonas aeruginosa.

PubMed Central

Poole, K; Young, L; Neshat, S

1990-01-01

A pyoverdine-deficient strain of Pseudomonas aeruginosa was unable to grow in an iron-deficient minimal medium in the presence of the nonmetabolizable iron chelator ethylene diamine-di(omega-hydroxyphenol acetic acid) (EDDHA), although addition of enterobactin to EDDHA-containing minimal media did restore growth of the pyoverdine-deficient P. aeruginosa. Consistent with the apparent ability of enterobactin to provide iron to P. aeruginosa, enterobactin-dependent 55Fe3+ uptake was observed in cells of P. aeruginosa previously grown in an iron-deficient medium containing enterobactin (or enterobactin-containing Escherichia coli culture supernatant). This uptake was energy dependent, was observable at low concentrations (60 nM) of FeCl3, and was absent in cells cultured without enterobactin. A novel protein with a molecular weight of approximately 80,000 was identified in the outer membranes of cells grown in iron-deficient minimal medium containing enterobactin, concomitant with the induction of enterobactin-dependent iron uptake. A Tn501 insertion mutant lacking this protein was isolated and shown to be deficient in enterobactin-mediated iron transport at 60 nM FeCl3, although it still exhibited enterobactin-dependent growth in iron-deficient medium containing EDDHA. It was subsequently observed that the mutant was, however, capable of enterobactin-mediated iron transport at much higher concentrations (600 nM) of FeCl3. Indeed, enterobactin-dependent iron uptake at this concentration of iron was observed in both the mutant and parent strains irrespective of whether they had been cultured in the presence of enterobactin.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:2174865

Tissue distribution of manganese in iron-sufficient or iron-deficient rats after stainless steel welding-fume exposure.

PubMed

Park, Jung-Duck; Kim, Ki-Young; Kim, Dong-Won; Choi, Seong-Jin; Choi, Byung-Sun; Chung, Yong Hyun; Han, Jeong Hee; Sung, Jae Hyuck; Kwon, Il Hoon; Mun, Je-Hyeok; Yu, Il Je

2007-05-01

Welders can be exposed to high levels of manganese through welding fumes. Although it has already been suggested that excessive manganese exposure causes neurotoxicity, called manganism, the pathway of manganese transport to the brain with welding-fume exposure remains unclear. Iron is an essential metal that maintains a homeostasis in the body. The divalent metal transporter 1 (DMT1) transports iron and other divalent metals, such as manganese, and the depletion of iron is known to upregulate DMT1 expression. Accordingly, this study investigated the tissue distribution of manganese in iron-sufficient and iron-deficient rats after welding-fume exposure. The feeding of an iron-deficient diet for 4 wk produced a depletion of body iron, such as decreased iron levels in the serum and tissues, and upregulated the DMT1 expression in the rat duodenum. The iron-sufficient and iron-deficient rats were then exposed to welding fumes generated from manual metal arc stainless steel at a concentration of 63.5 +/- 2.3 mg/m3 for 2 h per day over a 30-day period. Animals were sacrificed on days 1, 15, and 30. The level of body iron in the iron-deficient rats was restored to the control level after the welding-fume exposure. However, the tissue distributions of manganese after the welding-fume exposure showed similar patterns in both the iron-sufficient and iron-deficient groups. The concentration of manganese increased in the lungs and liver on days 15 and 30, and increased in the olfactory bulb on day 30. Slight and heterogeneous increases of manganese were observed in different brain regions. Consequently, these findings suggest that the presence of Fe in the inhaled welding fumes may not have a significant effect on the uptake of Mn into the brain. Thus, the condition of iron deficiency did not seem to have any apparent effect on the transport of Mn into the brain after the inhalation of welding fumes.

Genetics Home Reference: myopathy with deficiency of iron-sulfur cluster assembly enzyme

MedlinePlus

... Myopathy with deficiency of iron-sulfur cluster assembly enzyme Printable PDF Open All Close All Enable Javascript ... Myopathy with deficiency of iron-sulfur cluster assembly enzyme is an inherited disorder that primarily affects muscles ...

Is red meat required for the prevention of iron deficiency among children and adolescents?

PubMed

Savva, Savvas C; Kafatos, Anthony

2014-01-01

Iron deficiency remains the most common nutritional deficiency worldwide despite the fact that global prevention is a high priority. Recent guidelines suggest intake of red meat both in infants and toddlers to prevent iron deficiency. However frequent consumption of red and processed meat may be associated with an increased risk for cancer, cardiovascular disease and diabetes. Evidence also suggests that even in vegetarian diets or diets with little consumption of white or red meat, iron status may not be adversely affected. The Eastern Orthodox Christian Church dietary recommendations which is a type of periodic vegetarian diet, has proved beneficial for the prevention of iron deficiency and avoidance of excess iron intake. This paper aims to provide examples of meals for children and adolescents that may be sufficient to meet age specific iron requirements without consumption of red meat beyond the recommended consumption which is once or twice per month.

[Diagnosis and treatment of iron deficiency, with or without anemia, before and after bariatric surgery].

PubMed

Jericó, Carlos; Bretón, Irene; García Ruiz de Gordejuela, Amador; de Oliveira, Ana Carla; Rubio, Miguel Ángel; Tinahones, Francisco J; Vidal, Josep; Vilarrasa, Nuria

2016-01-01

Bariatric surgery (BS) is an increasingly used therapeutic option for severe obesity which allows patients to achieve sustained weight loss over time and resolution or improvement in most associated pathological conditions. Major mid- and long-term complications of BS include iron deficiency and iron-deficient anemia, which may occur in up to 50% of cases and significantly impair patient quality of life. These changes may be present before surgery. The aim of this review was to prepare schemes for diagnosis and treatment of iron deficiency and iron-deficient anemia before and after bariatric surgery. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Arabidopsis copper transport protein COPT2 participates in the cross talk between iron deficiency responses and low-phosphate signaling.

PubMed

Perea-García, Ana; Garcia-Molina, Antoni; Andrés-Colás, Nuria; Vera-Sirera, Francisco; Pérez-Amador, Miguel A; Puig, Sergi; Peñarrubia, Lola

2013-05-01

Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes, including respiration, photosynthesis, and oxidative stress protection. In many eukaryotic organisms, including yeast (Saccharomyces cerevisiae) and mammals, copper and iron homeostases are highly interconnected; yet, such interdependence is not well established in higher plants. Here, we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis (Arabidopsis thaliana). COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 could play a dual role under iron deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation, possibly to minimize further iron consumption. Second, global expression analyses of copt2-1 versus wild-type Arabidopsis plants indicate that low-phosphate responses increase in the mutant. These results open up new biotechnological approaches to fight iron deficiency in crops.

Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

PubMed Central

Hudson, Benjamin H.; Hale, Andrew T.; Irving, Ryan P.; Li, Shenglan; York, John D.

2018-01-01

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis. PMID:29507250

Beneficial effects of postnatal choline supplementation on long-Term neurocognitive deficit resulting from fetal-Neonatal iron deficiency.

PubMed

Kennedy, Bruce C; Tran, Phu V; Kohli, Maulika; Maertens, Jamie J; Gewirtz, Jonathan C; Georgieff, Michael K

2018-01-15

Early-life iron deficiency is a common nutrient condition worldwide and can result in cognitive impairment in adulthood despite iron treatment. In rodents, prenatal choline supplementation can diminish long-term hippocampal gene dysregulation and neurocognitive deficits caused by iron deficiency. Since fetal iron status is generally unknown in humans, we determined whether postnatal choline supplementation exerts similar beneficial effects. Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (3-6ppm Fe) from gestational day (G) 3 through postnatal day (P) 7, and an iron-sufficient (IS) diet (200ppm Fe) thereafter. Control pups were provided IS diet throughout. Choline (5ppm) was given to half the nursing dams and weanlings in each group from P11-P30. P65 rat cognitive performance was assessed by novel object recognition (NOR). Real-time PCR was performed to validate expression levels of synaptic plasticity genes known to be dysregulated by early-life iron deficiency. Postnatal choline supplementation prevented impairment of NOR memory in formerly iron-deficient (FID) adult rats but impaired NOR memory in IS controls. Gene expression analysis revealed a recovery of 4 out of 10 dysregulated genes compared to 8 of the same 10 genes that we previously demonstrated to recover following prenatal choline supplementation. Recognition memory deficits induced by early-life iron deficiency can be prevented by postnatal choline supplementation and disrupted expression of a subset of synaptic plasticity genes can be ameliorated. The positive response to postnatal choline represents a potential adjunctive therapeutic supplement to treat iron-deficient anemic children in order to spare long-term neurodevelopmental deficits. Copyright © 2017. Published by Elsevier B.V.

Systems genetic analysis of multivariate response to iron deficiency in mice

PubMed Central

Yin, Lina; Unger, Erica L.; Jellen, Leslie C.; Earley, Christopher J.; Allen, Richard P.; Tomaszewicz, Ann; Fleet, James C.

2012-01-01

The aim of this study was to identify genes that influence iron regulation under varying dietary iron availability. Male and female mice from 20+ BXD recombinant inbred strains were fed iron-poor or iron-adequate diets from weaning until 4 mo of age. At death, the spleen, liver, and blood were harvested for the measurement of hemoglobin, hematocrit, total iron binding capacity, transferrin saturation, and liver, spleen and plasma iron concentration. For each measure and diet, we found large, strain-related variability. A principal-components analysis (PCA) was performed on the strain means for the seven parameters under each dietary condition for each sex, followed by quantitative trait loci (QTL) analysis on the factors. Compared with the iron-adequate diet, iron deficiency altered the factor structure of the principal components. QTL analysis, combined with PosMed (a candidate gene searching system) published gene expression data and literature citations, identified seven candidate genes, Ptprd, Mdm1, Picalm, lip1, Tcerg1, Skp2, and Frzb based on PCA factor, diet, and sex. Expression of each of these is cis-regulated, significantly correlated with the corresponding PCA factor, and previously reported to regulate iron, directly or indirectly. We propose that polymorphisms in multiple genes underlie individual differences in iron regulation, especially in response to dietary iron challenge. This research shows that iron management is a highly complex trait, influenced by multiple genes. Systems genetics analysis of iron homeostasis holds promise for developing new methods for prevention and treatment of iron deficiency anemia and related diseases. PMID:22461179

Nippostronglylus brasiliensis infection in the rat: effect of iron and protein deficiency and dexamethasone on the efficacy of benzimidazole anthelmintics.

PubMed Central

Duncombe, V M; Bolin, T D; Davis, A E; Kelly, J D

1977-01-01

Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities. PMID:590849

Postpartum anemia II: prevention and treatment.

PubMed

Milman, Nils

2012-02-01

This review focuses on the prevention and treatment of anemia in women who have just given childbirth (postpartum anemia). The problem of anemia both prepartum and postpartum is far more prevalent in developing countries than in the Western societies. The conditions for mother and child in the postpartum, nursing, and lactation period should be as favorable as possible. Many young mothers have a troublesome life due to iron deficiency and iron deficiency anemia (IDA) causing a plethora of symptoms including fatigue, physical disability, cognitive problems, and psychiatric disorders. Routine screening for postpartum anemia should be considered as part of the national maternal health programs. Major causes of postpartum anemia are prepartum iron deficiency and IDA in combination with excessive blood losses at delivery. Postpartum anemia should be defined as a hemoglobin level of <110 g/l at 1 week postpartum and <120 g/l at 8 weeks postpartum. Bleeding exceeding normal blood losses of approximately 300 ml may lead to rapid depletion of body iron reserves and may, unless treated, elicit long-standing iron deficiency and IDA in the postpartum period. The prophylaxis of postpartum anemia should begin already in early pregnancy in order to ensure a good iron status prior to delivery. The most reliable way to obtain this goal is to give prophylactic oral ferrous iron supplements 30-50 mg daily from early pregnancy and take obstetric precautions in pregnancies at risk for complications. In the treatment of slight-to-moderate postpartum IDA, the first choice should be oral ferrous iron 100 to 200 mg daily; it is essential to analyze hemoglobin after approximately 2 weeks in order to check whether treatment works. In severe IDA, intravenous ferric iron in doses ranging from 800 to 1,500 mg should be considered as first choice. In a few women with severe anemia and blunted erythropoiesis due to infection and/or inflammation, additional recombinant human erythropoietin may be considered. Blood transfusion should be restricted to women who develop circulatory instability due to postpartum hemorrhage. National health authorities should establish guidelines to combat iron deficiency in pregnancy and postpartum in order to facilitate a prosperous future for both mothers and children in a continuing globalized world.

Morbidity and Mortality Weekly Report. Volume 47, Number RR-3. Recommendations to Prevent and Control Iron Deficiency in the United States.

DTIC Science & Technology

1998-04-03

adverse birth outcomes. Some studies have indicated that adequate iron supplementation during pregnancy reduces the prevalence of iron- deficiency...iron intake during pregnancy has not resulted in a reduced prevalence of anemia among low-income, pregnant women (4,9,105). Evidence on iron...during pregnancy . Am J Obstet Gynecol 1995;173(1):205-9. 45. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in

NOD promoter-controlled AtIRT1 expression functions synergistically with NAS and FERRITIN genes to increase iron in rice grains.

PubMed

Boonyaves, Kulaporn; Gruissem, Wilhelm; Bhullar, Navreet K

2016-02-01

Rice is a staple food for over half of the world's population, but it contains only low amounts of bioavailable micronutrients for human nutrition. Consequently, micronutrient deficiency is a widespread health problem among people who depend primarily on rice as their staple food. Iron deficiency anemia is one of the most serious forms of malnutrition. Biofortification of rice grains for increased iron content is an effective strategy to reduce iron deficiency. Unlike other grass species, rice takes up iron as Fe(II) via the IRON REGULATED TRANSPORTER (IRT) in addition to Fe(III)-phytosiderophore chelates. We expressed Arabidopsis IRT1 (AtIRT1) under control of the Medicago sativa EARLY NODULIN 12B promoter in our previously developed high-iron NFP rice lines expressing NICOTIANAMINE SYNTHASE (AtNAS1) and FERRITIN. Transgenic rice lines expressing AtIRT1 alone had significant increases in iron and combined with NAS and FERRITIN increased iron to 9.6 µg/g DW in the polished grains that is 2.2-fold higher as compared to NFP lines. The grains of AtIRT1 lines also accumulated more copper and zinc but not manganese. Our results demonstrate that the concerted expression of AtIRT1, AtNAS1 and PvFERRITIN synergistically increases iron in both polished and unpolished rice grains. AtIRT1 is therefore a valuable transporter for iron biofortification programs when used in combination with other genes encoding iron transporters and/or storage proteins.

Elevation of NO production increases Fe immobilization in the Fe-deficiency roots apoplast by decreasing pectin methylation of cell wall

PubMed Central

Ye, Yi Quan; Jin, Chong Wei; Fan, Shi Kai; Mao, Qian Qian; Sun, Cheng Liang; Yu, Yan; Lin, Xian Yong

2015-01-01

Cell wall is the major component of root apoplast which is the main reservoir for iron in roots, while nitric oxide (NO) is involved in regulating the synthesis of cell wall. However, whether such regulation could influence the reutilization of iron stored in root apoplast remains unclear. In this study, we observed that iron deficiency elevated NO level in tomato (Solanum lycopersicum) roots. However, application of S-nitrosoglutathione, a NO donor, significantly enhanced iron retention in root apoplast of iron-deficient plants, accompanied with a decrease of iron level in xylem sap. Consequently, S-nitrosoglutathione treatment increased iron concentration in roots, but decreased it in shoots. The opposite was true for the NO scavenging treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, S-nitrosoglutathione treatment increased pectin methylesterase activity and decreased degree of pectin methylation in root cell wall of both iron-deficient and iron-sufficient plants, which led to an increased iron retention in pectin fraction, thus increasing the binding capacity of iron to the extracted cell wall. Altogether, these results suggested that iron-deficiency-induced elevation of NO increases iron immobilization in root apoplast by decreasing pectin methylation in cell wall. PMID:26073914

Iron deficiency and iron deficiency anaemia in women.

PubMed

Percy, Laura; Mansour, Diana; Fraser, Ian

2017-04-01

Iron deficiency (ID) is the most common micronutrient deficiency worldwide with >20% of women experiencing it during their reproductive lives. Hepcidin, a peptide hormone mostly produced by the liver, controls the absorption and regulation of iron. Understanding iron metabolism is pivotal in the successful management of ID and iron deficiency anaemia (IDA) using oral preparations, parenteral iron or blood transfusion. Oral preparations vary in their iron content and can result in gastrointestinal side effects. Parenteral iron is indicated when there are compliance/tolerance issues with oral iron, comorbidities which may affect absorption or ongoing iron losses that exceed absorptive capacity. It may also be the preferred option when rapid iron repletion is required to prevent physiological decompensation or given preoperatively for non-deferrable surgery. As gynaecologists, we focus on managing women's heavy menstrual bleeding (HMB) and assume that primary care clinicians are treating the associated ID/IDA. We now need to take the lead in diagnosing, managing and initiating treatment for ID/IDA and treating HMB simultaneously. This dual management will significantly improve their quality of life. In this chapter we will summarise the importance of iron in cellular functioning, describe how to diagnose ID/IDA and help clinicians choose between the available treatment options. Copyright © 2016. Published by Elsevier Ltd.

Iron assessment to protect the developing brain.

PubMed

Georgieff, Michael K

2017-12-01

Iron deficiency (ID) before the age of 3 y can lead to long-term neurological deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID alters neurobehavioral function and is 3 times more common than IDA in toddlers. Given the global prevalence of ID and the enormous societal cost of developmental disabilities across the life span, better methods are needed to detect the risk of inadequate concentrations of iron for brain development (i.e., brain tissue ID) before dysfunction occurs and to monitor its amelioration after diagnosis and treatment. The current screening and treatment strategy for IDA fails to achieve this goal for 3 reasons. First, anemia is the final state in iron depletion. Thus, the developing brain is already iron deficient when IDA is diagnosed owing to the prioritization of available iron to red blood cells over all other tissues during negative iron balance in development. Second, brain ID, independently of IDA, is responsible for long-term neurological deficits. Thus, starting iron treatment after the onset of IDA is less effective than prevention. Multiple studies in humans and animal models show that post hoc treatment strategies do not reliably prevent ID-induced neurological deficits. Third, most currently used indexes of ID are population statistical cutoffs for either hematologic or iron status but are not bioindicators of brain ID and brain dysfunction in children. Furthermore, their relation to brain iron status is not known. To protect the developing brain, there is a need to generate serum measures that index brain dysfunction in the preanemic stage of ID, assess the ability of standard iron indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of early iron treatment in preventing ID-induced brain dysfunction. © 2017 American Society for Nutrition.

Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency-Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus.

PubMed

Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T; Won, Kyoung-Jae; Gewirtz, Jonathan C; Simmons, Rebecca A; Georgieff, Michael K

2016-03-01

Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring's hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. Fetal-neonatal iron deficiency reprograms molecular networks associated with the pathogenesis of neurologic and psychological disorders in adult rats. The positive response to prenatal choline represents a potential adjunctive therapeutic supplement to the high-risk group. © 2016 American Society for Nutrition.

Position paper on management of iron deficiency in adult cancer patients.

PubMed

Barni, Sandro; Gascòn, Pere; Petrelli, Fausto; García-Erce, José Antonio; Pedrazzoli, Paolo; Rosti, Giovanni; Giordano, Giulio; Mafodda, Antonio; Múñoz, Manuel

2017-08-01

Disorders of iron metabolism are commonly seen in onco-hematological clinical practice. Iron-deficiency anemia and cancer-associated anemia are usually treated with supportive therapies. Optimal management of these conditions are discussed in this perspective paper. Areas covered: A position paper discussing a number of hot topics on anemia in cancer patients is presented. The main areas covered by experts in the field are: definitions, prevalence and consequences of anemia and iron deficiency, incidence of anemia resulting from targeted therapies, importance of anemia diagnosis and monitoring, evaluation of iron status before and during treatment, role of transfusions and erythropoiesis-stimulating agents, management of iron deficiency with or without anemia, parenteral iron supplementation, role of new oral iron formulations, safety and cost issues regarding different iron compounds and administration routes. Expert commentary: Despite the availability of newer therapeutic options for its management, anemia still represents a major complication of treatment in cancer patients (surgery, chemotherapy, radiotherapy, targeted therapies), aggravating physical impairment, and negatively affecting general outcome. The view expressed by the panelists, attendees of the 4th Mediterranean Course on Iron Anemia, summarizes what they consider optimal clinical practice for screening, diagnosis, treatment and monitoring of iron deficiency and anemia in cancer patients.

Presence and Characterisation of Anaemia in Diabetic Foot Ulceration

PubMed Central

Wright, J. A.; Oddy, M. J.; Richards, T.

2014-01-01

Introduction. Diabetic foot ulceration (DFU) is the commonest cause of severe limb ischaemia in the western world. In diabetes mellitus, anaemia is frequently unrecognized, yet studies have shown that it is twice as common in diabetics compared with nondiabetics. We aimed to assess the incidence of anaemia and further classify the iron deficiency seen in a high-risk DFU patient group. Methods. An observational study was undertaken in a multidisciplinary diabetic foot clinic setting. All patients with DFU attending over a four-month period were included. Anaemia was defined as haemoglobin (Hb) levels <12 g/dL. Iron deficiency was classified according to definitions of AID (absolute iron deficiency) and FID (functional iron deficiency). Results. 27 patients had DFU; 14 (51.9%) were anaemic; two (7.41%) had severe anaemia (Hb < 10 g/dL). No patient had B12 or Folate deficiency. In patients with anaemia, there was significant spread of indices. Only one patient had “textbook” absolute iron deficiency (AID) defined as low Hb, MCV, MCH, and ferritin. Functional iron deficiency (FID) was seen in a further seven patients (25.5%). Conclusion. Anaemia and iron deficiency are a common problem in patients with DFU. With current clinical markers, it is incredibly difficult to determine causal relationships and further in-depth scientific study is required. PMID:25197565

A Nanoparticulate Ferritin-Core Mimetic Is Well Taken Up by HuTu 80 Duodenal Cells and Its Absorption in Mice Is Regulated by Body Iron12

PubMed Central

Latunde-Dada, Gladys O; Pereira, Dora IA; Tempest, Bethan; Ilyas, Hibah; Flynn, Angela C; Aslam, Mohamad F; Simpson, Robert J; Powell, Jonathan J

2014-01-01

Background: Iron (Fe) deficiency anemia remains the largest nutritional deficiency disorder worldwide. How the gut acquires iron from nano Fe(III), especially at the apical surface, is incompletely understood. Objective: We developed a novel Fe supplement consisting of nanoparticulate tartrate-modified Fe(III) poly oxo-hydroxide [here termed nano Fe(III)], which mimics the Fe oxide core of ferritin and effectively treats iron deficiency anemia in rats. Methods: We determined transfer to the systemic circulation of nano Fe(III) in iron-deficient and iron-sufficient outbread Swiss mouse strain (CD1) mice with use of 59Fe-labeled material. Iron deficiency was induced before starting the Fe-supplementation period through reduction of Fe concentrations in the rodent diet. A control group of iron-sufficient mice were fed a diet with adequate Fe concentrations throughout the study. Furthermore, we conducted a hemoglobin repletion study in which iron-deficient CD1 mice were fed for 7 d a diet supplemented with ferrous sulfate (FeSO4) or nano Fe(III). Finally, we further probed the mechanism of cellular acquisition of nano Fe(III) by assessing ferritin formation, as a measure of Fe uptake and utilization, in HuTu 80 duodenal cancer cells with targeted inhibition of divalent metal transporter 1 (DMT1) and duodenal cytochrome b (DCYTB) before exposure to the supplemented iron sources. Differences in gene expression were assessed by quantitative polymerase chain reaction. Results: Absorption (means ± SEMs) of nano Fe(III) was significantly increased in iron-deficient mice (58 ± 19%) compared to iron-sufficient mice (18 ± 17%) (P = 0.0001). Supplementation of the diet with nano Fe(III) or FeSO4 significantly increased hemoglobin concentrations in iron-deficient mice (170 ± 20 g/L, P = 0.01 and 180 ± 20 g/L, P = 0.002, respectively). Hepatic hepcidin mRNA expression reflected the nonheme-iron concentrations of the liver and was also comparable for both nano Fe(III)– and FeSO4-supplemented groups, as were iron concentrations in the spleen and duodenum. Silencing of the solute carrier family 11 (proton-coupled divalent metal ion transporter), member 2 (Slc11a2) gene (DMT1) significantly inhibited ferritin formation from FeSO4 (P = 0.005) but had no effect on uptake and utilization of nano Fe(III). Inhibiting DCYTB with an antibody also had no effect on uptake and utilization of nano Fe(III) but significantly inhibited ferritin formation from ferric nitrilotriacetate chelate (Fe-NTA) (P = 0.04). Similarly, cellular ferritin formation from nano Fe(III) was unaffected by the Fe(II) chelator ferrozine, which significantly inhibited uptake and utilization from FeSO4 (P = 0.009) and Fe-NTA (P = 0.005). Conclusions: Our data strongly support direct nano Fe(III) uptake by enterocytes as an efficient mechanism of dietary iron acquisition, which may complement the known Fe(II)/DMT1 uptake pathway. PMID:25342699

The effects of iron deficiency on rat liver enzymes.

PubMed Central

Bailey-Wood, R.; Blayney, L. M.; Muir, J. R.; Jacobs, A.

1975-01-01

The effect of iron deficiency on a number or iron containing enzymes in rat liver has been examined. In addition, 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase have been assayed. Of the mitochondrial electron transport reactions only succinate-cytochrome C reductase activity was decreased in iron deficient animals. Microsomal reductase enzymes associated with the NADPH-oxidase system were also markedly decreased although cytochrome P450 concentrations were unaffected. Both 6-phosphogluconate dehydrogenase and glucose 6-phosphate dehydrogenase were reduced in young iron deficient rats but the former had returned to control levels at the age of 14 weeks. PMID:172099

Effect of iron and zinc deficiency on short term memory in children.

PubMed

Umamaheswari, K; Bhaskaran, Mythily; Krishnamurthy, Gautham; Vasudevan, Hemamalini; Vasudevan, Kavita

2011-04-01

To evaluate the effect of iron and zinc deficiency on short term memory of children in the age group of 6-11 years and to assess the response to supplementation therapy. Interventional study. 100 children in the age group of 6-11 years (subdivided into 6-8 yr and 9-11 yr groups) from an urban corporation school. After collection of demographic data, the study children underwent hematological assessment which included serum iron, serum zinc, and hemoglobin estimation. Based on the results, they were divided into Iron deficient, Zinc deficient, and Combined deficiency groups. Verbal and nonverbal memory assessment was done in all the children. Iron (2mg/kg bodyweight in two divided doses) and zinc (5mg once-a-day) supplementation for a period of 3 months for children in the deficient group. All children with iron and zinc deficiency in both the age groups had memory deficits. Combined deficiency in 9-11 years group showed severe degree of affectation in verbal (P<0.01) and non-verbal memory (P<0.01), and improved after supplementation (P = 0.05 and P< 0.01, respectively). In 6-8 years group, only non-verbal form of memory (P =0.02) was affected, which improved after supplementation. Iron and zinc deficiency is associated with memory deficits in children. There is a marked improvement in memory after supplementation. Post supplementation IQ scores do not show significant improvement in deficient groups in 6-8 year olds.

Importance of pre-pregnancy and pregnancy iron status: can long-term weekly preventive iron and folic acid supplementation achieve desirable and safe status?

PubMed

Viteri, Fernando E; Berger, Jacques

2005-12-01

Most women worldwide enter pregnancy without adequate iron reserves or are already iron deficient. Estimates of iron needs during pregnancy are markedly reduced when iron reserves are available. The needs of absorbed iron to correct mild to moderate anemia in the last two trimesters are estimated. Pre-pregnancy and prenatal weekly supplementation can improve iron reserves effectively and safely, preventing excess iron and favoring better pregnancy outcomes. We explain how the weekly supplementation idea was developed, why current hemoglobin norms may be inadequately high (especially in pregnancy), and why excess iron as recommended by many agencies for developing populations can be undesirable.

Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study

PubMed Central

Gebreegziabher, Tafere; Stoecker, Barbara J.

2017-01-01

Background Anemia, which has many etiologies, is a moderate/severe public health problem in young children and women of reproductive age in many developing countries. The aim of this study was to investigate prevalence of iron deficiency, anemia, and iron deficiency anemia using multiple biomarkers and to evaluate their association with food insecurity and food consumption patterns in non-pregnant women from a rural area of southern Ethiopia. Methods A cross-sectional study was conducted in 202 rural women of reproductive age in southern Ethiopia. Anthropometrics and socio-demographic data were collected. A venipuncture blood sample was analyzed for hemoglobin (Hb) and for biomarkers of iron status. Biomarkers were skewed and were log transformed before analysis. Mean, median, Pearson’s correlations and ordinary least-squares regressions were calculated. Results Median (IQR) Hb was 138 (127, 151) g/L. Based on an altitude-adjusted (1708 m) cutoff of 125 g/L for Hb, 21.3% were anemic. Plasma ferritin was <15 μg/L in 18.6% of the women. Only one woman had α-1-acid glycoprotein (AGP) >1.0 g/L; four women (2%) had > 5 mg/L of C-reactive protein (CRP). Of the 43 women who were anemic, 23.3% (10 women) had depleted iron stores based on plasma ferritin. Three of these had elevated soluble transferrin receptors (sTfR). Hemoglobin (Hb) concentration was negatively correlated with sTfR (r = -0.24, p = 0.001), and positively correlated with ferritin (r = 0.17, p = 0.018), plasma iron (r = 0.15, p = 0.046), transferrin saturation (TfS) (r = 0.15, p = 0.04) and body iron (r = 0.14, p = 0.05). Overall prevalence of iron deficiency anemia was only 5%. Conclusion Iron deficiency anemia was not prevalent in the study population, despite the fact that anemia would be classified as a moderate public health problem. PMID:28898272

Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study.

PubMed

Gebreegziabher, Tafere; Stoecker, Barbara J

2017-01-01

Anemia, which has many etiologies, is a moderate/severe public health problem in young children and women of reproductive age in many developing countries. The aim of this study was to investigate prevalence of iron deficiency, anemia, and iron deficiency anemia using multiple biomarkers and to evaluate their association with food insecurity and food consumption patterns in non-pregnant women from a rural area of southern Ethiopia. A cross-sectional study was conducted in 202 rural women of reproductive age in southern Ethiopia. Anthropometrics and socio-demographic data were collected. A venipuncture blood sample was analyzed for hemoglobin (Hb) and for biomarkers of iron status. Biomarkers were skewed and were log transformed before analysis. Mean, median, Pearson's correlations and ordinary least-squares regressions were calculated. Median (IQR) Hb was 138 (127, 151) g/L. Based on an altitude-adjusted (1708 m) cutoff of 125 g/L for Hb, 21.3% were anemic. Plasma ferritin was <15 μg/L in 18.6% of the women. Only one woman had α-1-acid glycoprotein (AGP) >1.0 g/L; four women (2%) had > 5 mg/L of C-reactive protein (CRP). Of the 43 women who were anemic, 23.3% (10 women) had depleted iron stores based on plasma ferritin. Three of these had elevated soluble transferrin receptors (sTfR). Hemoglobin (Hb) concentration was negatively correlated with sTfR (r = -0.24, p = 0.001), and positively correlated with ferritin (r = 0.17, p = 0.018), plasma iron (r = 0.15, p = 0.046), transferrin saturation (TfS) (r = 0.15, p = 0.04) and body iron (r = 0.14, p = 0.05). Overall prevalence of iron deficiency anemia was only 5%. Iron deficiency anemia was not prevalent in the study population, despite the fact that anemia would be classified as a moderate public health problem.

Iron status determination in pregnancy using the Thomas plot.

PubMed

Weyers, R; Coetzee, M J; Nel, M

2016-04-01

Physiological changes during pregnancy affect routine tests for iron deficiency. The reticulocyte haemoglobin equivalent (RET-He) and serum-soluble transferrin receptor (sTfR) assay are newer diagnostic parameters for the detection of iron deficiency, combined in the Thomas diagnostic plot. We used this plot to determine the iron status of pregnant women presenting for their first visit to an antenatal clinic in Bloemfontein, South Africa. Routine laboratory tests (serum ferritin, full blood count and C-reactive protein) and RET-He and sTfR were performed. The iron status was determined using the Thomas plot. For this study, 103 pregnant women were recruited. According to the Thomas plot, 72.8% of the participants had normal iron stores and erythropoiesis. Iron-deficient erythropoiesis was detected in 12.6%. A third of participants were anaemic. Serum ferritin showed excellent sensitivity but poor specificity for detecting depleted iron stores. HIV status had no influence on the iron status of the participants. Our findings reiterate that causes other than iron deficiency should be considered in anaemic individuals. When compared with the Thomas plot, a low serum ferritin is a sensitive but nonspecific indicator of iron deficiency. The Thomas plot may provide useful information to identify pregnant individuals in whom haematologic parameters indicate limited iron availability for erythropoiesis. © 2015 John Wiley & Sons Ltd.

Usefulness of Iron Deficiency Correction in Management of Patients With Heart Failure [from the Registry Analysis of Iron Deficiency-Heart Failure (RAID-HF) Registry].

PubMed

Wienbergen, Harm; Pfister, Otmar; Hochadel, Matthias; Michel, Stephan; Bruder, Oliver; Remppis, Björn Andrew; Maeder, Micha Tobias; Strasser, Ruth; von Scheidt, Wolfgang; Pauschinger, Matthias; Senges, Jochen; Hambrecht, Rainer

2016-12-15

Iron deficiency (ID) has been identified as an important co-morbidity in patients with heart failure (HF). Intravenous iron therapy reduced symptoms and rehospitalizations of iron-deficient patients with HF in randomized trials. The present multicenter study investigated the "real-world" management of iron status in patients with HF. Consecutive patients with HF and ejection fraction ≤40% were recruited and analyzed from December 2010 to October 2015 by 11 centers in Germany and Switzerland. Of 1,484 patients with HF, iron status was determined in only 923 patients (62.2%), despite participation of the centers in a registry focusing on ID and despite guideline recommendation to determine iron status. In patients with determined iron status, a prevalence of 54.7% (505 patients) for ID was observed. Iron therapy was performed in only 8.5% of the iron-deficient patients with HF; 2.6% were treated with intravenous iron therapy. The patients with iron therapy were characterized by a high rate of symptomatic HF and anemia. In conclusion, despite strong evidence of beneficial effects of iron therapy on symptoms and rehospitalizations, diagnostic and therapeutic efforts on ID in HF are low in the actual clinical practice, and the awareness to diagnose and treat ID in HF should be strongly enforced. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron-induced hypophosphatemia: an emerging complication.

PubMed

Zoller, Heinz; Schaefer, Benedikt; Glodny, Bernhard

2017-07-01

Iron-induced hypophosphatemia is a well documented side-effect but associated complications are largely neglected, because the results from single dosing studies suggest that transient decreases in plasma phosphate concentrations are asymptomatic and fully reversible. However, an increasing number of case reports and case series suggest that some patients develop severe and symptomatic hypophosphatemia. Long-term complications from hypophosphatemia include osteomalacia and bone fractures, which can result from repeated intravenous administration of certain high-dose iron preparations. Results from clinical trials suggest that the highest risk for the development of hypophosphatemia is associated with ferric carboxymaltose, iron polymaltose, and saccharated iron oxide. Clinical studies show that renal phosphate wasting mediated by increased fibroblast growth factor 23 causes hypophosphatemia after iron therapy. Impaired renal function therefore protects from hypophosphatemia, whereas the highest incidences and most severe manifestations have been reported in patients in whom the underlying cause of iron deficiency cannot be corrected. Diagnosis of iron-induced hypophosphatemia requires clinical suspicion. Treatment is guided by the severity of hypophosphatemia, and most patients will require oral or intravenous phosphate substitution. Future treatment options could involve therapeutic anti-FGF23 antibody (KRN23). Prevention and correction of vitamin D deficiency represents a supportive treatment option.

Roles of chemical signals in regulation of the adaptive responses to iron deficiency.

PubMed

Liu, Xing Xing; He, Xiao Lin; Jin, Chong Wei

2016-05-03

Iron is an essential micronutrient for plants but is not readily accessible in most calcareous soils. Although the adaptive responses of plants to iron deficiency have been well documented, the signals involved in the regulatory cascade leading to their activation are not well understood to date. Recent studies revealed that chemical compounds, including sucrose, auxin, ethylene and nitric oxide, positively regulated the Fe-deficiency-induced Fe uptake processes in a cooperative manner. Nevertheless, cytokinins, jasmonate and abscisic acid were shown to act as negative signals in transmitting the iron deficiency information. The present mini review is to briefly address the roles of chemical signals in regulation of the adaptive responses to iron deficiency based on the literatures published in recent years.

Safety, therapeutic effectiveness, and cost of parenteral iron therapy.

PubMed

Asma, Suheyl; Boga, Can; Ozdogu, Hakan

2009-07-01

Patients have to discontinue the use of oral iron therapy due to the development of side effects and lack of long-term adherence to medication for iron deficiency anemia. This study aimed to evaluate the therapeutic effectiveness, safety, and cost of intravenous iron sucrose therapy. The computerized database and medical records of 453 patients diagnosed with iron deficiency anemia who received intravenous iron sucrose therapy for iron deficiency anemia between 2004 and 2008 were reviewed. The improvement of hematologic parameters and cost of therapy were evaluated 4 weeks after therapy. 453 patients (443 females, 10 males; age: 44.2 +/- 12.3 years) received iron sucrose therapy. Mean hemoglobin, hematocrit, and mean corpuscular volume values were 8.2 +/- 1.4 g/dL, 26.9 +/- 3.8%, and 66.1 +/- 7.8 fL, respectively, before therapy and 11.5 +/- 1.0 g/dL, 35.8 +/- 2.5%, 76.5 +/- 6.1 fL, respectively, after therapy (P < 0.001). A mean ferritin level of 3.4 +/- 2.4 ng/mL before therapy increased to 65.9 +/- 40.6 ng/mL after therapy (P < 0.001). All patients responded to intravenous iron therapy (transferrin saturation values of the patients were >50%). The mean cost of therapy was 143.07 +/- 29.13 US dollars. The therapy was well tolerated. Although the cost of intravenous iron sucrose therapy may seem high, a lack of adherence to therapy and side effects including gastrointestinal irritation during oral iron therapy were not experienced during intravenous therapy.

[Immune, inflammatory, and nutritional protein profile in children with iron deficiency in Côte d'Ivoire].

PubMed

Yapi, Houphouët Félix; Ahiboh, Hugues; Yayo, Eric; Edjeme, Angele; Attoungbre-Hauhouot, Marie Laure; Allico, Joseph Djaman; Monnet, Dagui

2009-01-01

Throughout the world and particularly in sub-Saharan Africa, deficiencies in trace elements constitute a real public health problem because of the insufficient nutritional quality of food. These trace elements are necessary for many of the body's biochemical reactions. The role of microelements such as vitamin A and zinc has been established in the functioning of the immune system and secretion of inflammatory reaction proteins, but the role of iron in these functions remains to be elucidated. The sample consists of 186 children (3/4) 80 with an iron deficiency and 106 with normal iron status. They range in age from 5 to 15 years and all attend school in the department of Adzope. The study excluded all children with parasites that might affect blood iron, protein and other hematological indicators, in particular, Plasmodium falciparum, Giardia intestinalis, Trichomonas intestinalis, Ascaris lumbricoides, and Ancylostoma. Inflammatory, immune and nutritional proteins were measured by radial immunodiffusion (Mancini's method). Ferritin was measured by a specific immunoenzymatic assay. Hematological indicators were tested by an automatic blood cell counter. Nutritional status was estimated by the weight/height ratio (W/H). This analysis showed that iron deficiency was associated with reduced IgG levels (p < 0.05), although immunoglobulins A and M remained stable (p > 0.05. Iron deficiency was also associated with reduced levels of thyroxine-binding prealbumin (TBPA) and albumin (p < 0.05). Inflammatory proteins did not differ significantly between the two groups (p > 0.05). Furthermore, the prognostic inflammatory and nutritional index (PINI) did not show any inflammatory, vital or nutritional risk, because it was lower than or equal to 2. Finally, malnutrition was not observed in the iron-deficient children: the difference in the weight/height ratio (W/H = 96.58 +/- 2.4%) between the children with iron deficiency and those with normal iron status (98.7 +/- 4.3%) did not differ significantly. The reduced IgG associated with iron deficiency may be attributed to the role that iron plays in the proliferation and maturation of lymphocytes. Reduced iron levels would thus lead to slowing down the hematopoietic mechanism, resulting in a decrease in B lymphocyte production and thus inevitably a reduction in IgG synthesis. The reduction in albumin and TBPA associated with the iron deficiency but in the absence of any sign of malnutrition (W/H > 96%) or inflammatory risk (PINI < 2) in either study group shows that iron may play a dominant role during protein synthesis. Iron deficiency might limit the energy of cellular tissues, leading to a reduction in RNA activity (transcription and translation), which would in turn decrease ribosome activity in tissues and thus reduce amino acid synthesis in cells, resulting in the reduction observed in protein synthesis. The lack of difference between the study groups in inflammatory proteins, notably CRP and alpha1-GPA, indicates that iron deficiency does not appear to be related to an inflammatory process. This study of children without any apparent clinical signs of iron deficiency shows that such a deficiency may be associated with a disruption in protein production. The proteins concerned include IgG, TBPA and albumin. The public authorities should pay particular attention to improving children's diets, especially their micronutrient levels, including for iron, vitamin A and zinc.

Impact of Iron Deficiency on Response to and Remodeling After Cardiac Resynchronization Therapy.

PubMed

Martens, Pieter; Verbrugge, Frederik; Nijst, Petra; Dupont, Matthias; Tang, W H Wilson; Mullens, Wilfried

2017-01-01

Iron deficiency is prevalent in heart failure with reduced ejection fraction and relates to symptomatic status, readmission, and all-cause mortality. The relation between iron status and response to cardiac resynchronization therapy (CRT) remains insufficiently elucidated. This study assesses the impact of iron deficiency on clinical response and reverse cardiac remodeling and outcome after CRT. Baseline characteristics, change in New York Heart Association functional class, reverse cardiac remodeling on echocardiography, and clinical outcome (i.e., all-cause mortality and heart failure readmissions) were retrospectively evaluated in consecutive CRT patients who had full iron status and complete blood count available at implantation, implanted at a single tertiary care center with identical dedicated multidisciplinary CRT follow-up from October 2008 to August 2015. A total of 541 patients were included with mean follow-up of 38 ± 22 months. Prevalence of iron deficiency was 56% at implantation. Patients with iron deficiency exhibited less symptomatic improvement 6 months after implantation (p value <0.001). In addition, both the decrease in left ventricular end-diastolic diameter (-3.1 vs -6.2 mm; p value = 0.011) and improvement in ejection fraction (+11% vs +15%, p value = 0.001) were significantly lower in patients with iron deficiency. Iron deficiency was significantly associated with an increased risk for heart failure admission or all-cause mortality (adjusted hazard ratio 1.718, 95% confidence interval 1.178 to 2.506), irrespectively of the presence of anemia (Hemoglobin <12 g/dl in women and <13 g/dl in men). In conclusion, iron deficiency is prevalent and affects both clinical response and reverse cardiac remodeling after CRT implantation. Moreover, it is a powerful predictor of adverse clinical outcomes in CRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron sources effects on growth, physiological parameters and nutrition of cacao

USDA-ARS?s Scientific Manuscript database

Productivity and sustainability of cacao (Theobroma cacao L.) in tropical soils are affected by deficiency of micronutrients. Iron deficiency is one of the main yield limiting constraints, especially in highly weathered, coarse textured and leached soils. To correct iron deficiency, different form...

Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

PubMed Central

Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

2012-01-01

Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

[Iron deficiency: A diagnostic and therapeutic perspective in psychiatry].

PubMed

Kassir, A

2017-02-01

Iron plays an essential role in balancing the various metabolism in the body. It is also involved in the synthesis of several neurotransmitters. Nutritional iron deficiency is one of the most widespread worldwide; it poses a great health challenge due to the consequences it entails. The aim of this research study is to explore the percentage of psychiatric patients who have a deficiency in iron. In addition, the study investigates the efficacy of iron administered by oral treatment on psychiatric symptomatology among iron deficient patients. The research study utilized the martial biological results, which involved the observation of the level of iron deficiency among the outpatients of a local psychiatrist and assessor from the period of January 2012 until December 2013. Out of 412 patients, 295 were women and 117 men. The age of the participants ranged from 16 to 89years, with an average age of 45years. The only exclusion criterion was a patient's refusal or inability to take the prescribed iron assessment test. We considered a transferrin saturation coefficient (TSC)<30% and/or a serum ferritin level≤50ng/mL to be "indicative" of obvious iron deficiency, and a ferritin level between 51 and 100ng/mL to be "suggestive" of iron deficiency. A plasma ferritin assay was performed at least once on all of the participants prior to any proposed iron treatment. A calculation of the TSC in 138 patients was requested due to suspected iron deficiency despite a blood ferritin level of>100ng/ml. A single method was utilized in the various laboratories to analyse the blood samples to determine whether there was a deficiency in iron. Only those patients with blood ferritin levels ≤100ng/mL and/or a TSC of<30% (335 patients) were subsequently given exclusively an oral iron treatment prescribed on its own or as a supplement or simultaneously with psychotropic treatment. The daily administered dose of elemental iron varied between 50 and 200mg a day. About half of the women - 145 (35.19% of the subjects) - and 15 men (3.64% of the subjects) certainly had a deficiency in iron (blood ferritin level≤50ng/mL). Ninety women and 24 men (27.6% of the subjects) had blood ferritin levels between 51 and 100ng/mL indicating iron deficiency, and 28 women and 33 men (14.8% of the subjects) had a TSC of<30% despite a blood ferritin level of>100ng/mL. Overall, 335 patients (81.3% of the subjects) showed an iron deficiency based on the criteria we set. In the remaining 77 patients (18.7% of the subjects), all of them had blood ferritin levels>100ng/mL and some had TSC≤30%, while the remaining patients' TSC was unknown because it was not measured. The results indicated that there is an iron deficiency in 198 out of 240 patients suffering mostly from mood and behavioural disorders, in 101 out of 126 patients suffering mostly from anxiety disorders, in 18 out of 27 patients suffering mostly from sleep disorders, in 14 out of 15 patients suffering mostly from delusions of persecution, and in the 4 patients suffering mostly from burn out. There was evidence of regression/remission of psychiatric symptoms in 193 responsive patients whereas the remaining 142 patients were considered non-responsive. In the responsive patient category, 37 participants were treated with just iron, 52 received iron supplemented to the initial psychotropic treatment which was not fully effective, and 104 patients were treated with iron and prescribed psychotropic drugs simultaneously. The iron treatment seems to bring about a reduction - particularly through its mono-aminergic neurotransmitter synthesis-promoting action - in hyperemotivity, anxiety, irritability, aggressiveness, sadness, anhedonia, apathy, asthenia, sleep disorders, dysautonomia symptoms, eating disorders, restless-leg syndrome, cognitive performance and the likelihood of resorting to psychiatric admission. A daily elemental iron dose intake between 50 and 200mg/day by deficient patients appears to likely enhance the effects of the psychotropic drugs and even to act as an actual antidepressant. Many patients who received a prescription for iron and antidepressants showed few side effects related to antidepressants and a small number required psychiatric hospitalization. Patients considered unresponsive to iron therapy were those who left the study, were not assessed because the study's timeframe ended, still had an iron deficiency because they did not continuously take the medication, or suffered from somatic diseases which explains their resistance to treat the low iron level (nutritional imbalance, digestive or urinary or gynecological or iatrogenic diseases, sleep apnea). Our clinical observation of two years in a local psychiatrist's clinic revealed that over 80% of patients had iron deficiency. Although the low iron level cannot explain all physical and psychiatric symptoms in patients, it is useful to note that more than half of the iron deficient patients responded favorably after an oral treatment of iron. This result leads to further investigation of the level of iron in psychiatric patients and to reconsider the iron range placed by the laboratories. In addition, it is crucial not to eliminate the possibility of iron deficiency in psychiatric patients. Further research studies are needed to set more specific and detailed criteria to determine the range of iron deficiency in order to support the findings of this study and optimize the care given to patients suffering from various disorders and psychiatric syndromes. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

The Effect of Iron Deficiency on Osmotic Sensitivity of Red Blood Cells from Neonatal Rats and Their Mothers.

PubMed

Al-Hashimi, L Mossa; Gambling, Lorraine; McArdle, H J

2015-12-01

Iron deficiency during pregnancy has many effects on both the mother and her developing foetus. These can be both short and long term. One effect is an alteration in fatty acid metabolism and we hypothesised that these changes may result in alterations in membrane function and structure. In order to test this hypothesis, we measured osmotic sensitivity in red blood cells isolated from neonates and their mothers at different times following birth. We fed female rats control or iron-deficient diets for 4 weeks prior to mating and kept them on the same diet until term. At that time, we returned one group of deficient dams to the control diet. The others were kept on the same diet. We showed that iron deficiency results in a decrease in osmotic sensitivity in the mothers but not in their neonates. Returning the dams to the control diet resulted in a return of their red cell osmotic sensitivity to control levels. In the neonates, there was no recovery in haematocrit or in any other parameter, though they did not get any worse, in contrast to the pups being suckled by deficient mothers. The data show two things. The first is that following birth, the mother restores her own iron stores at the expense of the pups, and secondly, there are differences in properties and sensitivities between red cells from mothers and their neonates. This latter observation cannot be explained by differences in the membrane fatty acid profiles, which were not significantly different.

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach

PubMed Central

Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-01-01

Introduction Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. Aim The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Materials and Methods Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli’s method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. Results There was a statistically significant difference in serum iron and haemoglobin level in all three groups (p<0.05). The serum iron level was lowest in OSMF group and haemoglobin was lowest in iron deficiency anaemia group. A progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF was also observed. The iron deficiency anaemia group was not found to be suffering from OSMF in the absence of areca-nut or tobacco chewing habits, but OSMF patients with chewing habits were found to be suffering from iron deficiency anaemia. Conclusion There is a progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF so it can be used as an auxillary test in assessment of prognosis of the disease. PMID:28209005

Impairment of ntcA gene revealed its role in regulating iron homeostasis, ROS production and cellular phenotype under iron deficiency in cyanobacterium Anabaena sp. PCC 7120.

PubMed

Kaushik, Manish Singh; Srivastava, Meenakshi; Singh, Anumeha; Mishra, Arun Kumar

2017-08-01

Iron deficiency ends up into several unavoidable consequences including damaging oxidative stress in cyanobacteria. NtcA is a global nitrogen regulator controls wide range of metabolisms in addition to regulation of nitrogen metabolism. In present communication, NtcA based regulation of iron homeostasis, ROS production and cellular phenotype under iron deficiency in Anabaena 7120 has been investigated. NtcA regulates the concentration dependent iron uptake by controlling the expression of furA gene. NtcA also regulated pigment synthesis and phenotypic alterations in Anabaena 7120. A significant increase in ROS production and corresponding reduction in the activities of antioxidative enzymes (SOD, CAT, APX and GR) in CSE2 mutant strain in contrast to wild type Anabaena 7120 also suggested the possible involvement of NtcA in protection against oxidative stress in iron deficiency. NtcA has no impact on the expression of furB and furC in spite of presence of consensus NtcA binding site (NBS) and -10 boxes in their promoter. NtcA also regulates the thylakoid arrangement as well as related photosynthetic and respiration rates under iron deficiency in Anabaena 7120. Overall results suggested that NtcA regulates iron acquisition and in turn protect Anabaena cells from the damaging effects of oxidative stress induced under iron deficiency.

Arabidopsis Copper Transport Protein COPT2 Participates in the Cross Talk between Iron Deficiency Responses and Low-Phosphate Signaling1[C][W

PubMed Central

Perea-García, Ana; Garcia-Molina, Antoni; Andrés-Colás, Nuria; Vera-Sirera, Francisco; Pérez-Amador, Miguel A.; Puig, Sergi; Peñarrubia, Lola

2013-01-01

Copper and iron are essential micronutrients for most living organisms because they participate as cofactors in biological processes, including respiration, photosynthesis, and oxidative stress protection. In many eukaryotic organisms, including yeast (Saccharomyces cerevisiae) and mammals, copper and iron homeostases are highly interconnected; yet, such interdependence is not well established in higher plants. Here, we propose that COPT2, a high-affinity copper transport protein, functions under copper and iron deficiencies in Arabidopsis (Arabidopsis thaliana). COPT2 is a plasma membrane protein that functions in copper acquisition and distribution. Characterization of the COPT2 expression pattern indicates a synergic response to copper and iron limitation in roots. We characterized a knockout of COPT2, copt2-1, that leads to increased resistance to simultaneous copper and iron deficiencies, measured as reduced leaf chlorosis and improved maintenance of the photosynthetic apparatus. We propose that COPT2 could play a dual role under iron deficiency. First, COPT2 participates in the attenuation of copper deficiency responses driven by iron limitation, possibly to minimize further iron consumption. Second, global expression analyses of copt2-1 versus wild-type Arabidopsis plants indicate that low-phosphate responses increase in the mutant. These results open up new biotechnological approaches to fight iron deficiency in crops. PMID:23487432

Iron Bioavailability and Provitamin A from Sweet Potato- and Cereal-Based Complementary Foods

PubMed Central

Christides, Tatiana; Amagloh, Francis Kweku; Coad, Jane

2015-01-01

Iron and vitamin A deficiencies in childhood are public health problems in the developing world. Introduction of cereal-based complementary foods, that are often poor sources of both vitamin A and bioavailable iron, increases the risk of deficiency in young children. Alternative foods with higher levels of vitamin A and bioavailable iron could help alleviate these micronutrient deficiencies. The objective of this study was to compare iron bioavailability of β-carotene-rich sweet potato-based complementary foods (orange-flesh based sweet potato (OFSP) ComFa and cream-flesh sweet potato based (CFSP) ComFa with a household cereal-based complementary food (Weanimix) and a commercial cereal (Cerelac®), using the in vitro digestion/Caco-2 cell model. Iron bioavailability relative to total iron, concentrations of iron-uptake inhibitors (fibre, phytates, and polyphenols), and enhancers (ascorbic acid, ß-carotene and fructose) was also evaluated. All foods contained similar amounts of iron, but bioavailability varied: Cerelac® had the highest, followed by OFSP ComFa and Weanimix, which had equivalent bioavailable iron; CFSP ComFa had the lowest bioavailability. The high iron bioavailability from Cerelac® was associated with the highest levels of ascorbic acid, and the lowest levels of inhibitors; polyphenols appeared to limit sweet potato-based food iron bioavailability. Taken together, the results do not support that CFSP- and OFSP ComFa are better sources of bioavailable iron compared with non-commercial/household cereal-based weaning foods; however, they may be a good source of provitamin A in the form of β-carotene. PMID:28231217

Role of Intravenous Ferric Carboxy-maltose in Pregnant Women with Iron Deficiency Anaemia.

PubMed

Mishra, Vineet; Gandhi, Khusaili; Roy, Priyankur; Hokabaj, Shaheen; Shah, Kunur N

2017-09-08

Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia is associated with significant maternal, foetal and infant morbidity. Current options for treatment include oral iron, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a modern treatment option. The study was designed to assess the safety and efficacy of intravenous ferric carboxymaltose for correction of iron deficiency anaemia in pregnant women. A prospective study was conducted at Institute of Kidney Disease and Research Centre, Ahmedabad from January 2014 to December 2016. Antenatal women (108) with iron deficiency anaemia were the study subjects. Socio-demographic profile was recorded and anaemia was assessed based on recent haemoglobin reports. Iron deficiency was diagnosed on basis of serum ferritin value. Intravenous ferric carboxymaltose as per total correction dose (maximum 1500mg) was administered to all women; the improvement in haemoglobin levels were assessed after 3 weeks of total dose infusion. Most of the women(n= 45, 41.7%), were in the age group of 27-30 years. Most of the women (n = 64, 59.3%) had moderate anaemia as per WHO guidelines. Mean haemoglobin levels significantly increased over a period of 3 weeks after Ferric carboxymaltose administrationand no serious life threatening adverse events were observed. Intravenous ferric carboxymaltose was safe and effective in pregnent women with iron deficiency anaemia.

Optimizing early child development for young children with non-anemic iron deficiency in the primary care practice setting (OptEC): study protocol for a randomized controlled trial.

PubMed

Abdullah, Kawsari; Thorpe, Kevin E; Mamak, Eva; Maguire, Jonathon L; Birken, Catherine S; Fehlings, Darcy; Hanley, Anthony J; Macarthur, Colin; Zlotkin, Stanley H; Parkin, Patricia C

2015-04-02

Three decades of research suggests that prevention of iron deficiency anemia (IDA) in the primary care setting may be an unrealized and unique opportunity to prevent poor developmental outcomes in children. A longitudinal study of infants with IDA showed that the developmental disadvantage persists long term despite iron therapy. Early stages of iron deficiency, termed non-anemic iron deficiency (NAID), provide an opportunity for early detection and treatment before progression to IDA. There is little research regarding NAID, which may be associated with delayed development in young children. The aim of this study is to compare the effectiveness of four months of oral iron treatment plus dietary advice, with placebo plus dietary advice, in improving developmental outcomes in children with NAID and to conduct an internal pilot study. From a screening cohort, those identified with NAID (hemoglobin ≥110 g/L and serum ferritin <14 μg/L) are invited to participate in a pragmatic, multi-site, placebo controlled, blinded, parallel group, superiority randomized trial. Participating physicians are part of a primary healthcare research network called TARGet Kids! Children between 12 and 40 months of age and identified with NAID are randomized to receive four months of oral iron treatment at 6 mg/kg/day plus dietary advice, or placebo plus dietary advice (75 per group). The primary outcome, child developmental score, is assessed using the Mullen Scales of Early Learning at baseline and at four months after randomization. Secondary outcomes include an age appropriate behavior measure (Children's Behavior Questionnaire) and two laboratory measures (hemoglobin and serum ferritin levels). Change in developmental and laboratory measures from baseline to the end of the four-month follow-up period will be analyzed using linear regression (analysis of covariance method). This trial will provide evidence regarding the association between child development and NAID, and the effectiveness of oral iron to improve developmental outcomes in children with NAID. The sample size of the trial will be recalculated using estimates taken from an internal pilot study. This trial was registered with Clinicaltrials.gov (identifier: NCT01481766 ) on 22 November 2011.

Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

PubMed Central

Burns, Monika; Amaya, Aldo; Bodi, Caroline; Ge, Zhongming; Bakthavatchalu, Vasudevan; Ennis, Kathleen; Wang, Timothy C.; Georgieff, Michael

2017-01-01

Helicobacter pylori (H.pylori), a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA), enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40) were used; half were placed on a moderately iron deficient (ID) diet immediately post-weaning, and the other half were maintained on an iron replete (IR) diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet) as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet). All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001). Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05), independent of infection status. At 12 months postinfection, hematocrit (Hct) and hemoglobin (Hgb) concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA. PMID:28355210

A Program of Nutritional Education in Schools Reduced the Prevalence of Iron Deficiency in Students

PubMed Central

García-Casal, María Nieves; Landaeta-Jiménez, Maritza; Puche, Rafael; Leets, Irene; Carvajal, Zoila; Patiño, Elijú; Ibarra, Carlos

2011-01-01

The objective was to determine the prevalence of iron, folates and retinol deficiencies in school children and to evaluate the changes after an intervention of nutritional education. The project was developed in 17 schools. The sample included 1,301 children (678 males and 623 females). A subsample of 480 individuals, was randomly selected for drawing blood for biochemical determinations before and after the intervention of nutritional education, which included in each school: written pre and post-intervention tests, 6 workshops, 2 participative talks, 5 game activities, 1 cooking course and 1 recipe contest. Anthropometrical and biochemical determinations included weight, height, body-mass index, nutritional status, hematocrit, serum ferritin, retinol and folate concentrations. There was high prevalence of iron (25%), folates (75%) and vitamin A (43%) deficiencies in school children, with a low consumption of fruit and vegetables, high consumption of soft drinks and snacks and almost no physical activity. The nutritional education intervention produced a significant reduction in iron deficiency prevalence (25 to 14%), and showed no effect on vitamin A and folates deficiencies. There was a slight improvement in nutritional status. This study shows, through biochemical determinations, that nutritional education initiatives and programs have an impact improving nutritional health in school children. PMID:21547083

Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

PubMed Central

Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

2015-01-01

Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

The spatial expression and regulation of transcription factors IDEF1 and IDEF2

PubMed Central

Kobayashi, Takanori; Ogo, Yuko; Aung, May Sann; Nozoye, Tomoko; Itai, Reiko Nakanishi; Nakanishi, Hiromi; Yamakawa, Takashi; Nishizawa, Naoko K.

2010-01-01

Background and Aims Under conditions of low iron availability, rice plants induce genes involved in iron uptake and utilization. The iron deficiency-responsive cis-acting element binding factors 1 and 2 (IDEF1 and IDEF2) regulate transcriptional response to iron deficiency in rice roots. Clarification of the functions of IDEF1 and IDEF2 could uncover the gene regulation mechanism. Methods Spatial patterns of IDEF1 and IDEF2 expression were analysed by histochemical staining of IDEF1 and IDEF2 promoter-GUS transgenic rice lines. Expression patterns of the target genes of IDEF1 and IDEF2 were analysed using transformants with induced or repressed expression of IDEF1 or IDEF2 grown in iron-rich or in iron-deficient solutions for 1 d. Key Results IDEF1 and IDEF2 were highly expressed in the basal parts of the lateral roots and vascular bundles. IDEF1 and IDEF2 expression was dominant in leaf mesophyll and vascular cells, respectively. These expression patterns were similar under both iron-deficient and iron-sufficient conditions. IDEF1 was strongly expressed in pollen, ovaries, the aleurone layer and embryo. IDEF2 was expressed in pollen, ovaries and the dorsal vascular region of the endosperm. During seed germination, IDEF1 and IDEF2 were expressed in the endosperm and embryo. Expression of IDEF1 target genes was regulated in iron-rich roots similar to early iron-deficiency stages. In addition, the expression patterns of IDEF2 target genes were similar between iron-rich conditions and early or subsequent iron deficiency. Conclusions IDEF1 and IDEF2 are constitutively expressed during both vegetative and reproductive stages. The spatial expression patterns of IDEF1 and IDEF2 overlap with their target genes in restricted cell types, but not in all cells. The spatial expression patterns and gene regulation of IDEF1 and IDEF2 in roots are generally conserved under conditions of iron sufficiency and deficiency, suggesting complicated interactions with unknown factors for sensing and transmitting iron-deficiency signals. PMID:20197292

Inflammatory bowel disease registries for collection of patient iron parameters in Europe

PubMed Central

Halfvarson, Jonas; Cummings, Fraser; Grip, Olof; Savoye, Guillaume

2018-01-01

Iron deficiency without anemia and iron deficiency anemia are common and frequently overlooked complications of inflammatory bowel disease. Despite the frequency and impact of iron deficiency in inflammatory bowel disease, there are gaps in our understanding about its incidence, prevalence and natural history and, consequently, patients may be undertreated. Medical registries have a key role in collecting data on the disease’s natural history, the safety and effectiveness of drugs in routine clinical practice, and the quality of care delivered by healthcare services. Even though iron deficiency impacts inflammatory bowel disease patients and healthcare systems substantially, none of the established European inflammatory bowel disease registries systematically collects information on iron parameters and related outcomes. Collection of robust iron parameter data from patient registries is one way to heighten awareness about the importance of iron deficiency in this disease and to generate data to improve the quality of patient care, patient outcomes, and thus quality of life. This objective could be achieved through collection of specific laboratory, clinical, and patient-reported measurements that could be incorporated into existing registries. This review describes the status of current European inflammatory bowel disease registries and the data they generate, in order to highlight their potential role in collecting iron data, to discuss how such information gathering could contribute to our understanding of iron deficiency anemia, and to provide practical information in regard to the incorporation of accumulated iron parameter data into registries. PMID:29563751

Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency–Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus123

PubMed Central

Tran, Phu V; Kennedy, Bruce C; Pisansky, Marc T; Won, Kyoung-Jae; Gewirtz, Jonathan C; Simmons, Rebecca A; Georgieff, Michael K

2016-01-01

Background: Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. Objectives: We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring’s hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. Methods: Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. Results: Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. Conclusions: Fetal-neonatal iron deficiency reprograms molecular networks associated with the pathogenesis of neurologic and psychological disorders in adult rats. The positive response to prenatal choline represents a potential adjunctive therapeutic supplement to the high-risk group. PMID:26865644

Management of Iron Deficiency Anemia

PubMed Central

Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

2015-01-01

Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blood transfusions. Treatment options include oral and intravenous iron therapy; however, the efficacy of oral iron is limited in certain gastrointestinal conditions, such as inflammatory bowel disease, celiac disease, and autoimmune gastritis. This article provides a critical summary of the diagnosis and treatment of iron deficiency anemia. In addition, it includes a management algorithm that can help the clinician determine which patients are in need of further gastrointestinal evaluation. This facilitates the identification and treatment of the underlying condition and avoids the unnecessary use of invasive methods and their associated risks. PMID:27099596

Symptoms of Celiac Disease

MedlinePlus

... cholangitis etc.) • Weight loss • Pale, foul-smelling stool • Iron-deficiency anemia that does not respond to iron therapy • ... common sign of celiac disease in adults is iron deficiency anemia that does not respond to iron therapy. ...

Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

PubMed Central

Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

2011-01-01

Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

Practical guidance for the management of iron deficiency in patients with inflammatory bowel disease

PubMed Central

Niepel, Dorothea; Klag, Thomas; Malek, Nisar P.; Wehkamp, Jan

2018-01-01

Iron deficiency or iron deficiency anemia (IDA) are some of the most common systemic complications of inflammatory bowel diseases (IBD). Symptoms such as fatigue, reduced ability to concentrate and reduced exercise tolerance can mimic common symptoms of IBD and can therefore easily be overseen. Furthermore, clinicians tend to see mild to moderate anemia as an inevitable accompaniment of IBD that is sufficiently explained by the underlying disease and does not require further workup. But in contrast to these clinical routines, current guidelines recommend that any degree of anemia in patients with IBD should be further evaluated and treated. Multiple studies have shown that anemia is a main factor for decreased quality of life (QoL) in patients with IBD. Correction of anemia, however, can significantly improve the QoL of patients with IBD. It is therefore recommended that every patient with IBD is regularly screened for iron deficiency and anemia. If detected, appropriate workup and treatment should be initiated. Over the last years, a number of new diagnostic tools and treatment options have been developed. Multiple studies have demonstrated the safety of newer formulations of intravenous iron in patients with IBD and have compared oral and intravenous iron in various situations. Treatment recommendations have changed and new evidence-based guidelines were developed. However, to date these guidelines are still not widely implemented in clinical practice. The aim of this review is to draw attention to the need for treatment for every level of anemia in patients with IBD and to provide some practical guidance for screening, diagnostics, treatment and follow up of IDA in patients with IBD following current international guidelines. PMID:29760784

ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders

PubMed Central

Nam, Hyeyoung; Wang, Chia-Yu; Zhang, Lin; Zhang, Wei; Hojyo, Shintaro; Fukada, Toshiyuki; Knutson, Mitchell D.

2013-01-01

The liver, pancreas, and heart are particularly susceptible to iron-related disorders. These tissues take up plasma iron from transferrin or non-transferrin-bound iron, which appears during iron overload. Here, we assessed the effect of iron status on the levels of the transmembrane transporters, ZRT/IRT-like protein 14 and divalent metal-ion transporter-1, which have both been implicated in transferrin- and non-transferrin-bound iron uptake. Weanling male rats (n=6/group) were fed an iron-deficient, iron-adequate, or iron-overloaded diet for 3 weeks. ZRT/IRT-like protein 14, divalent metal-ion transporter-1 protein and mRNA levels in liver, pancreas, and heart were determined by using immunoblotting and quantitative reverse transcriptase polymerase chain reaction analysis. Confocal immunofluorescence microscopy was used to localize ZRT/IRT-like protein 14 in the liver and pancreas. ZRT/IRT-like protein 14 and divalent metal-ion transporter-1 protein levels were also determined in hypotransferrinemic mice with genetic iron overload. Hepatic ZRT/IRT-like protein 14 levels were found to be 100% higher in iron-loaded rats than in iron-adequate controls. By contrast, hepatic divalent metal-ion transporter-1 protein levels were 70% lower in iron-overloaded animals and nearly 3-fold higher in iron-deficient ones. In the pancreas, ZRT/IRT-like protein 14 levels were 50% higher in iron-overloaded rats, and in the heart, divalent metal-ion transporter-1 protein levels were 4-fold higher in iron-deficient animals. At the mRNA level, ZRT/IRT-like protein 14 expression did not vary with iron status, whereas divalent metal-ion transporter-1 expression was found to be elevated in iron-deficient livers. Immunofluorescence staining localized ZRT/IRT-like protein 14 to the basolateral membrane of hepatocytes and to acinar cells of the pancreas. Hepatic ZRT/IRT-like protein 14, but not divalent metal-ion transporter-1, protein levels were elevated in iron-loaded hypotransferrinemic mice. In conclusion, ZRT/IRT-like protein 14 protein levels are up-regulated in iron-loaded rat liver and pancreas and in hypotransferrinemic mouse liver. Divalent metal-ion transporter-1 protein levels are down-regulated in iron-loaded rat liver, and up-regulated in iron-deficient liver and heart. Our results provide insight into the potential contributions of these transporters to tissue iron uptake during iron deficiency and overload. PMID:23349308

[A neonate with anaemia of prematurity: zinc protoporphyrin identifies iron deficiency anaemia without iron deficiency].

PubMed

van der Feen, Diederik E; van Hillegersberg, Jacqueline L A M; Schippers, Johannes A

2015-01-01

Anaemia is a common problem in premature infants and is generally easy to treat with iron supplementation. If the anaemia persists despite appropriate correction of deficiencies, more extensive evaluation is required. We describe a case of a premature male infant with a production-deficient anaemia without metabolic deficiencies, eventually identified as anaemia of prematurity. This type of anaemia is commonly diagnosed but its highly variable and complex aetiology and phenotype are often poorly understood. A probable explanation for the anaemia of prematurity in this case was a transient iron incorporation defect, identifiable by high levels of zinc protoporphyrin.

Integrating themes, evidence gaps, and research needs identified by workshop on iron screening and supplementation in iron-replete pregnant women and young children.

PubMed

Brannon, Patsy M; Stover, Patrick J; Taylor, Christine L

2017-12-01

This report addresses the evidence and the uncertainties, knowledge gaps, and research needs identified by participants at the NIH workshop related to iron screening and routine iron supplementation of largely iron-replete pregnant women and young children (6-24 mo) in developed countries. The workshop presentations and panel discussions focused on current understanding and knowledge gaps related to iron homeostasis, measurement of and evidence for iron status, and emerging concerns about supplementing iron-replete members of these vulnerable populations. Four integrating themes emerged across workshop presentations and discussion and centered on 1 ) physiologic or developmental adaptations of iron homeostasis to pregnancy and early infancy, respectively, and their implications, 2 ) improvement of the assessment of iron status across the full continuum from iron deficiency anemia to iron deficiency to iron replete to iron excess, 3 ) the linkage of iron status with health outcomes beyond hematologic outcomes, and 4 ) the balance of benefit and harm of iron supplementation of iron-replete pregnant women and young children. Research that addresses these themes in the context of the full continuum of iron status is needed to inform approaches to the balancing of benefits and harms of screening and routine supplementation. © 2017 American Society for Nutrition.

PLASMA AND RED CELL RADIOIRON FOLLOWING INTRAVENOUS INJECTION

PubMed Central

Yuile, C. L.; Bly, C. G.; Stewart, W. B.; Izzo, A. J.; Wells, J. C.; Whipple, G. H.

1949-01-01

Sterile inflammation induced by repeated subcutaneous injections of turpentine in non-anemic, non-iron—deficient dogs, leads to a fall in plasma iron concentration, the development of a moderate anemia, and a marked delay in the uptake by the red blood cells of intravenous radioiron. Similar periods of inflammation in anemic, iron-deficient dogs on a diet low in iron cause no increase in the degree of anemia and no inhibition of red blood cell uptake of intravenous radioiron. Radioiron appears only in traces in abscess exudates. Intravenous iron disappearance curves following a single injection are uninfluenced by sterile inflammation in either anemic or non-anemic dogs. The impairment of hemoglobin synthesis caused by inflammation is at most a relative matter, since the anemia that develops is seldom severe or progressive, and since the inhibition can be overcome if the marrow is sufficiently stimulated by the demands of a severe continuing anemia. PMID:18140660

Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

PubMed

Noronha, Vanita; Joshi, Amit; Patil, Vijay Maruti; Banavali, Shripad D; Gupta, Sudeep; Parikh, Purvish M; Marfatia, Shalaka; Punatar, Sachin; More, Sucheta; Goud, Supriya; Nakti, Dipti; Prabhash, Kumar

2018-04-01

We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia. © 2017 John Wiley & Sons Australia, Ltd.

Recurrent selection to alter grain phytic acid concentration and iron bioavailability

USDA-ARS?s Scientific Manuscript database

Most of the phosphorus (P) in cereal grains is in the form of phytic acid, a potent inhibitor of iron absorption that cannot be digested by monogastric livestock or humans. High phytate content in staple crops contributes to the high incidence of iron deficiency in developing countries. Low phytic a...

Arabidopsis glutaredoxin s17 contributes to vegetative growth, mineral accumulation, and redox balance during iron deficiency

USDA-ARS?s Scientific Manuscript database

Iron (Fe) is an essential mineral nutrient and a metal cofactor required for many proteins and enzymes involved in the processes of DNA synthesis, respiration, and photosynthesis. Iron limitation can have detrimental effects on plant growth and development. Such effects are mediated, at least in par...

Effects of cooking methods on the iron and zinc contents in cowpea (Vigna unguiculata) to combat nutritional deficiencies in Brazil

PubMed Central

Pereira, Elenilda J.; Carvalho, Lucia M. J.; Dellamora-Ortiz, Gisela M.; Cardoso, Flávio S. N.; Carvalho, José L. V.; Viana, Daniela S.; Freitas, Sidinea C.; Rocha, Maurisrael M.

2014-01-01

Background Because iron deficiency anemia is prevalent in developing countries, determining the levels of iron and zinc in beans, the second most consumed staple food in Brazil, is essential, especially for the low-income people who experience a deficiency of these minerals in their diet. Objectives This study aimed to evaluate the effect of cooking methods by measuring the iron and zinc contents in cowpea cultivars before and after soaking to determine the retention of these minerals. Methods The samples were cooked in both regular pans and pressure cookers with and without previous soaking. Mineral analyses were carried out by Spectrometry of Inductively Coupled Plasma (ICP). Results The results showed high contents of iron and zinc in raw samples as well as in cooked ones, with the use of regular pan resulting in greater percentage of iron retention and the use of pressure cooker ensuring higher retention of zinc. Conclusions The best retention of iron was found in the BRS Aracê cultivar prepared in a regular pan with previous soaking. This cultivar may be indicated for cultivation and human consumption. The best retention of zinc was found for the BRS Tumucumaque cultivar prepared in a pressure cooker without previous soaking. PMID:24624050

Anaemia, iron deficiency and susceptibility to infection in children in sub-Saharan Africa, guideline dilemmas.

PubMed

Jonker, Femkje A M; Te Poel, Elodie; Bates, Imelda; Boele van Hensbroek, Michael

2017-06-01

Globally, anaemia, iron deficiency and infections are responsible for a majority of the morbidity and mortality that occurs among children. As iron is essential for erythropoiesis and the human immune system, as well as a crucial element for many pathogens, these three conditions often interact. This article considers the question - have the studies conducted so far unravelled the potential complex interaction between these factors sufficiently enough to be able to develop universally applicable guidelines about iron treatment in children? It is possible, however, that the area is too complex and diverse, with many sub-populations, and that not universal, but tailor-made guidelines are needed based on some agreed principles. © 2017 John Wiley & Sons Ltd.

Autoimmune gastritis.

PubMed

Kulnigg-Dabsch, Stefanie

2016-10-01

Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

Hfe and Hjv exhibit overlapping functions for iron signaling to hepcidin.

PubMed

Kent, Patricia; Wilkinson, Nicole; Constante, Marco; Fillebeen, Carine; Gkouvatsos, Konstantinos; Wagner, John; Buffler, Marzell; Becker, Christiane; Schümann, Klaus; Santos, Manuela M; Pantopoulos, Kostas

2015-05-01

Functional inactivation of HFE or hemojuvelin (HJV) is causatively linked to adult or juvenile hereditary hemochromatosis, respectively. Systemic iron overload results from inadequate expression of hepcidin, the iron regulatory hormone. While HJV regulates hepcidin by amplifying bone morphogenetic protein (BMP) signaling, the role of HFE in the hepcidin pathway remains incompletely understood. We investigated the pathophysiological implications of combined Hfe and Hjv ablation in mice. Isogenic Hfe (-)/(-) and Hjv (-)/(-) mice were crossed to generate double Hfe (-)/(-) Hjv (-)/(-) progeny. Wild-type control and mutant mice of all genotypes were analyzed for serum, hepatic, and splenic iron content, expression of iron metabolism proteins, and expression of hepcidin and Smad signaling in the liver, in response to a standard or an iron-enriched diet. As expected, Hfe (-)/(-) and Hjv (-)/(-) mice developed relatively mild or severe iron overload, respectively, which corresponded to the degree of hepcidin inhibition. The double Hfe (-)/(-) Hjv (-)/(-) mice exhibited an indistinguishable phenotype to single Hjv (-)/(-) counterparts with regard to suppression of hepcidin, serum and hepatic iron overload, splenic iron deficiency, tissue iron metabolism, and Smad signaling, under both dietary regimens. We conclude that the hemochromatotic phenotype caused by disruption of Hjv is not further aggravated by combined Hfe/Hjv deficiency. Our results provide genetic evidence that Hfe and Hjv operate in the same pathway for the regulation of hepcidin expression and iron metabolism. Combined disruption of Hfe and Hjv phenocopies single Hjv deficiency. Single Hjv(-)/(-) and double Hfe(-)/(-)Hjv(-)/(-) mice exhibit comparable iron overload. Hfe and Hjv regulate hepcidin via the same pathway.

Iron Deficiency Induces a Partial Inhibition of the Photosynthetic Electron Transport and a High Sensitivity to Light in the Diatom Phaeodactylum tricornutum.

PubMed

Roncel, Mercedes; González-Rodríguez, Antonio A; Naranjo, Belén; Bernal-Bayard, Pilar; Lindahl, Anna M; Hervás, Manuel; Navarro, José A; Ortega, José M

2016-01-01

Iron limitation is the major factor controlling phytoplankton growth in vast regions of the contemporary oceans. In this study, a combination of thermoluminescence (TL), chlorophyll fluorescence, and P700 absorbance measurements have been used to elucidate the effects of iron deficiency in the photosynthetic electron transport of the marine diatom P. tricornutum. TL was used to determine the effects of iron deficiency on photosystem II (PSII) activity. Excitation of iron-replete P. tricornutum cells with single turn-over flashes induced the appearance of TL glow curves with two components with different peaks of temperature and contributions to the total signal intensity: the B band (23°C, 63%), and the AG band (40°C, 37%). Iron limitation did not significantly alter these bands, but induced a decrease of the total TL signal. Far red excitation did not increase the amount of the AG band in iron-limited cells, as observed for iron-replete cells. The effect of iron deficiency on the photosystem I (PSI) activity was also examined by measuring the changes in P700 redox state during illumination. The electron donation to PSI was substantially reduced in iron-deficient cells. This could be related with the important decline on cytochrome c 6 content observed in these cells. Iron deficiency also induced a marked increase in light sensitivity in P. tricornutum cells. A drastic increase in the level of peroxidation of chloroplast lipids was detected in iron-deficient cells even when grown under standard conditions at low light intensity. Illumination with a light intensity of 300 μE m(-2) s(-1) during different time periods caused a dramatic disappearance in TL signal in cells grown under low iron concentration, this treatment not affecting to the signal in iron-replete cells. The results of this work suggest that iron deficiency induces partial blocking of the electron transfer between PSII and PSI, due to a lower concentration of the electron donor cytochrome c 6. This decreased electron transfer may induce the over-reduction of the plastoquinone pool and consequently the appearance of acceptor side photoinhibition in PSII even at low light intensities. The functionality of chlororespiratory electron transfer pathway under iron restricted conditions is also discussed.

Iron Deficiency Induces a Partial Inhibition of the Photosynthetic Electron Transport and a High Sensitivity to Light in the Diatom Phaeodactylum tricornutum

PubMed Central

Roncel, Mercedes; González-Rodríguez, Antonio A.; Naranjo, Belén; Bernal-Bayard, Pilar; Lindahl, Anna M.; Hervás, Manuel; Navarro, José A.; Ortega, José M.

2016-01-01

Iron limitation is the major factor controlling phytoplankton growth in vast regions of the contemporary oceans. In this study, a combination of thermoluminescence (TL), chlorophyll fluorescence, and P700 absorbance measurements have been used to elucidate the effects of iron deficiency in the photosynthetic electron transport of the marine diatom P. tricornutum. TL was used to determine the effects of iron deficiency on photosystem II (PSII) activity. Excitation of iron-replete P. tricornutum cells with single turn-over flashes induced the appearance of TL glow curves with two components with different peaks of temperature and contributions to the total signal intensity: the B band (23°C, 63%), and the AG band (40°C, 37%). Iron limitation did not significantly alter these bands, but induced a decrease of the total TL signal. Far red excitation did not increase the amount of the AG band in iron-limited cells, as observed for iron-replete cells. The effect of iron deficiency on the photosystem I (PSI) activity was also examined by measuring the changes in P700 redox state during illumination. The electron donation to PSI was substantially reduced in iron-deficient cells. This could be related with the important decline on cytochrome c6 content observed in these cells. Iron deficiency also induced a marked increase in light sensitivity in P. tricornutum cells. A drastic increase in the level of peroxidation of chloroplast lipids was detected in iron-deficient cells even when grown under standard conditions at low light intensity. Illumination with a light intensity of 300 μE m-2 s-1 during different time periods caused a dramatic disappearance in TL signal in cells grown under low iron concentration, this treatment not affecting to the signal in iron-replete cells. The results of this work suggest that iron deficiency induces partial blocking of the electron transfer between PSII and PSI, due to a lower concentration of the electron donor cytochrome c6. This decreased electron transfer may induce the over-reduction of the plastoquinone pool and consequently the appearance of acceptor side photoinhibition in PSII even at low light intensities. The functionality of chlororespiratory electron transfer pathway under iron restricted conditions is also discussed. PMID:27536301

Air pollution particles and iron homeostasis | Science ...

EPA Pesticide Factsheets

Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

Iron chelated cyclic peptide, ferrichrysin, for oral treatment of iron deficiency: solution properties and efficacy in anemic rats.

PubMed

Suzuki, Sachiko; Fukuda, Katsuharu; Irie, Motoko; Hata, Yoji

2007-01-01

Ferrichrysin (Fcy), which is produced by Aspergillus oryzae and is present in foods used for human consumption, belongs to a group of hydroxamate siderophore ferric iron chelators. Fcy (100 mg/mL) dissolves completely at both pH 2.0 and 7.0, being very stable at a wide range of pH, high temperatures and pressures, with little reactivity to dietary iron absorption inhibitors, phytic acid, tannic acid, and catechin. We studied the effect of Fcy in male Sprague-Dawley rats with iron-deficiency anemia, which were separated into three different dietary groups (n=5) and supplementing diets as follows: (i) ferric citrate, (ii) heme iron concentrate, and (iii) Fcy (35 mg Fe/kg diet) for three weeks. Fcy exhibited the same beneficial effect in improving iron deficiency anemia as ferric citrate, being significantly greater than the effect of heme iron. The iron concentration of liver in the Fcy group was 35% greater than that in the ferric citrate group. These findings indicate that Fcy could be an efficient oral iron supplement to prevent or treat iron deficiency.

Risk-Based Questionnaires Fail to Detect Adolescent Iron Deficiency and Anemia.

PubMed

Sekhar, Deepa L; Murray-Kolb, Laura E; Schaefer, Eric W; Paul, Ian M

2017-08-01

To evaluate the predictive ability of screening questionnaires to identify adolescent women at high-risk for iron deficiency or iron deficiency anemia who warrant objective laboratory testing. Cross-sectional study of 96 female individuals 12-21 years old seen at an academic medical center. Participants completed an iron deficiency risk assessment questionnaire including the 4 Bright Futures Adolescent Previsit Questionnaire anemia questions, along with depression, attention, food insecurity, and daytime sleepiness screens. Multiple linear regression controlling for age, race, and hormonal contraception use compared the predictive ability of 2 models for adolescent iron deficiency (defined as ferritin <12 mcg/L) and anemia (hemoglobin <12 g/dL). Model 1, the Bright Futures questions, was compared with model 2, which included the 4 aforementioned screens and body mass index percentile. Among participants, 18% (17/96) had iron deficiency and 5% (5/96) had iron deficiency anemia. Model 1 (Bright Futures) poorly predicted ferritin and hemoglobin values (R 2  = 0.03 and 0.08, respectively). Model 2 demonstrated similarly poor predictive ability (R 2  = 0.05 and 0.06, respectively). Mean differences for depressive symptoms (0.3, 95% CI -0.2, 0.8), attention difficulty (-0.1, 95% CI -0.5, 0.4), food insecurity (0.04, 95% CI -0.5, 0.6), daytime sleepiness (0.1, 95% CI -0.1, 0.3), and body mass index percentile (-0.04, 95% CI -0.3, 0.2) were not significantly associated with ferritin in model 2. Mean differences for hemoglobin were also nonsignificant. Risk-based surveys poorly predict objective measures of iron status using ferritin and hemoglobin. Next steps are to establish the optimal timing for objective assessment of adolescent iron deficiency and anemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Are there anamnestic risk factors for iron deficiency in pregnancy? Results from a feasibility study.

PubMed

Kirschner, Wolf; Dudenhausen, Joachim W; Henrich, Wolfgang

2016-04-01

The conditions of iron deficiency are highly incident in pregnancy with elevated risks for preterm birth and low birth weight. In our recent study, we found 6% of participants having anemia, whereas between 39% and 47% showed iron deficiency without anemia. In many countries in prenatal care solely hemoglobin (Hb) measurement is applied. For the gynecologists till date there is no indication to determine other markers (e.g., serum-ferritin). As iron deficiency results from an imbalance between intake and loss of iron, our aim was to find out if the risk of iron deficiency conditions can be estimated by a diet history protocol as well as questionnaires to find about iron loss. We found that the risk of having iron deficiency in upper gestational week (>=21) increased by a factor of five. Thus, additional diagnostics should be done in this group by now. Using the questionnaire as a screening instrument, we further estimated the probability of disease in terms of a positive likelihood ratio (LR+). The positive LR for the group below 21th week of gestation is 1.9 thus, increasing the post-test probability to 52% from 36% as before. Further research based on higher sample sizes will show if the ratios can be increased further.

[Iron absorption of the habitual diet in a population of low socioeconomic level].

PubMed

Morón, C; Kremenchuzky, S; Passamai, M I; D'Andrea de Rivero, S; Pérez de Galíndez, G; Gerschcovich, C

1985-06-01

Iron absorption using the extrinsic double-tag method was determined in the habitual diet consumed by a group of 32 volunteers of both sexes, pertaining to the low socioeconomic strata. The diet was made up of bread, spaghetti, vegetables and meat, totalling 2,022 kcal, 65.0 g protein, 17.57 mg iron, and 28.75 mg ascorbic acid. According to our findings, men were found to be neither anemic nor iron-deficient. Among the women, however, 4.8% had anemia and 57.1% suffered from iron deficiency. The non-heme iron absorption was very low: 1.35% at breakfast, 3.29% at lunch, and 3.82% at dinner. Among those subjects found to be normal, the absorption was half the above figures, whereas among those with iron deficiency it was threefold, the differences being highly significant. The absorption of heme-iron for lunch and dinner was 17.53%. The iron deficient group had an absorption value four times greater than the normal group, the differences also being highly significant. The daily availability of non-heme, heme and total iron was 0.44, 1.13 and 1.57 mg, respectively. In the subjects who formed the normal group, total iron available was 1.14 mg, barely covering a man's daily requirements, but not those of a woman. In the iron-deficient group, it was 4.31 mg, that is, four times greater than in the normal group; while this value improves the balance, it does not prevent deficiency in women, with great blood losses. Bearing these results in mind, it is suggested that measures tending to improve dietary iron content and bio-availability, be enforced.

Arabidopsis bHLH100 and bHLH101 Control Iron Homeostasis via a FIT-Independent Pathway

PubMed Central

Sivitz, Alicia B.; Hermand, Victor; Curie, Catherine; Vert, Grégory

2012-01-01

Iron deficiency induces a complex set of responses in plants, including developmental and physiological changes, to increase iron uptake from soil. In Arabidopsis, many transporters involved in the absorption and distribution of iron have been identified over the past decade. However, little is known about the signaling pathways and networks driving the various responses to low iron. Only the basic helix–loop–helix (bHLH) transcription factor FIT has been shown to control the expression of the root iron uptake machinery genes FRO2 and IRT1. Here, we characterize the biological role of two other iron-regulated transcription factors, bHLH100 and bHLH101, in iron homeostasis. First direct transcriptional targets of FIT were determined in vivo. We show that bHLH100 and bHLH101 do not regulate FIT target genes, suggesting that they play a non-redundant role with the two closely related bHLH factors bHLH038 and bHLH039 that have been suggested to act in concert with FIT. bHLH100 and bHLH101 play a crucial role in iron-deficiency responses, as attested by their severe growth defects and iron homeostasis related phenotypes on low-iron media. To gain further insight into the biological role of bHLH100 and bHLH101, we performed microarray analysis using the corresponding double mutant and showed that bHLH100 and bHLH101 likely regulate genes involved in the distribution of iron within the plant. Altogether, this work establishes bHLH100 and bHLH101 as key regulators of iron-deficiency responses independent of the master regulator FIT and sheds light on new regulatory networks important for proper growth and development under low iron conditions. PMID:22984573

Prevalence and Risk Factors for Iron Deficiency Anemia and Iron Depletion During Pregnancy: A Prospective Study.

PubMed

Gomes da Costa, Ana; Vargas, Sara; Clode, Nuno; M Graça, Luís

2016-09-01

Anemia and iron deficiency during pregnancy are a worldwide concern and are more frequent among women of reproductive age, pregnant women, and young children. The aim of this study was to assess the prevalence of iron deficiency anemia and the risk factors for iron depletion during the first half of pregnancy, in a Portuguese population. A prospective study was conducted at a tertiary hospital and included pregnant women, until the 20th week of gestation. Data was collected regarding demographic and pregnancy features and hemoglobin and serum ferritin concentrations were determined. A multivariate logistic regression was performed to identify potential risk factors for iron deficiency. Two hundred and one women were included, from which five (2.49%) presented anemia. Additionally, 77 (38.3%) exhibited iron deficiency and 22 (10.9%) revealed severe iron depletion. Maternal age was the only risk factor identified. The odds ratio (OR) was equal to 12.99 (95% CI 2.41 - 70.0) for women under twenty years of age and 2.09 (95% CI 1.05 - 4.14) for women older than thirty years of age. The prevalence of maternal anemia in the first half of pregnancy was lower than in other studies. However, more than one-third of the women exhibited iron deficiency. With the exception of maternal age, no other risk factors were identified.

Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging

PubMed Central

Atamna, Hani; Killilea, David W.; Killilea, Alison Nisbet; Ames, Bruce N.

2002-01-01

Heme, a major functional form of iron in the cell, is synthesized in the mitochondria by ferrochelatase inserting ferrous iron into protoporphyrin IX. Heme deficiency was induced with N-methylprotoporphyrin IX, a selective inhibitor of ferrochelatase, in two human brain cell lines, SHSY5Y (neuroblastoma) and U373 (astrocytoma), as well as in rat primary hippocampal neurons. Heme deficiency in brain cells decreases mitochondrial complex IV, activates nitric oxide synthase, alters amyloid precursor protein, and corrupts iron and zinc homeostasis. The metabolic consequences resulting from heme deficiency seem similar to dysfunctional neurons in patients with Alzheimer's disease. Heme-deficient SHSY5Y or U373 cells die when induced to differentiate or to proliferate, respectively. The role of heme in these observations could result from its interaction with heme regulatory motifs in specific proteins or secondary to the compromised mitochondria. Common causes of heme deficiency include aging, deficiency of iron and vitamin B6, and exposure to toxic metals such as aluminum. Iron and B6 deficiencies are especially important because they are widespread, but they are also preventable with supplementation. Thus, heme deficiency or dysregulation may be an important and preventable component of the neurodegenerative process. PMID:12417755

The Effects of Iron and/or Zinc Supplementation on Maternal Reports of Sleep in Infants from Nepal and Zanzibar

PubMed Central

Kordas, Katarzyna; Siegel, Emily H.; Olney, Deanna K.; Katz, Joanne; Tielsch, James M.; Kariger, Patricia K.; Khalfan, Sabra S.; LeClerq, Steven C.; Khatry, Subarna K.; Stoltzfus, Rebecca J.

2009-01-01

Background There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a randomized iron supplementation trial. Objective We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 randomized, placebo-controlled trials from Pemba Island, Zanzibar, and Nepal. Design In both studies, which had parallel designs and were carried out in years 2002 to 2003, infants received iron–folic acid with or without zinc daily for 12 months, and assessments of development were made every 3 months for the duration of the study. Eight hundred seventy-seven Pemban (12.5 ± 4.0 months old) and 567 Nepali (10.8 ± 4.0 months) infants participated. Maternal reports of sleep patterns (napping frequency and duration, nighttime sleep duration, frequency of night waking) were collected. Results Mean Hb concentration was 9.2 ± 1.1 for Pemban and 10.1 ± 1.2 g/dL for Nepali infants. Approximately, one-third of the children were stunted. Supplemental iron was consistently associated with longer night and total sleep duration. The effects of zinc supplementation also included longer sleep duration. Conclusions Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking. PMID:19322104

Review: The Potential of the Common Bean (Phaseolus vulgaris) as a Vehicle for Iron Biofortification

PubMed Central

Petry, Nicolai; Boy, Erick; Wirth, James P.; Hurrell, Richard F.

2015-01-01

Common beans are a staple food and the major source of iron for populations in Eastern Africa and Latin America. Bean iron concentration is high and can be further increased by biofortification. A major constraint to bean iron biofortification is low iron absorption, attributed to inhibitory compounds such as phytic acid (PA) and polyphenol(s) (PP). We have evaluated the usefulness of the common bean as a vehicle for iron biofortification. High iron concentrations and wide genetic variability have enabled plant breeders to develop high iron bean varieties (up to 10 mg/100 g). PA concentrations in beans are high and tend to increase with iron biofortification. Short-term human isotope studies indicate that iron absorption from beans is low, PA is the major inhibitor, and bean PP play a minor role. Multiple composite meal studies indicate that decreasing the PA level in the biofortified varieties substantially increases iron absorption. Fractional iron absorption from composite meals was 4%–7% in iron deficient women; thus the consumption of 100 g biofortified beans/day would provide about 30%–50% of their daily iron requirement. Beans are a good vehicle for iron biofortification, and regular high consumption would be expected to help combat iron deficiency (ID). PMID:25679229

Infant anaemia is associated with infection, low birthweight and iron deficiency in rural Bangladesh.

PubMed

Eneroth, Hanna; Persson, Lars-Åke; El Arifeen, Shams; Ekström, Eva-Charlotte

2011-02-01

To estimate the prevalence of infant anaemia and its association with iron deficiency, growth, infection and other micronutrient deficiencies. Using data from MINIMat, a randomized maternal food and micronutrient supplementation trial, we assessed the associations between anaemia (haemoglobin < 105 g/L) in 580 infants at 6 months and deficiencies of iron, vitamin A, vitamin B12, zinc and folate, infection and anthropometric indices. Variables associated with anaemia in bivariate analyses were evaluated in logistic regression models, adjusting for potential confounders. Anaemia was found in 46% of the infants, and among these, 28% had iron deficiency (plasma ferritin <9 μg/L). Elevated C-reactive protein (>10mg/L) (OR = 2.7, 95% CI: 1.6, 4.7), low birthweight (OR = 2.3, 95% CI: 1.5, 3.5) and iron deficiency (OR = 2.2, 95% CI: 1.4, 3.6) were independently associated with increased risk for anaemia. We also observed a seasonal variation in anaemia not mediated through the other factors studied. In a cohort in rural Bangladesh, anaemia at age 6 months was common and associated with infection, low birthweight and iron deficiency. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

Heart failure in patients with kidney disease and iron deficiency; the role of iron therapy.

PubMed

Cases Amenós, Aleix; Ojeda López, Raquel; Portolés Pérez, José María

Chronic kidney disease and anaemia are common in heart failure (HF) and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a posthoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin) and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Iron excess in recreational marathon runners.

PubMed

Mettler, S; Zimmermann, M B

2010-05-01

Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. We investigated the iron status of 170 male and female recreational runners participating in the Zürich marathon. Iron deficiency was defined either as a plasma ferritin (PF) concentration <15 microg/l (iron depletion) or as the ratio of the concentrations of transferrin receptor (sTfR) to PF (sTfR:log(PF) index) of > or =4.5 (functional iron deficiency). After excluding subjects with elevated C-reactive protein concentrations, iron overload was defined as PF >200 microg/l. Iron depletion was found in only 2 out of 127 men (1.6% of the male study population) and in 12 out of 43 (28.0%) women. Functional iron deficiency was found in 5 (3.9%) and 11 (25.5%) male and female athletes, respectively. Body iron stores, calculated from the sTfR/PF ratio, were significantly higher (P<0.001) among male compared with female marathon runners. Median PF among males was 104 microg/l, and the upper limit of the PF distribution in males was 628 microg/l. Iron overload was found in 19 out of 127 (15.0%) men but only 2 out of 43 in women (4.7%). Gender (male sex), but not age, was a predictor of higher PF (P<0.001). Iron depletion was present in 28% of female runners but in <2% of males, whereas one in six male runners had signs of iron overload. Although iron supplements are widely used by athletes in an effort to increase performance, our findings indicate excess body iron may be common in male recreational runners and suggest supplements should only be used if tests of iron status indicate deficiency.

Prenatal iron deficiency and monoamine oxidase A (MAOA) polymorphisms: combined risk for later cognitive performance in rhesus monkeys.

PubMed

Golub, Mari; Hogrefe, Casey

2014-03-01

Monoamine oxidase A (MAOA) gene polymorphisms resulting in high and low transcription rates are associated with individual differences in reward efficacy and response inhibition. Iron deficiency (ID) is the most frequent single-nutrient deficiency worldwide, and prenatal ID has recently been shown to carry a risk for lower mental development scores in infants. In this study, a potential interaction of MAOA genotype and prenatal ID was studied in young male rhesus monkeys. Cognitive tasks, including problem solving, responsiveness to reward and attention, were used to characterize the potential interaction of these two fetal risks. ID was induced by feeding rhesus monkey dams an iron-deficient (10 ppm, ID) or an iron-sufficient (100 ppm, IS) diet during gestation (n = 10/group). Subgroups of the ID and IS diet offspring had low-MAOA or high-MAOA transcription rate polymorphisms. ID combined with low-MAOA genotype showed distinctive effects on reward preference and problem solving while ID in hi-MAOA juveniles modified response inhibition. Given the incidence of ID and MAOA polymorphisms in humans, this interaction could be a significant determinant of cognitive performance.

Iron deficiency regulated OsOPT7 is essential for iron homeostasis in rice.

PubMed

Bashir, Khurram; Ishimaru, Yasuhiro; Itai, Reiko Nakanishi; Senoura, Takeshi; Takahashi, Michiko; An, Gynheung; Oikawa, Takaya; Ueda, Minoru; Sato, Aiko; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K

2015-05-01

The molecular mechanism of iron (Fe) uptake and transport in plants are well-characterized; however, many components of Fe homeostasis remain unclear. We cloned iron-deficiency-regulated oligopeptide transporter 7 (OsOPT7) from rice. OsOPT7 localized to the plasma membrane and did not transport Fe(III)-DMA or Fe(II)-NA and GSH in Xenopus laevis oocytes. Furthermore OsOPT7 did not complement the growth of yeast fet3fet4 mutant. OsOPT7 was specifically upregulated in response to Fe-deficiency. Promoter GUS analysis revealed that OsOPT7 expresses in root tips, root vascular tissue and shoots as well as during seed development. Microarray analysis of OsOPT7 knockout 1 (opt7-1) revealed the upregulation of Fe-deficiency-responsive genes in plants grown under Fe-sufficient conditions, despite the high Fe and ferritin concentrations in shoot tissue indicating that Fe may not be available for physiological functions. Plants overexpressing OsOPT7 do not exhibit any phenotype and do not accumulate more Fe compared to wild type plants. These results indicate that OsOPT7 may be involved in Fe transport in rice.

Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012.

PubMed

Shamah-Levy, Teresa; Villalpando, Salvador; Mejía-Rodríguez, Fabiola; Cuevas-Nasu, Lucía; Gaona-Pineda, Elsa Berenice; Rangel-Baltazar, Eduardo; Zambrano-Mujica, Norma

2015-01-01

To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut) 2012. Data came from a national probabilistic survey, representative from rural and urban areas, and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate concentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. The deficiency of folate was 1.9% (95%CI 1.3-2.8), B12 deficiency was 8.5% (95%CI 6.7-10.1) and iron deficiency was 29.4% (95%CI 26.5-32.2). No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2). The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico, while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies.

Iron Deficiency Anemia: Problems in Diagnosis and Prevention at the Population Level.

PubMed

Pasricha, Sant-Rayn; Drakesmith, Hal

2016-04-01

Anemia is common among people living in low- and middle-income countries, and alleviation of the global burden of anemia is an essential global health target over the next decade. Estimates have attributed about half the cases of anemia worldwide to iron deficiency; a range of other causes probably make a similar overall contribution. Individuals living in low-income settings experience a simultaneous high burden of infection with inflammation and iron deficiency. At least in children, iron supplementation exacerbates the risk of infection in both malaria-endemic and nonendemic low-income countries, whereas iron deficiency is protective against clinical and severe malaria. Copyright © 2016 Elsevier Inc. All rights reserved.

Iron Status of Pregnant Women in Rural and Urban Communities of Cross River State, South-South Nigeria.

PubMed

Okafor, I M; Okpokam, D C; Antai, A B; Usanga, E A

2017-03-06

Anaemia in pregnancy is a major public health problem in Nigeria. Iron deficiency is one of the major causes of anaemia in pregnancy.  Inadequate iron intake during pregnancy can be dangerous to both baby and mother. Iron status of pregnant women was assessed in two rural and one urban communities in Cross River State Nigeria. Packed cell volume, haemoglobin, mean cell haemoglobin, mean cell haemoglobin concentration, red cell count, serum iron, total iron binding capacity, transferrin saturation, serum ferritin, soluble transferrin receptor and soluble transferrin receptor/ferritin ratio were measured in plasma/serum of 170 pregnant women within the age range of 15-45 years. Seventy participants were from antenatal clinic of University of Calabar Teaching Hospital Calabar (urban community), 50 from St Joseph Hospital Ikot Ene (rural community) in Akpabuyo Local Government Area and the remaining 50 from University of Calabar Teaching Hospital   extension clinic in Okoyong (rural community), Odukpani Local Government Area of Cross River state. The prevalence of   anaemia, iron deficiency, iron depletion and iron deficiency anaemia were found to be significantly higher among pregnant women from the two rural communities when compared to the urban community. it was also observed that  the prevalence of  anaemia, iron deficiency, iron depletion and iron deficiency anaemia   were significantly higher (p<0.05) among pregnant women from Akpabuyo   38(76.00%),   20(40.00%),   23(46.0%)   ,   16(32.00%)   respectively followed   by  Okoyong 24(48.0%),  20(40.0%),  16(32.0%),  6(12.0)     and  then  those  from     Calabar  14(20%), 12(17.90%) , 14(20.0%).  The mean haemoglobin and haematocrit were significantly reduced in pregnant women from the two rural communities. Serum iron, serum ferritin and transferrin saturation showed no significant difference while total iron binding capacity and soluble transferrin receptor significantly increased among pregnant women from Okoyong when compared to those from Calabar. It was also shown that pregnant women in their third trimesters and multigravidae had the highest prevalence of iron depletion and iron deficiency anaemia while prevalence of iron deficiency and anaemia were higher in primigravidae and the pregnant women in their second trimester. In conclusion, this study has shown that the prevalence of anaemia and iron deficiency anaemia are higher among pregnant women in the rural communities when compared to those in the urban areas.

Functional Significance of Iron Deficiency. Annual Nutrition Workshop Series, Volume III.

ERIC Educational Resources Information Center

Enwonwu, Cyril O., Ed.

Iron deficiency anemia impairs cognitive performance, physical capacity, and thermoregulation. Recent evidence suggests that these functional impairments are also evident in subclinical nonanemic iron deficiency. Very little is known about the relevance of the latter to the health of blacks, who have been shown to have the highest prevalence of…

[Iron deficiency in ND-CKD: from diagnosis to treatment].

PubMed

Liberti, Maria Elena; Garofalo, Carlo; Sagliocca, Adelia; Borrelli, Silvio; Conte, Giuseppe; De Nicola, Luca; Minutolo, Roberto

2017-09-28

In non-dialysis-chronic kidney disease (CKD), iron deficiency is a frequent nutritional disorder due to either the greater tendency to occult gastrointestinal bleeding or to the chronic inflammatory state resulting in a reduced intestinal iron reabsorption through an increased synthesis of hepcidin. These phenomenon are responsible for a negative iron balance that compromises erythropoiesis and contributes to the pathogenesis of anemia in CKD. Several laboratory tests are now available to allow an adequate diagnosis of iron deficiency. Among the new parameters, the percentage of hypochromic red cells (% HYPO) and the reticulocyte hemoglobin content (CHr) are now considered as the most specific markers for diagnosing iron-deficiency erythropoiesis. Unfortunately, their implementation in clinical practice is limited by the scarce availability. In non-dialyzed CKD , subjects intolerant or non-responsive to oral iron therapy, can be effectively treated with novel intravenous iron preparations, such as iron carboxymaltose, that allow a complete and rapid correction of iron deficient anemia. Furthermore, this iron compound is associated with lower rate of adverse effects since the carbohydrate shell (carboxymaltose) is more stable than gluconate and saccarate thus reducing the release of free iron in the bloodstream. Of note, the possibility of administering this drug at high doses and reduced frequency decreases the risk of infusion reactions. Finally, a substantial economic saving mainly dependent on a reduction in indirect costs represents a further advantage in the use of iron carboxymaltose in this population. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.

PubMed

Tran, Phu V; Kennedy, Bruce C; Lien, Yu-Chin; Simmons, Rebecca A; Georgieff, Michael K

2015-02-15

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency. Copyright © 2015 the American Physiological Society.

Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus

PubMed Central

Kennedy, Bruce C.; Lien, Yu-Chin; Simmons, Rebecca A.; Georgieff, Michael K.

2014-01-01

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency. PMID:25519736

Reduced risk for placental malaria in iron deficient women

PubMed Central

2011-01-01

Background Nutritional iron deficiency may limit iron availability to the malaria parasite reducing infection risk, and/or impair host immunity thereby increasing this risk. In pregnant women, there is evidence of an adverse effect with iron supplementation, but the few reported studies are strongly confounded. Methods A case control study in pregnant Malawian women was undertaken in Chikhwawa southern Malawi in order to describe iron status in relation to placental malaria controlling for several confounding factors. Pregnancy characteristics were obtained and a blood sample at delivery. A full blood count was performed and serum ferritin and transferrin receptor quantified by enzyme-linked immunoassay. DNA analysis was used to identify genetic polymorphisms for ABO phenotype, hemoglobin HbS, and glucose -6 phosphate dehydrogenase deficiency. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection. Results 112 cases with placental malaria were identified and 110 women with no evidence of placental infection. Iron deficiency was less frequent in women with placental Plasmodium falciparum infection. In those with acute, chronic or past placental infections the odds ratio for iron deficiency was 0.4, 95% CI 0.2-0.8, p = 0.01; for acute and chronic infections 0.4, 0.2-0.8, p = 0.006; for acute infection 0.3, 0.1-0.7, p = 0.001. The association was greater in multigravidae. Conclusion Women with either acute, or acute and chronic placental malaria were less likely to have iron deficiency than women without placental malaria infection There is a priority to establish if reversing iron deficiency through iron supplementation programs either prior to or during pregnancy enhances malaria risk. PMID:21345193

Iron deficiency across chronic kidney disease stages: Is there a reverse gender pattern?

PubMed

Aoun, Mabel; Karam, Rita; Sleilaty, Ghassan; Antoun, Leony; Ammar, Walid

2018-01-01

In non-dialysis chronic kidney disease patients, looking for iron deficiency is highly variable in practice and there is a great variability regarding the cutoffs used to treat iron deficiency. The aim of this study is to investigate the degree of iron deficiency in non-dialysis chronic kidney disease patients on erythropoiesis-stimulating agents. We included all non-dialysis chronic kidney disease patients that applied to the Lebanese Ministry of Public Health for erythropoiesis-stimulating agents' coverage during a 5-month period. Iron requirement was assessed based on two guidelines' target-to-treat cutoffs: 1-ferritin <100 ng/ml and/or TSAT < 20% (KDOQI 2006), 2- ferritin ≤500 ng/ml and TSAT ≤30% (KDIGO 2012). A total of 238 CKD patients were included over 5 months. All patients had a ferritin level in their record and 64% had an available TSAT. Median age was 71.0 (59.8-79.3) years and 61.8% were female. All had an eGFR<60 ml/min. The proportion of patients found to require iron therapy ranged between 48 and 78% with a trend towards higher values when using KDIGO-based criteria. Using ANCOVA test, inverse normal transformations of ferritin and TSAT showed a reverse pattern between men and women with women being more iron deficient in the early stage. Iron deficiency is highly prevalent in non-dialysis chronic kidney disease patients on erythropoiesis-stimulating agents' therapy. These findings reflect a lack in effective iron supplementation when managing anemia in pre-dialysis patients, especially in men at advanced stages. Renal societies should spread awareness about iron deficiency screening in those patients.

Unexplained chronic leukopenia treated with oral iron supplements.

PubMed

Abuirmeileh, Ayman; Bahnassi, Anas; Abuirmeileh, Amjad

2014-04-01

A 67-year-old woman known to have iron deficiency anemia and persistent unexplained chronic leukopenia was cared for by our medical center for about 16 years. During this period she was examined thoroughly and diagnosed to have chronic idiopathic neutropenia (also known as chronic benign neutropenia). Her iron deficiency was attributed to nutritional factors and she was non-compliant with her oral iron supplements. The patient fully received her iron supplement medication by nursing staff for two and a half months during an unexpected prolonged hospital stay after her suffering an acute ischemic cerebrovascular accident. An astonishing outcome was that in addition to having her iron deficiency anemia treated, her long-term unexplained neutropenia was also corrected. Some patients diagnosed with chronic idiopathic neutropenia and clinically present as having unexplained chronic neutropenia might actually be suffering from a form of not yet described iron deficiency induced neutropenia.

Evaluation of Ferric and Ferrous Iron Therapies in Women with Iron Deficiency Anaemia

PubMed Central

Berber, Ilhami; Erkurt, Mehmet Ali; Aydogdu, Ismet; Kuku, Irfan

2014-01-01

Introduction. Different ferric and ferrous iron preparations can be used as oral iron supplements. Our aim was to compare the effects of oral ferric and ferrous iron therapies in women with iron deficiency anaemia. Methods. The present study included 104 women diagnosed with iron deficiency anaemia after evaluation. In the evaluations performed to detect the aetiology underlying the iron deficiency anaemia, it was found and treated. After the detection of the iron deficiency anaemia aetiology and treatment of the underlying aetiology, the ferric group consisted of 30 patients treated with oral ferric protein succinylate tablets (2 × 40 mg elemental iron/day), and the second group consisted of 34 patients treated with oral ferrous glycine sulphate tablets (2 × 40 mg elemental iron/day) for three months. In all patients, the following laboratory evaluations were performed before beginning treatment and after treatment. Results. The mean haemoglobin and haematocrit increases were 0.95 g/dL and 2.62% in the ferric group, while they were 2.25 g/dL and 5.91% in the ferrous group, respectively. A significant difference was found between the groups regarding the increase in haemoglobin and haematocrit values (P < 0.05). Conclusion. Data are submitted on the good tolerability, higher efficacy, and lower cost of the ferrous preparation used in our study. PMID:25006339

METABOLISM OF IRON STORES

PubMed Central

SAITO, HIROSHI

2014-01-01

ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since the pioneering research by Shoden in 1953. However, we recently developed a new method for determining ferritin iron and hemosiderin iron by computer-assisted serum ferritin kinetics. Serum ferritin increase or decrease curves were measured in patients with normal storage iron levels (chronic hepatitis C and iron deficiency anemia treated by intravenous iron injection), and iron overload (hereditary hemochromatosis and transfusion dependent anemia). We thereby confirmed the existence of two iron pathways where iron flows followed the numbered order (1) labile iron, (2) ferritin and (3) hemosiderin in iron deposition and mobilization among many previously proposed but mostly unproven routes. We also demonstrated the increasing and decreasing phases of ferritin iron and hemosiderin iron in iron deposition and mobilization. The author first demonstrated here the change in proportion between pre-existing ferritin iron and new ferritin iron synthesized by removing iron from hemosiderin in the course of iron removal. In addition, the author disclosed the cause of underestimation of storage iron turnover rate which had been reported by previous investigators in estimating storage iron turnover rate of normal subjects. PMID:25741033

Iron status and its determinants in a nationally representative sample of pregnant women.

PubMed

Vandevijvere, Stefanie; Amsalkhir, Sihame; Van Oyen, Herman; Egli, Ines; Ines, Egli; Moreno-Reyes, Rodrigo

2013-05-01

Iron-deficiency anemia is associated with adverse neonatal health outcomes. Iron status and its determinants were assessed in a representative sample of Belgian pregnant women. Blood samples were collected and a questionnaire was completed face-to-face. Hemoglobin (Hb) and mean cell volume were measured using a Beckman Coulter Hematology Analyzer and serum ferritin (SF) and transferrin receptor (sTfr) concentrations by immunoassay. In total, 55 obstetric clinics and 1,311 pregnant women were included. Approximately 40% of third-trimester and 6% of first-trimester women had SF levels less than 15 μg/L. Approximately 21% of third-trimester and 4% of first-trimester women had anemia (Hb <110 g/L). Of the third-trimester women, 23% were iron-deficient nonanemic (SF <15 μg/L and Hb ≥110 g/L), 16% had iron-deficiency anemia (SF <15 μg/L and Hb <110 g/L), and approximately 7% had tissue iron deficiency (sTfr >8.5 mg/L). The median body iron stores were 8.1 mg/kg among first-trimester women, but only 3.6 mg/kg among third-trimester women. SF levels were significantly positively associated with age and education level, and were higher among nulliparous women and lower among North-African women. sTfr concentrations were significantly negatively associated with age and were lower among smokers, nulliparous women, and women who planned their pregnancy. Despite the fact that two thirds of Belgian pregnant women took iron-containing supplements, iron deficiency and iron-deficiency anemia were frequent in third-trimester women. The World Health Organization regards this as a moderate public health problem. National iron supplementation guidelines are needed in Belgium to optimize iron status during pregnancy. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

[Iron deficiency in infants and toddlers: impact on health and preventive strategies].

PubMed

Moráis López, A; Dalmau Serra, J

2011-06-01

Infants and toddlers represent a risk population for iron deficiency (ID), due to their relatively high requirements, which are frequently associated with a poor intake of iron-rich foods. A possible association between ID and impaired cognitive and psychomotor development has been described, and it has been suggested that some of these effects can be irreversible. For this reason, prevention of ID has become a subject of much concern. To promote an adequate dietetic iron intake is the most important approach for the prevention of ID. Exclusive breast-feeding provides adequate amounts of iron during the first 4-6 months of life, and iron-fortified formula should be used when an alternative is necessary. Fortified cereals and foods containing haem iron, such as meat, should be introduced early in complementary feeding. In toddlers, iron requirements can be satisfied with a daily consumption of at least one serving of iron-containing foods, along with enhancers of iron absorption. When daily requirements are not properly met by food intake, and in some high-risk populations, screening for ID and iron supplementation should be considered. Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

High-dose intravenously administered iron versus orally administered iron in blood donors with iron deficiency: study protocol for a randomised, controlled trial.

PubMed

Macher, Susanne; Drexler, Camilla; Lindenau, Ines; Sareban, Nazanin; Schlenke, Peter; Amrein, Karin

2016-10-28

About 2-3 % of the population participates in blood donation programmes. Each whole blood donation or ten apheresis donations cause a loss of 200-250 mg of iron. As a result, one of the most common risks of regular blood donors is iron deficiency. Although this has been known for decades, in most countries, iron status is currently not assessed or treated in this population. Premenopausal women are particularly affected, as they have lower iron reserves and higher daily requirements. Besides anaemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Current iron preparations for intravenous administration are well tolerated and allow for application of large doses up to 1 g in one visit. Our hypothesis is that in blood donors with iron deficiency, intravenously administered iron is more efficient and as safe as oral iron supplementation. Since anaemia is one of the most frequent reasons for permanent or intermittent donor deferral, maintaining an iron-replete donor pool may help to prevent shortages in blood supply and to avoid iron deficiency-related comorbidities. In this randomised clinical trial we include male and female blood donors aged ≥18 and ≤65 years with a ferritin value of ≤30 ng/ml. Stratified by gender, participants are randomized with a web-based randomisation tool in a 1:1 ratio to either 1 g of intravenously administered ferric carboxymaltose or 10 g of iron fumarate supplements at one to two daily doses of 100 mg each. Eight to 12 weeks after the first visit, iron status, blood count and symptoms are assessed in both groups. The primary endpoint is the difference in transferrin saturation (%) following the intervention between both groups. Secondary endpoints include other parameters of iron metabolism and red blood cell count, the number of patients with drug-related adverse events, and subjective symptoms including those of the restless legs syndrome, quality of life, and fatigue. Iron supplementation administered intravenously in non-anaemic but iron-deficient blood donors could represent an effective strategy to protect blood donors from comorbidities related with iron deficiency and therefore improve blood donor wellbeing. Furthermore, iron supplementation will help to maintain an iron-replete blood donor pool. EudraCT: 2013-000327-14, Clinical Trials Identifier: NCT01787526 . Registered on 6 February 2013.

Cerebral sinovenous thrombosis associated with iron deficiency anemia secondary to severe menorrhagia: a case report.

PubMed

Corrales-Medina, Fernando F; Grant, Leon; Egas-Bejar, Daniela; Valdivia-Ascuna, Zoila; Rodriguez, Nidra; Mancias, Pedro

2014-09-01

Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia associated with cerebral sinovenous thrombosis in teenagers is rare. We present a teenage patient with complete thrombosis of the vein of Galen, straight sinus, and left internal cerebral vein associated with iron deficiency anemia due to severe menorrhagia. Mechanisms that can explain the association between iron deficiency anemia and thrombosis are discussed. © The Author(s) 2013.

[Micronutrient deficiencies and linear growth: a systematic review of observational studies].

PubMed

Pedraza, Dixis Figueroa; Rocha, Ana Carolina Dantas; Sales, Márcia Cristina

2013-11-01

This article seeks to evaluate the association of iron, vitamin A and zinc deficiencies with linear growth retardation. A systematic review of electronic databases in PubMed, LILACS and SciELO was conducted. Scientific papers published between January 1995 and March 2010 were selected, inserting the key words: (growth OR nutritional status) AND (child, preschool OR infant) AND (zinc AND iron AND vitamin A) OR (zinc AND iron) OR (zinc AND vitamin A) OR (iron AND vitamin A). Fourteen observational design studies were reviewed. In the cohort studies (two), one indicated a statistical association between iron levels and stunting; and the other revealed a statistical association between serum ferritin concentrations and an increase in height. Ten cross-sectional studies investigated the statistical association between micronutrient deficiencies and stunting, three of which resulted in an association with iron, two with vitamin A and none with zinc. Elucidation of the association between stunting and iron, vitamin A and zinc deficiencies involves difficulties of a biological nature and also related to the magnitude of these deficiencies, indicating the importance of a methodological standardization of the studies.

Effect of iron deficiency anemia in pregnancy on child mental development in rural China.

PubMed

Chang, Suying; Zeng, Lingxia; Brouwer, Inge D; Kok, Frans J; Yan, Hong

2013-03-01

To determine the impact of iron deficiency anemia (IDA) in pregnancy on young child development. A 2-year follow-up of 850 children born to women who participated in a double-blind cluster randomized controlled trial of prenatal micronutrient supplementation in western rural China. These women were randomly assigned to receive either daily folic acid, iron/folic acid (60 mg iron), or multiple micronutrients (with 30 mg iron) during pregnancy. Children were categorized into the prenatal-IDA and prenatal-non-IDA groups based on the mother's hemoglobin in the third trimester. Each group contained 3 subgroups based on mother's treatment: folic acid, iron/folic acid, and multiple micronutrients. Bayley scales of infant development were administered to the children to assess their development at 3, 6, 12, 18, and 24 months of age. Compared with the prenatal-non-IDA group, the prenatal-IDA group showed a significantly lower mental development index at 12, 18, and 24 months of age. The adjusted mean difference was 5.8 (95% confidence interval [CI], 1.1-10.5), 5.1 (95% CI, 1.2-9.0), and 5.3 (95% CI, 0.9-9.7), respectively. Further analysis showed that the mental development indexes in the prenatal-IDA group and prenatal-non-IDA group were similar with supplementation of iron/folic acid but were significantly lower in the prenatal-IDA group with supplementation of folic acid or multiple micronutrients. Prenatal IDA in the third trimester is associated with mental development of the child. However, prenatal supplementation with sufficient iron protects child development even when the woman's IDA was not properly corrected in pregnancy.

[Review by expert group in the diagnosis and treatment of anemia in pregnant women. Federación Mexicana de Colegios de Obstetricia y Ginecología].

PubMed

Montoya Romero, Jose de Jesús; Castelazo Morales, Ernesto; Valerio Castro, Emilio; Velázquez Cornejo, Gerardo; Nava Muñoz, David Antonio; Escárcega Preciado, Jaime Arturo; Montoya Cossío, Javier; Pichardo Villalón, Guadalupe Mireya; Maldonado Aragón, Aristeo; Santana García, Héctor Rogelio; Fajardo Dueñas, Sergio; Mondragón Galindo, César Germán; García Lee, Teresa; García, Angel; Hernández de Morán, Marcela; Chávez Güitrón, Luis Eduardo; Jiménez Gutiérrez, Carlos

2012-09-01

According to data from the World Health Organization and UNICEF from year 2009, iron deficiency is the most widespread nutritional deficiency worldwide. This deficiency causes an imbalance between needs and iron supply, which consequently results in anemia. Around the world, two million people suffer from anemia, half of which is due to iron deficiency. The most impacted groups are children and teenagers, due to their highest requirements derived from the growing process, and women in their reproductive age, due to their loss of iron derived from menstruating or to their highest iron needs during pregnancy. This increase in needs is not satisfied by the regular diet, since it includes an insufficient amount and/or low bioavailability of iron. To share with the medical community treating pregnant women the experience of an expert group so that they always bear in mind the repercussions caused by anemia during pregnancy, know more about the diagnostic possibilities and have a reference point for prescribing iron supplements. The consensus method was used through the expert panel group technique. Two rounds were taken for structuring the clinical questions. The first one was to facilitate working groups their focusing in the clinical topics and the population of interest; the second one was to aid in posing specific questions observing the Patient, Intervention, Compare and Outcome (PICO) structure. The primary and clinical secondary study variables were defined by the working groups from the previously developed questions and during the face-to-face working period, according to the natural history of the disease: risk factors, diagnostic classification, (either pharmacological or non pharmacological) treatment and prognosis. The level of evidence and clinical recommendation was classified based on the Evidence Classification Level and Clinical Recommendation of the Medicine Group based on Evidence from Oxford University. In Mexico, 20.6% of pregnant women suffer from anemia, especially those between 15 and 16 years old, who prevail in 42.4% and 34.3% percent, respectively. Almost half the cases are due to iron deficiency. This type of anemia is associated with a higher risk of pre-term delivery, of low birth weight and perinatal death. The first assessment of an anemic pregnant woman shall include the medical history, a physical examination and the quantification of the erythrocyte indices, serum concentrations of iron and ferritin. The measurement of this last one has the highest sensitivity and specificity for diagnosing iron deficiency. Daily oral iron supplementation, at a 60-to-120 mg dosage, may correct most of mild-to-moderate anemias. The most appropriate treatment is with iron salts (iron sulfate, polimaltose iron complex or iron fumarate). In case of intolerance to iron sulfate or fumarate, polimaltose iron is a better tolerated option. Treatment shall be administered until the hemoglobin values are > 10.5 g and ferritin is between 300 and 360 microg/dL, and such levels shall be observed for at least one year. Parenteral administration is an alternative for patients with a severe intolerance to oral administration; even when the possibility of anaphylaxis shall be considered it is lower when using ferrous sacarate. Transfusion is reserved for patients with hemoglobin lower than 7 g/dL or having an imminent cardio-respiratory decompensation. Iron deficiency is the highest prevailing nutritional deficiency worldwide and its consequences during pregnancy may be highly risky for both the mother and her child. Anemia diagnosis may easily be achieved through a blood analysis including the serum ferritin determination. Serum iron measurement shall not be used as the only marker to set the diagnosis. It is important to rule out other causes, in addition to the deficiencies, which produce anemia in a patient. It is essential to suggest the administration of iron supplements not only during the antenatal period but also after birth o even after a miscarriage to fulfill the need for depleted iron. In severe anemias (hemoglobin being lower than 9.0 g/L), iron doses higher than 120 mg a day may be required. Treatment shall always begin orally, and if this is not well tolerated, parenteral administration shall be used.

Disruption of the potassium channel regulatory subunit KCNE2 causes iron-deficient anemia

PubMed Central

Salsbury, Grace; Cambridge, Emma L.; McIntyre, Zoe; Arends, Mark J.; Karp, Natasha A.; Isherwood, Christopher; Shannon, Carl; Hooks, Yvette; Ramirez-Solis, Ramiro; Adams, David J.; White, Jacqueline K.; Speak, Anneliese O.

2014-01-01

Iron homeostasis is a dynamic process that is tightly controlled to balance iron uptake, storage, and export. Reduction of dietary iron from the ferric to the ferrous form is required for uptake by solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 (Slc11a2) into the enterocytes. Both processes are proton dependent and have led to the suggestion of the importance of acidic gastric pH for the absorption of dietary iron. Potassium voltage-gated channel subfamily E, member 2 (KCNE2), in combination with potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1), form a gastric potassium channel essential for gastric acidification. Deficiency of either Kcne2 or Kcnq1 results in achlorhydia, gastric hyperplasia, and neoplasia, but the impact on iron absorption has not, to our knowledge, been investigated. Here we report that Kcne2-deficient mice, in addition to the previously reported phenotypes, also present with iron-deficient anemia. Interestingly, impaired function of KCNQ1 results in iron-deficient anemia in Jervell and Lange-Nielsen syndrome patients. We speculate that impaired function of KCNE2 could result in the same clinical phenotype. PMID:25127743

New perspectives on the regulation of iron absorption via cellular zinc concentrations in humans.

PubMed

Knez, Marija; Graham, Robin D; Welch, Ross M; Stangoulis, James C R

2017-07-03

Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.

Hookworm infection

MedlinePlus

... intestinal wall and suck blood, which results in iron deficiency anemia and protein loss. Adult worms and larvae ... problems that may result from hookworm infection include: Iron deficiency anemia , caused by loss of blood Nutritional deficiencies ...

Endothelial cells are critical regulators of iron transport in a model of the human blood-brain barrier.

PubMed

Chiou, Brian; Neal, Emma H; Bowman, Aaron B; Lippmann, Ethan S; Simpson, Ian A; Connor, James R

2018-01-01

Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood-brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release. Our model reveals a new function for H-ferritin to transport iron across the BBB by binding to the T-cell immunoglobulin and mucin receptor 1. We show that huECs secrete both transferrin and H-ferritin, which can serve as iron sources for the brain. Based on our data, brain iron status can exert control of iron transport across the endothelial cells that constitute the BBB. These data address a number of pertinent questions such as how brain iron uptake is regulated at the regional level, the source of iron delivery to the brain, and the clinical strategies for attempting to treat brain iron deficiency.

Oral versus intravenous iron therapy in patients with inflammatory bowel disease and iron deficiency with and without anemia in Germany – a real-world evidence analysis

PubMed Central

Haas, Jennifer Scarlet; Ong, Siew Hwa; Borchert, Kathrin; Hardt, Thomas; Lechat, Elmira; Nip, Kerry; Foerster, Douglas; Braun, Sebastian; Baumgart, Daniel C

2018-01-01

Background Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. Aim This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. Methods IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. Results In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48%) and ID/A-related hospitalizations (5% vs 14%) than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were calculated to be €367. While higher expenditure for medication (€1,876) was observed in the intravenous iron group, the inpatient setting achieved most cost savings (€1,887). Conclusion IBD patients receiving intravenous iron were less frequently hospitalized and incurred lower total health care costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains. PMID:29440920

Oral versus intravenous iron therapy in patients with inflammatory bowel disease and iron deficiency with and without anemia in Germany - a real-world evidence analysis.

PubMed

Stein, Jürgen; Haas, Jennifer Scarlet; Ong, Siew Hwa; Borchert, Kathrin; Hardt, Thomas; Lechat, Elmira; Nip, Kerry; Foerster, Douglas; Braun, Sebastian; Baumgart, Daniel C

2018-01-01

Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48%) and ID/A-related hospitalizations (5% vs 14%) than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were calculated to be €367. While higher expenditure for medication (€1,876) was observed in the intravenous iron group, the inpatient setting achieved most cost savings (€1,887). IBD patients receiving intravenous iron were less frequently hospitalized and incurred lower total health care costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains.

Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia.

PubMed

Bah, Amat; Pasricha, Sant-Rayn; Jallow, Momodou W; Sise, Ebrima A; Wegmuller, Rita; Armitage, Andrew E; Drakesmith, Hal; Moore, Sophie E; Prentice, Andrew M

2017-06-01

Background: Antenatal anemia is a risk factor for adverse maternal and fetal outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal anemia is considered responsive to iron; identifying women in need of iron may help target interventions. Iron absorption is governed by the iron-regulatory hormone hepcidin. Objective: We sought to characterize changes in hepcidin and its associations with indexes of iron stores, erythropoiesis, and inflammation at weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential as an index of iron deficiency. Methods: We measured hemoglobin and serum hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein (CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women recruited to a randomized controlled trial. Associations with hepcidin were measured by using linear regression, and hepcidin's diagnostic test accuracy [area under the receiver operating characteristic curve (AUC ROC ), sensitivity, specificity, cutoffs] for iron deficiency at each time point was analyzed. Results: The prevalence of anemia increased from 34.6% at 14 wk of gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP declined over pregnancy. The AUC ROC values for hepcidin to detect iron deficiency (defined as ferritin <15 μg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk, respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of iron deficiency. Conclusions: In Gambian pregnant women, hepcidin appears to be a useful diagnostic test for iron deficiency and may enable the identification of cases for whom iron would be beneficial. Hepcidin suppression in the second trimester suggests a window for optimal timing for antenatal iron interventions. Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial was registered at www.isrctn.com as ISRCTN49285450.

Developmental Scores of Iron Deficient Infants and the Effects of Therapy.

ERIC Educational Resources Information Center

Honig, Alice S.; Oski, Frank A.

This study investigated the cognitive and behavioral functions associated with iron deficiency anemia in infants and toddlers and the short-term effects of therapy on such behaviors. Subjects were 24 iron deficient and anemic infants, 9 to 26 months old. The subjects were randomly assigned to a treatment or control group. The Bayley Scales of…

Infant Iron Deficiency, Child Affect, and Maternal Unresponsiveness: Testing the Long-Term Effects of Functional Isolation

ERIC Educational Resources Information Center

East, Patricia; Lozoff, Betsy; Blanco, Estela; Delker, Erin; Delva, Jorge; Encina, Pamela; Gahagan, Sheila

2017-01-01

Children who are iron deficient (ID) or iron-deficient anemic (IDA) have been shown to seek and receive less stimulation from their caregivers, contributing to "functional isolation". Over time, the reduced interactions between child and caregiver are thought to interfere with the acquisition of normative social competencies and…

Menorrhagia (Heavy Menstrual Bleeding)

MedlinePlus

... red blood cells to carry oxygen to tissues. Iron deficiency anemia occurs as your body attempts to make ... iron levels enough to increase the risk of iron deficiency anemia. Signs and symptoms include pale skin, weakness ...

A high prevalence of zinc- but not iron-deficiency among women in rural Malawi: a cross-sectional study.

PubMed

Siyame, Edwin W P; Hurst, Rachel; Wawer, Anna A; Young, Scott D; Broadley, Martin R; Chilimba, Allan D C; Ander, Louise E; Watts, Michael J; Chilima, Benson; Gondwe, Jellita; Kang'ombe, Dalitso; Kalimbira, Alexander; Fairweather-Tait, Susan J; Bailey, Karl B; Gibson, Rosalind S

2013-01-01

Zinc deficiency is often associated with nutritional iron deficiency (ID), and may be exacerbated by low selenium status. To investigate risk of iron and zinc deficiency in women with contrasting selenium status. In a cross-sectional study, 1-day diet composites and blood samples were collected from self-selected Malawian women aged 18-50 years from low- (Zombwe) (n=60) and high-plant-available soil selenium (Mikalango) (n=60) districts. Diets were analyzed for trace elements and blood for biomarkers. Zinc deficiency (>90 %) was greater than ID anemia (6 %), or ID (5 %), attributed to diets low in zinc (median 5.7 mg/day) with high phytate:zinc molar ratios (20.0), but high in iron (21.0 mg/day) from soil contaminant iron. Zombwe compared to Mikalango women had lower (p<0.05) intakes of selenium (6.5 vs. 55.3 µg/day), zinc (4.8 vs. 6.4 mg/day), iron (16.6 vs. 29.6 mg/day), lower plasma selenium (0.72 vs. 1.60 µmol/L), and higher body iron (5.3 vs. 3.8 mg/kg), although plasma zinc was similar (8.60 vs. 8.87 µmol/L). Body iron and plasma zinc were positive determinants of hemoglobin. Risk of zinc deficiency was higher than ID and was shown not to be associated with selenium status. Plasma zinc was almost as important as body iron as a hemoglobin determinant.

Deficient dietary iron intakes among women and children in Russia: evidence from the Russian Longitudinal Monitoring Survey.

PubMed Central

Kohlmeier, L; Mendez, M; Shalnova, S; Martinchik, A; Chakraborty, H; Kohlmeier, M

1998-01-01

OBJECTIVES: This study evaluated the iron sufficiency of the Russian diet. METHODS: Data were obtained from 24-hour dietary recalls conducted in 4 rounds (1992 through 1994) of a nationally representative longitudinal survey of 10,548 women and children. Iron bioavailability was estimated via algorithms adjusting for enhancers (heme, vitamin C) and inhibitors (tannins in tea, phytates in grains) consumed at the same meal. RESULTS: Dietary iron intakes were deficient in the most vulnerable groups: young children and women of reproductive age. Poverty status was strongly associated with deficiency. After adjustment for enhancers and inhibitors, estimated bioavailable iron intakes at 3% to 4% of total iron were inadequate in all women and children. CONCLUSIONS: These dietary data suggest that Russian women and children are at high risk of iron deficiency. Grain products rich in phytates, which inhibit absorption, were the major food source of iron in Russia. High intakes of tea and low consumption of vitamin C also inhibited iron bioavailability. Since changes in eating behavior could potentially double iron bioavailability, educational programs should be explored as a strategy for improving iron nutriture. PMID:9550997

Haemolysis and Perturbations in the Systemic Iron Metabolism of Suckling, Copper-Deficient Mosaic Mutant Mice – An Animal Model of Menkes Disease

PubMed Central

Lenartowicz, Małgorzata; Starzyński, Rafał R.; Krzeptowski, Wojciech; Grzmil, Paweł; Bednarz, Aleksandra; Ogórek, Mateusz; Pierzchała, Olga; Staroń, Robert; Gajowiak, Anna; Lipiński, Paweł

2014-01-01

The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1). This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb) from the circulation, as well as the induction of haem oxygenase 1 (HO1) in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism. PMID:25247420

Deletion of Iron Regulatory Protein 1 Causes Polycythemia and Pulmonary Hypertension in Mice through Translational De-repression of HIF2α

PubMed Central

Ghosh, Manik C.; Zhang, De-Liang; Jeong, Suh Young; Kovtunovych, Gennadiy; Ollivierre-Wilson, Hayden; Noguchi, Audrey; Tu, Tiffany; Senecal, Thomas; Robinson, Gabrielle; Crooks, Daniel R.; Tong, Wing-Hang; Ramaswamy, Kavitha; Singh, Anamika; Graham, Brian B.; Tuder, Rubin M.; Yu, Zu-Xi; Eckhaus, Michael; Lee, Jaekwon; Springer, Danielle A.; Rouault, Tracey A.

2013-01-01

SUMMARY Iron regulatory proteins 1 and 2 (Irps) post-transcriptionally control the expression of transcripts that contain iron responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor and hypoxia inducible factor 2α (HIF2α). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2α protein expression in kidneys of Irp1−/− mice, which led to increased erythropoietin (EPO) expression, polycythemia and concomitant tissue iron deficiency. Increased HIF2α expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1−/− mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. PMID:23395173

Anaemia and iron deficiency in peri-urban school children born in a National HIV Prevention Programme in Zimbabwe: A cross-sectional study.

PubMed

Kuona, P; Mashavave, G; Kandawasvika, G Q; Mapingure, M P; Masanganise, M; Chandiwanda, P; Munjoma, M; Nathog, K J; Stray-Pedersen, B

2014-01-01

To determine the prevalence of anaemia, iron deficiency and iron deficiency anaemia in school children who were born in a national HIV prevention programme. This was a community based cross-sectional study. A resource poor peri-urban setting with high prevalence of HIV infection. School aged children six to 10 years old who were born in a national mother-to-child HIV prevention programme. Haemoglobin (Hb), serum Ferritin (F) and serum Transferrin receptor (sTfR) levels. Three hundred and eighteen children were recruited including 21 HIV positive. The prevalence of anaemia (Hb < 11.5 grams per litre), iron deficiency (F<15 micrograms per litre) and iron deficiency anaemia (Hb < 11.5 g/L and either F < 15 μg/L or sTfR > 8.3 μg/L) were 15%, 4% and 2% respectively. When a higher cut-off for ferritin of 30 micrograms per litre was applied to adjust for high infection disease burden, iron deficiency prevalence increased to 32% and iron deficiency anaemia increased to 5%. Anaemia was 4.9 (C.I 1.9-12.4) times more likely to occur in HIV infected children compared to the HIV uninfected children. Maternal HIV status at birth was not related to presence of anaemia in the school children. Anaemia was of mild public health significance in this cohort of children. Iron deficiency anaemia contributed less than a quarter of the cases of anaemia. HIV infection was an important determinant for presence of anaemia. Therefore continued efforts to eliminate paediatric HIV infection as a way of reducing anaemia in children are essential.

Soybean Fe-S cluster biosynthesis regulated by external iron or phosphate fluctuation.

PubMed

Qin, Lu; Wang, Meihuan; Chen, Liyu; Liang, Xuejiao; Wu, Zhigeng; Lin, Zhihao; Zuo, Jia; Feng, Xiangyang; Zhao, Jing; Liao, Hong; Ye, Hong

2015-03-01

Iron and phosphorus are essential for soybean nodulation. Our results suggested that the deficiency of Fe or P impairs nodulation by affecting the assembly of functional iron-sulfur cluster via different mechanisms. Iron (Fe) and phosphorus (P) are important mineral nutrients for soybean and are indispensable for nodulation. However, it remains elusive how the pathways of Fe metabolism respond to the fluctuation of external Fe or P. Iron is required for the iron-sulfur (Fe-S) cluster assembly in higher plant. Here, we investigated the expression pattern of Fe-S cluster biosynthesis genes in the nodulated soybean. Soybean genome encodes 42 putative Fe-S cluster biosynthesis genes, which were expressed differently in shoots and roots, suggesting of physiological relevance. Nodules initiated from roots of soybean after rhizobia inoculation. In comparison with that in shoots, iron concentration was three times higher in nodules. The Fe-S cluster biosynthesis genes were activated and several Fe-S protein activities were increased in nodules, indicating that a more effective Fe-S cluster biosynthesis is accompanied by nodulation. Fe-S cluster biosynthesis genes were massively repressed and some Fe-S protein activities were decreased in nodules by Fe deficiency, leading to tiny nodules. Notably, P deficiency induced a similar Fe-deficiency response in nodules, i.e, certain Fe-S enzyme activity loss and tiny nodules. However, distinct from Fe-deficient nodules, higher iron concentration was accumulated and the Fe-S cluster biosynthesis genes were not suppressed in the P-deficiency-treated nodules. Taken together, our results showed that both Fe deficiency and P deficiency impair nodulation, but they affect the assembly of Fe-S cluster maybe via different mechanisms. The data also suggested that Fe-S cluster biosynthesis likely links Fe metabolism and P metabolism in root and nodule cells of soybean.

Differences on Brain Connectivity in Adulthood Are Present in Subjects with Iron Deficiency Anemia in Infancy

PubMed Central

Algarin, Cecilia; Karunakaran, Keerthana Deepti; Reyes, Sussanne; Morales, Cristian; Lozoff, Betsy; Peirano, Patricio; Biswal, Bharat

2017-01-01

Iron deficiency continues to be the most prevalent micronutrient deficit worldwide. Since iron is involved in several processes including myelination, dopamine neurotransmission and neuronal metabolism, the presence of iron deficiency anemia (IDA) in infancy relates to long-lasting neurofunctional effects. There is scarce data regarding whether these effects would extend to former iron deficient anemic human adults. Resting state functional magnetic resonance imaging (fMRI) is a novel technique to explore patterns of functional connectivity. Default Mode Network (DMN), one of the resting state networks, is deeply involved in memory, social cognition and self-referential processes. The four core regions consistently identified in the DMN are the medial prefrontal cortex, posterior cingulate/retrosplenial cortex and left and right inferior parietal cortex. Therefore to investigate the DMN in former iron deficient anemic adults is a particularly useful approach to elucidate de long term effects on functional brain. We conducted this research to explore the connection between IDA in infancy and altered patterns of resting state brain functional networks in young adults. Resting-state fMRI studies were performed to 31 participants that belong to a follow-up study since infancy. Of them, 14 participants were former iron deficient anemic in infancy and 17 were controls, with mean age of 21.5 years (±1.5) and 54.8% were males. Resting-state fMRI protocol was used and the data was analyzed using the seed based connectivity statistical analysis to assess the DMN. We found that compared to controls, former iron deficient anemic subjects showed posterior DMN decreased connectivity to the left posterior cingulate cortex (PCC), whereas they exhibited increased anterior DMN connectivity to the right PCC. Differences between groups were also apparent in the left medial frontal gyrus, with former iron deficient anemic participants having increased connectivity with areas included in DMN and dorsal attention networks. These preliminary results suggest different patterns of functional connectivity between former iron deficient anemic and control young adults. Indeed, IDA in infancy, a common nutritional problem among human infants, may turn out to be important for understanding the mechanisms of cognitive alterations, common in adulthood. PMID:28326037

Sleep alterations and iron deficiency anemia in infancy

PubMed Central

Peirano, Patricio D.; Algarín, Cecilia R.; Chamorro, Rodrigo A.; Reyes, Sussanne C.; Durán, Samuel A.; Garrido, Marcelo I.; Lozoff, Betsy

2013-01-01

Iron-deficiency anemia (IDA) continues to be the most common single nutrient deficiency in the world. An estimated 20-25% of the world’s infants have IDA, with at least as many having iron deficiency without anemia. Infants are at particular risk due to rapid growth and limited dietary sources of iron. We found that infants with IDA showed different motor activity patterning in all sleep-waking states and several differences in sleep states organization. Sleep alterations were still apparent years after correction of anemia with iron treatment in the absence of subsequent IDA. We suggest that altered sleep patterns may represent an underlying mechanism that interferes with optimal brain functioning during sleep and wakefulness in former IDA children. PMID:20620103

Physicochemical Characterization of Iron Carbohydrate Colloid Drug Products.

PubMed

Zou, Peng; Tyner, Katherine; Raw, Andre; Lee, Sau

2017-09-01

Iron carbohydrate colloid drug products are intravenously administered to patients with chronic kidney disease for the treatment of iron deficiency anemia. Physicochemical characterization of iron colloids is critical to establish pharmaceutical equivalence between an innovator iron colloid product and generic version. The purpose of this review is to summarize literature-reported techniques for physicochemical characterization of iron carbohydrate colloid drug products. The mechanisms, reported testing results, and common technical pitfalls for individual characterization test are discussed. A better understanding of the physicochemical characterization techniques will facilitate generic iron carbohydrate colloid product development, accelerate products to market, and ensure iron carbohydrate colloid product quality.

Periconceptional iron and folate status is inadequate among married, nulliparous women in rural Bangladesh.

PubMed

Khambalia, Amina; O'Connor, Deborah L; Zlotkin, Stanley

2009-06-01

Recent evidence suggests that poor fetal growth is associated with preconception anemia and first trimester iron deficiency. Periconceptional iron and folate supplementation may improve the effectiveness of iron supplementation programs during pregnancy by treating preexisting anemia, building iron stores, and reducing risk of neural tube defects. Our objective in this study was to describe the iron and folate status of married, nulliparous women in rural Bangladesh from March to May 2007. Of 272 women, 37% were anemic (hemoglobin <120 g/L), 13% were folate deficient (plasma folate 4.4 mg/L), 11% were iron deficient and anemic, and 81% were estimated to have <500 mg of iron stores. Risk of anemia was 4 times greater among nonstudents than students (95% CI: 1.23, 14.69), twice as likely among women with a previous miscarriage compared with those who had never been pregnant (95% CI: 1.04, 5.47), and 6 times greater among iron-deficient compared to iron-replete women (95% CI: 2.76, 11.81). Adolescents (80% will have inadequate iron stores, and more than one-tenth will be folate deficient. Further research is needed on risk factors of poor nutritional status before the start of a woman's childbearing years.

Effects of iron deficiency on anisotropy and ferromagnetic resonance linewidth in Bi-doped LiZn ferrite

NASA Astrophysics Data System (ADS)

Jiang, Xiaona; Wang, Wei; Yu, Zhong; Sun, Ke; Lan, Zhongwen; Zhang, Xinran; Harris, Vincent G.

2017-05-01

Bi-doped LiZn ferrites with different iron deficiencies were fabricated by a conventional ceramic method. Anisotropy constant (K1) was calculated and ferromagnetic resonance (FMR) linewidth (ΔH) was investigated. Crystalline anisotropy broadening linewidth (ΔHa) and porosity broadening linewidth (ΔHp) were derived by an approximate calculation based on dipolar narrowing theory, which play a significant role in contributions to FMR linewidth and occupy more than 90 % of ΔH. Physical and static magnetic properties of LiZn ferrite with iron deficiency are presented, which supports a decline in linewidths with increasing iron deficiency. Iron deficiency makes K1, ΔHa and ΔHp reduce. The results also show that ΔHp is the majority of contributions to ΔH in Bi-doped LiZn ferrite and densification is an effective method to decrease ΔH.

[Characterization of anemia in children under five years of age from urban areas of Huancavelica and Ucayali, Peru].

PubMed

Gonzales, Elena; Huamán-Espino, Lucio; Gutiérrez, César; Aparco, Juan Pablo; Pillaca, Jenny

2015-01-01

Characterize anemia in children aged between 12 and 59 months from urban areas in the provinces of Coronel Portillo and Huancavelica in Peru. Cross-sectional study carried out in two stages: a) population-based study to identify children with anemia using multistage probability sampling, and b) characterization of the serum levels of ferritin, vitamin B12, intraerythrocytic folic acid and presence of parasitosis in children with anemia. For the statistical analysis, expansion factors calculated from the sampling plan were applied. The prevalence of anemia was 55.9% in Huancavelica and 36.2% in Coronel Portillo. In Huancavelica, the coexistence of anemia with iron deficiency was 22.8% and anemia with vitamin B12 deficiency was 11%. In Coronel Portillo, the coexistence of anemia with iron deficiency and vitamin B12 deficiency was 15.2% and 29.7%, respectively. The most common types of anemia in Huancavelica were anemia with concurrent parasitosis (50.9%), iron deficiency anemia and parasitosis (12.3%), and iron deficiency alone (6.4%). In Coronel Portillo, it was anemia and parasitosis (54.4%), vitamin B12 deficiency and parasitosis (18.4%), and iron deficiency anemia and parasitosis (6.3%). The prevalence of anemia is higher than the national average, with anemia concurrent with parasitosis and anemia concurrent with two or more causes as the most common type. Consideration should be given to different causes other than iron deficiency in the programs of anemia contol for Peruvian children.

Low haemoglobin density for detecting iron deficiency across a large population, including pregnancy.

PubMed

Crispin, P; Sinclair, F; Andriolo, K

2016-08-01

Low haemoglobin density (LHD%) from Coulter counters has been suggested as a means to detect iron deficiency. Its performance in a broad population group, including pregnancy, has not been evaluated. A retrospective study of adult and paediatric (under 12 years old) patient samples referred for blood counts and iron studies between October 2013 and March 2015. Receiver operator characteristic (ROC) curves were constructed to evaluate the performance of LHD% adults, children, and in the antenatal subgroup. Using a strict definition for iron deficiency, compared with a selected normal cohort, LHD% had a ROC area under the curve (AUC) of 0.90 (0.89-0.91), but in an unselected cohort, the AUC fell to 0.74 (0.73-0.75) with a sensitivity of 74% and specificity of 60% at a cut-off value of 5.9%. In the paediatric cohort, the AUC was 0.79(0.73-0.85), giving a sensitivity and specificity of 75% and 68%, respectively. LHD% did not effectively identify iron deficiency in pregnancy with an AUC of 0.60 (0.54-0.65) and was no better than MCV at detecting iron deficiency. LHD% detects iron deficiency in adult and paediatric populations, but not in the antenatal setting, and does not appear superior to MCV. © 2016 John Wiley & Sons Ltd.

[Iron deficiency anaemia: clinical presentation, biological diagnosis and management].

PubMed

Espanel, C; Kafando, E; Hérault, B; Petit, A; Herault, O; Binet, C

2007-05-01

The iron deficiency is the first cause of anaemia. In healthy young adult, anemia is well tolerated because of its progressive installation. The most common symptoms of anemia are pallor, fatigue and dyspnea. In biological exams, anemia is classically associated with microcytosis and hypochromia. The origins of microcytic anemia are iron deficiency, inflammatory aetiologies, thalassemia and sideroblastic anaemia. The iron-deficiency diagnosis includes two explorations: biological and clinical. The biological exploration is based on interpretation of serum biologics tests as blood iron, ferritin, transferrin with saturation, total iron-binding capacity and its soluble receptors. This interpretation is simple if it is not associated with clinical disorders influencing the internal iron cycle. The clinical exploration must always be followed by a careful assessment of the underlying cause as blood loss. The most common causes in women of reproductive age are gynaecologic. In men and menopausal women, the gastrointestinal tract bleeding is source of anemia. Therapeutic management of anemia is oral iron therapy. Etiological diagnostic of microcytosis is essential before iron therapy. If not, the treatment could be inefficient or it could mask or delay the etiological diagnostic.

[Iron deficiency and pernicious anemia: a rare association?].

PubMed

Zulfiqar, Abrar-Ahmad; Dramé, Moustapha; Pennaforte, Jean-Loup; Novella, Jean-Luc; Vogel, Thomas; Andres, Emmanuel

2015-01-01

The aim of this study was to determine the prevalence of iron deficiency among patients with pernicious anemia. We realized a retrospective study from 2000 to 2010 including 55 patients suffering from pernicious anemia who were followed in Reims and Strasbourg university hospitals. Inclusion criteria were histological diagnosis of immune atrophic fundic gastritis and criteria of gastric autoimmuninty, and for which ferritin was measured. Iron deficiency is defined as serum ferritin level <20 μg/L in women and <30 μg/L in men. 45 (81.8%) patients were female. The mean age was 61 ± 17 years (range: 25/98).There was anemia in 32 patients (58.2%). Macrocytosis was noted, with or without anemia, in 30 patients (54.5%); microcytosis, with or without anemia, was noted in 8 (14.5%) patients. 17 patients (30.9%) had normal mean corpuscular volume. Vitamin B12 deficiency was objectived in 42 patients (76.4%) in our series. 16 patients (29%) had iron deficiency. 14 patients were female. They were significantly younger than female subjects without iron deficiency (p =0.004). In conclusion, iron deficiency is not rare in patients with pernicious anemia. It could be a complication of achlorhydria. We suggest a dosage of serum ferritin for all patients with pernicious anemia.

Prenatal choline supplementation ameliorates the long-term neurobehavioral effects of fetal-neonatal iron deficiency in rats.

PubMed

Kennedy, Bruce C; Dimova, Jiva G; Siddappa, Asha J M; Tran, Phu V; Gewirtz, Jonathan C; Georgieff, Michael K

2014-11-01

Gestational iron deficiency in humans and rodents produces long-term deficits in cognitive and socioemotional function and alters expression of plasticity genes in the hippocampus that persist despite iron treatment. Prenatal choline supplementation improves cognitive function in other rodent models of developmental insults. The objective of this study was to determine whether prenatal choline supplementation prevents the long-term effects of fetal-neonatal iron deficiency on cognitive and social behaviors and hippocampal gene expression. Pregnant rat dams were administered an iron-deficient (2-6 g/kg iron) or iron-sufficient (IS) (200 g/kg iron) diet from embryonic day (E) 3 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline chloride, E11-18). Novel object recognition (NOR) in the test vs. acquisition phase, social approach (SA), and hippocampal mRNA expression were compared at P65 in 4 male adult offspring groups: formerly iron deficient (FID), FID with choline supplementation (FID-C), IS, and IS with choline supplementation. Relative to the intact NOR in IS rats (acquisition: 47.9%, test: 60.2%, P < 0.005), FID adult rats had impaired recognition memory at the 6-h delay (acquisition: 51.4%, test: 55.1%, NS), accompanied by a 15% reduction in hippocampal expression of brain-derived neurotrophic factor (Bdnf) (P < 0.05) and myelin basic protein (Mbp) (P < 0.05). Prenatal choline supplementation in FID rats restored NOR (acquisition: 48.8%, test: 64.4%, P < 0.0005) and increased hippocampal gene expression (FID-C vs. FID group: Bdnf, Mbp, P < 0.01). SA was also reduced in FID rats (P < 0.05 vs. IS rats) but was only marginally improved by prenatal choline supplementation. Deficits in recognition memory, but not social behavior, resulting from gestational iron deficiency are attenuated by prenatal choline supplementation, potentially through preservation of hippocampal Bdnf and Mbp expression. Prenatal choline supplementation may be a promising adjunct treatment for fetal-neonatal iron deficiency. © 2014 American Society for Nutrition.

Elimination of Iron Deficiency Anemia and Soil Transmitted Helminth Infection: Evidence from a Fifty-four Month Iron-Folic Acid and De-worming Program

PubMed Central

Casey, Gerard J.; Montresor, Antonio; Cavalli-Sforza, Luca T.; Thu, Hoang; Phu, Luong B.; Tinh, Ta T.; Tien, Nong T.; Phuc, Tran Q.; Biggs, Beverley-Ann

2013-01-01

Background Intermittent iron-folic acid supplementation and regular de-worming are effective initiatives to reduce anemia, iron deficiency, iron deficiency anemia, and soil transmitted helminth infections in women of reproductive age. However, few studies have assessed the long-term effectiveness of population-based interventions delivered in resource-constrained settings. Methodology/Principal Findings The objectives were to evaluate the impact of weekly iron-folic acid supplementation and de-worming on mean hemoglobin and the prevalence of anaemia, iron deficiency, and soil transmitted helminth infection in a rural population of women in northern Vietnam and to identify predictive factors for hematological outcomes. A prospective cohort design was used to evaluate a population-based supplementation and deworming program over 54 months. The 389 participants were enrolled just prior to commencement of the intervention. After 54 months 76% (95% CI [68%, 84%]) were taking the iron-folic acid supplement and 95% (95% CI [93%, 98%]) had taken the most recently distributed deworming treatment. Mean hemoglobin rose from 122 g/L (95% CI [120, 124]) to 131 g/L (95% CI [128, 134]) and anemia prevalence fell from 38% (95% CI [31%, 45%]) to 18% (95% CI [12%, 23%]); however, results differed significantly between ethnic groups. Iron deficiency fell from 23% (95% CI [17%, 29%]) to 8% (95% CI [4%, 12%]), while the prevalence of iron deficiency anemia was reduced to 4% (95% CI [1%, 7%]). The prevalence of hookworm infection was reduced from 76% (95% CI [68%, 83%]) to 11% (95% CI [5%, 18%]). The level of moderate or heavy infestation of any soil-transmitted helminth was reduced to less than 1%. Conclusions/Significance Population-based interventions can efficiently and effectively reduce anemia and practically eliminate iron deficiency anemia and moderate to heavy soil transmitted helminth infections, maintaining them below the level of public health concern. PMID:23593517

The Metabolic Status Drives Acclimation of Iron Deficiency Responses in Chlamydomonas reinhardtii as Revealed by Proteomics Based Hierarchical Clustering and Reverse Genetics*

PubMed Central

Höhner, Ricarda; Barth, Johannes; Magneschi, Leonardo; Jaeger, Daniel; Niehues, Anna; Bald, Till; Grossman, Arthur; Fufezan, Christian; Hippler, Michael

2013-01-01

Iron is a crucial cofactor in numerous redox-active proteins operating in bioenergetic pathways including respiration and photosynthesis. Cellular iron management is essential to sustain sufficient energy production and minimize oxidative stress. To produce energy for cell growth, the green alga Chlamydomonas reinhardtii possesses the metabolic flexibility to use light and/or carbon sources such as acetate. To investigate the interplay between the iron-deficiency response and growth requirements under distinct trophic conditions, we took a quantitative proteomics approach coupled to innovative hierarchical clustering using different “distance-linkage combinations” and random noise injection. Protein co-expression analyses of the combined data sets revealed insights into cellular responses governing acclimation to iron deprivation and regulation associated with photosynthesis dependent growth. Photoautotrophic growth requirements as well as the iron deficiency induced specific metabolic enzymes and stress related proteins, and yet differences in the set of induced enzymes, proteases, and redox-related polypeptides were evident, implying the establishment of distinct response networks under the different conditions. Moreover, our data clearly support the notion that the iron deficiency response includes a hierarchy for iron allocation within organelles in C. reinhardtii. Importantly, deletion of a bifunctional alcohol and acetaldehyde dehydrogenase (ADH1), which is induced under low iron based on the proteomic data, attenuates the remodeling of the photosynthetic machinery in response to iron deficiency, and at the same time stimulates expression of stress-related proteins such as NDA2, LHCSR3, and PGRL1. This finding provides evidence that the coordinated regulation of bioenergetics pathways and iron deficiency response is sensitive to the cellular and chloroplast metabolic and/or redox status, consistent with systems approach data. PMID:23820728

The role of iron in the skin and cutaneous wound healing

PubMed Central

Wright, Josephine A.; Richards, Toby; Srai, Surjit K. S.

2014-01-01

In this review article we discuss current knowledge about iron in the skin and the cutaneous wound healing process. Iron plays a key role in both oxidative stress and photo-induced skin damage. The main causes of oxidative stress in the skin include reactive oxygen species (ROS) generated in the skin by ultraviolet (UVA) 320–400 nm portion of the UVA spectrum and biologically available iron. We also discuss the relationships between iron deficiency, anemia and cutaneous wound healing. Studies looking at this fall into two distinct groups. Early studies investigated the effect of anemia on wound healing using a variety of experimental methodology to establish anemia or iron deficiency and focused on wound-strength rather than effect on macroscopic healing or re-epithelialization. More recent animal studies have investigated novel treatments aimed at correcting the effects of systemic iron deficiency and localized iron overload. Iron overload is associated with local cutaneous iron deposition, which has numerous deleterious effects in chronic venous disease and hereditary hemochromatosis. Iron plays a key role in chronic ulceration and conditions such as rheumatoid arthritis (RA) and Lupus Erythematosus are associated with both anemia of chronic disease and dysregulation of local cutaneous iron hemostasis. Iron is a potential therapeutic target in the skin by application of topical iron chelators and novel pharmacological agents, and in delayed cutaneous wound healing by treatment of iron deficiency or underlying systemic inflammation. PMID:25071575

Potential impacts of iron biofortification in India.

PubMed

Stein, Alexander J; Meenakshi, J V; Qaim, Matin; Nestel, Penelope; Sachdev, H P S; Bhutta, Zulfiqar A

2008-04-01

Iron deficiency is a widespread nutrition and health problem in developing countries, causing impairments in physical activity and cognitive development, as well as maternal mortality. Although food fortification and supplementation programmes have been effective in some countries, their overall success remains limited. Biofortification, that is, breeding food crops for higher micronutrient content, is a relatively new approach, which has been gaining international attention recently. We propose a methodology for ex ante impact assessment of iron biofortification, building on a disability-adjusted life years (DALYs) framework. This methodology is applied in an Indian context. Using a large and representative data set of household food consumption, the likely effects of iron-rich rice and wheat varieties are simulated for different target groups and regions. These varieties, which are being developed by an international public research consortium, based on conventional breeding techniques, might be ready for local distribution within the next couple of years. The results indicate sizeable potential health benefits. Depending on the underlying assumptions, the disease burden associated with iron deficiency could be reduced by 19-58%. Due to the relatively low institutional cost to reach the target population, the expected cost-effectiveness of iron biofortification compares favourably with other micronutrient interventions. Nonetheless, biofortification should not be seen as a substitute for other interventions. Each approach has its particular strengths, so they complement one another.

Iron-binding haemerythrin RING ubiquitin ligases regulate plant iron responses and accumulation

PubMed Central

Kobayashi, Takanori; Nagasaka, Seiji; Senoura, Takeshi; Itai, Reiko Nakanishi; Nakanishi, Hiromi; Nishizawa, Naoko K.

2013-01-01

Iron is essential for most living organisms. Plants transcriptionally induce genes involved in iron acquisition under conditions of low iron availability, but the nature of the deficiency signal and its sensors are unknown. Here we report the identification of new iron regulators in rice, designated Oryza sativa Haemerythrin motif-containing Really Interesting New Gene (RING)- and Zinc-finger protein 1 (OsHRZ1) and OsHRZ2. OsHRZ1, OsHRZ2 and their Arabidopsis homologue BRUTUS bind iron and zinc, and possess ubiquitination activity. OsHRZ1 and OsHRZ2 are susceptible to degradation in roots irrespective of iron conditions. OsHRZ-knockdown plants exhibit substantial tolerance to iron deficiency, and accumulate more iron in their shoots and grains irrespective of soil iron conditions. The expression of iron deficiency-inducible genes involved in iron utilization is enhanced in OsHRZ-knockdown plants, mostly under iron-sufficient conditions. These results suggest that OsHRZ1 and OsHRZ2 are iron-binding sensors that negatively regulate iron acquisition under conditions of iron sufficiency. PMID:24253678

Nuclear magnetic resonance metabolomics of iron deficiency in soybean leaves

USDA-ARS?s Scientific Manuscript database

Iron (Fe) deficiency is an important agricultural concern leading to lower yields and crop quality. A better understanding of the condition, at the metabolome level, could contribute to the design of strategies to ameliorate Fe deficiency problems. Fe-sufficient and Fe-deficient soybean leaf extract...

Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

PubMed

Choudhury, Vivek; Amin, Sanjiv B; Agarwal, Asha; Srivastava, L M; Soni, Arun; Saluja, Satish

2015-11-01

In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score <5 at 5 min, sepsis, cord blood not collected, or auditory evaluation unable to be performed. Sixty consecutive infants with risk factors for iron deficiency, such as small for gestational age and maternal diabetes, and 30 without risk factors for iron deficiency were enrolled. Absolute wave latencies and interpeak latencies, evaluated by auditory brainstem response within 48 h after birth, were measured and compared between infants with latent iron deficiency (serum ferritin ≤75 ng/mL) and infants with normal iron status (serum ferritin >75 ng/mL) at birth. Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P < 0.05). This difference remained significant on regression analyses after control for confounders. No difference was noted between latencies I and III and interpeak latencies I-III. Latent iron deficiency is associated with abnormal auditory neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397. © 2015 American Society for Nutrition.

Effect of iron deficiency on the expression of insulin-like growth factor-II and its receptor in neuronal and glial cells.

PubMed

Morales González, E; Contreras, I; Estrada, J A

2014-09-01

Many studies have demonstrated that iron deficiency modifies the normal function of the central nervous system and alters cognitive abilities. When cellular damage occurs in the central nervous system, neuroprotective mechanisms, such as the production of neurotrophic factors, are essential in order for nervous tissue to function correctly. Insulin-like growth factor II (IGF- II) is a neurotrophic factor that was recently shown to be involved in the normal functioning of cognitive processes in animal models. However, the impact of iron deficiency on the expression and function of this molecule has not yet been clarified. Mixed primary cell cultures from the central nervous system were collected to simulate iron deficiency using deferoxamine. The expression of IGF-I, IGF-II, IGF-IR, and IGF-IIR was determined with the western blot test. We observed increased expression of IGF-II, along with a corresponding decrease in the expression of IGF-IIR, in iron-deficient mixed primary cell cultures. We did not observe alterations in the expression of these proteins in isolated microglia or neuronal cultures under the same conditions. We did not detect differences in the expression of IGF-I and IGF-IR in iron-deficient cultures. In vitro iron deficiency increases the expression of IGF-II in mixed glial cell cultures, which may have a beneficial effect on brain tissue homeostasis in a situation in which iron availability is decreased. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Effect of iron-deficiency anemia on cognitive skills and neuromaturation in infancy and childhood.

PubMed

Walter, Tomas

2003-12-01

Iron-deficiency anemia in infancy has been consistently shown to negatively influence performance in tests of psychomotor development. In most studies of short-term follow-up, lower scores did not improve with iron therapy, despite complete hematologic replenishment. The negative impact on psychomotor development of iron-deficiency anemia (IDA) in infancy has been well documented in more than a dozen studies during the last two decades. Two studies will be presented here to further support this assertion. Additionally, we will present some data referring to longer follow-up at 5 and 10 years as well as data concerning recent descriptions of the neurologic derangements that may underlie these behavioral effects. To evaluate whether these deficits may revert after long-term observation, a cohort of infants was re-evaluated at 5 and 10 years of age. Two studies have examined children aged 5 years who had anemia as infants using comparable tools of cognitive development showing persisting and consistent important disadvantages in those who were formerly anemic. These tests were better predictors of future achievement than psychomotor scores. These children were again examined at 10 years and showed lower school achievement and poorer fine-hand movements. Studies of neurologic maturation in a new cohort of infants aged 6 months included auditory brain stem responses and naptime 18-lead sleep studies. The central conduction time of the auditory brain stem responses was slower at 6, 12, and 18 months and at 4 years, despite iron therapy beginning at 6 months. During the sleep-wakefulness cycle, heart-rate variability--a developmental expression of the autonomic nervous system--was less mature in anemic infants. The proposed mechanisms are altered auditory-nerve and vagal-nerve myelination, respectively, as iron is required for normal myelin synthesis.

Genetically engineered Escherichia coli Nissle 1917 synbiotic counters fructose-induced metabolic syndrome and iron deficiency.

PubMed

Chaudhari, Archana Somabhai; Raghuvanshi, Ruma; Kumar, G Naresh

2017-06-01

Consumption of fructose leads to metabolic syndrome, but it is also known to increase iron absorption. Present study investigates the effect of genetically modified Escherichia coli Nissle 1917 (EcN) synbiotic along with fructose on non-heme iron absorption. Charles foster rats weighing 150-200 g were fed with iron-deficient diet for 2 months. Probiotic treatment of EcN (pqq) and EcN (pqq-glf-mtlK) was given once per week, 10 9  cells after 2 months with fructose in drinking water. Iron levels, blood, and liver parameters for oxidative stress, hyperglycemia, and dyslipidemia were estimated. Transferrin-bound iron levels in the blood decreased significantly after 10 weeks of giving iron-deficient diet. Probiotic treatment of EcN (pqq-glf-mtlK) and fructose together led to the restoration of normal transferrin-bound iron levels and blood and hepatic antioxidant levels as compared to iron-deficient control group. The probiotic also led to the restoration of body weight along with levels of serum and hepatic lipid, blood glucose, and antioxidant in the blood and liver as compared to iron-deficient control group. Restoration of liver injury marker enzymes was also seen. Administration of EcN-producing PQQ and mannitol dehydrogenase enzyme together with fructose led to increase in the transferrin-bound iron levels in the blood and amelioration of consequences of metabolic syndrome caused due to fructose consumption.

The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal.

PubMed

Chandyo, R K; Henjum, S; Ulak, M; Thorne-Lyman, A L; Ulvik, R J; Shrestha, P S; Locks, L; Fawzi, W; Strand, T A

2016-04-01

Iron deficiency anemia is a widespread public health problem, particularly in low- and middle-income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal. In a cross-sectional survey, we randomly selected 500 mother-infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein. The altitude-adjusted prevalence of anemia was 49% among infants 2-6-month-old (hemaglobin (Hb) <10.8 g/dl) and 72% among infants 7-12-month-old (Hb <11.3 g/dl). Iron deficiency anemia, defined as anemia and serum ferritin <20 or <12 μg/l, affected 9 and 26% of infants of these same age groups. Twenty percent of mothers had anemia (Hb <12.3 g/dl), but only one-fifth was explained by depletion of iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations. Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants.

Two soybean bHLH factors regulate response to iron deficiency.

PubMed

Li, Lin; Gao, Wenwen; Peng, Qi; Zhou, Bin; Kong, Qihui; Ying, Yinghui; Shou, Huixia

2018-03-25

Iron is an indispensable micronutrient for plant growth and development. Limited bioavailability of Fe in the soil leads to iron deficiency chlorosis in plants and yield loss. In this study, two soybean basic helix-loop-helix transcription factors, GmbHLH57 and GmbHLH300, were identified in response to Fe-deficiency. Both transcription factors are expressed in roots and nodules, and are induced by Fe deficiency; these patterns were confirmed in transgenic hairy roots expressing constructs of the endogenous promoters fused to a GUS reporter gene. Bimolecular fluorescence complementation, yeast two-hybrid and coimmunoprecipitation (co-IP) assays indicated a physical interaction between GmbHLH57 and GmbHLH300. Studies on transgenic soybeans overexpressing GmbHLH57 and GmbHLH300 revealed that overexpression of each transcription factor, alone, results in no change of the responses to Fe deficiency, whereas overexpression of both transcription factors upregulated the downstream Fe uptake genes and increased the Fe content in these transgenic plants. Compared to wild type, these double overexpression transgenic plants were more tolerant to Fe deficiency. Taken together, our findings establish that GmbHLH57 and GmbHLH300 are important transcription factors involved in Fe homeostasis in soybean. © 2018 Institute of Botany, Chinese Academy of Sciences.

Effect of dietary intervention treatment on children with iron deficiency anemia in China: a meta-analysis.

PubMed

Sun, Jian; Zhang, Lei; Cui, Jing; Li, Shanshan; Lu, Hongting; Zhang, Yong; Li, Haiming; Sun, Jianping; Baloch, Zulqarnain

2018-05-10

Previous studies have shown beneficial effects of dietary approaches for iron deficiency anemia (IDA) control. This study was design to investigate the effect of dietary intervention treatment on children with iron deficiency anemia. We performed a systematic review of published dietary interventions effect on IDA treatment through meta-analysis. CBM, CNKI, Wanfang database, EMBASE, VIP, PubMed and Web of science database were searched to identify studies published between January, 1980 and December, 2016. Statistical analysis was performed by Revmen5.2 software. Initially we retrieved for 373 studies, and then 6 studies with a total of 676 individuals were included in the analysis according to the inclusion and exclusion criteria for meta-analysis. The overall pooled estimate of odds ratio [(OR), 95% confidence intervals (95% CI)] in the dietary intervention on children with iron deficiency anemia was 6.54 (95% CI: 3.48-12.31, Z = 5.82, p<0.001) and funnel plot is symmetric. Our meta-analysis suggested that dietary interventions are effective in improving the iron deficiency in children with iron deficiency anemia (IDA) and should be considered in the overall strategy of IDA management.

National Trauma Institute: A National Coordinating Center for Trauma Research Funding

DTIC Science & Technology

2012-10-28

and why anemia does not resolve. Hepcidin, a peptide made in the liver, has recently been identified as the key regulator of iron homeostasis, and...plays a major role in how and why anemia develops. Hepcidin reduces iron availability by: (1) decreased iron absorption across the intestine and (2... iron deficiency . Hepcidin is Page | 11 increased in states of inflammation, and likely plays an important role in the acute inflammation that

Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency

NASA Technical Reports Server (NTRS)

Mukhopadhyay, C. K.; Mazumder, B.; Fox, P. L.

2000-01-01

A role of the copper protein ceruloplasmin (Cp) in iron metabolism is suggested by its ferroxidase activity and by the tissue iron overload in hereditary Cp deficiency patients. In addition, plasma Cp increases markedly in several conditions of anemia, e.g. iron deficiency, hemorrhage, renal failure, sickle cell disease, pregnancy, and inflammation. However, little is known about the cellular and molecular mechanism(s) involved. We have reported that iron chelators increase Cp mRNA expression and protein synthesis in human hepatocarcinoma HepG2 cells. Furthermore, we have shown that the increase in Cp mRNA is due to increased rate of transcription. We here report the results of new studies designed to elucidate the molecular mechanism underlying transcriptional activation of Cp by iron deficiency. The 5'-flanking region of the Cp gene was cloned from a human genomic library. A 4774-base pair segment of the Cp promoter/enhancer driving a luciferase reporter was transfected into HepG2 or Hep3B cells. Iron deficiency or hypoxia increased luciferase activity by 5-10-fold compared with untreated cells. Examination of the sequence showed three pairs of consensus hypoxia-responsive elements (HREs). Deletion and mutation analysis showed that a single HRE was necessary and sufficient for gene activation. The involvement of hypoxia-inducible factor-1 (HIF-1) was shown by gel-shift and supershift experiments that showed HIF-1alpha and HIF-1beta binding to a radiolabeled oligonucleotide containing the Cp promoter HRE. Furthermore, iron deficiency (and hypoxia) did not activate Cp gene expression in Hepa c4 hepatoma cells deficient in HIF-1beta, as shown functionally by the inactivity of a transfected Cp promoter-luciferase construct and by the failure of HIF-1 to bind the Cp HRE in nuclear extracts from these cells. These results are consistent with in vivo findings that iron deficiency increases plasma Cp and provides a molecular mechanism that may help to understand these observations.

Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency.

PubMed

Lam, Jameson R; Schneider, Jennifer L; Quesenberry, Charles P; Corley, Douglas A

2017-03-01

Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) suppress gastric acid production, which can inhibit iron absorption. However, few data exist regarding whether these medications increase the risk of clinical iron deficiency. A community-based case-control study evaluated the association between acid-suppressing medication use and the subsequent risk of iron deficiency. It contrasted 77,046 patients with new iron deficiency diagnoses (January 1999-December 2013), with 389,314 controls. Medication exposures, outcomes, and potential confounders used electronic databases. We excluded patients with pre-existing risk factors for iron deficiency. Associations were estimated using conditional logistic regression. Among cases, 2343 (3.0%) received a prior ≥2-year supply of PPIs and 1063 (1.4%) received H2RAs (without PPI use). Among controls, 3354 (0.9%) received a prior ≥2-year supply of PPIs and 2247 (0.6%) H2RAs. Both ≥2 years of PPIs (adjusted odds ratio, 2.49; 95% confidence interval, 2.35-2.64) and ≥2 years of H2RAs (odds ratio, 1.58; 95% CI, 1.46-1.71) were associated with an increased subsequent risk for iron deficiency. Among PPI users, the associations were stronger for higher daily doses (>1.5 vs <0.75 PPI pills/d; P value interaction = .004) and decreased after medication discontinuation (P-trend < .001). Some of the strongest associations were among persons taking >1.5 pills per day for at least 10 years (odds ratio, 4.27; 95% CI, 2.53-7.21). No similar strong associations were found for other commonly used prescription medications. Among patients without known risk factors for iron deficiency, gastric acid inhibitor use for ≥2 years was associated with an increased subsequent risk of iron deficiency. The risk increased with increasing potency of acid inhibition and decreased after medication discontinuation. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Medication adherence to oral iron therapy in patients with iron deficiency anemia

PubMed Central

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

2016-01-01

Objective: This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. Methods: A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Results: Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Conclusion: Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment. PMID:27375698

Medication adherence to oral iron therapy in patients with iron deficiency anemia.

PubMed

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

2016-01-01

This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment.

Intravenous iron therapy in non-anemic iron-deficient menstruating adolescent females with fatigue.

PubMed

Sharma, Ruchika; Stanek, Joseph R; Koch, Terah L; Grooms, Linda; O'Brien, Sarah H

2016-10-01

Menstruating women, with or without underlying bleeding disorders, are at increased risk for developing iron deficiency-related fatigue, even in the absence of anemia. Oral iron therapy has limitations which include poor absorption and non-adherence due to gastrointestinal side effects. We performed a prospective clinical trial of post-menarchal adolescent females with iron-deficiency with or without mild anemia and fatigue who received a standardized regimen of intravenous iron sucrose. The baseline mean (SD) hemoglobin was 11.96 g dl(-1) (1.05) in 20 girls (ages 14-21 years); with a range of 10.3-14.1 g dl(-1) . In this cohort, intravenous iron was well tolerated and patients demonstrated a sustained increase in ferritin levels with means (SD) of 13.4 ng ml(-1) (13.1) at baseline to 141.5 ng ml(-1) (104.5) at 6 weeks and 85.2 ng ml(-1) (128.4) at 6 months after the infusions. We used a standardized (Peds QL(TM) Multidimensional) fatigue scale to objectively measure fatigue and proxy scores by parents with mean screening scores (SD) of 35.2 (16.8) and 31.9 (19.6), respectively. We demonstrated a clinically significant improvement both in patient as well as parent fatigue scores (in 19 out of 20 subjects) at 6 weeks (Mean (SD) 58.3 (21.3) [P < 0.0001] and 57 (24.4) [P < 0.0001], respectively); as well as 3 and 6 months after the iron infusions. In nonanemic patients, iron administration did not significantly influence hemoglobin concentration. Therefore, the fatigue-reducing effects of iron therapy reflect the nonhematological functions of iron. Am. J. Hematol. 91:973-977, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism.

PubMed

Mayeur, Claire; Leyton, Patricio A; Kolodziej, Starsha A; Yu, Binglan; Bloch, Kenneth D

2014-09-25

Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is regulated by bone morphogenetic protein (BMP) signaling. We sought to identify which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is responsible for regulating hepcidin gene expression. We studied Bmpr2 heterozygous mice (Bmpr2(+/-)), mice with hepatocyte-specific deficiency of BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum hepcidin and iron levels, and tissue iron levels did not differ in wild-type mice, Bmpr2(+/-) mice, and mice in which either BMPR2 or ActR2a was deficient. Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene expression and serum hepcidin levels leading to severe iron overload. Iron injection increased hepatic hepcidin mRNA levels in mice deficient in either BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression. These results suggest that BMP type II receptors, BMPR2 and ActR2a, have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism. © 2014 by The American Society of Hematology.

Overview of the nutritional status of selected micronutrients in Mexican children in 2006.

PubMed

Shamah-Levy, Teresa; Villalpando, Salvador; Jáuregui, Alejandra; Rivera, Juan A

2012-01-01

To present an overview of micronutrient status of Mexican children in 2006. Data on iron, zinc, folate and vitamin B12 deficiencies and low serum copper and magnesium were gathered and critically analyzed from the 2006 National Health and Nutrition Survey. Iron deficiency is still the main nutritional deficiency in children (13%-26%). Zinc deficiency was high in all age groups (≈25%) but reduced 5.6 PP in children <5 y from 1999 to 2006. Folate deficiency was 3.2% and vitamin B12 deficiency 7.7% in children. Low serum magnesium and copper were high (22.6% and 30.6%, respectively). The prevalence of iron deficiency seems to be lowering, and zinc deficiency has reduced in Mexican children. A high prevalence of copper and magnesium deficiencies warrants further research on their public health implications.

Iron absorption from intrinsically-labeled lentils

USDA-ARS?s Scientific Manuscript database

Low iron (Fe) absorption from important staple foods may contribute to Fe deficiency in developing countries. To date, there are few studies examining the Fe bioavailability of pulse crops as commonly prepared and consumed by humans. The objectives of this study were to characterize the Fe absorpt...

Assessment of iron deficiency and anemia in pregnant women: an observational French study.

PubMed

Harvey, Thierry; Zkik, Asmaa; Auges, Marie; Clavel, Thierry

2016-01-01

We explored the prevalence and management of iron deficiency and anemia among pregnant women in France. In this prospective, observational, multicenter registry study, randomly selected investigators (gynecologists/obstetricians/midwives registered in the CEGEDIM(®) database) assessed pregnant women presenting for a consultation. Participants completed a questionnaire at study inclusion. A total of 1506 patients were enrolled by 95 investigators. Overall, investigators estimated a moderate or significant risk of iron deficiency in almost 60% of women. The overall prevalence of anemia (15.8%) increased with longer pregnancy duration. Medication (mainly iron-based) was prescribed to 57.3% of patients. In French clinical practice, the estimated risk of iron deficiency and prevalence of anemia during pregnancy align with expectations and are managed according to national/international recommendations.

When Less is More: Novel Mechanisms of Iron Conservation

PubMed Central

Bayeva, Marina; Chang, Hsiang-Chun; Wu, Rongxue; Ardehali, Hossein

2016-01-01

Disorders of iron homeostasis are very common, yet the molecular mechanisms of iron regulation remain understudied. Over 20 years have passed since the first characterization of iron regulatory proteins (IRP) as mediators of cellular iron deficiency response in mammals through iron acquisition. However, little is known about other mechanisms necessary for adaptation to low-iron states. In this review we present recent evidence that establishes existence of a new iron regulatory pathway aimed at iron conservation and optimization of iron use through suppression of non-essential iron-consuming processes. Moreover, we discuss the possible links between iron homeostasis and energy metabolism uncovered by studies of iron deficiency response. PMID:23948590

Using event-related potentials to study perinatal nutrition and brain development in infants of diabetic mothers.

PubMed

deRegnier, Raye-Ann; Long, Jeffrey D; Georgieff, Michael K; Nelson, Charles A

2007-01-01

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birth weights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant.

Using Event-Related Potentials to Study Perinatal Nutrition and Brain Development in Infants of Diabetic Mothers

PubMed Central

deRegnier, Raye-Ann; Long, Jeffrey D.; Georgieff, Michael K.; Nelson, Charles A.

2009-01-01

Proper prenatal and postnatal nutrition is essential for optimal brain development and function. The early use of event-related potentials enables neuroscientists to study the development of cognitive function from birth and to evaluate the role of specific nutrients in development. Perinatal iron deficiency occurs in severely affected infants of diabetic mothers. In animal models, severe perinatal iron deficiency targets the explicit memory system of the brain. Cross-sectional ERP studies have shown that infants of diabetic mothers have impairments in recognition memory from birth through 8 months of age. The purpose of this study was to evaluate longitudinal development of recognition memory using ERPs in infants of diabetic mothers compared with control infants. Infants of diabetic mothers were divided into high and low risk status based upon their birthweights and iron status and compared with healthy control infants. Infants were tested in the newborn period for auditory recognition memory, at 6 months for visual recognition memory and at 8 months for cross modal memory. ERPs were evaluated for developmental changes in the slow waves that are thought to reflect memory and the Nc component that is thought to reflect attention. The results of the study showed differences in development between the IDMs and control infants in the development of the slow waves over the left anterior temporal leads and age-related patterns of development in the NC component. These results are consistent with animal models showing that perinatal iron deficiency affects the development of the memory networks of the brain. This study highlights the value of using ERPs to translate basic science information obtained from animal models to the development of the human infant. PMID:17559331

Budget Impact Analysis of Oral Fisiogen Ferro Forte® versus Intravenous Iron for the Management of Iron Deficiency in Chronic Kidney Disease in Spain.

PubMed

Darbà, Josep; Ascanio, Meritxell

2018-06-22

Iron deficiency is a frequent complication of chronic kidney disease (CKD) that is associated with a decrease in the quality of life of patients and an increase in the risk of other clinical complications. Iron therapy represents one of the fundamentals of patients with CKD. Sucrosomial ® oral iron allows Fisiogen Ferro Forte ® to be used in all patients who are intolerant to treatment by the oral route of administration, or who present with malabsorption of conventional oral iron preparations. The main objective of this study was to assess the economic impact of the oral iron Fisiogen Ferro Forte ® for the management of iron deficiency in CKD patients in Spain. A 4-year budget impact model was developed for the period 2017-2020 for CKD patients with iron deficiency who were candidates for intravenous iron due to a lack of response to oral iron, from the perspective of the Spanish healthcare system. Three subgroups of CKD patients were included in the analysis: predialysis, peritoneal dialysis, and post-transplant. The intravenous iron formulations Ferinject ® , Venofer ® , and Feriv ® were considered appropriate comparators to be used in the model. National data on the prevalence of CKD for the three subgroups of patients were obtained from the literature, and input data on drug utilization and outpatient hospitalizations associated with iron administration were obtained by consulting nephrologists. Nephrology experts were also asked about resources used during medical visits and monitoring tests. Based on the unit costs for each iron therapy and the resources used, the total treatment cost per patient associated with each product was obtained to estimate the global budget impact of increasing the use of Fisiogen Ferro Forte ® . The average annual budget savings due to an increase in Fisiogen Ferro Forte ® and a decrease in intravenous iron have been estimated at €398,685, €180,937, and €195,842 over 4 years for the predialysis, peritoneal dialysis, and post-transplant groups, respectively. The increase in the use of Fisiogen Ferro Forte ® leads to overall budget savings of €775,464 for the Spanish National Health Service over 4 years.

Potential of Phytase-Mediated Iron Release from Cereal-Based Foods: A Quantitative View

PubMed Central

Nielsen, Anne V. F.; Tetens, Inge; Meyer, Anne S.

2013-01-01

The major part of iron present in plant foods such as cereals is largely unavailable for direct absorption in humans due to complexation with the negatively charged phosphate groups of phytate (myo-inositol (1,2,3,4,5,6)-hexakisphosphate). Human biology has not evolved an efficient mechanism to naturally release iron from iron phytate complexes. This narrative review will evaluate the quantitative significance of phytase-catalysed iron release from cereal foods. In vivo studies have shown how addition of microbially derived phytases to cereal-based foods has produced increased iron absorption via enzyme-catalysed dephosphorylation of phytate, indicating the potential of this strategy for preventing and treating iron deficiency anaemia. Despite the immense promise of this strategy and the prevalence of iron deficiency worldwide, the number of human studies elucidating the significance of phytase-mediated improvements in iron absorption and ultimately in iron status in particularly vulnerable groups is still low. A more detailed understanding of (1) the uptake mechanism for iron released from partially dephosphorylated phytate chelates, (2) the affinity of microbially derived phytases towards insoluble iron phytate complexes, and (3) the extent of phytate dephosphorylation required for iron release from inositol phosphates is warranted. Phytase-mediated iron release can improve iron absorption from plant foods. There is a need for development of innovative strategies to obtain better effects. PMID:23917170

Research needed to strengthen science and programs for the control of iron deficiency and its consequences in young children.

PubMed

Stoltzfus, Rebecca J

2008-12-01

The purpose of this article is to highlight critical research needs for the effective prevention and control of iron deficiency and its consequences in children living in low-income countries. Four types of research are highlighted: The first involves scaling up interventions that we know are effective, namely iron supplementation of pregnant women, delayed cord clamping at delivery, immediate and exclusive breast-feeding, and continued exclusive breast-feeding for approximately 6 mo. The second entails evaluation research of alternative interventions that are likely to work, to find the most cost-effective strategies for a given social, economic, and epidemiological context. This research is especially needed to expand the implementation of appropriate complementary feeding interventions. In this area, research needs to be designed to provide causal evidence, to measure cost-effectiveness, and to measure potential effect modifiers. The third is efficacy research to discover promising practices where we lack proven interventions. Examples include how to detect infants younger than 6 mo who are at high risk of iron deficiency, efficacious and safe interventions for those young high-risk infants, and best protocols for the treatment of severe anemia. The fourth includes basic research to elucidate physiological processes and mechanisms underlying the risks and benefits of supplemental iron for children exposed to infectious diseases, especially malaria. Strategic research in all 4 areas will ensure that interventions to control pediatric iron deficiency are integrated into national programs and global initiatives to make pregnancy safer, reduce newborn deaths, and promote child development, health, and survival.

Comparison of food habits, iron intake and iron status in adolescents before and after the withdrawal of the general iron fortification in Sweden.

PubMed

Sjöberg, A; Hulthén, L

2015-04-01

Sifted flour was fortified with carbonyl iron for 50 years in Sweden. This study evaluates changes in food habits, intake of iron, factors affecting iron absorption and iron status after the discontinuation of the general iron fortification in adolescents with the highest requirements. A total of 2285 15- to 16-year-old students in 1994 (634 girls and 611 boys) and in 2000 (534 girls and 486 boys) in 13 schools in Gothenburg, Sweden, were included in two cross-sectional surveys assessing food habits with diet history interviews and iron deficiency defined with serum ferritin stores ⩽ 15 μg/l and no preceding infection. In girls, iron deficiency increased from 37 to 45%, while in boys, it was stable at 23%. Total iron intake decreased from 15.7 to 9.5 mg/day and 22.5 to 13.9 mg/day in girls and boys, respectively. Cereals were the main iron source. Among girls, the increase of fish and decrease of calcium intake may not counteract the effect of decreased intake of fortification iron. Among boys, more meat, less calcium and more vitamin C may have favoured the bioavailability of iron. The discontinuation of the general iron fortification resulted in a 39% decrease in total iron intake and iron deficiency increased substantially in girls. However, in boys no change in iron deficiency was observed. Whether this was a result of changed bioavailability of dietary iron or simultaneous changes of non-dietary factors remains to be explored.

Post-Transcriptional Coordination of the Arabidopsis Iron Deficiency Response is Partially Dependent on the E3 Ligases RING DOMAIN LIGASE1 (RGLG1) and RING DOMAIN LIGASE2 (RGLG2)*

PubMed Central

Pan, I-Chun; Tsai, Huei-Hsuan; Cheng, Ya-Tan; Wen, Tuan-Nan; Buckhout, Thomas J.; Schmidt, Wolfgang

2015-01-01

Acclimation to changing environmental conditions is mediated by proteins, the abundance of which is carefully tuned by an elaborate interplay of DNA-templated and post-transcriptional processes. To dissect the mechanisms that control and mediate cellular iron homeostasis, we conducted quantitative high-resolution iTRAQ proteomics and microarray-based transcriptomic profiling of iron-deficient Arabidopsis thaliana plants. A total of 13,706 and 12,124 proteins was identified with a quadrupole-Orbitrap hybrid mass spectrometer in roots and leaves, respectively. This deep proteomic coverage allowed accurate estimates of post-transcriptional regulation in response to iron deficiency. Similarly regulated transcripts were detected in only 13% (roots) and 11% (leaves) of the 886 proteins that differentially accumulated between iron-sufficient and iron-deficient plants, indicating that the majority of the iron-responsive proteins was post-transcriptionally regulated. Mutants harboring defects in the RING DOMAIN LIGASE1 (RGLG1)1 and RING DOMAIN LIGASE2 (RGLG2) showed a pleiotropic phenotype that resembled iron-deficient plants with reduced trichome density and the formation of branched root hairs. Proteomic and transcriptomic profiling of rglg1 rglg2 double mutants revealed that the functional RGLG protein is required for the regulation of a large set of iron-responsive proteins including the coordinated expression of ribosomal proteins. This integrative analysis provides a detailed catalog of post-transcriptionally regulated proteins and allows the concept of a chiefly transcriptionally regulated iron deficiency response to be revisited. Protein data are available via ProteomeXchange with identifier PXD002126. PMID:26253232

Dynamic Changes of IsiA-Containing Complexes during Long-Term Iron Deficiency in Synechocystis sp. PCC 6803.

PubMed

Ma, Fei; Zhang, Xin; Zhu, Xi; Li, Tianpei; Zhan, Jiao; Chen, Hui; He, Chenliu; Wang, Qiang

2017-01-09

Iron stress-induced protein A (IsiA), a major chlorophyll-binding protein in the thylakoid membrane, is significantly induced under iron deficiency conditions. Using immunoblot analysis and 77 K fluorescence spectroscopy combined with sucrose gradient fractionation, we monitored dynamic changes of IsiA-containing complexes in Synechocystis sp. PCC 6803 during exposure to long-term iron deficiency. Within 3 days of exposure to iron deficiency conditions, the initially induced free IsiA proteins preferentially conjugated to PS I trimer to form IsiA 18 -PS I trimers, which serve as light energy collectors for efficiently transmitting energy to PS I. With prolonged iron deficiency, IsiA proteins assembled either into IsiA aggregates or into two other types of IsiA-PS I supercomplexes, namely IsiA-PS I high fluorescence supercomplex (IHFS) and IsiA-PS I low fluorescence supercomplex (ILFS). Further analysis revealed a role for IsiA as an energy dissipater in the IHFS and as an energy collector in the ILFS. The trimeric structure of PS I mediated by PsaL was found to be indispensable for the formation of IHFS/ILFS. Dynamic changes in IsiA-containing complexes in cyanobacteria during long-term iron deficiency may represent an adaptation to iron limitation stress for flexible light energy distribution, which balances electron transfer between PS I and PS II, thus minimizing photooxidative damage. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Inheritance of seed iron and zinc concentrations in common bean (Phaseolus vulgaris L.)

USDA-ARS?s Scientific Manuscript database

Micronutrients are essential elements needed in small amounts for adequate human nutrition and include the elements iron and zinc. Both of these minerals are essential to human well-being, and an adequate supply of iron and zinc helps to prevent iron deficiency anemia and zinc deficiency, two preva...

Lentil (Lens culinaris L) as a candidate crop for iron biofortification: Is there a genetic potential for iron bioavailability?

USDA-ARS?s Scientific Manuscript database

Iron (Fe) deficiency is the most prevalent nutrient deficiency worldwide. Biofortification of staple food crops, such as the lentil (Lens culinaris L.), may be an effective solution. We analyzed the iron (Fe) concentration, Fe bioavailability, and phytic acid (PA) concentration of 23 lentil genotype...

Identification of candidate genes involved in early iron deficiency chlorosis signaling in soybean (Glycine max) roots and leaves

USDA-ARS?s Scientific Manuscript database

Iron is an essential micronutrient for all living things, required in plants for photosynthesis, respiration and metabolism. A lack of bioavailable iron in soil leads to iron deficiency chlorosis (IDC), causing a reduction in photosynthesis and interveinal yellowing of leaves. Soybeans (Glycine ma...

New insights into iron deficiency and iron deficiency anemia.

PubMed

Camaschella, Clara

2017-07-01

Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of artistic gymnastics on iron nutritional status and exercise-induced hemolysis in female athletes.

PubMed

Sureira, Thaiz Mattos; Amancio, Olga Silverio; Pellegrini Braga, Josefina Aparecida

2012-08-01

This study evaluates the relationship between body iron losses and gains in artistic gymnastics female athletes. It shows that despite the low iron intake and exercise-induced hemolysis, iron deficiency or iron-deficiency anemia does not occur, but partial changes in the hematological profile do. The hypothesis that gymnasts' nutritional behavior contributes to anemia, which may be aggravated by exercise-induced hemolysis, led to this cross-sectional study, conducted with 43 female artistic gymnasts 6-16 yr old. The control group was formed by 40 nontraining girls, paired by age. Hemogram, serum iron, ferritin, soluble transferrin receptor, haptoglobin, total and fractional bilirubin, Type I urine, and parasitologic and occult fecal blood tests were evaluated. The athletes presented mean hematimetric and serum iron values (p = .020) higher than those of the control group. The bilirubin result discarded any hemolytic alteration in both groups. The haptoglobin results were lower in the athlete group (p = .002), confirming the incidence of exercise-induced hemolysis. Both groups presented low iron intake. The results suggest that artistic gymnastics practice leads to exercise-induced hemolysis and partially changes the hematological profile, although not causing iron deficiency or iron-deficiency anemia, even in the presence of low iron intake.

Identification of genes induced in proteoid roots of white lupin under nitrogen and phosphorus deprivation, with functional characterization of a formamidase

USDA-ARS?s Scientific Manuscript database

White lupin (Lupinus albus L.) is considered a model system for understanding plant acclimation to nutrient deficiency. It acclimates to phosphorus (P) and iron (Fe) deficiency by the development of short, densely clustered lateral roots called proteoid (or cluster) roots; proteoid-root development ...

Iron deficiency anaemia in chronic kidney disease.

PubMed

Wittwer, Iain

2013-09-01

Iron Deficiency Anaemia (IDA) has been shown to be the most common cause of anaemia worldwide. It is accepted that people with chronic kidney disease (CKD) develop anaemia as their kidney function declines. To better understand IDA in CKD, it is necessary to appreciate the normal iron metabolism and utilisation of iron and how these processes can be disordered in patients with CKD. The problems related to infection / inflammation and oxidative stress are examined. Whilst National and international guidelines recommend specific tests for IDA, these and alternative tests are reviewed. Whilst iron supplementation is necessary for CKD patients with IDA, iron metabolism and utilisation can be affected by factors such as infection or inflammation. Iron is essential element for all life, it can be toxic to cells through the process of oxidative stress. The recommended tests for IDA may be affected by factors such as infection and inflammation. Alternative tests are available, which may be a more accurate indicator of IDA as they are not affected by external factors. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Vitamin and mineral deficiencies in the developed world and their effect on the eye and vision.

PubMed

Whatham, Andrew; Bartlett, Hannah; Eperjesi, Frank; Blumenthal, Caron; Allen, Jane; Suttle, Catherine; Gaskin, Kevin

2008-01-01

Vitamin and mineral deficiencies are common in developing countries, but also occur in developed countries. We review micronutrient deficiencies for the major vitamins A, cobalamin (B(12)), biotin (vitamin H), vitamins C and E, as well as the minerals iron, and zinc, in the developed world, in terms of their relationship to systemic health and any resulting ocular disease and/or visual dysfunction. A knowledge of these effects is important as individuals with consequent poor ocular health and reduced visual function may present for ophthalmic care.

Iron-Binding E3 Ligase Mediates Iron Response in Plants by Targeting Basic Helix-Loop-Helix Transcription Factors1[OPEN

PubMed Central

Selote, Devarshi; Samira, Rozalynne; Matthiadis, Anna; Gillikin, Jeffrey W.; Long, Terri A.

2015-01-01

Iron uptake and metabolism are tightly regulated in both plants and animals. In Arabidopsis (Arabidopsis thaliana), BRUTUS (BTS), which contains three hemerythrin (HHE) domains and a Really Interesting New Gene (RING) domain, interacts with basic helix-loop-helix transcription factors that are capable of forming heterodimers with POPEYE (PYE), a positive regulator of the iron deficiency response. BTS has been shown to have E3 ligase capacity and to play a role in root growth, rhizosphere acidification, and iron reductase activity in response to iron deprivation. To further characterize the function of this protein, we examined the expression pattern of recombinant ProBTS::β-GLUCURONIDASE and found that it is expressed in developing embryos and other reproductive tissues, corresponding with its apparent role in reproductive growth and development. Our findings also indicate that the interactions between BTS and PYE-like (PYEL) basic helix-loop-helix transcription factors occur within the nucleus and are dependent on the presence of the RING domain. We provide evidence that BTS facilitates 26S proteasome-mediated degradation of PYEL proteins in the absence of iron. We also determined that, upon binding iron at the HHE domains, BTS is destabilized and that this destabilization relies on specific residues within the HHE domains. This study reveals an important and unique mechanism for plant iron homeostasis whereby an E3 ubiquitin ligase may posttranslationally control components of the transcriptional regulatory network involved in the iron deficiency response. PMID:25452667

Prevalence of thalassaemia, iron-deficiency anaemia and glucose-6-phosphate dehydrogenase deficiency among Arab migrating nomad children, southern Islamic Republic of Iran.

PubMed

Pasalar, M; Mehrabani, D; Afrasiabi, A; Mehravar, Z; Reyhani, I; Hamidi, R; Karimi, M

2014-12-17

This study investigated the prevalence of iron-deficiency anaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency and β-thalassaemia trait among Arab migrating nomad children in southern Islamic Republic of Iran. Blood samples were analysed from 134 schoolchildren aged < 18 years (51 males, 83 females). Low serum ferritin (< 12 ng/dL) was present in 17.9% of children (21.7% in females and 11.8% in males). Low haemoglobin (Hb) correlated significantly with a low serum ferritin. Only 1 child had G6PD deficiency. A total of 9.7% of children had HbA2 ≥ 3.5 g/dL, indicating β-thalassaemia trait (10.8% in females and 7.8% in males). Mean serum iron, serum ferritin and total iron binding capacity were similar in males and females. Serum ferritin index was as accurate as Hb index in the diagnosis of iron-deficiency anaemia. A high prevalence of β-thalassaemia trait was the major potential risk factor in this population.

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

PubMed

Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

[Biomarkers of Metabolism and Iron Nutrition].

PubMed

Sermini, Carmen Gloria; Acevedo, María José; Arredondo, Miguel

2017-01-01

Iron deficiency anemia is the most common nutritional deficiency worldwide, and the most susceptible groups are infants, preschoolers, women of childbearing age, and pregnant women. It is therefore essential to understand the mechanisms of regulation of iron uptake, transport, and absorption at the cellular level, particularly in enterocytes, and to identify blood biomarkers that allow the evaluation of iron status. This review describes how iron absorption is regulated by intestinal epithelial cells, the main proteins involved (iron transporters, oxidoreductases, storage proteins), and the main blood biomarkers of iron metabolism.

Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

PubMed

Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C; Donnelly, Ryan F; Banga, Ajay; Murthy, S Narasimha

2016-03-01

Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Rosette iron deficiency transcript and microRNA profiling reveals links between copper and iron homeostasis in Arabidopsis thaliana

PubMed Central

Waters, Brian M.; Stein, Ricardo J.

2012-01-01

Iron (Fe) is an essential plant micronutrient, and its deficiency limits plant growth and development on alkaline soils. Under Fe deficiency, plant responses include up-regulation of genes involved in Fe uptake from the soil. However, little is known about shoot responses to Fe deficiency. Using microarrays to probe gene expression in Kas-1 and Tsu-1 ecotypes of Arabidopsis thaliana, and comparison with existing Col-0 data, revealed conserved rosette gene expression responses to Fe deficiency. Fe-regulated genes included known metal homeostasis-related genes, and a number of genes of unknown function. Several genes responded to Fe deficiency in both roots and rosettes. Fe deficiency led to up-regulation of Cu,Zn superoxide dismutase (SOD) genes CSD1 and CSD2, and down-regulation of FeSOD genes FSD1 and FSD2. Eight microRNAs were found to respond to Fe deficiency. Three of these (miR397a, miR398a, and miR398b/c) are known to regulate transcripts of Cu-containing proteins, and were down-regulated by Fe deficiency, suggesting that they could be involved in plant adaptation to Fe limitation. Indeed, Fe deficiency led to accumulation of Cu in rosettes, prior to any detectable decrease in Fe concentration. ccs1 mutants that lack functional Cu,ZnSOD proteins were prone to greater oxidative stress under Fe deficiency, indicating that increased Cu concentration under Fe limitation has an important role in oxidative stress prevention. The present results show that Cu accumulation, microRNA regulation, and associated differential expression of Fe and CuSOD genes are coordinated responses to Fe limitation. PMID:22962679

Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding.

PubMed

Johnson, Stephen; Lang, Abigail; Sturm, Mollie; O'Brien, Sarah H

2016-12-01

To assess the proportion of iron deficiency that is not detected with a screening hemoglobin or complete blood count (CBC) alone in young women with heavy menstrual bleeding. Retrospective review of electronic medical records. Nationwide Children's Hospital in Columbus, Ohio. One hundred fourteen young women aged 9-19 years consecutively referred to a young women's hematology clinic with a complaint of heavy menstrual bleeding. Fifty-eight (50.9%) of all patients had ferritin <20 ng/mL indicating iron deficiency. Of the 58 patients with iron deficiency, only 24 (41.4%) were anemic and 25 (46.3%) were microcytic. The sensitivity of hemoglobin alone and CBC alone for identifying women with ferritin <20 ng/mL was 41.4% (95% confidence interval [CI], 28.7-54.1) and 46.3% (95% CI, 33.0-59.6), respectively. Both tests had reasonable specificity at 91.1% (95% CI, 83.6-98.5) for hemoglobin and 83.9% for CBC (95% CI, 74.3-93.6). Patients had significantly higher odds of having iron deficiency if they were overweight or obese (odds ratio, 2.81; 95% CI, 1.25-6.29) compared with patients with normal body mass index. Age at presentation for heavy menstrual bleeding, presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency. In adolescents with heavy menstrual bleeding, fewer than half of iron deficiency cases are detected when screening is performed with hemoglobin or blood count alone. Measuring ferritin levels in at-risk patients might allow for earlier implementation of iron therapy and improvement in symptoms. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

National Trauma Institute: A National Coordinating Center for Trauma Research Funding

DTIC Science & Technology

2013-10-01

identified as the key regulator of iron homeostasis, and plays a major role in how and why anemia develops. Hepcidin reduces iron availability by: (1...cells. High levels of hepcidin induce a state of functional iron deficiency . Hepcidin is increased in states of inflammation, and likely plays an...elevated in trauma, this will confirm that inability to use iron stores is key to the anemia of trauma. Dr Napolitano suspects that hepcidin will be

Effect of a nutrition education program and diet modification in Beninese adolescent girls suffering from mild iron deficiency anemia.

PubMed

Alaofé, Halimatou; Zee, John; Dossa, Romain; O'Brien, Huguette Turgeon

2009-01-01

A 26-week nutrition intervention, including 4 weeks of nutrition education, combined with an increase in the content and bioavailability of dietary iron for 22 weeks was carried out in 34 intervention and 34 control adolescent girls suffering from mild iron deficiency anemia (IDA). In post-intervention, hemoglobin and serum ferritin were significantly higher in the intervention group, whereas the incidence of IDA was significantly lower in the intervention group compared to the control group. Nutrition knowledge scores were significantly higher in intervention girls compared to control girls. Dietary changes to improve available dietary iron can reduce iron deficiency anemia.

Iron and ferritin accumulate in separate cellular locations in Phaseolus seeds

PubMed Central

2010-01-01

Background Iron is an important micronutrient for all living organisms. Almost 25% of the world population is affected by iron deficiency, a leading cause of anemia. In plants, iron deficiency leads to chlorosis and reduced yield. Both animals and plants may suffer from iron deficiency when their diet or environment lacks bioavailable iron. A sustainable way to reduce iron malnutrition in humans is to develop staple crops with increased content of bioavailable iron. Knowledge of where and how iron accumulates in seeds of crop plants will increase the understanding of plant iron metabolism and will assist in the production of staples with increased bioavailable iron. Results Here we reveal the distribution of iron in seeds of three Phaseolus species including thirteen genotypes of P. vulgaris, P. coccineus, and P. lunatus. We showed that high concentrations of iron accumulate in cells surrounding the provascular tissue of P. vulgaris and P. coccineus seeds. Using the Perls' Prussian blue method, we were able to detect iron in the cytoplasm of epidermal cells, cells near the epidermis, and cells surrounding the provascular tissue. In contrast, the protein ferritin that has been suggested as the major iron storage protein in legumes was only detected in the amyloplasts of the seed embryo. Using the non-destructive micro-PIXE (Particle Induced X-ray Emission) technique we show that the tissue in the proximity of the provascular bundles holds up to 500 μg g-1 of iron, depending on the genotype. In contrast to P. vulgaris and P. coccineus, we did not observe iron accumulation in the cells surrounding the provascular tissues of P. lunatus cotyledons. A novel iron-rich genotype, NUA35, with a high concentration of iron both in the seed coat and cotyledons was bred from a cross between an Andean and a Mesoamerican genotype. Conclusions The presented results emphasize the importance of complementing research in model organisms with analysis in crop plants and they suggest that iron distribution criteria should be integrated into selection strategies for bean biofortification. PMID:20149228

Pathogenic Mechanisms Underlying Iron Deficiency and Iron Overload: New Insights for Clinical Application

PubMed Central

van Velden, DP; van Rensburg, SJ; Erasmus, R

2009-01-01

Iron uptake, utilisation, release and storage occur at the gene level. Individuals with variant forms of genes involved in iron metabolism may have different requirements for iron and are likely to respond differently to the same amount of iron in the diet, a concept termed nutrigenetics. Iron deficiency, iron overload and the anemia of inflammation are the commonest iron-related disorders. While at least four types of hereditary iron overload have been identified to date, our knowledge of the genetic basis and consequences of inherited iron deficiency remain limited. The importance of genetic risk factors in relation to iron overload was highlighted with the identification of the HFE gene in 1996. Deleterious mutations in this gene account for 80-90% of inherited iron overload and are associated with loss of iron homeostasis, alterations in inflammatory responses, oxidative stress and in its most severe form, the disorder hereditary haemochromatosis (HH). Elucidation of the genetic basis of HH has led to rapid clinical benefit through drastic reduction in liver biopsies performed as part of the diagnostic work-up of affected patients. Today, detection of a genetic predisposition in the presence of high serum ferritin and transferrin saturation levels is usually sufficient to diagnose HH, thereby addressing the potential danger of inherited iron overload which starts with the same symptoms as iron deficiency, namely chronic fatigue. This review provides the scientific back-up for application of pathology supported genetic testing, a new test concept that is well placed for optimizing clinical benefit to patients with regard to iron status. PMID:27683335

SCIENTIFIC PAPER PRESENTATION DURING CONCURRENT INTEREST SESSION. Community Health Nursing (Speciality). Iron-deficiency anemia.

PubMed

Kala, K

2015-01-01

Iron deficiency anaemia is the most common form of malnutrition in the world. The global prevalence of anaemia mainly in South East Asia is 65.5 percent, in India 56 percent among adolescent girls. A study conducted to assess the effectiveness of structured teaching programme on knowledge and attitude of adolescent girls in prevention of iron and folic acid deficiency anaemia at a selected corporation school. It adopted one group pre-test post-test design with 60 samples selected by employing stratified random sampling technique. The study revealed that during pre-test 90 percent of them had inadequate knowledge and 65 percent of them had unfavourable attitude towards iron and folic acid deficiency anaemia. After the structured teaching programme the knowledge and attitude was improved (73% had adequate knowledge and 79% had most favourable attitude). Overall the structured teaching programme was found effective in improving the knowledge and attitude of adolescent girls in prevention of iron and folic acid deficiency anaemia.

A Novel Model for Predicting Incident Moderate to Severe Anemia and Iron Deficiency in Patients with Newly Diagnosed Ulcerative Colitis.

PubMed

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Yang, Yu-Xiao

2017-05-01

Anemia and iron deficiency are common complications of ulcerative colitis (UC). We aimed to develop and internally validate a prediction model for the incidence of moderate to severe anemia and iron deficiency anemia (IDA) in newly diagnosed patients with UC. Multivariable logistic regression was performed among a nationwide cohort of patients who were newly diagnosed with UC in the VA health-care system. Model development was performed in a random two-third of the total cohort and then validated in the remaining one-third of the cohort. As candidate predictors, we examined routinely available data at the time of UC diagnosis including demographics, medications, laboratory results, and endoscopy findings. A total of 789 patients met the inclusion criteria. For the outcome of moderate to severe anemia, age, albumin level and mild anemia at UC diagnosis were predictors selected for the model. The AUC for this model was 0.69 (95% CI 0.64-0.74). For the outcome of moderate to severe anemia with evidence of iron deficiency, the predictors included African-American ethnicity, mild anemia, age, and albumin level at UC diagnosis. The AUC was 0.76, (95% CI 0.69-0.82). Calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit p > 0.05). The models performed similarly in the internal validation cohort. We developed and internally validated a prognostic model for predicting the risk of moderate to severe anemia and IDA among newly diagnosed patients with UC. This will help identify patients at high risk of these complications, who could benefit from surveillance and preventive measures.

Anemia in inflammatory bowel disease: A neglected issue with relevant effects

PubMed Central

Guagnozzi, Danila; Lucendo, Alfredo J

2014-01-01

Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients. PMID:24707137

Iron status of women is associated with the iron concentration of potable groundwater in rural Bangladesh.

PubMed

Merrill, Rebecca D; Shamim, Abu Ahmed; Ali, Hasmot; Jahan, Nusrat; Labrique, Alain B; Schulze, Kerry; Christian, Parul; West, Keith P

2011-05-01

Women of reproductive age are at a high risk of iron deficiency, often as a result of diets low in bioavailable iron. In some settings, the iron content of domestic groundwater sources is high, yet its contribution to iron intake and status has not been examined. In a rural Bangladeshi population of women deficient in dietary iron, we evaluated the association between groundwater iron intake and iron status. In 2008, participants (n = 209 with complete data) were visited to collect data on 7-d food frequency, 7-d morbidity history, 24-h drinking water intake, and rice preparation, and to measure the groundwater iron concentration. Blood was collected to assess iron and infection status. Plasma ferritin (μg/L) and body iron (mg/kg) concentrations were [median (IQR)] 67 (46, 99) and 10.4 ± 2.6, respectively, and the prevalence of iron deficiency (ferritin < 12 μg/L) was 0%. Daily iron intake from water [42 mg (18, 71)] was positively correlated with plasma ferritin (r = 0.36) and total body iron (r = 0.35) (P < 0.001 for both). In adjusted linear regression analyses, plasma ferritin increased by 6.1% (95% CI: 3.8, 8.4%) and body iron by 0.3 mg/kg (0.2, 0.4) for every 10-mg increase in iron intake from water (P < 0.001). In this rural area of northern Bangladesh, women of reproductive age had no iron deficiency likely attributable to iron consumed from drinking groundwater, which contributed substantially to dietary intake. These findings suggest that iron intake from water should be included in dietary assessments in such settings.

Integration of P, S, Fe, and Zn nutrition signals in Arabidopsis thaliana: potential involvement of PHOSPHATE STARVATION RESPONSE 1 (PHR1)

PubMed Central

Briat, Jean-François; Rouached, Hatem; Tissot, Nicolas; Gaymard, Frédéric; Dubos, Christian

2015-01-01

Phosphate and sulfate are essential macro-elements for plant growth and development, and deficiencies in these mineral elements alter many metabolic functions. Nutritional constraints are not restricted to macro-elements. Essential metals such as zinc and iron have their homeostasis strictly genetically controlled, and deficiency or excess of these micro-elements can generate major physiological disorders, also impacting plant growth and development. Phosphate and sulfate on one hand, and zinc and iron on the other hand, are known to interact. These interactions have been partly described at the molecular and physiological levels, and are reviewed here. Furthermore the two macro-elements phosphate and sulfate not only interact between themselves but also influence zinc and iron nutrition. These intricated nutritional cross-talks are presented. The responses of plants to phosphorus, sulfur, zinc, or iron deficiencies have been widely studied considering each element separately, and some molecular actors of these regulations have been characterized in detail. Although some scarce reports have started to examine the interaction of these mineral elements two by two, a more complex analysis of the interactions and cross-talks between the signaling pathways integrating the homeostasis of these various elements is still lacking. However, a MYB-like transcription factor, PHOSPHATE STARVATION RESPONSE 1, emerges as a common regulator of phosphate, sulfate, zinc, and iron homeostasis, and its role as a potential general integrator for the control of mineral nutrition is discussed. PMID:25972885

21 CFR 522.1182 - Iron injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... follows: (i) For prevention of iron deficiency anemia, inject 100 mg (1 mL) by intramuscular injection at 2 to 4 days of age. (ii) For treatment of iron deficiency anemia, inject 100 mg (1 mL) by... described in paragraph (a)(1)(i) of this section as follows: (i) For the prevention of anemia due to iron...

21 CFR 522.1182 - Iron injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... and conditions of use. It is used in baby pigs by sponsors in § 510.600(c) of this chapter as follows... baby pig anemia due to iron deficiency, intramuscularly inject 200 mg of elemental iron (1 mL) at 1 to 3 days of age. (ii) For treatment of baby pig anemia due to iron deficiency, intramuscularly inject...

21 CFR 522.1182 - Iron injection.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and conditions of use. It is used in baby pigs by sponsors in § 510.600(c) of this chapter as follows... baby pig anemia due to iron deficiency, intramuscularly inject 200 mg of elemental iron (1 mL) at 1 to 3 days of age. (ii) For treatment of baby pig anemia due to iron deficiency, intramuscularly inject...

21 CFR 522.1182 - Iron injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... and conditions of use. It is used in baby pigs by sponsors in § 510.600(c) of this chapter as follows... baby pig anemia due to iron deficiency, intramuscularly inject 200 mg of elemental iron (1 mL) at 1 to 3 days of age. (ii) For treatment of baby pig anemia due to iron deficiency, intramuscularly inject...

21 CFR 522.1182 - Iron injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and conditions of use. It is used in baby pigs by sponsors in § 510.600(c) of this chapter as follows... baby pig anemia due to iron deficiency, intramuscularly inject 200 mg of elemental iron (1 mL) at 1 to 3 days of age. (ii) For treatment of baby pig anemia due to iron deficiency, intramuscularly inject...

Aneuploidy assessed by DNA index influences the effect of iron status on plasma and/or supernatant cytokine levels and progression of cells through the cell cycle in a mouse model.

PubMed

Kuvibidila, Solo; Porretta, Connie; Baliga, Surendra

2014-02-01

Aneuploidy, a condition associated with altered chromosome number, hence DNA index, is frequently seen in many diseases including cancers and affects immunity. Iron, an essential nutrient for humans, modulates the immune function and the proliferation of normal and cancer cells. To determine whether impaired immunity seen in iron-deficient subjects may be related to aneuploidy, we measured spleen cell DNA index, percent of cells in different phases of the cell cycle, plasma and/or supernatant IL-2, IL-10, IL-12, and interferon-gamma in control, pair-fed, iron-deficient, and iron-replete mice (N=20-22/group). The test and control diets differed only in iron content (0.09mmol/kg versus 0.9mmol/kg) and were fed for 68days. Mean levels of hemoglobin and liver iron stores of iron-deficient and iron-replete mice were 40-60% lower than those of control and pair-fed mice (P<0.05). Mean plasma levels of IL-10, interferon-gamma and percent of cells in S+G2/M phases were lower in mice with than in those without aneuploidy (P<0.05). Lowest plasma IL-12 and interferon-gamma concentrations were observed in iron-deficient mice with aneuploidy. Mean percents of cultures with aneuploidy and DNA indexes were higher in iron-deficient and iron-replete than in control and pair-fed mice likely due to delayed cell division (P<0.05). Aneuploidy decreased the concentration of IL-2 and interferon-gamma in baseline cultures while it increased that of interferon-gamma in anti-CD3 treated cultures. Aneuploidic indexes negatively correlated with cytokine levels, percents of cells in S+G2/M phases and indicators of iron status (P<0.05). Although chromosome cytogenetics was not performed, for the first time, we report that increased aneuploidy rate may modulate the immune function during iron-deficiency. Copyright © 2014. Published by Elsevier Ltd.

Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.

PubMed

Stroh, Matthew A; Winter, Michelle K; Swerdlow, Russell H; McCarson, Kenneth E; Zhu, Hao

2016-08-01

Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. (59)Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain.

Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice

PubMed Central

Stroh, Matthew A.; Winter, Michelle K.; Swerdlow, Russell H.; McCarson, Kenneth E.; Zhu, Hao

2018-01-01

Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. 59Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 weeks and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain. PMID:27188291

The effect of feeding a low iron diet prior to and during gestation on fetal and maternal iron homeostasis in two strains of rat

PubMed Central

2013-01-01

Background Iron deficiency anaemia during pregnancy is a global problem, with short and long term consequences for maternal and child health. Animal models have demonstrated that the developing fetus is vulnerable to maternal iron restriction, impacting on postnatal metabolic and blood pressure regulation. Whilst long-term outcomes are similar across different models, the commonality in mechanistic events across models is unknown. This study examined the impact of iron deficiency on maternal and fetal iron homeostasis in two strains of rat. Methods Wistar (n=20) and Rowett Hooded Lister (RHL, n=19) rats were fed a control or low iron diet for 4 weeks prior to and during pregnancy. Tissues were collected at day 21 of gestation for analysis of iron content and mRNA/protein expression of regulatory proteins and transporters. Results A reduction in maternal liver iron content in response to the low iron diet was associated with upregulation of transferrin receptor expression and a reduction in hepcidin expression in the liver of both strains, which would be expected to promote increased iron absorption across the gut and increased turnover of iron in the liver. Placental expression of transferrin and DMT1+IRE were also upregulated, indicating adaptive responses to ensure availability of iron to the fetus. There were considerable differences in hepatic maternal and fetal iron content between strains. The higher quantity of iron present in livers from Wistar rats was not explained by differences in expression of intestinal iron transporters, and may instead reflect greater materno-fetal transfer in RHL rats as indicated by increased expression of placental iron transporters in this strain. Conclusions Our findings demonstrate substantial differences in iron homeostasis between two strains of rat during pregnancy, with variable impact of iron deficiency on the fetus. Whilst common developmental processes and pathways have been observed across different models of nutrient restriction during pregnancy, this study demonstrates differences in maternal adaptation which may impact on the trajectory of the programmed response. PMID:23635304

Prenatal Choline Supplementation Ameliorates the Long-Term Neurobehavioral Effects of Fetal-Neonatal Iron Deficiency in Rats123

PubMed Central

Kennedy, Bruce C.; Dimova, Jiva G.; Siddappa, Asha J. M.; Tran, Phu V.; Gewirtz, Jonathan C.; Georgieff, Michael K.

2014-01-01

Background: Gestational iron deficiency in humans and rodents produces long-term deficits in cognitive and socioemotional function and alters expression of plasticity genes in the hippocampus that persist despite iron treatment. Prenatal choline supplementation improves cognitive function in other rodent models of developmental insults. Objective: The objective of this study was to determine whether prenatal choline supplementation prevents the long-term effects of fetal-neonatal iron deficiency on cognitive and social behaviors and hippocampal gene expression. Methods: Pregnant rat dams were administered an iron-deficient (2–6 g/kg iron) or iron-sufficient (IS) (200 g/kg iron) diet from embryonic day (E) 3 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline chloride, E11–18). Novel object recognition (NOR) in the test vs. acquisition phase, social approach (SA), and hippocampal mRNA expression were compared at P65 in 4 male adult offspring groups: formerly iron deficient (FID), FID with choline supplementation (FID-C), IS, and IS with choline supplementation. Results: Relative to the intact NOR in IS rats (acquisition: 47.9%, test: 60.2%, P < 0.005), FID adult rats had impaired recognition memory at the 6-h delay (acquisition: 51.4%, test: 55.1%, NS), accompanied by a 15% reduction in hippocampal expression of brain-derived neurotrophic factor (Bdnf) (P < 0.05) and myelin basic protein (Mbp) (P < 0.05). Prenatal choline supplementation in FID rats restored NOR (acquisition: 48.8%, test: 64.4%, P < 0.0005) and increased hippocampal gene expression (FID-C vs. FID group: Bdnf, Mbp, P < 0.01). SA was also reduced in FID rats (P < 0.05 vs. IS rats) but was only marginally improved by prenatal choline supplementation. Conclusions: Deficits in recognition memory, but not social behavior, resulting from gestational iron deficiency are attenuated by prenatal choline supplementation, potentially through preservation of hippocampal Bdnf and Mbp expression. Prenatal choline supplementation may be a promising adjunct treatment for fetal-neonatal iron deficiency. PMID:25332485

Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

NASA Technical Reports Server (NTRS)

Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

1999-01-01

The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

Iron for Africa—Report of an Expert Workshop

PubMed Central

Mwangi, Martin N.; Phiri, Kamija S.; Abkari, Abdelhak; Gbané, Mory; Bourdet-Sicard, Raphaelle; Braesco, Véronique Azaïs; Zimmermann, Michael B.; Prentice, Andrew M.

2017-01-01

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue. PMID:28587263

Genomics of mineral nutrient biofortification: calcium, iron and zinc

USDA-ARS?s Scientific Manuscript database

Dietary deficiencies affect nearly half of the people on the planet, who simply do not receive sufficient nutrition from the food they buy or grow. Inadequate calcium, iron, and zinc consumption create short and long term health problems, which in turn can magnify and stagnate national development. ...

Association Between Meat and Meat-Alternative Consumption and Iron Stores in Early Childhood.

PubMed

Cox, Kelly Anne; Parkin, Patricia C; Anderson, Laura N; Chen, Yang; Birken, Catherine S; Maguire, Jonathon L; Macarthur, Colin; Borkhoff, Cornelia M

To prevent iron deficiency, 2014 Canadian recommendations for healthy term infants from 6 to 24 months recommend iron-rich complementary foods such as meat and meat alternatives 2 or more times a day. The purpose of our study was to evaluate the association between meat and meat-alternative consumption and iron status in young children and the association between red meat consumption and iron status among children meeting recommendations. Healthy children aged 12 to 36 months were recruited. A cross-sectional study was conducted. Meat and meat-alternative consumption was measured using the NutriSTEP questionnaire. Adjusted multivariable regression analyses were used to evaluate an association between meat consumption and serum ferritin, and iron deficiency (serum ferritin <14 μg/L). A total of 1043 children were included. Seventy-three percent of children met the recommended daily intake of meat and meat alternatives, and 66% ate red meat in the past 3 days. Eating meat and meat alternatives was not associated with serum ferritin (0.13 μg/L, 95% confidence interval -0.05, 0.31, P = .16), but it was associated with a decreased odds of iron deficiency (odds ratio 0.97, 95% confidence interval 0.94, 0.99, P = .03). Associations between red meat consumption and iron status were not statistically significant. Statistically significant covariates associated with increased odds of iron deficiency included longer breast-feeding duration, daily cow's milk intake of >2 cups, and a higher body mass index z score. Daily cow's milk intake of >2 cups, longer breast-feeding duration, and a higher body mass index z score were modifiable risk factors associated with iron deficiency. Eating meat according to recommendations may be a promising additional target for the prevention of iron deficiency in early childhood. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Ups and downs of a transcriptional landscape shape iron deficiency associated chlorosis of the maize inbreds B73 and Mo17

PubMed Central

2013-01-01

Background Improving nutrient homeostasis is a major challenge of a sustainable maize cultivation, and cornerstone to ensure food supply for a growing world population. Although, iron constitutes an important nutrient, iron availability is limited. In this respect, iron deficiency associated chlorosis causes severe yield losses every year. Natural variation of the latter trait has yet not been addressed in maize and was therefore studied in the present analysis. Results In this study, we i) report about the contrasting chlorosis phenotypes of the inbreds B73 and Mo17 at 10 and 300 μM iron regime, ii) identified over 400 significantly regulated transcripts (FDR < 0.05) within both inbreds at these growth conditions by deep RNA-Sequencing, iii) linked the gained knowledge with QTL information about iron deficiency related traits within the maize intermated B73 by Mo17 (IBM) population, and iv) highlighted contributing molecular pathways. In this respect, several genes within methionine salvage pathway and phytosiderophore synthesis were found to present constitutively high expression in Mo17, even under sufficient iron supply. Moreover, the same expression pattern could be observed for two putative bHLH transcription factors. In addition, a number of differentially expressed genes showed a co-localisation with QTL confidence intervals for iron deficiency related traits within the IBM population. Conclusions Our study highlights differential iron deficiency associated chlorosis between B73 and Mo17 and represents a valuable resource for differentially expressed genes upon iron limitation and chlorosis response. Besides identifying two putative bHLH transcription factors, we propose that methionine salvage pathway and sterol metabolism amongst others; underlie the contrasting iron deficiency related chlorosis phenotype of both inbreds. Altogether, this study emphasizes a contribution of selected genes and pathways on natural trait variation within the IBM population. PMID:24330725

Higher iron bioavailability of a human-like collagen iron complex.

PubMed

Zhu, Chenhui; Yang, Fan; Fan, Daidi; Wang, Ya; Yu, Yuanyuan

2017-07-01

Iron deficiency remains a public health problem around the world due to low iron intake and/or bioavailability. FeSO 4 , ferrous succinate, and ferrous glycinate chelate are rich in iron but have poor bioavailability. To solve the problem of iron deficiency, following previous research studies, a thiolated human-like collagen-ironcomplex supplement with a high iron content was prepared in an anaerobic workstation. In addition, cell viability tests were evaluated after conducting an MTT assay, and a quantitative analysis of the thiolated human-like collagen-iron digesta samples was performed using the SDS-PAGE method coupled with gel filtration chromatography. The iron bioavailability was assessed using Caco-2 cell monolayers and iron-deficiency anemia mice models. The results showed that (1) one mole of thiolated human-like collagen-iron possessed approximately 35.34 moles of iron; (2) thiolated human-like collagen-iron did not exhibit cytotoxity and (3) thiolated human-like collagen- iron digesta samples had higher bioavailability than other iron supplements, including FeSO 4 , ferrous succinate, ferrous glycine chelate and thiolated human-like collagen-Fe iron. Finally, the iron bioavailability was significantly enhanced by vitamin C. These results indicated that thiolated human-like collagen-iron is a promising iron supplement for use in the future.

Encapsulation of Iron and Other Micronutrients for Food Fortification

NASA Astrophysics Data System (ADS)

Zimmermann, Michael B.; Windhab, Erich J.

Iodine, vitamin A and iron deficiencies are important global public health problems, particularly for preschool children and pregnant women in low-income countries (World Health Organization 2000). These deficiencies are mainly due to monotonous, poor-quality diets that do not meet nutrient requirements. In countries where existing food supplies and/or limited access fail to provide adequate levels of these nutrients in the diet, food fortification is a promising approach. Co-fortification of foods with iron, iodine and vitamin A may be advantageous due to beneficial interactions of these micronutrients in metabolism. Studies in animals and humans have shown that iron deficiency anemia (IDA) impairs thyroid metabolism (Zimmermann et al. 2000a, 2000b; Hess et al. 2002a, 2002b). Vitamin A deficiency may exacerbate anemia through impairment of iron metabolism (Semba and Bloem 2002). Vitamin A, together with iodine, may reduce thyroid hyperstimulation and risk for goiter (Zimmermann et al. 2007). These micronutrient interactions strongly argue for multiple micronutrient fortification. However, food fortification with iron is not straightforward.

Consensus Document of the Spanish Society of Cardiology and the Spanish Society of Internal Medicine on the diagnosis and treatment of iron deficiency in heart failure.

PubMed

Manito, N; Cerqueiro, J M; Comín-Colet, J; García-Pinilla, J M; González-Franco, A; Grau-Amorós, J; Peraira, J R; Manzano, L

Iron deficiency in patients with heart failure is a medical problem of recent particular interest. This interest has resulted from the publication of several clinical trials that demonstrated that the administration of intravenous iron to such patients improved their functional capacity and even reduced the number of hospitalisations for heart failure decompensation. However, applying the evidence from these studies in clinical practice is still controversial, both in terms of the diagnostic criteria for iron deficiency (absolute and functional) and the optimal method for iron replenishment. This article is a consensus document that integrates the recommendations of the Spanish Society of Internal Medicine and the Spanish Society of Cardiology. The article reviews the scientific evidence and proposes a diagnostic and therapeutic performance protocol for iron deficiency in heart failure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Low prevalence of iron deficiency anemia between 1981 and 2010 in Chilean women of childbearing age.

PubMed

Ríos-Castillo, Israel; Brito, Alex; Olivares, Manuel; López-de Romaña, Daniel; Pizarro, Fernando

2013-01-01

To determine the prevalence of anemia and iron status among Chilean women of childbearing age between 1981 and 2010. Calculation of the prevalence of anemia and iron status was based on multiple cross-sectional iron absorption studies performed in 888 women during this period of time. All studies included measurements of hemoglobin, mean corpuscular volume, zinc protoporphyrin, percentage of transferrin saturation and serum ferritin. Data were grouped by decade (1981-1990, 1991-2000, and 2001-2010). Prevalence of anemia for these decades was 9, 6 and 10%, respectively (p=NS). Iron deficiency anemia was the main cause of anemia in all periods (55, 85 and 75%, respectively; p=NS). A high prevalence of women with normal iron status was observed for all periods (64, 69, and 67, respectively; p=NS). Prevalence of iron deficiency without anemia in 1981-1990, 1991-2000 and 2001-2010 was 7, 20 and 12%, respectively (p<0.05). Finally, prevalence of iron depleted stores was 20, 6 and 10%, respectively (p<0.05). Prevalence of iron deficiency anemia in Chilean women of childbearing age was mild between 1981 and 2010. More than 60% of childbearing age women presented normal iron status in all periods. However, prevalence of iron depleted stores was moderate during 1981-1990, and was mild during 1991-2000 and 2001-2010.

Report of the World Health Organization Technical Consultation on Prevention and Control of Iron Deficiency in Infants and Young Children in Malaria-Endemic Areas

USDA-ARS?s Scientific Manuscript database

The objectives were to review the scientific evidence on scientific evidence on safety and efficacy of iron administration to prevent and control iron deficiency at population levels; to provide guidance on the most feasible, effective, and safe progammatic ways to administer additional iron; and to...

Anemia and iron deficiency in gastrointestinal and liver conditions

PubMed Central

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-01-01

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice. PMID:27672287

Anemia and iron deficiency in gastrointestinal and liver conditions.

PubMed

Stein, Jürgen; Connor, Susan; Virgin, Garth; Ong, David Eng Hui; Pereyra, Lisandro

2016-09-21

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

[Ferrous sulfate in the treatment of iron deficiency anemia: The positions continue].

PubMed

Dvoretsky, L I

The paper discusses treatment strategy and tactics for iron deficiency anemia. It gives data on the comparative efficacy of different iron sulfate drugs, their bioavailability, effects on peroxidation processes, and side effects. The paper also considers the clinical significance of a dosage form of iron-containing drugs with a sustained iron release, as well as ways to reduce the frequency and magnitude of side effects when ferrous sulfate is used.

Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

PubMed Central

Hardy, S.; Vandemergel, X.

2015-01-01

Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p = 0.04) but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed. PMID:26000018

Iron bioavailability from cereal products enriched with Pleurotus ostreatus mushrooms in rats with induced anaemia.

PubMed

Reguła, Julita; Krejpcio, Zbigniew; Staniek, Halina

2016-06-02

Oyster mushroom Pleurotus ostreatus is good source of iron. However, there is a limited data concerning bioavailability of iron from oyster mushroom and also cereal products containing this mushroom. The aim of this study was to assess bioavailability of iron from products with an addition of Pleurotus ostreatus in male rats with anaemia. Investigations were conducted in two stages. In the first stage iron deficiency was developed in rats. For this purpose 6 weeks old 36 male Wistar rats were fed a AIN-93M diet deficient in iron and 6 males received a standard AIN-93M diet. In the second stage of the study the assessment of Fe bioavailability from cereal products enriched with dried Pleurotus ostreatus. After experiment the animals were killed and blood and heart, liver, spleen and kidneys were collected for biochemical tests. Feeding male Wistar rats supplemented with dried Pleurotus ostreatus mushrooms diets resulted in the restitution of the systemic Fe level, as manifested by an increase of the level comparable to the control group for: iron transferrin saturation rate, haemoglobin and mean corpuscular volume. Values of hematocrit, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration in animals fed products supplemented with Pleurotus ostreatus were significantly higher compared to animals fed products with no Fe added. The highest MCV value was recorded when 20% of dried oyster mushrooms were added. Iron levels in the blood serum, the liver and kidneys in animals fed cereal products considerably exceeded values recorded at the beginning of the experiment and were similar to the control values. Product may be a valuable source of iron in the nutrition of individuals with a deficiency of this element, first of all patients with absorption and metabolism disorders, but also may add variety to the traditional daily diet.

High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

PubMed Central

Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R.; Collins, James F.

2016-01-01

Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

Review on iron and its importance for human health

PubMed Central

Abbaspour, Nazanin; Hurrell, Richard; Kelishadi, Roya

2014-01-01

It is well-known that deficiency or over exposure to various elements has noticeable effects on human health. The effect of an element is determined by several characteristics, including absorption, metabolism, and degree of interaction with physiological processes. Iron is an essential element for almost all living organisms as it participates in a wide variety of metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and electron transport. However, as iron can form free radicals, its concentration in body tissues must be tightly regulated because in excessive amounts, it can lead to tissue damage. Disorders of iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases. In this review, we discuss the latest progress in studies of iron metabolism and bioavailability, and our current understanding of human iron requirement and consequences and causes of iron deficiency. Finally, we discuss strategies for prevention of iron deficiency. PMID:24778671

Iron Deficiency in Adolescents and Young Adults.

ERIC Educational Resources Information Center

Risser, William L.; Risser, Jan M. H.

1990-01-01

Reviews the prevalence, natural history, causes, impact on performance, diagnosis, and treatment of iron deficiency in adolescent and young adult athletes. All athletes should be screened and treated. The best diagnosis involves determining serum ferritin and hemoglobin levels. Treatment requires therapeutic doses of oral ferrous iron for several…

Reversing Sports-Related Iron and Zinc Deficiencies.

ERIC Educational Resources Information Center

Loosli, Alvin R.

1993-01-01

Many active athletes do not consume enough zinc or iron, which are important for oxygen activation, electron transport, and injury healing. Subclinical deficiencies may impair performance and impair healing times. People who exercise regularly need counseling about the importance of adequate dietary intake of iron and zinc. (SM)

[Anemia in obstetrics and gynecological surgery].

PubMed

Gredilla Díaz, E

2015-06-01

Iron deficiency is more common in women due to uterine bleeding, which affects them throughout their fertile life. Additionally, iron needs increase physiologically during pregnancy and breastfeeding. Pregnant women therefore constitute one of the risk groups for iron deficiency. During the postpartum period, iron deficiency is the most common cause of anemia. Longer hospital stays and greater susceptibility to infections are potential consequences of postpartum anemia. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

PubMed

Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

2017-08-01

Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P < 0.001) higher levels of mean fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

Copper and ectopic expression of the Arabidopsis transport protein COPT1 alter iron homeostasis in rice (Oryza sativa L.).

PubMed

Andrés-Bordería, Amparo; Andrés, Fernando; Garcia-Molina, Antoni; Perea-García, Ana; Domingo, Concha; Puig, Sergi; Peñarrubia, Lola

2017-09-01

Copper deficiency and excess differentially affect iron homeostasis in rice and overexpression of the Arabidopsis high-affinity copper transporter COPT1 slightly increases endogenous iron concentration in rice grains. Higher plants have developed sophisticated mechanisms to efficiently acquire and use micronutrients such as copper and iron. However, the molecular mechanisms underlying the interaction between both metals remain poorly understood. In the present work, we study the effects produced on iron homeostasis by a wide range of copper concentrations in the growth media and by altered copper transport in Oryza sativa plants. Gene expression profiles in rice seedlings grown under copper excess show an altered expression of genes involved in iron homeostasis compared to standard control conditions. Thus, ferritin OsFER2 and ferredoxin OsFd1 mRNAs are down-regulated whereas the transcriptional iron regulator OsIRO2 and the nicotianamine synthase OsNAS2 mRNAs rise under copper excess. As expected, the expression of OsCOPT1, which encodes a high-affinity copper transport protein, as well as other copper-deficiency markers are down-regulated by copper. Furthermore, we show that Arabidopsis COPT1 overexpression (C1 OE ) in rice causes root shortening in high copper conditions and under iron deficiency. C1 OE rice plants modify the expression of the putative iron-sensing factors OsHRZ1 and OsHRZ2 and enhance the expression of OsIRO2 under copper excess, which suggests a role of copper transport in iron signaling. Importantly, the C1 OE rice plants grown on soil contain higher endogenous iron concentration than wild-type plants in both brown and white grains. Collectively, these results highlight the effects of rice copper status on iron homeostasis, which should be considered to obtain crops with optimized nutrient concentrations in edible parts.

Dietary iron intake and iron status of German female vegans: results of the German vegan study.

PubMed

Waldmann, Annika; Koschizke, Jochen W; Leitzmann, Claus; Hahn, Andreas

2004-01-01

As shown in previous studies vegetarians and especially vegans are at risk for iron deficiency. Our study evaluated the iron status of German female vegans. In this cross-sectional study, the dietary intakes of 75 vegan women were assessed by two 9-day food frequency questionnaires. The iron status was analyzed on the basis of blood parameters. Mean daily iron intake was higher than recommended by the German Nutrition Society. Still 42% of the female vegans < 50 years (young women, YW) had a daily iron intake of < 18 mg/day, which is the recommended allowance by the US Food and Nutrition Board. The main dietary sources of iron were vegetables, fruits, cereals and cereal products. Median serum ferritin concentrations were 14 ng/ml for YW and 28 ng/ml for women > or = 50 years (old women, OW). In all, 40% (tri-index model (TIM) 20%) of the YW and 12% (TIM 12%) of the OW were considered iron-deficient based on either serum ferritin levels of < 12 ng/ml or a TIM. Only 3 women had blood parameters which are defined as iron deficiency anemia. Correlations between serum ferritin levels and dietary factors were not found. Although the mean iron intake was above the recommended level, 40% (TIM 20%) of the YW were considered iron-deficient. It is suggested that especially YM on a vegan diet should have their iron status monitored and should consider taking iron supplements in case of a marginal status. Copyright 2004 S. Karger AG, Basel

Excess iron intake as a factor in growth, infections, and development of infants and young children.

PubMed

Lönnerdal, Bo

2017-12-01

The provision of iron via supplementation or the fortification of foods has been shown to be effective in preventing and treating iron deficiency and iron deficiency anemia in infants and young children. However, iron is a pro-oxidative element and can have negative effects on biological systems even at moderate amounts. An increasing number of studies have reported adverse effects of iron that was given to infants and young-children populations who initially were iron replete. These effects include decreased growth (both linear growth and weight), increased illness (usually diarrhea), interactions with other trace elements such as copper and zinc, altered gut microbiota to more pathogenic bacteria, increased inflammatory markers, and impaired cognitive and motor development. If these results can be confirmed by larger and well-controlled studies, it may have considerable programmatic implications (e.g., the necessity to screen for iron status before interventions to exclude iron-replete individuals). A lack of understanding of the mechanisms underlying these adverse outcomes limits our ability to modify present supplementation and fortification strategies. This review summarizes studies on the adverse effects of iron on various outcomes; suggests possible mechanisms that may explain these observations, which are usually made in clinical studies and intervention trials; and gives examples from animal models and in vitro studies. With a better understanding of these mechanisms, it may be possible to find novel ways of providing iron in a form that causes fewer or no adverse effects even when subjects are iron replete. However, it is apparent that our understanding is limited, and research in this area is urgently needed. © 2017 American Society for Nutrition.

Fetal and Neonatal Iron Deficiency Exacerbates Mild Thyroid Hormone Insufficiency Effects on Male Thyroid Hormone Levels and Brain Thyroid Hormone-Responsive Gene Expression

PubMed Central

Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.

2014-01-01

Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone. Early gestation pregnant rats were assigned to 7 different treatment groups: control, Fe deficient (FeD), mild TH deficient (1 ppm PTU), moderate TH deficient (3 ppm PTU), severe TH deficient (10 ppm PTU), FeD/1 ppm PTU, or FeD/3 ppm PTU. FeD or 1 ppm PTU treatment alone reduced postnatal day 15 serum total T4 concentrations by 64% and 74%, respectively, without significantly altering serum total T3 concentrations. Neither treatment alone significantly altered postnatal day 16 cortical or hippocampal T3 concentrations. FeD combined with 1 ppm PTU treatment produced a more severe effect, reducing serum total T4 by 95%, and lowering hippocampal and cortical T3 concentrations by 24% and 31%, respectively. Combined FeD/PTU had a more severe effect on brain TH-responsive gene expression than either treatment alone, significantly altering Pvalb, Dio2, Mbp, and Hairless hippocampal and/or cortical mRNA levels. FeD/PTU treatment more severely impacted cortical and hippocampal parvalbumin protein expression compared with either individual treatment. These data suggest that combining 2 mild thyroidal insults during development significantly disrupts thyroid function and impairs TH-regulated brain gene expression. PMID:24424046

Iron Supplementation Decreases Severity of Allergic Inflammation in Murine Lung

PubMed Central

Hale, Laura P.; Kant, Erin Potts; Greer, Paula K.; Foster, W. Michael

2012-01-01

The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans. PMID:23029172

Management of Anemia in Patients with Inflammatory Bowel Disease (IBD).

PubMed

Patel, Dhruvan; Trivedi, Chinmay; Khan, Nabeel

2018-03-01

Anemia is the most common complication as well as an extra intestinal manifestation of inflammatory bowel disease (IBD). It is associated with a significant impact on patient's quality of life (QoL); as well it represents a common cause of frequent hospitalization, delay of hospital inpatient discharge and overall increased healthcare burden. In spite of all these, anemia is still often underdiagnosed and undertreated. Our aim in this review is to provide a pathway for physicians to help them achieve early diagnosis as well as timely and appropriate treatment of anemia which in turn would hopefully reduce the prevalence and subsequent complications of this condition among IBD patients. The etiology of anemia among IBD patients is most commonly due to iron deficiency anemia (IDA) followed by anemia of chronic disease. Despite this, more than a third of anemic ulcerative colitis (UC) patients are not tested for IDA and among those tested and diagnosed with IDA, a quarter are not treated with iron replacement therapy. A new algorithm has been validated to predict who will develop moderate to severe anemia at the time of UC diagnosis. While oral iron is effective for the treatment of mild iron deficiency-related anemia, the absorption of iron is influenced by chronic inflammatory states as a consequence of the presence of elevated levels of hepcidin. Also, it is important to recognize that ferritin is elevated in chronic inflammatory states and among patients with active IBD, ferritin levels less than 100 are considered to be diagnostic of iron deficiency. Newer formulations of intra-venous (IV) iron have a good safety profile and can be used for replenishment of iron stores and prevention of iron deficiency in the future. Routine screening for anemia is important among patients with IBD. The cornerstone for the accurate management of anemia in IBD patients lies in accurately diagnosing the type of anemia. All IBD patients with IDA should be considered appropriate for therapy with iron supplementation whereas IV administration of iron is recommended in patients with clinically active IBD, or for patients who are previously intolerant to oral iron, with hemoglobin levels below 10 g/dL, and in patients who need erythropoiesis-stimulating agents (ESAs). As the recurrence of anemia is common after resolution, the monitoring for recurrent anemia is equally important during the course of therapy.

Anaemia in elective orthopaedic surgery - Royal Adelaide Hospital, Australia.

PubMed

Kearney, B; To, J; Southam, K; Howie, D; To, B

2016-01-01

An anaemia clinic was established to improve the preoperative management of elective orthopaedic patients scheduled for arthroplasty. This paper is a report on the first 100 patients assessed. To assess the incidence and causes of anaemia in patients on a waiting list for elective arthroplasty in a public hospital and to assess the impact of anaemia detection in this patient population. Patients attending an Anaemia Clinic for elective orthopaedic surgical patients, during March 2010 to June 2013 were studied. Outcome measures included change in haemoglobin preoperative results and perioperative transfusion rates by preoperative haemoglobin. Seventeen per cent of patients scheduled for elective surgery were found to be anaemic. Of the 100 patients who attended, approximately half were found to be iron deficient and the remainder had anaemia of chronic disease. Serum ferritin <30 µg/L alone did not identify iron deficiency in 80% of patients with iron deficiency. Patients with iron deficient anaemia were able to be treated, in all cases, to achieve a significant increase in preoperative haemoglobin. The general unavailability of erythropoietin limited effective intervention for the non-iron-deficient anaemic patients. Seven patients had their surgery cancelled because of the screening programme. Half of the anaemic patients in a joint replacement screening clinic were iron deficient, and treatment was effective in improving the pre-operative haemoglobin and reducing perioperative transfusion rates. This screening process should improve patient outcome. Another important finding in this group of patients is that ferritin levels cannot be reliably used as the sole indicator in the diagnosis of iron deficiency anaemia in this group of patients undergoing elective arthroplasty. © 2015 Royal Australasian College of Physicians.

Influence of carotene-rich vegetable meals on the prevalence of anaemia and iron deficiency in Filipino schoolchildren.

PubMed

Maramag, C C; Ribaya-Mercado, J D; Rayco-Solon, P; Solon, J A A; Tengco, L W; Blumberg, J B; Solon, F S

2010-05-01

To determine the effects of eating carotene-rich green and yellow vegetables on the prevalence of anaemia, iron deficiency and iron-deficiency anaemia in schoolchildren. Schoolchildren (n=104), aged 9-12 years, received standardized meals containing 4.2 mg of provitamin A carotenoids/day (mainly beta-carotene) from yellow and green leafy vegetables and at least 7 g dietary fat/day. The meals were provided three times/day, 5 days/week, for 9 weeks at school. Before and after the dietary intervention, total-body vitamin A pool size was assessed by using the deuterated-retinol-dilution method; serum retinol and beta-carotene concentrations were measured by high-performance liquid chromatography; and whole blood haemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations were measured by using a photometer and a hematofluorometer, respectively. After 9 weeks, the mean total-body vitamin A pool size increased twofold (95% confidence interval (CI): -0.11, -0.07 micromol retinol; P<0.001), and serum beta-carotene concentration increased fivefold (95% CI: -0.97, -0.79 micromol/l; P<0.001). Blood Hb (95% CI: -1.02, -0.52 g per 100 ml; P<0.001) and ZnPP increased (95% CI: -11.82, -4.57 microol/mol haem; P<0.001). The prevalence of anaemia (Hb<11.5 g per 100 ml) decreased from 12.5 to 1.9% (P<0.001). There were no significant changes in the prevalence of iron deficiency or iron-deficiency anaemia. Ingestion of carotene-rich yellow and green leafy vegetables improves the total-body vitamin A pool size and Hb concentration, and decreases anaemia rates in Filipino schoolchildren, with no effect on iron deficiency or iron-deficiency anaemia rates.

Myeloid Neoplasms in the Guise of Nutritional Deficiency

PubMed Central

Parthasarathy, Veda

2012-01-01

The classic BCR-ABL-negative myeloproliferative neoplasms (MPNs) which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are among the most frequent hematologic neoplasms. Because of their relatively smooth clinical course, it is likely that many of these MPNs actually go undetected. Considering the high prevalence of iron, folic-acid, and vitamin B12 deficiencies in developing countries, their coexistence with MPN can be expected frequently. In such situations where both disorders coexist, MPN is often overlooked. This causes considerable diagnostic delay. In this paper, two cases of PMF and one case of PV where the diagnosis of MPN was delayed for about 3 years are discussed. Presence of concomitant vitamin B12, folate, and iron deficiencies perhaps camouflaged the underlying MPN. Bearing in mind the possibility of MPN, even in the setting of apparent nutritional deficiency and performing a bone marrow evaluation, is the crucial step in unveiling the hidden MPN. PMID:23227377

Plant features measurements for robotics

NASA Technical Reports Server (NTRS)

Miles, Gaines E.

1989-01-01

Initial studies of the technical feasibility of using machine vision and color image processing to measure plant health were performed. Wheat plants were grown in nutrient solutions deficient in nitrogen, potassium, and iron. An additional treatment imposed water stress on wheat plants which received a full complement of nutrients. The results for juvenile (less than 2 weeks old) wheat plants show that imaging technology can be used to detect nutrient deficiencies. The relative amount of green color in a leaf declined with increased water stress. The absolute amount of green was higher for nitrogen deficient leaves compared to the control plants. Relative greenness was lower for iron deficient leaves, but the absolute green values were higher. The data showed patterns across the leaf consistent with visual symptons. The development of additional color image processing routines to recognize these patterns would improve the performance of this sensor of plant health.

Treatment of Anemia in Heart Failure: Potential Risks and Benefits of Intravenous Iron Therapy in Cardiovascular Disease

PubMed Central

Jelani, Qurat-ul-ain; Katz, Stuart D.

2010-01-01

Iron-deficiency anemia is common is patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a sub-group analysis also suggests that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients. PMID:20699672

α-Lactalbumin and casein-glycomacropeptide do not affect iron absorption from formula in healthy term infants.

PubMed

Szymlek-Gay, Ewa A; Lönnerdal, Bo; Abrams, Steven A; Kvistgaard, Anne S; Domellöf, Magnus; Hernell, Olle

2012-07-01

Iron absorption from infant formula is relatively low. α-Lactalbumin and casein-glycomacropeptide have been suggested to enhance mineral absorption. We therefore assessed the effect of α-lactalbumin and casein-glycomacropeptide on iron absorption from infant formula in healthy term infants. Thirty-one infants were randomly assigned to receive 1 of 3 formulas (4 mg iron/L, 13.1 g protein/L) from 4-8 wk to 6 mo of age: commercially available whey-predominant standard infant formula (standard formula), α-lactalbumin-enriched infant formula (α-LAC), or α-lactalbumin-enriched/casein-glycomacropeptide-reduced infant formula (α-LAC/RGMP). Nine breast-fed infants served as a reference. At 5.5 mo of age, (58)Fe was administered to all infants in a meal. Blood samples were collected 14 d later for iron absorption and iron status indices. Iron deficiency was defined as depleted iron stores, iron-deficient erythropoiesis, or iron deficiency anemia. Iron absorption (mean ± SD) was 10.3 ± 7.0% from standard formula, 8.6 ± 3.8% from α-LAC, 9.2 ± 6.5% from α-LAC/RGMP, and 12.9 ± 6.5% from breast milk, with no difference between the formula groups (P = 0.79) or all groups (P = 0.44). In the formula-fed infants only, iron absorption was negatively correlated with serum ferritin (r = -0.49; P = 0.005) and was higher (P = 0.023) in iron-deficient infants (16.4 ± 12.4%) compared with those with adequate iron status (8.6 ± 4.4%). Our findings indicate that α-lactalbumin and casein-glycomacropeptide do not affect iron absorption from infant formula in infants. Low serum ferritin concentrations are correlated with increased iron absorption from infant formula.

Guidelines for the management of iron deficiency anaemia.

PubMed

Goddard, Andrew F; James, Martin W; McIntyre, Alistair S; Scott, Brian B

2011-10-01

Iron deficiency anaemia (IDA) occurs in 2-5% of adult men and postmenopausal women in the developed world and is a common cause of referral to gastroenterologists. Gastrointestinal (GI) blood loss from colonic cancer or gastric cancer, and malabsorption in coeliac disease are the most important causes that need to be sought. DEFINING IRON DEFICIENCY ANAEMIA: The lower limit of the normal range for the laboratory performing the test should be used to define anaemia (B). Any level of anaemia should be investigated in the presence of iron deficiency (B). The lower the haemoglobin the more likely there is to be serious underlying pathology and the more urgent is the need for investigation (B). Red cell indices provide a sensitive indication of iron deficiency in the absence of chronic disease or haemoglobinopathy (A). Haemoglobin electrophoresis is recommended when microcytosis and hypochromia are present in patients of appropriate ethnic background to prevent unnecessary GI investigation (C). Serum ferritin is the most powerful test for iron deficiency (A). Upper and lower GI investigations should be considered in all postmenopausal female and all male patients where IDA has been confirmed unless there is a history of significant overt non-GI blood loss (A). All patients should be screened for coeliac disease (B). If oesophagogastroduodenoscopy (OGD) is performed as the initial GI investigation, only the presence of advanced gastric cancer or coeliac disease should deter lower GI investigation (B). In patients aged >50 or with marked anaemia or a significant family history of colorectal carcinoma, lower GI investigation should still be considered even if coeliac disease is found (B). Colonoscopy has advantages over CT colography for investigation of the lower GI tract in IDA, but either is acceptable (B). Either is preferable to barium enema, which is useful if they are not available. Further direct visualisation of the small bowel is not necessary unless there are symptoms suggestive of small bowel disease, or if the haemoglobin cannot be restored or maintained with iron therapy (B). In patients with recurrent IDA and normal OGD and colonoscopy results, Helicobacter pylori should be eradicated if present. (C). Faecal occult blood testing is of no benefit in the investigation of IDA (B). All premenopausal women with IDA should be screened for coeliac disease, but other upper and lower GI investigation should be reserved for those aged 50 years or older, those with symptoms suggesting gastrointestinal disease, and those with a strong family history of colorectal cancer (B). Upper and lower GI investigation of IDA in post-gastrectomy patients is recommended in those over 50 years of age (B). In patients with iron deficiency without anaemia, endoscopic investigation rarely detects malignancy. Such investigation should be considered in patients aged >50 after discussing the risk and potential benefit with them (C). Only postmenopausal women and men aged >50 years should have GI investigation of iron deficiency without anaemia (C). Rectal examination is seldom contributory, and, in the absence of symptoms such as rectal bleeding and tenesmus, may be postponed until colonoscopy. Urine testing for blood is important in the examination of patients with IDA (B). All patients should have iron supplementation both to correct anaemia and replenish body stores (B). Parenteral iron can be used when oral preparations are not tolerated (C). Blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia (C).

Credibility of the measurement of serum ferritin and transferrin receptor as indicators of iron deficiency anemia in hemodialysis patients.

PubMed

Mahdavi, M R; Makhlough, A; Kosaryan, M; Roshan, P

2011-10-01

Anemia is a common complication in uremic patients. Erythropoietin therapy is prescribed in these cases; however, this treatment is not successful in iron deficient patients. Ferritin-based diagnosis of iron deficiency in these patients is a challenging task, as serum ferritin level may be high due to chronic inflammation and mask iron deficiency. In the current study we evaluated the credibility of another indicator of body iron supply, serum transferrin receptor, in hemodialysis patients in two University-based Hospitals in North of Iran. In a cross-sectional study, 53 hemodialysis patients with a mean age of 56 +/- 18.7 years and 30 persons with iron deficiency and normal renal function with a mean age of 20.1 +/- 14.4 years were examined. All hemodialysis patients were on hemodialysis 2-3 times per week for 3-4 hours. All cases were examined for blood hemoglobin content, serum iron, CRP, serum ferritin and serum transferrin receptor levels. The reference ranges introduced by manufacturers were considered as standard ranges for analysis of the results. Using one sample T-test and Fisher's exact test, data were analyzed. p<0.05 was considered as significant. Hemodialysis patients had blood hemoglobin content below normal range (p<0.05 for men, p<0.001 for women) and CRP levels above normal range (p<0.001). In hemodialysis patients, serum ferritin level was significantly higher than control group (p<0.001), whilst serum transferrin receptor levels in the two groups were not significantly different (p=0.69), and both were above defined normal upper limit (p<0.001 for iron deficient patients; p<0.05 for hemodialysis patients). This study showed measurement of serum ferritin in the presence of chronic inflammation induced by renal failure cannot be a credible indicator of body iron supply, while under this certain condition serum transferrin receptor can more appropriately reflect the amount of body iron supply.

Rising atmospheric CO2 lowers food zinc, iron, and protein concentrations

USDA-ARS?s Scientific Manuscript database

Dietary deficiencies of zinc and iron are a major global public health problem. Most people who experience these deficiencies depend on agricultural crops for zinc and iron. In this context, the influence of rising concentrations of atmospheric CO2 on the availability of these nutrients from crops i...

[Iron nutritional status in pregnant adolescents at the beginning of gestation].

PubMed

Hertrampf, E; Olivares, M; Letelier, A; Castillo, C

1994-12-01

The frequency of anemia and iron nutrition deficiency was assessed in 342 low socioeconomic level pregnant teenagers at entry to prenatal care in 5 outpatient clinics from a South Orient area of Santiago Chile. According to the Center for Disease Control Criteria, 1.2% of women had iron deficiency anemia. Iron stores were insufficient (defined as a serum ferritin lower than 20 g/L) in 55% for women and depleted (serum ferritin lower than 10 g/L) in 21%. Women with more than 14 weeks of gestation had lower packed red cell volumes, hemoglobin, mean corpuscular volumes and ferritin levels than women with less than 14 of gestation. It is concluded that the prevalence of iron deficiency anemia is lower than that predicted for a highly vulnerable group but the high frequency of low iron stores should encourage the use of iron supplementation in these teenagers.

MCPIP1 Deficiency in Mice Results in Severe Anemia Related to Autoimmune Mechanisms

PubMed Central

Zhou, Zhou; Miao, Ruidong; Huang, Shengping; Elder, Brandon; Quinn, Tim; Papasian, Christopher J.; Zhang, Jifeng; Fan, Daping; Chen, Y. Eugene; Fu, Mingui

2013-01-01

Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1-/- developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1-/- bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12) deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1-/- mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1-/- mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1-/- mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease. PMID:24324805

Prevalence of Iron Deficiency Anaemia Among School Children in Kenitra, Northwest of Morocco.

PubMed

Achouri, I; Aboussaleh, Y; Sbaibi, R; Ahami, A; El Hioui, M

2015-04-01

Iron deficiency anaemia is an important health problem in Morocco. This study was conducted to estimate the prevalence of anaemia among school children in Kenitra. The sample represents school children of all educational levels and age ranged between 6-15 years. The level of hemoglobin, haematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration was measured in a group of 271 school children. The seric iron was assessed and anaemia was defined when hemoglobin < 11.5 g dL(-1). A questionnaire was developed to obtain information about the daily food consumption and socio-economic conditions. The prevalence of anaemia was 16.2%. The mean hemoglobin concentration was 12.53 g dL(-1) in boys and 12.52 g dL(-1) in girls. The results suggest that iron deficiency is an important determinant of anaemia in this population. There was a significant relationship between education of the mother and anaemia in children (p = 0.004) but not with the family income. It is concluded that improving the economic status of the family, women education and health education about balanced animal and plant food consumption are recommended strategies to reduce the burden of anaemia.

Anemia after continuous-flow left ventricular assist device implantation: characteristics and implications.

PubMed

Amione-Guerra, Javier; Cruz-Solbes, Ana S; Bhimaraj, Arvind; Trachtenberg, Barry H; Pingali, Sai R; Estep, Jerry D; Park, Myung H; Guha, Ashrith

2017-09-15

Anemia is common in patients with heart failure and is associated with adverse outcomes. Management of anemia in CF-LVAD patients is not well studied. Our purpose is to characterize and identify the etiology of anemia in CF-LVAD patients. Secondary objectives are to describe the effect of CF-LVAD on pre-existing anemia and assess its impact after CF-LVAD support. Cross-sectional study from January to July 2015 of ambulatory patients supported with a CF-LVAD for at least 6-months that presented with hemoglobin <12 g/dL and no recent gastrointestinal bleeding. Patients were classified as iron-deficient and non-iron-deficient and compared. Additionally, a retrospective analysis of 116 consecutive patients who underwent CF-LVAD from 2008 to 2013 with reported hemoglobin at 6 months as outpatients were divided into anemic or non-anemic and compared. In our cross-sectional cohort, iron deficiency was the most common cause of anemia. Notably, 49% of the iron-deficient patients were already on iron supplementation. In our retrospective cohort, 59% of the patients were anemic after 6 months of support. Anemic patients were older, had lower albumin, higher brain natriuretic peptide (BNP), worse renal function and New York Heart Association (NYHA) class. Anemia had a HR of 3.16 (95%CI 1.38-7.26) to predict a composite of 1-year death and HF readmissions, as well as HF-readmissions alone. The most common cause of anemia in our study was iron-deficiency; almost half of the patients were iron deficient despite treatment, suggesting that oral iron may not be sufficient to reverse anemia. Anemia regardless of etiology was associated with adverse outcomes.

An infant and mother with severe B12 deficiency: vitamin B12 status assessment should be determined in pregnant women with anaemia.

PubMed

Sobczyńska-Malefora, A; Ramachandran, R; Cregeen, D; Green, E; Bennett, P; Harrington, D J; Lemonde, H A

2017-08-01

The vitamin B 12 status of infants depends on maternal B 12 status during pregnancy, and during lactation if breastfed. We present a 9-month-old girl who was admitted to the metabolic unit for assessment of developmental delay. She was exclusively breastfed and the introduction of solids at 5 months was unsuccessful. Investigations revealed pancytopenia, undetectable B 12 and highly elevated methylmalonic acid and homocysteine. Methylmalonic acid and homocysteine normalised following B 12 injections. Marked catch-up of developmental milestones was noted after treatment with B 12 . Investigations of parents showed normal B 12 in the father and combined B 12 and iron deficiency in the mother. Maternal B 12 deficiency, most likely masked by iron deficiency, led to severe B 12 deficiency in the infant. Exclusive breastfeeding and a subsequent failure to wean exacerbated the infant's B 12 deficiency leading to developmental delay. This case highlights the need for development of guidelines for better assessment of B 12 status during pregnancy.

Anemia, Micronutrient Deficiencies, and Malaria in Children and Women in Sierra Leone Prior to the Ebola Outbreak - Findings of a Cross-Sectional Study

PubMed Central

Wirth, James P; Rohner, Fabian; Woodruff, Bradley A; Chiwile, Faraja; Yankson, Hannah; Koroma, Aminata S; Russel, Feimata; Sesay, Fatmata; Dominguez, Elisa; Petry, Nicolai; Shahab-Ferdows, Setareh; de Onis, Mercedes; Hodges, Mary H

2016-01-01

To identify the factors associated with anemia and to document the severity of micronutrient deficiencies, malaria and inflammation, a nationally representative cross-sectional survey was conducted. A three-stage sampling procedure was used to randomly select children <5 years of age and adult women from households in two strata (urban and rural). Household and individual data were collected, and blood samples from children and women were used to measure the prevalence of malaria, inflammation, and deficiencies of iron, vitamin A, folate, and vitamin B12. 839 children and 945 non-pregnant women were included in the survey. In children, the prevalence rates of anemia (76.3%; 95% CI: 71.8, 80.4), malaria (52.6%; 95% CI: 46.0, 59.0), and acute and chronic inflammation (72.6%; 95% CI: 67.5, 77.1) were high. However, the prevalence of vitamin A deficiency (17.4%; 95% CI: 13.9, 21.6) was moderate, and the prevalence of iron deficiency (5.2%; 95% CI: 3.3, 8.1) and iron-deficiency anemia (3.8%; 95% CI: 2.5, 5.8) were low. Malaria and inflammation were associated with anemia, yet they explained only 25% of the population-attributable risk. In women, 44.8% (95% CI: 40.1, 49.5), 35.1% (95% CI: 30.1, 40.4), and 23.6% (95% CI: 20.4, 27.3) were affected by anemia, malaria, or inflammation, respectively. The prevalence rates of iron deficiency (8.3%; 95% CI: 6.2, 11.1), iron-deficiency anemia (6.1%; 95% CI: 4.4, 8.6), vitamin A deficiency (2.1%; 95% CI: 1.1, 3.1) and vitamin B12 deficiency (0.5%; 95% CI: 0.2, 1.4) were low, while folate deficiency was high (79.2%; 95% CI: 74.1, 83.5). Iron deficiency, malaria, and inflammation were significantly associated with anemia, but explained only 25% of cases of anemia. Anemia in children and women is a severe public health problem in Sierra Leone. Since malaria and inflammation only contributed to 25% of anemia, other causes of anemia, such as hemoglobinopathies, should also be explored. PMID:27163254

System analysis of metabolism and the transcriptome in Arabidopsis thaliana roots reveals differential co-regulation upon iron, sulfur and potassium deficiency.

PubMed

Forieri, Ilaria; Sticht, Carsten; Reichelt, Michael; Gretz, Norbert; Hawkesford, Malcolm J; Malagoli, Mario; Wirtz, Markus; Hell, Ruediger

2017-01-01

Deprivation of mineral nutrients causes significant retardation of plant growth. This retardation is associated with nutrient-specific and general stress-induced transcriptional responses. In this study, we adjusted the external supply of iron, potassium and sulfur to cause the same retardation of shoot growth. Nevertheless, limitation by individual nutrients resulted in specific morphological adaptations and distinct shifts within the root metabolite fingerprint. The metabolic shifts affected key metabolites of primary metabolism and the stress-related phytohormones, jasmonic, salicylic and abscisic acid. These phytohormone signatures contributed to specific nutrient deficiency-induced transcriptional regulation. Limitation by the micronutrient iron caused the strongest regulation and affected 18% of the root transcriptome. Only 130 genes were regulated by all nutrients. Specific co-regulation between the iron and sulfur metabolic routes upon iron or sulfur deficiency was observed. Interestingly, iron deficiency caused regulation of a different set of genes of the sulfur assimilation pathway compared with sulfur deficiency itself, which demonstrates the presence of specific signal-transduction systems for the cross-regulation of the pathways. Combined iron and sulfur starvation experiments demonstrated that a requirement for a specific nutrient can overrule this cross-regulation. The comparative metabolomics and transcriptomics approach used dissected general stress from nutrient-specific regulation in roots of Arabidopsis. © 2016 John Wiley & Sons Ltd.

Erythrocyte CuZn superoxide dismutase activity is decreased in iron-deficiency anemia.

PubMed

Olivares, M; Araya, M; Pizarro, F; Letelier, A

2006-09-01

Iron and copper are essential microminerals that are intimately related. The present study was performed to determine the effect of iron-deficiency anemia (IDA) and treatment with iron on laboratory indicators of copper status. Hemoglobin, mean corpuscular volume erythrocyte Zn protoporphyrin, serum ferritin, serum copper, serum ceruloplasmin, and erythrocyte CuZn-superoxide dismutase (SOD) activity were studied in 12 adult women with IDA before and after iron treatment for 60-90 d (100 mg/d Fe, as ferric polymaltose) and in 27 women with normal iron status. Prior to treatment with iron, serum copper and ceruloplasmin were not different between the groups and treatment with iron did not affect these measures. IDA women, before and after treatment with iron, presented a 2.9- and 2-fold decrease in erythrocyte CuZn-SOD activity compared to women with normal iron status (p < 0.001). Treatment with iron increased erythrocyte CuZn-SOD activity of the IDA group; however, this change was not statistically significant. In conclusion, CuZn-SOD activity is decreased in IDA. Measurement of this enzyme activity is not useful for evaluating copper nutrition in iron-deficient subjects.

Diagnosis of thalassemia and iron deficiency anemia using confocal and atomic force microscopy

NASA Astrophysics Data System (ADS)

Tariq, Saira; Bilal, Muhammad; Shahzad, Shaheen; Firdous, Shamaraz; Aziz, Uzma; Ahmed, Mushtaq

2017-11-01

Anemia is the most prevalent blood disorder, categorized into thalassemia and iron deficiency anemia. In anemia, the morphology of erythrocytes is disturbed, thus leading to abnormal functioning of the erythrocytes. Globally, thalassemia affects 1.3% of individuals and is one of the most widespread monogenic disorders in Pakistan. All over the World, women and children are most frequently affected by a type of nutritional deficiency known as iron deficiency anemia. The morphological changes that occur in erythrocytes due to these diseases are investigated in this study at the nano-scale level. Fifty samples of blood from individuals suffering from thalassemia or iron deficiency anemia were obtained from different hospitals in Rawalpindi and Islamabad. The blood samples were scanned using atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM) to check the morphological changes in both types of anemia. According to the present study, thalassemia is most prevalent in females in the age group between 5 and 15 years old, and iron deficiency is most prevalent in females in the age groups of 16-25 and 36-45 years old. Erythrocyte morphology is the significant determinant for diagnosing and discriminating between these two types of diseases. The study reports deformed erythrocytes in anemic patients, which were different from the ones that existed in the control. Thalassemia erythrocytes showed a crenated shape, iron deficiency anemia erythrocytes showed an elliptocyte shape and healthy erythrocytes showed a biconcave disk shape when using AFM and LSCM. These techniques seem to be very promising, cheap and less time consuming in determining the structure-function relationship of erythrocytes of thalassemic and iron deficiency anemic patients. The results of LSCM and AFM are quite useful in determining the morphological changes in erythrocytes and to study the disease at the molecular level within short period of time. Hence, we encourage employing these non-invasive techniques for the effective diagnosis of anemic patients.

Maize porridge enriched with a micronutrient powder containing low-dose iron as NaFeEDTA but not amaranth grain flour reduces anemia and iron deficiency in Kenyan preschool children.

PubMed

Macharia-Mutie, Catherine W; Moretti, Diego; Van den Briel, Natalie; Omusundi, Agnes M; Mwangi, Alice M; Kok, Frans J; Zimmermann, Michael B; Brouwer, Inge D

2012-09-01

Few studies have evaluated the impact of fortification with iron-rich foods such as amaranth grain and multi-micronutrient powder (MNP) containing low doses of highly bioavailable iron to control iron deficiency anemia (IDA) in children. We assessed the efficacy of maize porridge enriched with amaranth grain or MNP to reduce IDA in Kenyan preschool children. In a 16-wk intervention trial, children (n = 279; 12-59 mo) were randomly assigned to: unrefined maize porridge (control; 4.1 mg of iron/meal; phytate:iron molar ratio 5:1); unrefined maize (30%) and amaranth grain (70%) porridge (amaranth group; 23 mg of iron/meal; phytate:iron molar ratio 3:1); or unrefined maize porridge with MNP (MNP group; 6.6 mg iron/meal; phytate:iron molar ratio 2.6:1; 2.5 mg iron as NaFeEDTA). Primary outcomes were anemia and iron status with treatment effects estimated relative to control. At baseline, 38% were anemic and 30% iron deficient. Consumption of MNP reduced the prevalence of anemia [-46% (95% CI: -67, -12)], iron deficiency [-70% (95% CI: -89, -16)], and IDA [-75% (95% CI: -92, -20)]. The soluble transferrin receptor [-10% (95% CI: -16, -4)] concentration was lower, whereas the hemoglobin (Hb) [2.7 g/L (95% CI: 0.4, 5.1)] and plasma ferritin [40% (95% CI: 10, 95)] concentrations increased in the MNP group. There was no significant change in Hb or iron status in the amaranth group. Consumption of maize porridge fortified with low-dose, highly bioavailable iron MNP can reduce the prevalence of IDA in preschool children. In contrast, fortification with amaranth grain did not improve iron status despite a large increase in iron intake, likely due to high ratio of phytic acid:iron in the meal.

Ferric Carboxymaltose Injection

MedlinePlus

... carboxymaltose injection is used to treat iron-deficiency anemia (a lower than normal number of red blood ... medication is also used to treat iron deficiency anemia in adults with chronic kidney disease (damage to ...

The investigation of plasma glucose-6-phosphate dehydrogenase, 6-phoshogluconate dehydrogenase, glutathione reductase in premenauposal patients with iron deficiency anemia.

PubMed

Ozcicek, Fatih; Aktas, Mehmet; Türkmen, Kultigin; Coban, T Abdulkadir; Cankaya, Murat

2014-07-01

Iron is an essential element that is necessary for all cells in the body. Iron deficiency anemia (IDA) is one of the most common nutritional disorders in both developed and developing countries. The glutathione pathway is paramount to antioxidant defense and glucose-6-phosphate dehydrogenase (G6PD)-deficient cells do not cope well with oxidative damage. The goal of this study was to check the activities of G6PD, 6-phosphogluconate dehydrogenase, glutathione reductase in patients with IDA. We analyzed the plasma samples of 102 premenopausal women with IDA and 88 healthy control subjects. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activity as compared to the reduction of NADP +, glutathione reductase activity was performed based on the oxidation of NADPH. 2 ml of plasma were used in all analyzes. SPSS program was used for all of the statistical analysis. Diagnosis of iron deficiency in patients belonging to the analysis of blood were ferritin 3.60 ± 2.7 ng / mL, hemoglobin 9.4 ± 1.5 mg / dl and hematocrit 30.7 ± 4.1% ratio; in healthy subjects ferritin 53.5 ± 41.7 ng/ml, hemoglobin level 13.9 ± 1.3 mg / dl and hematocrit ratio 42 ± 3.53%. When compared to healthy subjects the glutathione reductase level (P<0.001) was found to be significantly higher in patients with IDA. IDA patients with moderate and severe anemia had lower GR activity when compared to IDA patients with mild anemia. But the plasma levels of glucose-6-phosphate dehydrogenase (P<0,600) and 6-phosphogluconate dehydrogenase (P<0,671) did not show any differences between healthy subjects and in patients with IDA. It was shown that Glucose-6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase have no effect on iron-deficiency anemia in patients. The plasma GR levels of premenopausal women with IDA were found to be higher compared to healthy subjects, which could be secondary to erythrocyte protection against oxidative stress being commonly seen in IDA.

Genome-wide microarray analysis of tomato roots showed defined responses to iron deficiency

PubMed Central

2012-01-01

Background Plants react to iron deficiency stress adopting different kind of adaptive responses. Tomato, a Strategy I plant, improves iron uptake through acidification of rhizosphere, reduction of Fe3+ to Fe2+ and transport of Fe2+ into the cells. Large-scale transcriptional analyses of roots under iron deficiency are only available for a very limited number of plant species with particular emphasis for Arabidopsis thaliana. Regarding tomato, an interesting model species for Strategy I plants and an economically important crop, physiological responses to Fe-deficiency have been thoroughly described and molecular analyses have provided evidence for genes involved in iron uptake mechanisms and their regulation. However, no detailed transcriptome analysis has been described so far. Results A genome-wide transcriptional analysis, performed with a chip that allows to monitor the expression of more than 25,000 tomato transcripts, identified 97 differentially expressed transcripts by comparing roots of Fe-deficient and Fe-sufficient tomato plants. These transcripts are related to the physiological responses of tomato roots to the nutrient stress resulting in an improved iron uptake, including regulatory aspects, translocation, root morphological modification and adaptation in primary metabolic pathways, such as glycolysis and TCA cycle. Other genes play a role in flavonoid biosynthesis and hormonal metabolism. Conclusions The transcriptional characterization confirmed the presence of the previously described mechanisms to adapt to iron starvation in tomato, but also allowed to identify other genes potentially playing a role in this process, thus opening new research perspectives to improve the knowledge on the tomato root response to the nutrient deficiency. PMID:22433273

New developments and controversies in iron metabolism and iron chelation therapy

PubMed Central

Kontoghiorghe, Christina N; Kontoghiorghes, George J

2016-01-01

Iron is essential for all organisms including microbial, cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients’ therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies. PMID:27019793

Four trace elements in pregnant women and their relationships with adverse pregnancy outcomes.

PubMed

Shen, P-J; Gong, B; Xu, F-Y; Luo, Y

2015-12-01

Lack of trace elements during pregnancy is detrimental to maternal and fetal health. Our aim is to study the changes in trace element levels in Chinese pregnant women and their association with adverse pregnancy outcomes. 1568 cases of Chinese pregnant women in remote areas were collected for a prospective cohort study. Serum copper, zinc, calcium and iron levels were measured at pre-pregnancy, 1st trimester (7w-12w), 2nd trimester (24w-28w) and 3rd trimester (35w-40w). (1) Serum copper levels was significantly higher after pregnancy than before, calcium and iron levels decreased, but zinc levels did not change significantly. (2) Copper and zinc deficiency in pregnant women was not a common finding, but lack of iron and calcium was frequently encountered; iron deficiency was especially common in the 3rd trimester (42.27%). (3) Serum zinc and iron levels in patients who either had a miscarriage or a preterm delivery were significantly lower than in the control group (p < 0.05). In patients with premature rupture of membranes, serum zinc levels were significantly lower (p < 0.05). In patients with intrauterine growth restriction (IUGR), serum copper, zinc, calcium and iron were significantly lower (p < 0.05). Trace elements is closely associated with fetal growth and development during pregnancy. Deficiency can lead to adverse pregnancy outcomes. Therefore, we should have a reasonable diet, replenish trace elements, therefore reducing the occurrence of adverse pregnancy outcomes.

Anemia and Iron Deficiency in Children With Potential Celiac Disease.

PubMed

Repo, Marleena; Lindfors, Katri; Mäki, Markku; Huhtala, Heini; Laurila, Kaija; Lähdeaho, Marja-Leena; Saavalainen, Päivi; Kaukinen, Katri; Kurppa, Kalle

2017-01-01

Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

Asthma as a disruption in iron homeostasis | Science ...

EPA Pesticide Factsheets

Over several decades, asthma has evolved from being recognized as a single disease to include a diverse group of phenotypes with dissimilar natural histories, pathophysiologies, responses to treatment, and distinctive molecular pathways. With the application of Occam’s razor to asthma, it is proposed that there is one cause underlying the numerous phenotypes of this disease and that the responsible molecular pathway is a deficiency of iron in the lung tissues. This deficiency can be either absolute (e.g. asthma in the neonate and during both pregnancy and menstruation) or functional (e.g. asthma associated with infections, smoking, and obesity). Comparable associations between asthma co-morbidity (e.g. eczema, urticaria, restless leg syndrome, and pulmonary hypertension) with iron deficiency support such a shared mechanistic pathway. Therapies directed at asthma demonstrate a capacity to impact iron homeostasis, further strengthening the relationship. Finally, pathophysiologic events producing asthma, including inflammation, increases in Th2 cells, and muscle contraction, can correlate with iron availability. Recognition of a potential association between asthma and an absolute and/or functional iron deficiency suggests specific therapeutic interventions including inhaled iron. Asthma is a public health issue that has environmental triggers. Iron homeostasis is an essential mechanism whereby the body manages the impact of environmental agents on overall

Iron deficiency anemia due to excessive green tea drinking.

PubMed

Fan, Frank S

2016-11-01

Tea interferes with iron absorption and can lead to iron deficiency anemia when consumed in large quantities. The rechallenge effect of green tea on anemia in a middle-aged man emphasizes the potential causal role of this beverage. Lifestyle and dietary habits are important diagnostic considerations in diseases of this type.

The effects of maternal iron deficiency on infant fibroblast growth factor-23 and mineral metabolism

PubMed Central

Braithwaite, V.S.; Prentice, A.; Darboe, M.K.; Prentice, A.M.; Moore, S.E.

2016-01-01

Fibroblast growth factor-23 (FGF23), a phosphate(Phos)-regulating hormone, is abnormally elevated in hypophosphataemic syndromes and an elevated FGF23 is a predictor of mortality in kidney disease. Recent findings suggest iron deficiency as a potential mediator of FGF23 expression and murine studies have shown in utero effects of maternal iron deficiency on offspring FGF23 and phosphate metabolism. Our aim was to investigate the impact of maternal iron status on infant FGF23 and mineral metabolites over the first 2 years of life. Infants born to mothers with normal (NIn = 25,) and low (LIn = 25) iron status during pregnancy, from a mother-infant trial (ISRCTN49285450) in rural Gambia, West Africa, had blood and plasma samples analysed at 12, 24, 52, 78 and 104 weeks (wk) of age. Circulating intact-FGF23 (I-FGF23), Phos, total alkaline phosphatase (TALP) and haemoglobin (Hb) decreased and estimated glomerular filtration rate increased over time [all P ≤ 0.0001)]. C-terminal-FGF23 (C-FGF23) and TALP were significantly higher in LI compared with NI, from 52 wk for C-FGF23 [Beta coefficient (SE) 18.1 (0.04) %, P = 0.04] and from 24 wk for TALP [44.7 (29.6) U/L, P = 0.04]. Infant Hb was the strongest negative predictor of C-FGF23 concentration [− 21% (4%) RU/mL, P ≤ 0.0001], Phos was the strongest positive predictor of I-FGF23 [32.0(3.9) pg/mL, P ≤ 0.0001] and I-FGF23 did not predict C-FGF23 over time [− 0.5% (0.5%), P = 0.3]. In conclusion, this study suggests that poor maternal iron status is associated with a higher infant C-FGF23 and TALP but similar I-FGF23 concentrations in infants and young children. These findings further highlight the likely public health importance of preventing iron deficiency during pregnancy. Whether or not children who are born to iron deficient mothers have persistently high concentrations of these metabolites and are more likely to be at risk of impaired bone development and pre-disposed to rickets requires further research. PMID:26453792

Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

PubMed Central

Singh, Ajay; Haldar, Swati; Horback, Katharine; Tom, Cynthia; Zhou, Lan; Meyerson, Howard; Singh, Neena

2017-01-01

Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP−/−). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP−/− mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP−/− mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP−/− mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP−/− BM-macrophages incorporate significantly less NTB-59Fe in the absence or presence of excess extracellular iron, indicating reduced uptake and/or storage of available iron in the absence of PrPC. When expressed in neuroblastoma cells, PrPC exhibits NAD(P)H-dependent cell-surface and intracellular FR activity that requires the copper-binding octa-peptide-repeat region and linkage to the plasma membrane for optimal function. Incorporation of NTB-59Fe by neuroblastoma cells correlates with FR activity of PrPC, implicating PrPC in cellular iron uptake and metabolism. These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. PMID:23478311

Elevated temperature inhibits recruitment of transferrin-positive vesicles and induces iron-deficiency genes expression in Aiptasia pulchella host-harbored Symbiodinium.

PubMed

Song, Po-Ching; Wu, Tsung-Meng; Hong, Ming-Chang; Chen, Ming-Chyuan

2015-10-01

Coral bleaching is the consequence of disruption of the mutualistic Cnidaria-dinoflagellate association. Elevated seawater temperatures have been proposed as the most likely cause of coral bleaching whose severity is enhanced by a limitation in the bioavailability of iron. Iron is required by numerous organisms including the zooxanthellae residing inside the symbiosome of cnidarian cells. However, the knowledge of how symbiotic zooxanthellae obtain iron from the host cells and how elevated water temperature affects the association is very limited. Since cellular iron acquisition is known to be mediated through transferrin receptor-mediated endocytosis, a vesicular trafficking pathway specifically regulated by Rab4 and Rab5, we set out to examine the roles of these key proteins in the iron acquisition by the symbiotic Symbiodinium. Thus, we hypothesized that the iron recruitments into symbiotic zooxanthellae-housed symbiosomes may be dependent on rab4/rab5-mediated fusion with vesicles containing iron-bound transferrins and will be retarded under elevated temperature. In this study, we cloned a novel monolobal transferrin (ApTF) gene from the tropical sea anemone Aiptasia pulchella and confirmed that the association of ApTF with A. pulchella Rab4 (ApRab4) or A. pulchella Rab5 (ApRab5) vesicles is inhibited by elevated temperature through immunofluorescence analysis. We confirmed the iron-deficient phenomenon by demonstrating the induced overexpression of iron-deficiency-responsive genes, flavodoxin and high-affinity iron permease 1, and reduced intracellular iron concentration in zooxanthellae under desferrioxamine B (iron chelator) and high temperature treatment. In conclusion, our data are consistent with algal iron deficiency being a contributing factor for the thermal stress-induced bleaching of symbiotic cnidarians. Copyright © 2015 Elsevier Inc. All rights reserved.

Duration of exclusive breast-feeding and infant iron and zinc status in rural Bangladesh.

PubMed

Eneroth, Hanna; El Arifeen, Shams; Persson, Lars-Ake; Kabir, Iqbal; Lönnerdal, Bo; Hossain, Mohammad Bakhtiar; Ekström, Eva-Charlotte

2009-08-01

There is a concern that exclusive breast-feeding (EBF) for 6 mo may lead to iron and zinc deficiency in low-birth weight (LBW) infants. We assessed the association between duration of EBF and infant iron and zinc status in the Maternal and Infant Nutrition Interventions in Matlab trial, Bangladesh, stratified for normal birth weigh (NBW) and LBW. Duration of EBF was classified into EBF <4 mo and EBF 4-6 mo based on monthly recalls of foods introduced to the infant. Blood samples collected at 6 mo were analyzed for plasma zinc (n = 1032), plasma ferritin (n = 1040), and hemoglobin (Hb) (n = 791). Infants EBF 4-6 mo had a higher mean plasma zinc concentration (9.9 +/- 2.3 micromol/L) than infants EBF <4mo (9.5 +/- 2.0 micromol/L) (P < 0.01). This association was apparent in only the NBW strata and was not reflected in a lower prevalence of zinc deficiency. Duration of EBF was not associated with concentration of plasma ferritin, Hb concentration, or prevalence of iron deficiency or anemia in any strata. Regardless of EBF duration, the prevalence of zinc deficiency, iron deficiency, and anemia was high in infants in this population and strategies to prevent deficiency are needed.

MYB10 and MYB72 are required for growth under iron-limiting conditions.

PubMed

Palmer, Christine M; Hindt, Maria N; Schmidt, Holger; Clemens, Stephan; Guerinot, Mary Lou

2013-11-01

Iron is essential for photosynthesis and is often a limiting nutrient for plant productivity. Plants respond to conditions of iron deficiency by increasing transcript abundance of key genes involved in iron homeostasis, but only a few regulators of these genes have been identified. Using genome-wide expression analysis, we searched for transcription factors that are induced within 24 hours after transferring plants to iron-deficient growth conditions. Out of nearly 100 transcription factors shown to be up-regulated, we identified MYB10 and MYB72 as the most highly induced transcription factors. Here, we show that MYB10 and MYB72 are functionally redundant and are required for plant survival in alkaline soil where iron availability is greatly restricted. myb10myb72 double mutants fail to induce transcript accumulation of the nicotianamine synthase gene NAS4. Both myb10myb72 mutants and nas4-1 mutants have reduced iron concentrations, chlorophyll levels, and shoot mass under iron-limiting conditions, indicating that these genes are essential for proper plant growth. The double myb10myb72 mutant also showed nickel and zinc sensitivity, similar to the nas4 mutant. Ectopic expression of NAS4 rescues myb10myb72 plants, suggesting that loss of NAS4 is the primary defect in these plants and emphasizes the importance of nicotianamine, an iron chelator, in iron homeostasis. Overall, our results provide evidence that MYB10 and MYB72 act early in the iron-deficiency regulatory cascade to drive gene expression of NAS4 and are essential for plant survival under iron deficiency.

Prevention of Iron-Deficiency Anemia in Infants and Children of Preschool Age.

ERIC Educational Resources Information Center

Fomon, Samuel J.

Iron-deficiency anemia is almost certainly the most prevalent nutritional disorder among infants and young children in the United States. Anemia is frequently seen among children of low socioeconomic status but is probably also the most frequent nutritional deficiency disease seen among children cared for by private doctors. Possible reasons for…

Breath holding spell

MedlinePlus

... such as Riley-Day syndrome or Rett syndrome Iron deficiency anemia A family history of breath holding spells ( ... tests may be done to check for an iron deficiency. Other tests that may be done include: EKG ...

Iron deficiency anaemia in Nigerian infants.

PubMed

Akinkugbe, F M; Ette, S I; Durowoju, T A

1999-01-01

Hematological parameters and the iron status of 50 randomly selected infants who were attending the research infant welfare clinic of the Institute of Child Health, Ibadan (ICHI), for routine immunization were studied. Investigations included estimations of packed cell volume (PCV), haemoglobin (Hb), serum iron (Fe), unsaturated iron-binding capacity (UIBC) and total iron-binding Capacity (TIBC). Forty percent of the infants had PCVs below 0.32, 48% had Hbs below 10 g/dl and 27% had mean corpuscular volume (MVC) less that 70fl. Thirty-seven percent of the children had serum Fe below 3.58 mmol/l, but only 4% had UIBC above 320 mmol/l. Fifty-two percent had Transferin Saturation Index (TSI) below 10%. Eighteen percent had MCV below 70fl associated with TSI below 10% and 67% of these had Hbs below 10 g/dl. The prevalence of iron deficiency anaemia in infants as shown in this study is very high. The ill effects of iron deficiency in childhood have been well documented. It is suggested that screening for anaemia should be offered at 9 months as part of a Child Survival Programme and that infants found to be anaemic should be treated. However, for cost-effectiveness and taking into consideration the high prevalence rate of iron deficiency in this age group, it might be preferable to give iron and weekly prophylactic antimalarias routinely to infants aged 9 to 15 months in lieu of screening.

Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery

PubMed Central

Crooks, Daniel R.; Ghosh, Manik C.; Haller, Ronald G.; Tong, Wing-Hang

2010-01-01

Mammalian ferrochelatase, the terminal enzyme in the heme biosynthetic pathway, possesses an iron-sulfur [2Fe-2S] cluster that does not participate in catalysis. We investigated ferrochelatase expression in iron-deficient erythropoietic tissues of mice lacking iron regulatory protein 2, in iron-deficient murine erythroleukemia cells, and in human patients with ISCU myopathy. Ferrochelatase activity and protein levels were dramatically decreased in Irp2−/− spleens, whereas ferrochelatase mRNA levels were increased, demonstrating posttranscriptional regulation of ferrochelatase in vivo. Translation of ferrochelatase mRNA was unchanged in iron-depleted murine erythroleukemia cells, and the stability of mature ferrochelatase protein was also unaffected. However, the stability of newly formed ferrochelatase protein was dramatically decreased during iron deficiency. Ferrochelatase was also severely depleted in muscle biopsies and cultured myoblasts from patients with ISCU myopathy, a disease caused by deficiency of a scaffold protein required for Fe-S cluster assembly. Together, these data suggest that decreased Fe-S cluster availability because of cellular iron depletion or impaired Fe-S cluster assembly causes reduced maturation and stabilization of apo-ferrochelatase, providing a direct link between Fe-S biogenesis and completion of heme biosynthesis. We propose that decreased heme biosynthesis resulting from impaired Fe-S cluster assembly can contribute to the pathogenesis of diseases caused by defective Fe-S cluster biogenesis. PMID:19965627

Blood donation, being Asian, and a history of iron deficiency are stronger predictors of iron deficiency than dietary patterns in premenopausal women.

PubMed

Beck, Kathryn L; Conlon, Cathryn A; Kruger, Rozanne; Heath, Anne-Louise M; Matthys, Christophe; Coad, Jane; Jones, Beatrix; Stonehouse, Welma

2014-01-01

This study investigated dietary patterns and nondietary determinants of suboptimal iron status (serum ferritin < 20 μg/L) in 375 premenopausal women. Using multiple logistic regression analysis, determinants were blood donation in the past year [OR: 6.00 (95% CI: 2.81, 12.82); P < 0.001], being Asian [OR: 4.84 (95% CI: 2.29, 10.20); P < 0.001], previous iron deficiency [OR: 2.19 (95% CI: 1.16, 4.13); P = 0.016], a "milk and yoghurt" dietary pattern [one SD higher score, OR: 1.44 (95% CI: 1.08, 1.93); P = 0.012], and longer duration of menstruation [days, OR: 1.38 (95% CI: 1.12, 1.68); P = 0.002]. A one SD change in the factor score above the mean for a "meat and vegetable" dietary pattern reduced the odds of suboptimal iron status by 79.0% [OR: 0.21 (95% CI: 0.08, 0.50); P = 0.001] in women with children. Blood donation, Asian ethnicity, and previous iron deficiency were the strongest predictors, substantially increasing the odds of suboptimal iron status. Following a "milk and yoghurt" dietary pattern and a longer duration of menstruation moderately increased the odds of suboptimal iron status, while a "meat and vegetable" dietary pattern reduced the odds of suboptimal iron status in women with children.

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection.

PubMed

Aron, Allegra T; Heffern, Marie C; Lonergan, Zachery R; Vander Wal, Mark N; Blank, Brian R; Spangler, Benjamin; Zhang, Yaofang; Park, Hyo Min; Stahl, Andreas; Renslo, Adam R; Skaar, Eric P; Chang, Christopher J

2017-11-28

Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals. ICL-1 utilizes a bioinspired endoperoxide trigger to release d-aminoluciferin for selective reactivity-based detection of Fe 2+ with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe 2+ levels in live cells and mice experiencing iron deficiency or overload. Application of ICL-1 in a model of systemic bacterial infection reveals increased iron accumulation in infected tissues that accompany transcriptional changes consistent with elevations in both iron acquisition and retention. The ability to assess iron status in living animals provides a powerful technology for studying the contributions of iron metabolism to physiology and pathology.

Management of inflammatory bowel disease-related anemia and iron deficiency with specific reference to the role of intravenous iron in current practice.

PubMed

Stein, Jürgen; Aksan, Ayşegül; Farrag, Karima; Dignass, Axel; Radeke, Heinfried H

2017-11-01

Anemia is a common extraintestinal manifestation in patients with inflammatory bowel disease, impacting disease prognosis, morbidity, hospitalization rates and time lost from work. While iron deficiency anemia and anemia of chronic inflammation predominate, combinations of hematimetric and biochemical markers facilitate the diagnosis and targeted therapy of other etiologies according to their underlying pathophysiological causes. Intravenous iron replacement is currently recommended in IBD patients with moderate to severe anemia or intolerance to oral iron. Areas covered: This review examines the impact, pathophysiology and diagnostics of iron deficiency and anemia, compares the characteristics and safety profiles of available oral and intravenous iron preparations, and highlights issues which require consideration in decision making for therapy administration and monitoring. Expert opinion: Modern intravenous iron formulations have been shown to be safe and effective in IBD patients, allowing rapid anemia correction and repletion of iron stores. While traditional oral iron preparations are associated with increased inflammation, negative effects on the microbiome, and poor tolerance and compliance, first clinical trial data indicate that newer oral compounds such as ferric maltol and sucrosomial iron offer improved tolerability and may thus offer a viable alternative for the future.

Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

PubMed

Meroño, Tomás; Dauteuille, Carolane; Tetzlaff, Walter; Martín, Maximiliano; Botta, Eliana; Lhomme, Marie; Saez, María Soledad; Sorroche, Patricia; Boero, Laura; Arbelbide, Jorge; Chapman, M John; Kontush, Anatol; Brites, Fernando

2017-04-01

Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p < 0.001). HDL particles from IDA patients showed higher triglyceride content (+30%,p < 0.05) and lower antioxidative capacity (-23%,p < 0.05). Although HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p < 0.05). Arylesterase activity of PON-1 was significantly lower in IDA patients than controls (-16%,p < 0.05). The intravenous administration of iron was associated with a decrease in malondialdehyde levels and an increase in arylesterase activity of PON-1 (-22% and +18%, respectively, p < 0.05). IDA is associated with oxidative stress and functionally deficient HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

PubMed

Goheen, M M; Wegmüller, R; Bah, A; Darboe, B; Danso, E; Affara, M; Gardner, D; Patel, J C; Prentice, A M; Cerami, C

2016-12-01

Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Facilitated citrate-dependent iron translocation increases rice endosperm iron and zinc concentrations.

PubMed

Wu, Ting-Ying; Gruissem, Wilhelm; Bhullar, Navreet K

2018-05-01

Iron deficiency affects one third of the world population. Most iron biofortification strategies have focused on genes involved in iron uptake and storage but facilitating internal long-distance iron translocation has been understudied for increasing grain iron concentrations. Citrate is a primary iron chelator, and the transporter FERRIC REDUCTASE DEFECTIVE 3 (FRD3) loads citrate into the xylem. We have expressed AtFRD3 in combination with AtNAS1 (NICOTIANAMINE SYNTHASE 1) and PvFER (FERRITIN) or with PvFER alone to facilitate long-distance iron transport together with efficient iron uptake and storage in the rice endosperm. The citrate and iron concentrations in the xylem sap of transgenic plants increased two-fold compared to control plants. Iron and zinc levels increased significantly in polished and unpolished rice grains to more than 70% of the recommended estimated average requirement (EAR) for iron and 140% of the recommended EAR for zinc in polished rice grains. Furthermore, the transformed lines showed normal phenotypic growth, were tolerant to iron deficiency and aluminum toxicity, and had grain cadmium levels similar to control plants. Together, our results demonstrate that deploying FRD for iron biofortification has no obvious anti-nutritive effects and should be considered as an effective strategy for reducing human iron deficiency anemia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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OPT3 Is a Phloem-Specific Iron Transporter That Is Essential for Systemic Iron Signaling and Redistribution of Iron and Cadmium in Arabidopsis.

PubMed

Zhai, Zhiyang; Gayomba, Sheena R; Jung, Ha-Il; Vimalakumari, Nanditha K; Piñeros, Miguel; Craft, Eric; Rutzke, Michael A; Danku, John; Lahner, Brett; Punshon, Tracy; Guerinot, Mary Lou; Salt, David E; Kochian, Leon V; Vatamaniuk, Olena K

2014-05-01

Iron is essential for both plant growth and human health and nutrition. Knowledge of the signaling mechanisms that communicate iron demand from shoots to roots to regulate iron uptake as well as the transport systems mediating iron partitioning into edible plant tissues is critical for the development of crop biofortification strategies. Here, we report that OPT3, previously classified as an oligopeptide transporter, is a plasma membrane transporter capable of transporting transition ions in vitro. Studies in Arabidopsis thaliana show that OPT3 loads iron into the phloem, facilitates iron recirculation from the xylem to the phloem, and regulates both shoot-to-root iron signaling and iron redistribution from mature to developing tissues. We also uncovered an aspect of crosstalk between iron homeostasis and cadmium partitioning that is mediated by OPT3. Together, these discoveries provide promising avenues for targeted strategies directed at increasing iron while decreasing cadmium density in the edible portions of crops and improving agricultural productivity in iron deficient soils. © 2014 American Society of Plant Biologists. All rights reserved.

Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review.

PubMed

García, Y; Díaz-Castro, J

2013-10-01

Iron deficiency is the most common nutritional deficiency in the world. Special molecules have evolved for iron acquisition, transport and storage in soluble, nontoxic forms. Studies about the effects of iron on health are focused on iron metabolism or nutrition to prevent or treat iron deficiency and anemia. These studies are focused in two main aspects: (1) basic studies to elucidate iron metabolism and (2) nutritional studies to evaluate the efficacy of iron supplementation to prevent or treat iron deficiency and anemia. This paper reviews the advantages and disadvantages of the experimental models commonly used as well as the methods that are more used in studies related to iron. In vitro studies have used different parts of the gut. In vivo studies are done in humans and animals such as mice, rats, pigs and monkeys. Iron metabolism is a complex process that includes interactions at the systemic level. In vitro studies, despite physiological differences to humans, are useful to increase knowledge related to this essential micronutrient. Isotopic techniques are the most recommended in studies related to iron, but their high cost and required logistic, making them difficult to use. The depletion-repletion of hemoglobin is a method commonly used in animal studies. Three depletion-repletion techniques are mostly used: hemoglobin regeneration efficiency, relative biological values (RBV) and metabolic balance, which are official methods of the association of official analytical chemists. These techniques are well-validated to be used as studies related to iron and their results can be extrapolated to humans. Knowledge about the main advantages and disadvantages of the in vitro and animal models, and methods used in these studies, could increase confidence of researchers in the experimental results with less costs.

Pre-operative anaemia.

PubMed

Clevenger, B; Richards, T

2015-01-01

Pre-operative anaemia is a relatively common finding, affecting a third of patients undergoing elective surgery. Traditionally associated with chronic disease, management has historically focused on the use of blood transfusion as a solution for anaemia in the peri-operative period. Data from large series now suggest that anaemia is an independent risk associated with poor outcome in both cardiac and non-cardiac surgery. Furthermore, blood transfusion does not appear to ameliorate this risk, and in fact may increase the risk of postoperative complications and hospital length of stay. Consequently, there is a need to identify, diagnose and manage pre-operative anaemia to reduce surgical risk. Discoveries in the pathways of iron metabolism have found that chronic disease can cause a state of functional iron deficiency leading to anaemia. The key iron regulatory protein hepcidin, activated in response to inflammation, inhibits absorption of iron from the gastrointestinal tract and further reduces bioavailability of iron stores for red cell production. Consequently, although iron stores (predominantly ferritin) may be normal, the transport of iron either from the gastrointestinal tract or iron stores to the bone marrow is inhibited, leading to a state of 'functional' iron deficiency and subsequent anaemia. Since absorption from the gastrointestinal tract is blocked, increasing oral iron intake is ineffective, and studies are now looking at the role of intravenous iron to treat anaemia in the surgical setting. In this article, we review the incidence and impact of anaemia on the pre-operative patient. We explain how anaemia may be caused by functional iron deficiency, and how iron deficiency anaemia may be diagnosed and treated. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Anemia--prevalence and risk factors in pregnancy.

PubMed

Bencaiova, Gabriela; Burkhardt, Tilo; Breymann, Christian

2012-09-01

To assess the prevalence of decreased iron stores and anemia in pregnant women. To determine whether the risk factors: socio-demographic background, age, BMI, and parity are associated with abnormal hemoglobin concentrations and/or abnormal iron status. A longitudinal study was carried out at the Department of Obstetrics, University Hospital of Zurich to establish the risk factors and prevalence of the decreased iron stores and anemia in early pregnancy. In order to determine the hematological parameters and ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and 20 pregnancy weeks were collected. According to hemoglobin and iron status, the patients were divided into four groups: patients with iron deficiency anemia, patients with decreased iron stores, patients with anemia for other reasons and normal patients. The determinants socio-demographic background, age, BMI and parity were explored using multiple logistic regression analysis. The prevalence of decreased iron stores (ferritin<20 μg/l) was observed in 31.8% of subjects (149/470) and anemia (Hb<110 g/l) in 18.5% (87/470). The prevalence of iron deficiency anemia was higher among women coming from former Yugoslavia and developing countries (p=0.004 and p=0.012). In patients coming from developing countries, a significant increase of anemia for other reasons was observed (p=0.027) and in patients older than 30 years, a significant increase of decreased iron stores (p=0.018). In our study population with low parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2% (236/470), and socio-demographic background was the most important risk factor of anemia. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Effects of daily iron supplementation in primary-school–aged children: systematic review and meta-analysis of randomized controlled trials

PubMed Central

Low, Michael; Farrell, Ann; Biggs, Beverley-Ann; Pasricha, Sant-Rayn

2013-01-01

Background: Anemia is an important public health and clinical problem. Observational studies have linked iron deficiency and anemia in children with many poor outcomes, including impaired cognitive development; however, iron supplementation, a widely used preventive and therapeutic strategy, is associated with adverse effects. Primary-school–aged children are at a critical stage in intellectual development, and optimization of their cognitive performance could have long-lasting individual and population benefits. In this study, we summarize the evidence for the benefits and safety of daily iron supplementation in primary-school–aged children. Methods: We searched electronic databases (including MEDLINE and Embase) and other sources (July 2013) for randomized and quasi-randomized controlled trials involving daily iron supplementation in children aged 5–12 years. We combined the data using random effects meta-analysis. Results: We identified 16 501 studies; of these, we evaluated 76 full-text papers and included 32 studies including 7089 children. Of the included studies, 31 were conducted in low- or middle-income settings. Iron supplementation improved global cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI] 0.11 to 0.90, p = 0.01), intelligence quotient among anemic children (mean difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and concentration. Iron supplementation also improved age-adjusted height among all children and age-adjusted weight among anemic children. Iron supplementation reduced the risk of anemia by 50% and the risk of iron deficiency by 79%. Adherence in the trial settings was generally high. Safety data were limited. Interpretation: Our analysis suggests that iron supplementation safely improves hematologic and nonhematologic outcomes among primary-school–aged children in low- or middle-income settings and is well-tolerated. PMID:24130243