Vitamin B12 deficiency after irradiation for bladder carcinoma

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

Kinn, A.C.; Lantz, B.

1984-05-01

Vitamin B12 deficiency was found in 10 of 41 patients who underwent radiotherapy before cystectomy with Bricker urinary diversion for carcinoma of the bladder. Of 13 patients given full irradiation because of inoperable bladder cancer 5 had malabsorption of vitamin B12. Serum folic acid was normal in these patients, indicating predominantly ileal irradiation sequelae. Routine evaluation of serum vitamin B12 after radiotherapy is recommended so that appropriate medication can be given, if possible before neurological symptoms appear.

Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians?

PubMed

Pawlak, Roman

2015-06-01

The goal of this paper is to describe the role of vitamin B12 deficiency in cardiovascular disease development among vegetarians. Vegetarians have a high prevalence of vitamin B12 deficiency. Deficiency of this vitamin is associated with a variety of atherogenic processes that are mainly, but not exclusively, due to vitamin B12 deficiency-induced hyperhomocysteinemia. Each 5-μmol/L increase above 10 μmol/L of serum homocysteine is associated with a 20% increased risk of circulatory health problems. Mean homocysteine concentration >10 μmol/L among vegetarians was reported in 32 of 34 reports. Macrocytosis associated with vitamin B12 deficiency is also associated with fatal and non-fatal coronary disease, myocardial infarction, stroke, and other circulatory health problems. Compared with non-vegetarians, vegetarians have an improved profile of the traditional cardiovascular disease risk factors, including serum lipids, blood pressure, serum glucose concentration, and weight status. However, not all studies that assessed cardiovascular disease incidence among vegetarians reported a protective effect. Among studies that did show a lower prevalence of circulatory health problems, the effect was not as pronounced as expected, which may be a result of poor vitamin B12 status due to a vegetarian diet. Vitamin B12 deficiency may negate the cardiovascular disease prevention benefits of vegetarian diets. In order to further reduce the risk of cardiovascular disease, vegetarians should be advised to use vitamin B12 supplements. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature.

PubMed

Pawlak, R; Lester, S E; Babatunde, T

2014-05-01

Individuals following vegetarian diets are at risk for developing vitamin B12 deficiency owing to suboptimal intake. As vitamin B12 is essential for the synthesis of nucleic acids, erythrocytes and in the maintenance of myelin, deficiency may result in a variety of symptoms. Some of these symptoms may be severe while others may be irreversible. The objective of this review was to assess vitamin B12 deficiency, based on reported serum vitamin B12, among individuals adhering to different types of vegetarian diets. A systematic literature search was carried out using multiple search engines including PubMed, Medline, CINAHL plus, ERIC, Nursing and Allied Health Collection and Nursing/Academic Edition. The inclusion criteria consisted of original studies that assessed serum vitamin B12, studies written in English, non-case studies and studies that reported actual percentages of vitamin B12 deficiency. Forty research studies were included. The deficiency prevalence among infants reached 45%. The deficiency among the children and adolescents ranged from 0 to 33.3%. Deficiency among pregnant women ranged from 17 to 39%, dependent on the trimester. Adults and elderly individuals had a deficiency range of 0-86.5%. Higher deficiency prevalence was reported in vegans than in other vegetarians. Thus, with few exceptions, the reviewed studies documented relatively high deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12 supplements were found to be at especially high risk. Vegetarians, especially vegans, should give strong consideration to the use of vitamin B12 supplements to ensure adequate vitamin B12 intake. Vegetarians, regardless of the type of vegetarian diet they adhere to, should be screened for vitamin B12 deficiency.

The human serum metabolome of vitamin B-12 deficiency and repletion, and associations with neurological function

USDA-ARS?s Scientific Manuscript database

We characterize the human serum metabolome in sub-clinical vitamin B-12 (B-12) deficiency and repletion. A pre-post treatment study provided one injection of 10 mg B-12 to 27 community-dwelling elderly Chileans with B-12 deficiency evaluated with serum B-12, plasma homocysteine, methylmalonic acid a...

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.

PubMed

Ahmed, Marwan A; Muntingh, George; Rheeder, Paul

2016-10-07

The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3

The effects of dietary vitamin B12 deficiency on sperm maturation in developing and growing male rats.

PubMed

Watanabe, Toshiaki; Ohkawa, Keiko; Kasai, Shigenobu; Ebara, Shuhei; Nakano, Yoshihisa; Watanabe, Yoshitaka

2003-03-01

To evaluate the role of vitamin B12 on spermatogenesis, the effects of dietary vitamin B12 deficiency on sperm maturation in developing rat fetuses and young growing rats were examined. The vitamin B12-deficient diet was given to all the animals for three different periods: whole period (gestation to mature), gestation period (gestation to weaning), or immature period (3-12 weeks postnatal). Sperm examination revealed that the sperm count was markedly lower in male progeny (F1) that were vitamin B12-deficient during the whole period. In addition, a significantly higher number of abnormal sperm, such as tailless and amorphous sperm, was observed. In male rats that were vitamin B12-deficient during the immature period, the incidence of abnormal sperms was 14.4% and 4.8% for tailless and short tail, respectively. The motion rates, such as path velocity and straight line velocity, were decreased to 20-40% of the control value in rats that were vitamin B12-deficient both during the whole and gestation periods. However, no effects of vitamin B12 deficiency on sperm motility were observed during the immature and mature periods. From these findings, we suggest that dietary vitamin B12 deficiency during pregnancy may induce irreversible damage in the germ cells of embryos and affect the maturation of spermatozoa.

Metformin Use Is Not Associated With B12 Deficiency or Neuropathy in Patients With Type 2 Diabetes Mellitus in Qatar.

PubMed

Elhadd, Tarik; Ponirakis, Georgios; Dabbous, Zeinab; Siddique, Mashhood; Chinnaiyan, Subitha; Malik, Rayaz A

2018-01-01

Metformin may lead to B 12 deficiency and neuropathy. There are no published data on the prevalence of Metformin-related B 12 deficiency and neuropathy in the Arabian Gulf. Determine whether Metformin intake is associated with B 12 deficiency and whether B 12 deficiency is associated with diabetic peripheral neuropathy (DPN) and painful diabetic neuropathy. Patients with type 2 diabetes mellitus (T2DM) ( n  = 362) attending outpatient clinics at HMC underwent assessment of B 12 levels, the DN4 questionnaire, and vibration perception threshold (VPT). Comparing Metformin to non-Metformin users there were no differences in B 12 levels, VPT, or DN4. The prevalence of B 12 deficiency (B 12 <133 pmol/l) was lower ( P  < 0.01) in Metformin (8%) compared to non-Metformin (19%) users. Patients with B 12 deficiency had a comparable prevalence and severity of sensory neuropathy and painful neuropathy to patients without B 12 deficiency. Serum B 12 levels were comparable between Metformin and non-Metformin users with T2DM in Qatar. T2DM patients on Metformin had a lower prevalence of B 12 deficiency. Furthermore, the prevalence and severity of neuropathy and painful diabetic neuropathy were comparable between patients with and without B 12 deficiency.

Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans.

PubMed

Bito, Tomohiro; Misaki, Taihei; Yabuta, Yukinori; Ishikawa, Takahiro; Kawano, Tsuyoshi; Watanabe, Fumio

2017-04-01

Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B 12 deficiency, although the underlying disease mechanisms associated with vitamin B 12 deficiency are poorly understood. Vitamin B 12 deficiency was found to significantly increase cellular H 2 O 2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B 12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B 12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B 12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B 12 deficiency is partially attributable to oxidative stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A Study of the Prevalence of Serum Vitamin B12 and Folic Acid Deficiency in Western Maharashtra

PubMed Central

Mahajan, Sanket K.; Aundhakar, Swati C.

2015-01-01

Context: This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice. Aims and Objectives: 1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels. Materials and Methods: The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency. Results: Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency

Dual pathology as a result of spinal stenosis and vitamin B12 deficiency.

PubMed

Patel, Mohammed Shakil; Rasul, Zurqa; Sell, Philip

2011-12-01

Vitamin B12 deficiency can confound the clinical assessment of patients presenting with features of spinal disorders. Speciality practice within spinal surgery may lead the clinician to a focus upon spinal explanations for symptoms and that belief may be reinforced by supporting imaging. In the presence of mainly sensory symptoms consideration and exclusion of non surgical causes needs to occur. This study aimed at identifying the prevalence of vitamin B12 deficiency; the presence of dual pathology on imaging performed; the implementation of replacement therapy and their subsequent clinical response as perceived by patients. This was performed through a retrospective review of patients presenting to specialist spine out-patient clinics over a 4-year period via access to pathology reports followed by a telephone survey. 457 patients were investigated of which 8.5% were vitamin B12 deficient. 70% of patients had repeat levels and 31% continued to be deficient. 26% of these patients were not placed on any supplemental therapy. 72% of patients on treatment had self perceived improved outcomes as compared with 55% not on treatment. 73% of patients underwent MRI/CT imaging. 59% of which had evidence of spinal stenosis. In older patients with sensory symptoms, the coexistence of B12 deficiency should be considered. Detection of deficiency with consequent treatment results in better global outcomes than no treatment. Unless the correct blood test is done, the pathology will remain undetected, and patients may continue with their primary symptoms despite high-risk spinal surgical procedures.

Vitamin B12 deficiency is associated with geographical latitude and solar radiation in the older population.

PubMed

Cabrera, Sebastián; Benavente, David; Alvo, Miriam; de Pablo, Paola; Ferro, Charles J

2014-11-01

Vitamin B12 and folic acid deficiency are common in the older and are associated with several conditions including anaemia, cardiovascular disease, cognitive impairment and cancer. Evidence from in vitro studies suggests that solar radiation can degrade both vitamins in the skin. Chile is the longest country in the world running perfectly North-South making it an ideal place to study potential associations of latitude and solar radiation on vitamin B12 and folic acid deficiency. The objective was to examine the association between vitamin B12 and folic acid deficiencies and latitude. Plasma samples were collected from Chileans aged 65+ years (n=1013) living across the whole country and assayed for vitamin B12 and folic acid concentrations as part of the Chilean Health Survey 2009-2010, which is a national representative sample study. Overall, the prevalence of vitamin B12 deficiency was 11.3%, with the prevalence in the North of the country being significantly greater than in the Central and South zones (19.1%,10.5%, and 5.7%, respectively; P<0.001). The prevalence of folic acid deficiency in the whole cohort was 0.7% with no difference between the 3 geographical zones. Using logistic regression analyses, vitamin B12 deficiency was significantly associated with geographical latitude (OR 0.910 [95% confidence intervals 0.890-0.940], P<0.001) and solar radiation (OR 1.203 [95% confidence intervals 1.119-1.294], P<0.001). These associations persisted after adjustments for confounders (OR 0.930, P<0.001 and 1.198, P=0.002, respectively). In the Chilean population of 65+, the prevalence of vitamin B12 deficiency is associated with living closer to the Equator and solar radiation. Although degradation by solar radiation might explain this observation, further work is required to establish the potential mechanisms. In countries that routinely fortify food with folic acid, efforts to identify vitamin B12 deficiency might be more cost-efficiently targeted in areas closest

Visual and brainstem auditory evoked potentials in infants with severe vitamin B12 deficiency.

PubMed

Demir, Nihat; Koç, Ahmet; Abuhandan, Mahmut; Calik, Mustafa; Işcan, Akin

2015-01-01

Vitamin B12 plays an important role in the development of mental, motor, cognitive, and social functions via its role in DNA synthesis and nerve myelination. Its deficiency in infants might cause neuromotor retardation as well as megaloblastic anemia. The objective of this study was to investigate the effects of infantile vitamin B12 deficiency on evoked brain potentials and determine whether improvement could be obtained with vitamin B12 replacement at appropriate dosages. Thirty patients with vitamin B12 deficiency and 30 age-matched healthy controls were included in the study. Hematological parameters, visual evoked potentials, and brainstem auditory evoked potentials tests were performed prior to treatment, 1 week after treatment, and 3 months after treatment. Visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) were found to be prolonged in 16 (53.3%) and 15 (50%) patients, respectively. Statistically significant improvements in VEP and BAEP examinations were determined 3 months after treatment. Three months after treatment, VEP and BAEP examinations returned to normal in 81.3% and 53.3% of subjects with prolonged VEPs and BAEPs, respectively. These results demonstrate that vitamin B12 deficiency in infants causes significant impairment in the auditory and visual functioning tests of the brain, such as VEP and BAEP.

B12 deficiency leading to marked poikilocytosis versus true schistocytosis, a pernicious problem.

PubMed

Hall, James A; Mason, James; Choi, Julia; Holguin, Mark

2017-08-01

Severe vitamin B12 deficiency is caused most commonly by autoimmune atrophic gastritis leading to loss of intrinsic factor. Vitamin B12 deficiency leading to megaloblastic anemia and demyelinating central nervous system disease is well known; however, a rare presentation of B12 deficiency described as pseudothrombotic microangiopathy is not well known. This complication presents with signs of mechanical hemolysis, elevated lactate dehydrogenase (LDH), thrombocytopenia, and a low reticulocyte count, which can be incorrectly diagnosed as thrombotic thrombocytopenic purpura and managed incorrectly. Decreased reticulocyte count and an LDH >2500IU/L is more commonly seen in B12 deficiency. However, recognizing the differences in marked poikilocytosis can be challenging, as seen with megaloblastic changes and true schistocytosis. To illustrate the challenge in differentiating between megaloblastic changes and true schistocytosis, we present the case of a 27-year-old woman who presented to her physician for symptomatic anemia and complaints of nausea, vomiting, and loose stool. She had a hemoglobin of 5.1g/dL, platelet count of 39×10 9 /L, LDH of 9915IU/L, haptoglobin below assay limit, and a reticulocyte count of 2.5%. Peripheral smear showed macrocytic anemia, rare hypersegmented neutrophils, and schistocytes. Vitamin B12 level was less than 50pg/mL, methylmalonic acid was 0.33μmol/L, anti-parietal cell antibody was >1:640, and intrinsic factor blocking antibody was positive-confirming the diagnosis of pernicious anemia. While hospitalized, she was treated with vitamin B12 1000μg intramuscular injections daily and thereafter continued with monthly injections, which ultimately resolved her severe macrocytic anemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistence of neurological damage induced by dietary vitamin B-12 deficiency in infancy

PubMed Central

von Schenck, U.; Bender-Gotze, C.; Koletzko, B.

1997-01-01

Accepted 9 April 1997
 A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother's vegan diet. Cinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy. Vitamin B-12 supplements led to a rapid improvement of haematological and neurological symptoms. Serum vitamin B-12 and urinary methylmalonate excretion were normal 10 days after treatment began. After six weeks, EEG was normal and cranial MRI after 10 weeks showed complete disappearance of all structural abnormalities. Cognitive and language development, however, remained seriously retarded at the age of 2 years. It is concluded that infantile vitamin B-12 deficiency induced by maternal vegan diets may cause lasting neurodisability even though vitamin B-12 supplementation leads to rapid resolution of cerebral atrophy and electroencephalographic abnormality.

 PMID:9301352

Chronic transgenerational vitamin B12 deficiency of severe and moderate magnitudes modulates adiposity-probable underlying mechanisms.

PubMed

Ghosh, Shampa; Sinha, Jitendra Kumar; Muralikrishna, Bojanapalli; Putcha, Uday Kumar; Raghunath, Manchala

2017-05-06

We have demonstrated previously that severe but not moderate vitamin B12 deficiency altered body composition and induced adiposity in female C57BL/6 mice. This study aims to elucidate the effects of chronic transgenerational dietary vitamin B12 restriction on body composition and various biochemical parameters in the F1 generation offspring of our mouse models of severe and moderate vitamin B12 deficiency established earlier. Female weanling C57BL/6 mice received, ad libitum, for 4 weeks a (i) control diet, (ii) vitamin B12-restricted diet with pectin as dietary fiber (severely deficient diet), or (iii) vitamin B12-restricted diet with cellulose as dietary fiber (moderately deficient diet) and then mated with control males. The offspring of control and severely deficient dams continued on the respective diets of their mothers. Few moderately deficient dams were rehabilitated to control diet from parturition and their pups were weaned to control diet. Also, some offspring born to moderately B12 deficient dams were weaned to control diet, while others continued on the same diet as their mothers. Various parameters were determined in the F1 offspring after 12 and 36 weeks of feeding. The results indicate that both severe and moderate maternal vitamin B12 restrictions were associated with accelerated catch-up growth, increased body fat percentage, visceral adiposity, dyslipidemia, fasting hyperglycemia and insulin resistance in the F1 offspring. Inflammation, increased glucocorticoid and oxidative stress and poor antioxidant defence probably underlie these adverse effects. Rehabilitation from parturition but not weaning was beneficial in delaying the onset of the adverse outcomes in the offspring. © 2016 BioFactors, 43(3):400-414, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

White centered retinal hemorrhages in vitamin b(12) deficiency anemia.

PubMed

Zehetner, Claus; Bechrakis, Nikolaos E

2011-05-01

To report a case of severe vitamin B(12) deficiency anemia presenting with white centered retinal hemorrhages. Interventional case report. A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B(12) deficiency requiring erythrocyte transfusions. Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B(12) deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

Hyperhomocysteinemia and vitamin B-12 deficiency are more striking in Syrians than in Germans--causes and implications.

PubMed

Herrmann, Wolfgang; Obeid, Rima; Jouma, Muhidien

2003-01-01

Hyperhomocysteinemia is an accepted risk factor for coronary artery disease, but the determining factors are not fully understood. We investigated hyperhomocysteinemia and vitamin deficiency in Syrian coronary patients and apparently healthy Syrian and German controls. We enrolled 273 Syrian patients with angiographically confirmed stenosis, along with 159 Syrian and 75 German controls. Plasma total homocysteine (HCY), cystathionine, methylmalonic acid (MMA), vitamin B-6, B-12, folate, lipids, apolipoproteins and methylenetetrahydrofolate reductase (C677T-MTHFR) mutation were analysed. There was a very high prevalence of hyperhomocysteinemia (>12 micromol/l) in Syrians (patients 61%, controls 44%, Germans 16%) together with functional vitamin B-12 deficiency diagnosed by elevated MMA (patients 49%, controls 47%, Germans 3%), which was in contrast to the low frequency of decreased serum vitamin B-12 (12% in patients, 7% in Syrian controls). The HCY concentration in German controls was lower than in Syrians, median 8.8 vs. 11.3 micromol/l. The vitamin B-12 deficiency induces folate trapping; higher levels of folate are needed to prevent hyperhomocysteinemia. Germans achieved the HCY level of < or =12 micromol/l at significantly lower folate concentrations > or =4.4 ng/ml, than Syrians with normal MMA (> or =16.7 nmol/l folate) or Syrians with high MMA (> or =23.3 nmol/l folate). Smoking and homozygous state for C677T-MTHFR mutation contributed to hyperhomocysteinemia. We could confirm that the reasons for hyperhomocysteinemia in Syrians were in fact mostly related to a relative folate deficiency, which is due to a vitamin B-12 shortage. Vitamin B-12 deficiency induces folate trapping. Besides lifestyle, other presently unknown factors may contribute to hyperhomocysteinemia and vitamin B-12 deficiency in Syrians.

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.

[Vitamin B12 deficiency associated with high doses od metformin in older people diabetic].

PubMed

Sánchez, Hugo; Masferrer, Dominique; Lera, Lydia; Arancibia, Estrella; Angel, Barbara; Albala, Cecilia

2014-06-01

The aim of the study was to estimate if B12 deficiency is associated with the use of metformin in the elderly diabetics. Case-control study in diabetic OP. Cases (n = 137) were defined as elderly with B12 < 221 pmol/L and controls (n = 279) elderly with B12 > 221 pmol/L. Four categories of metformin use were defined: non-users, ≤850 mg/day, > 850 and < 2,550 mg/day and ≥2,550 mg/day. Metformin ≥2,550 mg/day was high doses considered. The crude OR for B12 deficiency and consumption of Metformin were calculated. Logistic regression models were developed to explore the association between B12 deficiency and metformin dose. The research protocol was approved by the Ethics Committee of INTA. The age of cases and controls was (70.2 years vs 68.6 years (p < 0.05). The 62% were women in cases vs 74.9% in controls (p < 0.05). The 73% of cases and 76% of controls used metformin (p < 0.05) the average consumption of metformin was de 1,954.3 mg/day (SD: 1,063.2) in cases and 1,696.6 mg/day (SD: 1,074.4) in controls (p < 0.05). The use of 2,550 mg/day was observed in 29.2% of cases and 19.3% for controls (p < 0.05). It was observed that OP who consumed high doses of metformin had 1.9 times the risk of B12 deficiency (OR: 1.9; 95%CI: 1,08- 3,30). These results show a strong association between high doses of metformin and low levels of vitamin B12 in diabetic elderly. This project was funded by FONIS SA11I2092. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Vitamin B12 deficiency might be related to sarcopenia in older adults.

PubMed

Bulut, Esra Ates; Soysal, Pinar; Aydin, Ali Ekrem; Dokuzlar, Ozge; Kocyigit, Suleyman Emre; Isik, Ahmet Turan

2017-09-01

Sarcopenia and dynapenia are related to repeated falls, mobility restriction, depression, frailty, increased mortality and morbidity. The aim of this study is to evaluate the relationship between vitamin B12 deficiency and sarcopenia in older adults. 403 patients, who attended to outpatient clinic and underwent comprehensive geriatric assessment, were included study. All cases' skeletal muscle mass (SMM), walking speed and hand grip strength were recorded by bioimpedance, 4meter walking test and hand dynamometer respectively. The diagnosis of sarcopenia was defined according to the criteria of the European Working Group on Sarcopenia in Older People. Sarcopenia was accepted low SMM with low handgrip strength or low physical performance. Dynapenia was defined as handgrip strength <30kg (men) and <20kg (women). The prevalence of sarcopenia and dynapenia was 24.8% and 32.0%, respectively. In the patients with sarcopenia, mean age, osteoporosis and frailty were higher, and MMSE, and instrumental ADL scores were lower than the patients without sarcopenia (p<0.05). The frequency of sarcopenia and dynapenia were 31.6% and 35.4%, respectively, in patients with vitamin B12 levels <400pg/mL. In addition lean body mass, total skeletal mass and skeletal muscle mass index were lower in the patients with vitamin B12 levels <400pg/mL compared to higher than 400pg/mL (p<0.05). Sarcopenia, which results in lots of negative clinical outcomes in older adults, might be related to vitamin B12 deficiency. Therefore, these patients should be periodically examined for vitamin B12 deficiency due to the potential negative clinical outcomes such as sarcopenia in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal vitamin B12 deficiency affects spermatogenesis at the embryonic and immature stages in rats.

PubMed

Watanabe, Toshiaki; Ebara, Shuhei; Kimura, Sachiko; Maeda, Kunihiko; Watanabe, Yoshitaka; Watanabe, Hiroshi; Kasai, Shigenobu; Nakano, Yoshihisa

2007-03-01

To evaluate the role of cobalamin (Cbl) on spermatogenesis, the effect of dietary vitamin B(12) deficiency on early spermatogenesis was histologically investigated in male fetuses and newborns in the first filial generation (F(1) males) of rats. There was no difference in the number of gonocytes and supporting cells of Sertoli in the gonad in male fetuses on day 16 of gestation and in the testes in F(1) males at 0 days of age between vitamin B(12)-deficient (VB12-D) and vitamin B(12)-supplemented (VB12-S) groups. However, at 21 days of age, a decreased number of spermatogonia and no spermatocytes were observed in the VB12-D group. Numerous TUNEL positive cells were located among spermatocytes of the spermatogenic epithelium. The ultrastructural features examined using transmission electron microscopy were considered to be indicative of apoptosis. The incidence of seminiferous tubules having apoptotic cells was 51.5% in the VB12-D group. At 60 days of age, aplasia of the spermatids and spermatozoa was detected in the VB12-D group. In the connective tissue between the seminiferous tubules, many interstitial Leydig cells and blood vessels were observed in the VB12-D group, as compared with the VB12-S group. These changes produced by vitamin B(12) deficiency can be reversed by providing a VB12-S diet after weaning at 21 days of age. From these findings, such a vitamin B(12) deficiency during gestation and lactation could affect the germ cells and especially damage spermatocytes in F(1) male rats, which indicates that Cbl may be an essential constituent in the meiosis of spermatogenesis.

Vitamin B12 deficiency presenting as acute ataxia

PubMed Central

Crawford, John Ross; Say, Daphne

2013-01-01

A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient. PMID:23536622

Vitamin B12 deficiency presenting as acute ataxia.

PubMed

Crawford, John Ross; Say, Daphne

2013-03-26

A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient.

Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort.

PubMed

Margalit, Ili; Cohen, Eytan; Goldberg, Elad; Krause, Ilan

2018-01-01

Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18-65, who were provided with a routine medical evaluation during 2000-2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p < 0.001). Deficiency prevalence was greater for men (25.5%) in comparison with women (18.9%; p < 0.001). Men were strongly associated with severe deficiency (adjusted OR 2.26; 95% CI 1.43-3.56). Among the healthy population, men are susceptible to vitamin B12 deficiency. This can be explained by neither diet habits nor estrogen effects. Genetic variations are therefore hypothesized to play a role. © 2018 S. Karger AG, Basel.

Vitamin D and vitamin B12 deficiencies are common in patients with midgut carcinoid (SI-NET).

PubMed

Lind, A; Wängberg, B; Ellegård, L

2016-09-01

Patients with small intestinal neuroendocrine tumours (SI-NET) often have diarrhoea from hormonal overproduction, surgery and medical treatment, leading to malabsorption of bile salts, fats, vitamin B12 and fat-souble vitamins. This could lead to malnutrition. We assessed nutritional status in 50 consecutive out patients with disseminated SI-NET, 25 patients in each cohort. The first cohort was descriptive and the second cohort supplemented with vitamin D, B12 and calcium. Vitamin D deficiency was defined as <50 nmol/l. All patients were assessed by clinical chemistry and dual-energy X-ray absorptiometry (DXA) and interviewed about weight changes, appetite, gastrointestinal disorders, sunhabits and the use of supplements. In the first cohort, 29% of the patients were severely and 17% moderately vitamin D deficient. In patients without prior substitution, 32% had subnormal vitamin B12 levels. Seventy-six percent had low bone density. In the second cohort with vitamin and mineral supplementation, none had severe vitamin D deficiency, but 28% had moderate deficiency. No patient had subnormal vitamin B12 levels. Sixty percent had low bone density. The serum levels of vitamin D and B12 were higher and parathyroid hormone (PTH) lower in the second cohort compared with the first cohort (P⩽0,022). Vitamin D and PTH were negatively correlated, r=-30, P=⩽0.036. Low serum levels of vitamin D and vitamin B12, and low bone density are common in patients with disseminated SI-NET. Supplementation of vitamin D, B12 and calcium resulted in higher serum levels of vitamins, lower PTH levels and diminished severe vitamin D deficiency and is thus recommended as standard care.

Folate–vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency

USDA-ARS?s Scientific Manuscript database

Previous reports on pernicious anemia treatment suggested that high folic acid intake adversely influences the natural history of vitamin B-12 deficiency, which affects many elderly individuals. However, experimental investigation of this hypothesis is unethical, and the few existing observational d...

West Syndrome in an Infant with Vitamin B[subscript 12] Deficiency in the Absence of Macrocytic Anaemia

ERIC Educational Resources Information Center

Erol, Ilknur; Alehan, Fusun; Gumus, Ayten

2007-01-01

Vitamin B[subscript 12] deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B[subscript 12] deficiency can be difficult when the typical macrocytic…

Functional vitamin B12 deficiency in advanced malignancy: implications for the management of neuropathy and neuropathic pain.

PubMed

Solomon, Lawrence R

2016-08-01

Treatment of neuropathic pain and chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignancy is often unsuccessful. Functional vitamin B12 deficiency, defined by elevated levels of the B12-dependent metabolites, methylmalonic acid (MMA), and/or homocysteine, despite normal B12 values, may cause neuropathy and is associated with disorders linked to increased oxidative stress. Since both cancer and neurotoxic antineoplastic agents increase oxidative stress, a role for functional B12 deficiency in CIPN was considered. A retrospective record review of 241 cancer subjects evaluated by the adult palliative care service for B12 deficiency in a university-based cancer center between October 2008 and September 2012 with measurement of B12, MMA, and/or homocysteine levels was performed. B12 values were elevated (>900 pg/ml) in 30 % and low (≤300 pg/ml) in 17 % of subjects tested. Elevated MMA (>250 nmol/l) and homocysteine (>12.1 μmol/l) levels occurred in 38 and 23 % of subjects respectively and at least one metabolite was increased in 54 % of evaluable subjects. Even when B12 values were ≥1500 pg/ml (n = 36), increased MMA and homocysteine values occurred in 31 and 23 % of subjects, respectively. B12 therapy decreased MMA values in all four subjects studied and improved neurologic findings in the three subjects tested. Functional vitamin B12 deficiency is common in subjects with advanced malignancy. Further studies are needed to determine if this disorder is a risk factor for CIPN and if B12 therapy has a role in the management and/or prevention of neuropathy and neuropathic pain in this population.

Prevalence of Vitamin B12 and Folate Deficiency in School Children Residing at High Altitude Regions in India.

PubMed

Gupta, Aakriti; Kapil, Umesh; Ramakrishnan, Lakshmy; Pandey, Ravindra Mohan; Yadav, Chander Prakash

2017-04-01

To assess the prevalence of vitamin B 12 and folate deficiencies among children residing at high altitude regions of Himachal Pradesh, India. A total of 215 school children in the age group of 6-18 y were included. Biochemical estimation of serum vitamin B 12 and folate levels was undertaken using chemiluminescence immunoassay method. The consumption pattern of foods high in dietary vitamin B 12 and folate was recorded using Food Frequency Questionnaire. The median levels (interquartile range) of serum vitamin B 12 and folate were 326 (259-395) pg/ml and 7.7 (6-10) ng/ml respectively. The prevalence of vitamin B 12 and folate deficiency amongst school age children was found as 7.4% and 1.5% respectively. A low prevalence of vitamin B 12 and folate deficiencies was found amongst children aged 6-18 y living at high altitude regions in India. This is possibly due to high frequency of consumption of foods rich in vitamin B 12 and folate.

VITAMIN B-12 SUPPLEMENTATION OF DEFICIENT LACTATING GUATEMALAN WOMEN IMPROVES MATERNAL BUT NOT INFANT STATUS

USDA-ARS?s Scientific Manuscript database

Vitamin B-12 deficiency is common in mothers and infants where maternal intake of animals source foods is low. The first six months post-partum is a critical period of neurological development requiring vitamin B-12. A pilot study was designed to determine the dose of B-12 to the mothers that would ...

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

PubMed Central

Watson, Emma; Olin-Sandoval, Viridiana; Hoy, Michael J; Li, Chi-Hua; Louisse, Timo; Yao, Victoria; Mori, Akihiro; Holdorf, Amy D; Troyanskaya, Olga G; Ralser, Markus; Walhout, Albertha JM

2016-01-01

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild. DOI: http://dx.doi.org/10.7554/eLife.17670.001 PMID:27383050

Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients.

PubMed

Compher, Charlene W; Kinosian, Bruce P; Stoner, Nancy E; Lentine, Deborah C; Buzby, Gordon P

2002-01-01

Choline has recently been recognized as an essential nutrient, in part based on deficiency data in long-term home total parenteral nutrition (TPN) patients. Choline, a methyl donor in the metabolism of homocysteine, is intricately related to folate status, but little is known about choline and vitamin B12 status. Long-term TPN patients are also subject to vitamin B12 deficiency. The objective of the study was to evaluate any interaction between choline, vitamin B12, and folate in patients with severe malabsorption syndromes, requiring long-term TPN. Plasma free choline, serum and red blood cell (RBC) folate, serum vitamin B12 methylmalonic acid, B6, and plasma total homocysteine concentrations were assayed by standard methods. Low choline was defined as values that fall 1 to < or =3 and marked low choline concentration as >3 SD below the control mean. Both low choline concentrations (52% were marked low, 33% low, 14% normal) and elevated methylmalonic acid concentrations (47%) were prevalent. Choline concentration was significantly lower and RBC folate higher in patients with elevated methylmalonic acid. Total homocysteine elevations were rare (3 of 21) and mild. These data suggest a strong interaction between vitamin B12 and choline deficiencies and folate status in this population, which may be due in part to variations in vitamin and choline delivery by TPN. Folate adequacy may increase B12 use for homocysteine metabolism, thus limiting B12 availability for methylmaIonic acid metabolism. Choline use may also increase, and choline deficiency may worsen if choline substitutes when the vitamin B12 side of the homocysteine metabolic pathway cannot be used.

Helicobacter pylori associated vitamin B12 deficiency, pernicious anaemia and subacute combined degeneration of the spinal cord.

PubMed

Gowdappa, H Basavana; Mahesh, M; Murthy, K V K S N; Narahari, M G

2013-09-30

A 23-year-old man presented with weakness in the lower limbs, numbness in hands and feet over past 6 months. Examination revealed a combination of absent ankle jerk, extensor plantar response and reduced sensations in a glove and stocking distribution. MRI of the spinal cord was distinctive of subacute combined degeneration (SACD) of the spinal cord. Serum vitamin B12 was low and anti-intrinsic factor antibodies were positive. A biopsy of the stomach revealed intense inflammatory infiltrates in lamina propria with grade III Helicobacter pylori infection. Other work-up for the cause of vitamin B12 deficiency was unremarkable. H pylori infection triggers autoantibodies by a mechanism of molecular mimicry. This case report highlights H pylori as a causative agent in vitamin B12 deficiency and culminating in SACD of the spinal cord. H pylori treatment reverses the underlying pathogenesis and corrects vitamin B12 deficient state in selected individuals.

Isotope-dilution assay for urinary methylmalonic acid in the diagnosis of vitamin B12 deficiency. A prospective clinical evaluation

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

Matchar, D.B.; Feussner, J.R.; Millington, D.S.

1987-05-01

Vitamin B12 deficiency is a frequently considered diagnosis for which there is no single, commonly available and accurate test. A urinary methylmalonic acid assay using gas chromatography-mass spectrometry has been proposed as the preferred test. We reviewed vitamin B12 assays on 1599 consecutive patients and prospectively studied all patients with low serum B12 levels (n = 75) and a random sample of patients with normal levels (n = 68). Of 96 evaluable patients, 7 had clinical deficiency. All 7 deficient patients had urinary methylmalonic acid levels greater than 5 micrograms/mg creatine (sensitivity, 100%; confidence interval, 65% to 100%). Of themore » 89 patients who were not clinically deficient, 88 had urinary methylmalonic acid levels less than or equal to 5 micrograms/mg creatinine (specificity, 99%). The overall test accuracy in this population was 99%. If the high sensitivity and specificity of the gas chromatography-mass spectrometry assay for urinary methylmalonic acid is supported by other clinical studies, the methylmalonic acid assay may become the reference standard for the diagnosis of vitamin B12 deficiency.« less

SERUM VITAMIN B12, IRON AND FOLIC ACID DEFICIENCIES IN OBESE INDIVIDUALS SUBMITTED TO DIFFERENT BARIATRIC TECHNIQUES.

PubMed

Silva, Rafaella de Andrade; Malta, Flávia Monteiro França; Correia, Maria Flora Ferreira Sampaio Carvalho; Burgos, Maria Goretti Pessoa de Araújo

Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. A retrospective analysis was performed using the electronic charts of patients submitted to bariatric surgery involving adjustable gastric banding and Roux-en-Y gastric bypass at the São João Hospital Center in the city of Porto, Portugal, between 2005 and 2010. The following data were collected: surgical technique, sex, age, marital status, serum concentrations of vitamin B12, iron and folic acid and postoperative lifestyle. A 5% significance level was used for the statistical analysis (p<0.05). Among 286 individuals evaluated, females accounted for 90.9% of the overall sample (both techniques). Gastric banding was performed more (68.9%), but greater nutrient deficiencies were found following gastric bypass. Iron was the most prevalent deficiency (21.3%), followed by vitamin B12 (16.9%) and folic acid (4.5%). Mild to moderate alcohol intake, adherence to the diet and the use of multivitamins reduced the frequency, but did not avoid micronutrient deficiency. Vitamin B12, iron and folic acid deficiencies were found in the first and second year following the two bariatric techniques analyzed and were more frequent among individuals submitted to gastric bypass. As diferentes técnicas da cirurgia da obesidade combinam má absorção com procedimentos restritivos e podem levar à complicações metabólicas, entre as quais se destacam as deficiências de micronutrientes. Avaliar a deficiência de vitamina B12, ferro e ácido fólico e fatores associados ao estilo de vida de obesos submetidos a diferentes técnicas cirúrgicas. Análise retrospectiva dos prontuários eletrônicos de pacientes submetidos à cirurgia bariátrica pelas t

VIT. B12 DEFICIENCY IN CHILDREN (IMERSLUND-GRÄSBECK SYNDROME IN TWO PAIRS OF SIBLINGS).

PubMed

Krzemień, Grazyna; Turczyn, Agnieszka; Szmigielska, Agnieszka; Roszkowska-Blaim, Maria

2015-01-01

Improvement in the quality of life in Europe and North America in last decades caused that economical and social aspects of living conditions of the population have less effect and genetic defects of malabsorption of vitamin B12 became the main reason for cobalamin deficiency in children. Imerslund-Grasbeck syndrome (IGS) is characterized by vitamin B12 deficiency that leads usually to megaloblastic anemia and mild proteinuria. We described two pairs of siblings in two families with IGS. The diagnosis in first family (two brothers) was established at 33 and 22 months of age. The reason for diagnostic tests were proteinuria and anemia. Apart from respiratory tract infections, they didn't present other symptoms of cobalamin deficiency. In the second family IGS was diagnosed in children at 5 and 8 years of age. Diagnostic evaluation procedures wereperformedbecause ofneurologicalsigns, including weakness, loss of appetite, dysmorphia, psychomotor retardation. Laboratory tests revealed megaloblastic anemia, low concentration of vitamin B12 in serum and mild proteinuria. In the first pair low concentration of vitamin B12 was validated by the Schilling test, in the second pair methylomalonate acid was detected in the urinary metabolic test. All children were successfully treated with vitamin B12 and anemia and neurological signs disappeared. Long-term follow up showed failure to thrive in the girl and physical and mental retardation, microcephaly in her brother. Proteinuria in the range: 0.3-1.2 g/24 h was detected in each child, and the other laboratory tests were normal. Clinical symptoms, laboratory tests and good reaction to parenteral treatment with vitamin B12 allowed us to diagnose Imerslund-Grasbeck syndrome, even without genetic tests. A delayed diagnosis of congenital malabsorption of cobalamin can lead to physical and mental retardation in children. Children with megaloblastic anemia and proteinuria resistant to classical treatment should be tested for

Anaemia, folate and vitamin B12 deficiency among pregnant women in an area of unstable malaria transmission in eastern Sudan.

PubMed

Abdelrahim, Ishraga I; Adam, Gamal K; Mohmmed, Ahmed A; Salih, Magdi M; Ali, Naji I; Elbashier, Mustafa I; Adam, Ishag

2009-05-01

A cross-sectional study was carried out between October 2007 and January 2008 to investigate the prevalence and types of anaemia among pregnant women of eastern Sudan. Socio-demographic and obstetrical data were collected using a questionnaire. Haemoglobin (Hb), serum ferritin, serum folate and vitamin B(12) were assessed using standard laboratory methods. Two hundred and seventy-nine pregnant Sudanese women were recruited. Anaemia (Hb <11 gdl) and iron deficiency (ferritin <15 microg/l) were prevalent in 80.3 and 14.3% of the study sample, respectively. Of the total sample, 11.1% had iron-deficiency anaemia. Serum folate (<6.6 ng/ml) and vitamin B(12) (<150 pg/ml) deficiency was reported in 57.7 and 1%, respectively, and none of the women had both folate and vitamin B(12) deficiencies. Univariate and multivariate analyses showed that ferritin, serum folate and vitamin B(12) levels were not significantly associated with anaemia. Thus, there was a high prevalence of anaemia and folate deficiency. Measures to control these should be considered.

Brain MRI and MR Spectroscopy Findings in Children with Nutritional Vitamin B12 Deficiency.

PubMed

Ekici, F; Tekbas, G; Hattapoğlu, S; Yaramış, A; Önder, H; Bilici, A

2016-06-01

Our aim in this study was to analyze the findings of brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of children with vitamin B12 deficiency. This study included 14 cases. The findings of brain MRI and MRS in all cases were investigated. Four patients had been followed up and mean follow-up time 71.8 (59-85) day. Eight patients of the cases (57 %) had at least one abnormal MRI finding. The most commonly found MRI findings were thinning of the corpus callosum and brain atrophy, respectively. The mean ratio of NAA/Cr and Cho/Cr were measured in MRS, with values of 1.31 ± 0.17 and 1.04 ± 0.27, respectively. In two of three patients with abnormal MRI studies at presentation, subsequent MRI showed improvement while one patient remained unchanged. An increase in the ratios of metabolites were found in one case with control MRS. There was no lactate peak. Brain MRI was abnormal in more than half of the cases of children with vitamin B12 deficiency. Our radiologic findings similar with literature. There was no identifiable lactate peak. B12 deficiency could be the cause of the thinning of the corpus callosum and brain atrophy in the children that were given a brain MRI.

CA 15-3 predicting breast cancer relapse: beware of vitamin B12 deficiency.

PubMed

Rassy, Elie El; Ghor, Maya Al; Kattan, Joseph

2018-05-10

A sustained increase of cancer antigen 15-3 serum levels was found in a 54-year-old woman treated 2 years ago for early stage breast cancer, without any evidence of cancer recurrence. The patient thereafter developed severe megaloblastic anemia secondary to vitamin B12 deficiency. Supplementation with B12 to reverse the anemia led to the normalization of the cancer antigen 15-3 serum levels. As such, with the limited understanding of molecular biology, the integrative approach of clinical history, physical examination, and diagnostic imaging remain pivotal in the management of cancer patients.

Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain.

PubMed

Ozen, Serkan; Ozer, Murat Atabey; Akdemir, Mehmet Orçun

2017-06-01

This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED). Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively. The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p < 0.001 for each group). The mean vitamin B12 level at enrollment was 144.24 ±43.36 pg/ml in group 1 and 417.53 ±87.22 pg/ml in group 2. The mean vitamin B12 level in group 1 reached to 450 ±60.563 pg/ml after 12 weeks of treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2. These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular

Vitamin B12 in Health and Disease

PubMed Central

O’Leary, Fiona; Samman, Samir

2010-01-01

Vitamin B12 is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B12, and to evaluate the causes and consequences of sub-clinical vitamin B12 deficiency. Vitamin B12 deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B12 deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B12 is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health. PMID:22254022

Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice

PubMed Central

Ghosh, Shampa; Sinha, Jitendra Kumar; Putcha, Uday Kumar; Raghunath, Manchala

2016-01-01

Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4 weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12 weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24 h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects. PMID:26835453

Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice.

PubMed

Ghosh, Shampa; Sinha, Jitendra Kumar; Putcha, Uday Kumar; Raghunath, Manchala

2016-01-01

Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4 weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12 weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24 h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects.

The role of metformin on vitamin B12 deficiency: a meta-analysis review.

PubMed

Niafar, Mitra; Hai, Faizi; Porhomayon, Jahan; Nader, Nader Djalal

2015-02-01

Metformin is the only biguanide oral hypoglycemic drug, that is used to treat patients with type-2 diabetes mellitus. There are some reports of metformin being associated with decreased serum levels of vitamin B12 (VB12). The objective of this study is to systematically analyze the impact of metformin on the frequency of VB12 deficiency and serum levels of VB12. A search of various databases provided 18 retrospective cohort studies and 11 randomized controlled trials. Pooled estimates of odds ratio with 95% confidence interval using random effect model were conducted. Studies were examined for heterogeneity, publication bias and sensitivity analysis. Separate analysis of randomized control trials (RCTs) including both low-risk and high-risk bias was also conducted. 29 studies were selected with a total of 8,089 patients. 19 studies were rated intermediate or high quality. Primary outcome suggested increased incidence of VB12 deficiency in metformin group (OR = 2.45, 95% CI 1.74-3.44, P < 0.0001.) Heterogeneity was relatively high (I(2) = 53%), with minor publication bias. Secondary outcome suggested lower serum VB12 concentrations in metformin group (Mean difference = -65.8, 95% CI -78.1 to -53.6 pmol/L, P < 0.00001) with high heterogeneity (I(2) = 98%,) and low publication bias. RCTs analysis of low-and high-risk group revealed similar trends. We conclude that metformin treatment is significantly associated with an increase in incidence of VB12 deficiency and reduced serum VB12 levels.

The Human Serum Metabolome of Vitamin B-12 Deficiency and Repletion, and Associations with Neurological Function in Elderly Adults.

PubMed

Brito, Alex; Grapov, Dmitry; Fahrmann, Johannes; Harvey, Danielle; Green, Ralph; Miller, Joshua W; Fedosov, Sergey N; Shahab-Ferdows, Setareh; Hampel, Daniela; Pedersen, Theresa L; Fiehn, Oliver; Newman, John W; Uauy, Ricardo; Allen, Lindsay H

2017-08-09

Background: The specific metabolomic perturbations that occur in vitamin B-12 deficiency, and their associations with neurological function, are not well characterized. Objective: We sought to characterize the human serum metabolome in subclinical vitamin B-12 deficiency and repletion. Methods: A before-and-after treatment study provided 1 injection of 10 mg vitamin B-12 (with 100 mg pyridoxine and 100 mg thiamin) to 27 community-dwelling elderly Chileans (∼74 y old) with vitamin B-12 deficiency, as evaluated with serum vitamin B-12, total plasma homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin. The combined indicator of vitamin B-12 status (cB-12) was computed. Targeted metabolites [166 acylcarnitines, amino acids, sugars, glycerophospholipids, and sphingolipids (liquid chromatography-tandem mass spectrometry)], and untargeted metabolites [247 chemical entities (gas chromatography time-of-flight mass spectrometry)] were measured at baseline and 4 mo after treatment. A peripheral nerve score was developed. Differences before and after treatment were examined. For targeted metabolomics, the data from 18 individuals with adequate vitamin B-12 status (selected from the same population) were added to the before-and-after treatment data set. Network visualizations and metabolic pathways are illustrated. Results: The injection increased serum vitamin B-12, holotranscobalamin, and cB-12 ( P < 0.001), and reduced tHcy and serum MMA ( P < 0.001). Metabolomic changes from before to after treatment included increases ( P < 0.001) in acylcarnitines, plasmalogens, and other phospholipids, whereas proline and other intermediaries of one-carbon metabolism-that is, methionine and cysteine-were reduced ( P < 0.001). Direct significant correlations ( P < 0.05 after the false discovery rate procedure) were identified between acylcarnitines, plasmalogens, phospholipids, lyso-phospholipids, and sphingomyelins compared with vitamin B-12 status and nerve function

Prevalence of Vitamin B12 and folic acid deficiency in HIV-positive patients and its association with neuropsychiatric symptoms and immunological response.

PubMed

Adhikari, Prabha M R; Chowta, Mukta N; Ramapuram, John T; Rao, Satish; Udupa, Karthik; Acharya, Sahana Devdas

2016-01-01

Deficiency of micronutrients is prevalent even before the development of symptoms of HIV disease and is associated with accelerated HIV disease progression. This study evaluates the prevalence of folate and Vitamin B 12 deficiency in HIV-positive patients with or without tuberculosis (TB) and its association with neuropsychiatric symptoms and immunological response. Cross-sectional, observational study in an outpatient setting. Four groups of HIV-positive patients with TB (Group I), HIV-positive patients with neuropsychiatric symptoms (Group II), HIV-positive patients without neuropsychiatric symptoms or TB (Group III), and HIV-negative controls with neuropsychiatric symptoms (Group IV). Vitamin B 12 and folate estimation was done using carbonyl metallo-immunoassay method. ANOVA, Kruskal-Wallis and Mann-Whitney, Pearson's correlation. The prevalence of folic acid deficiency was 27.1% in the Group I, 31.9% in the Group II, 23.4% in the Group III, and 32% in the Group IV being higher in patients with neuropsychiatric symptoms in both HIV and non-HIV patients. The prevalence of Vitamin B 12 deficiency was 18.8% in Group I, 9.1% in Group II, 4.8% in Group III, and 16.7% in Group IV. The patients with folate deficiency had more severe depression and anxiety. Nearly, 30% of the HIV patients had a folic acid deficiency, and about 10% of the HIV patients had Vitamin B 12 deficiency. The folate deficiency was highest among neuropsychiatric patients with or without HIV infection and Vitamin B 12 deficiency was higher among HIV patients with TB.

Investigation of the vitamin B12 deficiency with peripheral neuropathy in patients with type 2 diabetes mellitus treated using metformin.

PubMed

Olt, Serdar; Oznas, Orhan

2017-01-01

The relationship between vitamin B12 deficiency and peripheral neuropathy has been shown in a number of previous studies. Metformin is the indispensable first-line treatment for type 2 diabetes mellitus (DM) worldwide. One of the adverse effects of the use of metformin is vitamin B12 deficiency. In the present study, we investigated the relationship between vitamin B12 deficiency and peripheral neuropathy due to the use of metformin. Patient's laboratory and electromyography (EMG) data were retrospectively reviewed. Patients with no EMG report and other necessary information were excluded from the study. Eighty-six patients with type 2 DM using metformin were included in the study. Of these patients, 26 were males and 60 were females. The mean age of the patients was 55.1±7.7 years. The mean body mass index of the patients was 29.1±9.01 kg/m 2 . The mean HbA1c level of the patients was 8.6%±2.1%. The mean duration of diabetes was 8.02±5.4 years. The incidence of vitamin B12 deficiency was 38.4%. Peripheral neuropathy was detected in 33.7% patients. There was no statistically significant difference in vitamin B12 levels between patients with peripheral neuropathy and those without peripheral neuropathy (p=0.64). Therefore, it can be concluded that the lack of vitamin B12 secondary to the use of metformin did not significantly increase the frequency of peripheral neuropathy.

Newborn screening for remethylation disorders and vitamin B12 deficiency-evaluation of new strategies in cohorts from Qatar and Germany.

PubMed

Gramer, Gwendolyn; Abdoh, Ghassan; Ben-Omran, Tawfeg; Shahbeck, Noora; Ali, Rehab; Mahmoud, Laila; Fang-Hoffmann, Junmin; Hoffmann, Georg F; Al Rifai, Hilal; Okun, Jürgen G

2017-04-01

Newborn screening is a precondition for early diagnosis and successful treatment of remethylation disorders and classical homocystinuria (cystathionine-ß-synthase deficiency). Newborn screening for classical homocystinuria using total homocysteine measurement in dried blood spots has been very successfully performed for many years for newborns from Qatar. A new optimized newborn screening strategy for remethylation disorders and homocystinuria was developed and evaluated for newborns from Qatar using total homocysteine measurement as first-tier and methionine, methionine-phenylalanine-ratio and propionylcarnitine as second-tiers. Proposed cut-offs were also retrospectively evaluated in newborn screening samples of 12 patients with remethylation disorders and vitamin B 12 deficiency from Qatar and Germany. Over a 12 months period, the proposed strategy led to a decrease in the recall rate in homocysteine screening for Qatar from 1.09% to 0.68%, while allowing for additional systematic inclusion of remethylation disorders and vitamin B 12 deficiency into the screening panel for Qatar. In the evaluated period the applied strategy would have detected all patients with classical homocystinuria identified by the previous strategy and in addition 5 children with maternal nutritional vitamin B 12 deficiency and one patient with an isolated remethylation disorder. Additional retrospective evaluation of newborn screening samples of 12 patients from Germany and Qatar with remethlyation disorders or vitamin B 12 deficiency showed that all of these patients would have been detected by the cut-offs used in the proposed new strategy. In addition, an adapted strategy for Germany using methionine, methionine-phenylalanine-ratio and propionylcarnitine as first-tier, and homocysteine as a second-tier test was also positively evaluated retrospectively. The proposed strategy for samples from Qatar allows inclusion of remethylation disorders and vitamin B 12 deficiency in the screening

Folate and Vitamin B12 Deficiency Among Non-pregnant Women of Childbearing-Age in Guatemala 2009-2010: Prevalence and Identification of Vulnerable Populations.

PubMed

Rosenthal, Jorge; Lopez-Pazos, Eunice; Dowling, Nicole F; Pfeiffer, Christine M; Mulinare, Joe; Vellozzi, Claudia; Zhang, Mindy; Lavoie, Donna J; Molina, Roberto; Ramirez, Nicte; Reeve, Mary-Elizabeth

2015-10-01

Information on folate and vitamin B12 deficiency rates in Guatemala is essential to evaluate the current fortification program. The objectives of this study were to describe the prevalence of folate and vitamin B12 deficiencies among women of childbearing age (WCBA) in Guatemala and to identify vulnerable populations at greater risk for nutrient deficiency. A multistage cluster probability study was designed with national and regional representation of nonpregnant WCBA (15-49 years of age). Primary data collection was carried out in 2009-2010. Demographic and health information was collected through face-to-face interviews. Blood samples were collected from 1473 WCBA for serum and red blood cell (RBC) folate and serum vitamin B12. Biochemical concentrations were normalized using geometric means. Prevalence rate ratios were estimated to assess relative differences among different socioeconomic and cultural groups including ethnicity, age, education level, wealth index and rural versus urban locality. National prevalence estimates for deficient serum [<10 nmol per liter (nmol/L)] and RBC folate (<340 nmol/L) concentrations were 5.1 % (95 % CI 3.8, 6.4) and 8.9 % (95 % CI 6.7, 11.7), respectively; for vitamin B12 deficiency (<148 pmol/L) 18.5 % (95 % CI 15.6, 21.3). Serum and RBC folate deficiency prevalences were higher for rural areas than for urban areas (8.0 vs. 2.0 % and 13.5 vs. 3.9 %, respectively). The prevalence of RBC folate deficiency showed wide variation by geographic region (3.2-24.9 %) and by wealth index (4.1-15.1 %). The prevalence of vitamin B12 deficiency also varied among regions (12.3-26.1 %). In Guatemala, folate deficiency was more prevalent among indigenous rural and urban poor populations. Vitamin B12 deficiency was widespread among WCBA. Our results suggest the ongoing need to monitor existing fortification programs, in particular regarding its reach to vulnerable populations.

Folate and Vitamin B12 Deficiency Among Nonpregnant Women of Childbearing Age in Guatemala 2009–2010: Prevalence and Identification of Vulnerable Populations

PubMed Central

Rosenthal, Jorge; Lopez-Pazos, Eunice; Dowling, Nicole F.; Pfeiffer, Christine M.; Mulinare, Joe; Vellozzi, Claudia; Zhang, Mindy; Lavoie, Donna J; Molina, Roberto; Ramirez, Nicte; Reeve, Mary-Elizabeth

2015-01-01

Introduction Information on folate and vitamin B12 deficiency rates in Guatemala is essential to evaluate the current fortification program. The objectives of this study were to describe the prevalence of folate and vitamin B12 deficiencies among women of childbearing age (WCBA) in Guatemala and to identify vulnerable populations at greater risk for nutrient deficiency. Methods A multistage cluster probability study was designed with national and regional representation of nonpregnant WCBA (15–49 years of age). Primary data collection was carried out in 2009–2010. Demographic and health information was collected through face-to-face interviews. Blood samples were collected from 1,473 WCBA for serum and red blood cell (RBC) folate and serum vitamin B12. Biochemical concentrations were normalized using geometric means. Prevalence rate ratios were estimated to assess relative differences among different socioeconomic and cultural groups including ethnicity, age, education level, wealth index and rural versus urban locality. Results National prevalence estimates for deficient serum (<10 nanomoles per liter [nmol/L]) and RBC folate (<340 nmol/L) concentrations were 5.1% (95% CI 3.8, 6.4) and 8.9% (95% CI 6.7, 11.7), respectively; for vitamin B12 deficiency (<148 pmol/L) 18.5% (95% CI 15.6, 21.3). Serum and RBC folate deficiency prevalences were higher for rural areas than for urban areas (8.0% vs. 2.0% and 13.5% vs. 3.9%, respectively). The prevalence of RBC folate deficiency showed wide variation by geographic region (3.2%–24.9%) and by wealth index (4.1%–15.1%). The prevalence of vitamin B12 deficiency also varied among regions (12.3% –26.1%). Conclusions In Guatemala, folate deficiency was more prevalent among indigenous rural and urban poor populations. Vitamin B12 deficiency was widespread among WCBA. Our results suggest the ongoing need to monitor existing fortification programs, in particular regarding its reach to vulnerable populations. PMID:26002178

Coma and respiratory failure in a child with severe vitamin B(12) deficiency.

PubMed

Codazzi, Daniela; Sala, Francesca; Parini, Rossella; Langer, Martin

2005-07-01

Psychofunctional follow-up of severe vitamin B(12) deficit. Case report. Pediatric intensive care unit. Ten-month-old boy. Follow-up at 3 yrs. A 10-month-old boy was admitted to the pediatric intensive care unit with respiratory failure, muscular hypotonia, and involuntary movements. Although a central nervous system infection was excluded, computed tomography scan showed a diffuse cortical-subcortical atrophy. Vitamin B(12) deficiency was suspected because of a red-cell count of 1,350,000/mm(3) and a hemoglobin value 5.9 g/dL (MCV 116). The baby had been exclusively breast-fed, but his mother had been a strict vegan for 10 yrs. Chronic dietary vitamin B(12) deprivation was confirmed by blood and urinary samples. Treatment with vitamin B(12) led in 2 wks to rapid and complete hematological improvement and to partial regression of neurologic symptoms. During the following 3 yrs the boy had normal vitamin intake and underwent intensive rehabilitative treatment. The brain atrophy regressed, but linguistic and psychomotor delay persisted. Rapid clinical improvement after vitamin supply does not correlate with a complete recovery.

Vitamin B-12 and Perinatal Health.

PubMed

Finkelstein, Julia L; Layden, Alexander J; Stover, Patrick J

2015-09-01

Vitamin B-12 deficiency (<148 pmol/L) is associated with adverse maternal and neonatal outcomes, including developmental anomalies, spontaneous abortions, preeclampsia, and low birth weight (<2500 g). The importance of adequate vitamin B-12 status periconceptionally and during pregnancy cannot be overemphasized, given its fundamental role in neural myelination, brain development, and growth. Infants born to vitamin B-12-deficient women may be at increased risk of neural tube closure defects, and maternal vitamin B-12 insufficiency (<200 pmol/L) can impair infant growth, psychomotor function, and brain development, which may be irreversible. However, the underlying causal mechanisms are unknown. This review was conducted to examine the evidence that links maternal vitamin B-12 status and perinatal outcomes. Despite the high prevalence of vitamin B-12 deficiency and associated risk of pregnancy complications, few prospective studies and, to our knowledge, only 1 randomized trial have examined the effects of vitamin B-12 supplementation during pregnancy. The role of vitamin B-12 in the etiology of adverse perinatal outcomes needs to be elucidated to inform public health interventions. © 2015 American Society for Nutrition.

Investigation of the vitamin B12 deficiency with peripheral neuropathy in patients with type 2 diabetes mellitus treated using metformin

PubMed Central

Olt, Serdar; Oznas, Orhan

2017-01-01

OBJECTIVE: The relationship between vitamin B12 deficiency and peripheral neuropathy has been shown in a number of previous studies. Metformin is the indispensable first-line treatment for type 2 diabetes mellitus (DM) worldwide. One of the adverse effects of the use of metformin is vitamin B12 deficiency. In the present study, we investigated the relationship between vitamin B12 deficiency and peripheral neuropathy due to the use of metformin. METHODS: Patient’s laboratory and electromyography (EMG) data were retrospectively reviewed. Patients with no EMG report and other necessary information were excluded from the study. RESULTS: Eighty-six patients with type 2 DM using metformin were included in the study. Of these patients, 26 were males and 60 were females. The mean age of the patients was 55.1±7.7 years. The mean body mass index of the patients was 29.1±9.01 kg/m2. The mean HbA1c level of the patients was 8.6%±2.1%. The mean duration of diabetes was 8.02±5.4 years. The incidence of vitamin B12 deficiency was 38.4%. Peripheral neuropathy was detected in 33.7% patients. There was no statistically significant difference in vitamin B12 levels between patients with peripheral neuropathy and those without peripheral neuropathy (p=0.64). CONCLUSION: Therefore, it can be concluded that the lack of vitamin B12 secondary to the use of metformin did not significantly increase the frequency of peripheral neuropathy. PMID:29270571

Brief Report: Childhood Disintegrative Disorder as a Likely Manifestation of Vitamin B12 Deficiency

ERIC Educational Resources Information Center

Malhotra, Savita; Subodh, B. N.; Parakh, Preeti; Lahariya, Sanjay

2013-01-01

Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case…

Nutritional vitamin B12 deficiency in a breast-fed infant of a vegan-diet mother.

PubMed

Sklar, R

1986-04-01

A 7-month-old male presented with lethargy and failure to thrive. The child was exclusively breast-fed from birth by a mother who was a strict vegetarian. Laboratory data revealed macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The patient responded well to supplementation with B12 alone and was developmentally normal by 11 months of age. This study emphasizes the need for assuring maternal dietary adequacy during pregnancy and after birth.

Neurologic Manifestations of Vitamin B Deficiency after Bariatric Surgery.

PubMed

Punchai, Suriya; Hanipah, Zubaidah Nor; Meister, Katherine M; Schauer, Philip R; Brethauer, Stacy A; Aminian, Ali

2017-08-01

The aim of this study was to assess the incidence, clinical presentation, and outcomes of neurologic disorders secondary to vitamin B deficiencies following bariatric surgery. Patients at a single academic institution who underwent bariatric surgery and developed neurologic complications secondary to low levels of vitamins B1, B2, B6, and B12 between the years 2004 and 2015 were studied. In total, 47 (0.7%) bariatric surgical patients (Roux-en-Y gastric bypass n = 36, sleeve gastrectomy n = 9, and duodenal switch n = 2) developed neurologic manifestations secondary to vitamin B deficiencies. Eleven (23%) patients developed postoperative anatomical complications contributed to poor oral intake. Median duration to onset of neurologic manifestation following surgery was 12 months (IQR, 5-32). Vitamin deficiencies reported in the cohort included B1 (n = 30), B2 (n = 1), B6 (n = 12), and B12 (n = 12) deficiency. The most common manifestations were paresthesia (n = 31), muscle weakness (n = 15), abnormal gait (n = 11), and polyneuropathy (n = 7). Four patients were diagnosed with Wernicke-Korsakoff syndrome (WKS) which was developed after gastric bypass (n = 3) and sleeve gastrectomy (n = 1). Seven patients required readmission for management of severe vitamin B deficiencies. Overall, resolution of neurologic symptoms with nutritional interventions and pharmacotherapy was noted in 40 patients (85%). The WKS was not reversible, and all four patients had residual mild ataxia and nystagmus at the last follow-up time. Nutritional neurologic disorders secondary to vitamin B deficiency are relatively uncommon after bariatric surgery. While neurologic disorders are reversible in most patients (85%) with vitamin replacements, persistent residual neurologic symptoms are common in patients with WKS.

B12 in fetal development.

PubMed

Pepper, M Reese; Black, Maureen M

2011-08-01

Vitamin B12 (cobalamin) is necessary for development of the fetus and child. Pregnant women who are vegetarian or vegan, have Crohn's or celiac disease, or have undergone gastric bypass surgery are at increased risk of B12 deficiency. Low serum levels of B12 have been linked to negative impacts in cognitive, motor, and growth outcomes. Low cobalamin levels also may be related to depression in adults. Some studies indicate that B12 supplementation may improve outcomes in children, although more research is needed in this area. Overall, the mechanisms of B12 action in development remain unclear. Further studies in this area to elucidate the pathways of cobalamin influence on development, as well as to prevent B12 deficiency in pregnant women and children are indicated. Copyright © 2011 Elsevier Ltd. All rights reserved.

High Serum Folate Is Associated with Brain Atrophy in Older Diabetic People with Vitamin B12 Deficiency.

PubMed

Deng, Y; Wang, D; Wang, K; Kwok, T

2017-01-01

Previous studies have reported the adverse cognitive effects of high folate status in older individuals with vitamin B12 (VB12) deficiency. Thus, the aim of this study was to investigate how high serum folate and VB12 deficiency could collaboratively aggravate neuronal degeneration. In total, 146 older non-demented diabetic individuals with an average age of 75 ± 3.9 were recruited. VB12 deficiency and high folate status were based on high serum methylmalonic acid (MMA) concentrations (> 0.3 μmol/L) and the serum folate concentration being in the top tertile (> 31.4 nmol/L) respectively. Among these subjects, there were 20 with elevated MMA and high folate. The structural magnetic resonance imaging data of these subjects were analyzed by performing flexible factorial analysis with the "folate level" and "MMA level" added as main effects, and the interaction effect of folate and VB12 on brain volume was evaluated. The results showed significant gray matter atrophy of the right middle occipital gyrus and the opercular part of the inferior frontal gyrus in subjects with a simultaneous high folate status and VB12 deficiency. Together with previous observational studies on cognitive function, this study lends support to the notion that high serum folate concentrations in older people with VB12 deficiency may be associated with increased neurodegeneration.

Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects.

PubMed

Watanabe, Fumio; Yabuta, Yukinori; Tanioka, Yuri; Bito, Tomohiro

2013-07-17

The usual dietary sources of vitamin B12 are animal-source based foods, including meat, milk, eggs, fish, and shellfish, although a few plant-based foods such as certain types of dried lavers (nori) and mushrooms contain substantial and considerable amounts of vitamin B12, respectively. Unexpectedly, detailed characterization of vitamin B12 compounds in foods reveals the presence of various corrinoids that are inactive in humans. The majority of edible blue-green algae (cyanobacteria) and certain edible shellfish predominately contain an inactive corrinoid known as pseudovitamin B12. Various factors affect the bioactivity of vitamin B12 in foods. For example, vitamin B12 is partially degraded and loses its biological activity during cooking and storage of foods. The intrinsic factor-mediated gastrointestinal absorption system in humans has evolved to selectively absorb active vitamin B12 from naturally occurring vitamin B12 compounds, including its degradation products and inactive corrinoids that are present in daily meal foods. The objective of this review is to present up-to-date information on various factors that can affect the bioactivity of vitamin B12 in foods. To prevent vitamin B12 deficiency in high-risk populations such as vegetarians and elderly subjects, it is necessary to identify plant-source foods that contain high levels of bioactive vitamin B12 and, in conjunction, to prepare the use of crystalline vitamin B12-fortified foods.

Vitamin B-12 and Perinatal Health123

PubMed Central

Finkelstein, Julia L; Layden, Alexander J; Stover, Patrick J

2015-01-01

Vitamin B-12 deficiency (<148 pmol/L) is associated with adverse maternal and neonatal outcomes, including developmental anomalies, spontaneous abortions, preeclampsia, and low birth weight (<2500 g). The importance of adequate vitamin B-12 status periconceptionally and during pregnancy cannot be overemphasized, given its fundamental role in neural myelination, brain development, and growth. Infants born to vitamin B-12-deficient women may be at increased risk of neural tube closure defects, and maternal vitamin B-12 insufficiency (<200 pmol/L) can impair infant growth, psychomotor function, and brain development, which may be irreversible. However, the underlying causal mechanisms are unknown. This review was conducted to examine the evidence that links maternal vitamin B-12 status and perinatal outcomes. Despite the high prevalence of vitamin B-12 deficiency and associated risk of pregnancy complications, few prospective studies and, to our knowledge, only 1 randomized trial have examined the effects of vitamin B-12 supplementation during pregnancy. The role of vitamin B-12 in the etiology of adverse perinatal outcomes needs to be elucidated to inform public health interventions. PMID:26374177

Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development.

PubMed

Molloy, Anne M; Kirke, Peadar N; Brody, Lawrence C; Scott, John M; Mills, James L

2008-06-01

The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects (NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B12 status have not been sufficiently researched.

Lessons to be learned: a case study approach. Vitamin B12 deficiency of nutritional origin.

PubMed

Donaldson, D

1997-10-01

The case is presented of a 14 year old boy who developed severe anaemia at the onset of puberty caused by nutritional deficiency of vitamin B12 of about 10 years duration. The dietary intake comprised mainly chips, ice-cream, fruit and Coca-Cola--with small amounts of vitamin B12 from occasional slices of chicken meat. His denial of abnormal nutritional intake, supported by his mother, delayed confirmation of the correct diagnosis. However, the true situation was eventually confessed--and following implementation of a normal diet he rapidly improved clinically, the haemoglobin value rose to normal and he subsequently remained well.

Vitamin B12 deficiency anemia

MedlinePlus

... diet Poor diet in infants Poor nutrition during pregnancy Certain health conditions can make it difficult for your body to absorb enough vitamin B12. They include: Chronic alcoholism Crohn disease, celiac disease, infection with the fish ...

Prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents from rural and urban localities and its relationship with various anthropometric indices: a cross-sectional study.

PubMed

Chakraborty, S; Chopra, M; Mani, K; Giri, A K; Banerjee, P; Sahni, N S; Siddhu, A; Tandon, N; Bharadwaj, D

2018-02-22

Micronutrient deficiency is a global health burden, especially among developing countries. The present cross-sectional study aimed to determine the prevalence of vitamin B 12 deficiency in healthy Indian school-going adolescents, based on area of residence, sex and body mass index (BMI). Furthermore, the relationship of serum B 12 concentration with dietary vitamin B 12 intake and anthropometric indices was assessed among adolescents from rural and urban India. A total of 2403 school-going adolescents (11-17 years) from National Capital Region and rural areas of Haryana, India were selected. Serum B 12 concentrations were estimated using an electrochemiluminescence immunoassay. Dietary assessments were conducted on 65% of total participants (n = 1556) by two 24-h diet recalls. The prevalence of vitamin B 12 deficiency in the total study population was 32.4% (rural: 43.9% versus urban: 30.1%, P < 0.001; male: 34.4% versus female: 31.0%, P < 0.05; normal weight: 28.1%, versus overweight: 39.8%, versus obese: 51.2%, P < 0.001). More than half (51.2%) of obese adolescents were vitamin B 12 deficient. On multiple linear regression analysis, serum B 12 in rural adolescents was associated with age (β = -0.12, P < 0.05). Among urban adolescents, serum B 12 was associated with BMI (β = -0.08, P < 0.05) and adjusted dietary vitamin B 12 intake (β = 0.14, P < 0.001). Serum vitamin B 12 levels were found to be lower in rural females (β = -0.12, P = 0.030) and urban males (β: 0.11, P < 0.001) compared to their respective contemporaries. Vitamin B 12 deficiency was higher among rural school-going adolescents. Boys had a higher B 12 deficiency than girls. Inverse associations of serum B 12 with adiposity indices were observed. Serum B 12 levels were positively associated with dietary vitamin B 12 intake. © 2018 The British Dietetic Association Ltd.

Proteomics of vitamin B12 processing.

PubMed

Hannibal, Luciana; DiBello, Patricia M; Jacobsen, Donald W

2013-03-01

The causes of cobalamin (B12, Cbl) deficiency are multifactorial. Whether nutritional due to poor dietary intake, or functional due to impairments in absorption or intracellular processing and trafficking events, the major symptoms of Cbl deficiency include megaloblastic anemia, neurological deterioration and in extreme cases, failure to thrive and death. The common biomarkers of Cbl deficiency (hyperhomocysteinemia and methylmalonic acidemia) are extremely valuable diagnostic indicators of the condition, but little is known about the changes that occur at the protein level. A mechanistic explanation bridging the physiological changes associated with functional B12 deficiency with its intracellular processers and carriers is lacking. In this article, we will cover the effects of B12 deficiency in a cblC-disrupted background (also referred to as MMACHC) as a model of functional Cbl deficiency. As will be shown, major protein changes involve the cytoskeleton, the neurological system as well as signaling and detoxification pathways. Supplementation of cultured MMACHC-mutant cells with hydroxocobalamin (HOCbl) failed to restore these variants to the normal phenotype, suggesting that a defective Cbl processing pathway produces irreversible changes at the protein level.

Evidence From Web-Based Dietary Search Patterns to the Role of B12 Deficiency in Non-Specific Chronic Pain: A Large-Scale Observational Study

PubMed Central

Giat, Eitan

2018-01-01

Background Profound vitamin B12 deficiency is a known cause of disease, but the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms, as well as the relationship between eating meat and B12 levels, is unclear. Objective The objective of our study was to investigate the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms. Methods We used food-related Internet search patterns from a sample of 8.5 million people based in the US as a proxy for B12 intake and correlated these searches with Internet searches related to possible effects of B12 deficiency. Results Food-related search patterns were highly correlated with known consumption and food-related searches (ρ=.69). Awareness of B12 deficiency was associated with a higher consumption of B12-rich foods and with queries for B12 supplements. Searches for terms related to neurological disorders were correlated with searches for B12-poor foods, in contrast with control terms. Popular medicines, those having fewer indications, and those which are predominantly used to treat pain, were more strongly correlated with the ability to predict neuropathic pain queries using the B12 contents of food. Conclusions Our findings show that Internet search patterns are a useful way of investigating health questions in large populations, and suggest that low B12 intake may be associated with a broader spectrum of neurological disorders than previously thought. PMID:29305340

Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

PubMed

Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

2014-01-01

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

Vitamin B-12 Deficiency in Children Is Associated with Grade Repetition and School Absenteeism, Independent of Folate, Iron, Zinc, or Vitamin A Status Biomarkers.

PubMed

Duong, Minh-Cam; Mora-Plazas, Mercedes; Marín, Constanza; Villamor, Eduardo

2015-07-01

Micronutrients are essential to neurocognitive development; yet their role in educational outcomes is unclear. We examined the associations of micronutrient status biomarkers with the risk of grade repetition and rates of school absenteeism in a cohort of school children. We recruited 3156 children aged 5-12 y from public schools in Bogota, Colombia. Circulating ferritin, hemoglobin, zinc, vitamin A, and vitamin B-12; erythrocyte folate; and mean corpuscular volume (MCV) were measured in blood samples obtained at the beginning of the year. Absenteeism was recorded weekly during the school year, and grade repetition was determined the next year. Risk ratios for grade repetition and rate ratios for absenteeism were estimated by categories of micronutrient status indicators with use of Poisson regression, adjusting for potential confounders. The risk of grade repetition was 4.9%, and the absenteeism rate was 3.8 d per child-year of observation. Vitamin B-12 deficiency (<148 pmol/L) was associated with an adjusted 2.36-fold greater risk of grade repetition (95% CI: 1.03, 5.41; P = 0.04) compared with plasma concentrations ≥148 pmol/L. Other micronutrients were not related to grade repetition. Vitamin B-12 deficiency was also associated with school absenteeism rates. Compared with children with plasma vitamin B-12 concentrations ≥148 pmol/L, vitamin B-12-deficient children had a 1.89-times higher adjusted rate (95% CI: 1.53, 2.34; P < 0.0001). Anemia was related to a 72% higher rate (95% CI: 48%, 99%; P < 0.0001), whereas every 5-fL difference in MCV was associated with a 7% lower adjusted rate (95% CI: 4%, 10%; P < 0.0001). Vitamin B-12 deficiency was associated with risk of grade repetition and school absenteeism rates in school children from Bogota, Colombia. The effects of correcting vitamin B-12 deficiency on educational outcomes and neurocognitive development of school children need to be determined in intervention studies. © 2015 American Society for

Vegan Diet, Subnormal Vitamin B-12 Status and Cardiovascular Health

PubMed Central

Woo, Kam S.; Kwok, Timothy C.Y.; Celermajer, David S.

2014-01-01

Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases. PMID:25195560

Vegan diet, subnormal vitamin B-12 status and cardiovascular health.

PubMed

Woo, Kam S; Kwok, Timothy C Y; Celermajer, David S

2014-08-19

Vegetarian diets have been associated with atherosclerosis protection, with healthier atherosclerosis risk profiles, as well as lower prevalence of, and mortality from, ischemic heart disease and stroke. However, there are few data concerning the possible cardiovascular effects of a vegan diet (with no meat, dairy or egg products). Vitamin B-12 deficiency is highly prevalent in vegetarians; this can be partially alleviated by taking dairy/egg products in lact-ovo-vegetarians. However, metabolic vitamin B-12 deficiency is highly prevalent in vegetarians in Australia, Germany, Italy and Austria, and in vegans (80%) in Hong Kong and India, where vegans rarely take vitamin B-12 fortified food or vitamin B-12 supplements. Similar deficiencies exist in northern Chinese rural communities consuming inadequate meat, egg or dairy products due to poverty or dietary habits. Vascular studies have demonstrated impaired arterial endothelial function and increased carotid intima-media thickness as atherosclerosis surrogates in such metabolic vitamin B-12 deficient populations, but not in lactovegetarians in China. Vitamin B-12 supplementation has a favourable impact on these vascular surrogates in Hong Kong vegans and in underprivileged communities in northern rural China. Regular monitoring of vitamin B-12 status is thus potentially beneficial for early detection and treatment of metabolic vitamin B-12 deficiency in vegans, and possibly for prevention of atherosclerosis-related diseases.

[Folate, vitamin B12 and human health].

PubMed

Brito, Alex; Hertrampf, Eva; Olivares, Manuel; Gaitán, Diego; Sánchez, Hugo; Allen, Lindsay H; Uauy, Ricardo

2012-11-01

During the past decade the role of folate and vitamin B12 in human nutrition have been under constant re-examination. Basic knowledge on the metabolism and interactions between these essential nutrients has expanded and multiple complexities have been unraveled. These micronutrients have shared functions and intertwined metabolic pathways that define the size of the "methyl donor" pool utilized in multiple metabolic pathways; these include DNA methylation and synthesis of nucleic acids. In Chile, folate deficiency is virtually nonexistent, while vitamin B12 deficiency affects approximately 8.5-51% depending on the cut-off value used to define deficiency. Folate is found naturally mainly in vegetables or added as folic acid to staple foods. Vitamin B12 in its natural form is present only in foods of animal origin, which is why deficit is more common among strict vegetarians and populations with a low intake of animal foods. Poor folate status in vulnerable women of childbearing age increases the risk of neural tube birth defects, so the critical time for the contribution of folic acid is several months before conception since neural tube closure occurs during the first weeks of life. The absorption of vitamin B12 from food is lower in older adults, who are considered to have higher risk of gastric mucosa atrophy, altered production of intrinsic factor and acid secretion. Deficiency of these vitamins is associated with hematological disorders. Vitamin B12 deficiency can also induce clinical and sub-clinical neurological and of other disorders. The purpose of this review is to provide an update on recent advances in the basic and applied knowledge of these vitamins relative to human health.

B-vitamin deficiency is protective against DSS-induced colitis in mice

PubMed Central

Benight, Nancy M.; Stoll, Barbara; Chacko, Shaji; da Silva, Vanessa R.; Marini, Juan C.; Gregory, Jesse F.; Stabler, Sally P.

2011-01-01

Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B6-B12-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-13C-methyl-2H3]methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-α and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B6, as markers of B12 function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B6 deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B6 deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology. PMID:21596995

Folic acid fortification: why not vitamin B12 also?

PubMed

Selhub, Jacob; Paul, Ligi

2011-01-01

Folic acid fortification of cereal grains was introduced in many countries to prevent neural tube defect occurrence. The metabolism of folic acid and vitamin B12 intersect during the transfer of the methyl group from 5-methyltetrahydrofolate to homocysteine catalyzed by B12-dependent methioine synthase. Regeneration of tetrahydrofolate via this reaction makes it available for synthesis of nucleotide precursors. Thus either folate or vitamin B12 deficiency can result in impaired cell division and anemia. Exposure to extra folic acid through fortification may be detrimental to those with vitamin B12 deficiency. Among participants of National Health And Nutrition Examination Survey with low vitamin B12 status, high serum folate (>59 nmol/L) was associated with higher prevalence of anemia and cognitive impairment when compared with normal serum folate. We also observed an increase in the plasma concentrations of total homocysteine and methylmalonic acid (MMA), two functional indicators of vitamin B12 status, with increase in plasma folate under low vitamin B12 status. These data strongly imply that high plasma folate is associated with the exacerbation of both the biochemical and clinical status of vitamin B12 deficiency. Hence any food fortification policy that includes folic acid should also include vitamin B12. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Folate and vitamin B12 status in the Americas.

PubMed

Allen, Lindsay H

2004-06-01

There is growing interest in the potential for folic acid fortification in the Americas and recognition of the high prevalence of low plasma vitamin B12 concentrations reported in various studies. This review summarized available data on plasma vitamin B12 and folate concentrations in the Americas. At least 40% of individuals had deficient or marginal plasma vitamin B12 concentrations in almost all locations and across age groups. Low plasma folate concentrations were less common. It is hypothesized that vitamin B12 deficiency may result from a low intake of animal source foods, while a higher intake of refined flour may result in low plasma folate.

Indications for Vitamin B12 Therapy

PubMed Central

Delva, M. Dianne; Anderson, J.E.

1992-01-01

A retrospective chart audit was undertaken to determine the clinical reasons for vitamin B12 therapy in family practice. Abnormal laboratory tests and symptoms were the most common reasons for initiating therapy. The high proportion of cases with little supporting evidence of B12 deficiency suggests that other factors influence treatment decisions. PMID:20469527

Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy.

PubMed

Guez, Sophie; Chiarelli, Gabriella; Menni, Francesca; Salera, Simona; Principi, Nicola; Esposito, Susanna

2012-06-24

In infants, vitamin B12 deficiency may be due to an inborn error of absorption and metabolism, or nutritional problems. An exclusively breastfed 5-month-old Italian male infant, who was born after a normal full-term pregnancy to a vegan mother who was apparently daily treated with a multivitamin oral preparation during the second and third trimester, was hospitalised because of poor weight gain, feeding difficulties, severe pallor, muscle hypotonia and somnolence. Upon admission, his weight, length and head circumference were below the third percentile, he had an enlarged liver and spleen, and showed a significant delay in developmental milestones and communicative reactions. He had a hemoglobin level of 4.7 g/dL with an MCV of 84.2 fL, a white blood cell count of 4,680/mm3, and a platelet count of 45,000/mm3. His serum vitamin B12 level was 57 pg/mL (normal value 180-500 pg/mL) and serum folate level 12.8 ng/mL (normal value >3 ng/mL). The results of metabolic examinations excluded a cobalamin C disorder, whereas nutritional screening showed a serum iron concentration of 9 μg/dL and serum ferritin of 4 ng/mL. Magnetic resonance imaging of the brain showed mild dilatation of the lateral ventricles with diffuse delayed myelination. The child was diagnosed as having vitamin B12 and iron deficiency due to nutritional inadequacy and was immediately treated with packed red blood cells, intramuscular vitamin B12 injections, and iron supplementation. A few days after the start of therapy, his hemoglobin levels and other hematological parameters rapidly improved, and a clinical improvement was observed within few weeks. There was an increase in his achievement of developmental milestones, but his development was still retarded seven months after the start of therapy. This case underlines the importance of adequately controlling maternal vitamin B12 intake during pregnancy by means of supplementation which, in the case of vegan mothers, should be significantly greater than

Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.

PubMed

Del Bo', Cristian; Riso, Patrizia; Gardana, Claudio; Brusamolino, Antonella; Battezzati, Alberto; Ciappellano, Salvatore

2018-02-15

Vegetarians and vegans are more vulnerable to vitamin B 12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 μg. However, single large oral doses of vitamin B 12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B 12 (350 μg/week vs 2000 μg/week) in improving cyanocobalamin (vitamin B 12 ) nutritional status in vegans and vegetarians with a marginal deficiency. A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B 12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 μg/week) and control group Hd (high dose, 2000 μg/week) vitamin B 12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B 12 , related metabolic markers, and blood cell counts. Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time × treatment interaction (P = 0.012) on serum concentration of vitamin B 12 that increased after 90-day supplementation (Ld and Hd) compared to baseline. Both the supplements increased (P < 0.0001, time effect) the levels of holotranscobalamin, succinic acid, methionine and wellness parameter, while decreased (P < 0.0001, time effect) the levels of methylmalonic acid, homocysteine and folate compared to baseline. No difference was observed between groups (LdvsHd). No effect was detected for vitamin B 6 and blood cell count. In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B 12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 μg/day (350�

Vitamin B12-responsive neuropathies: A case series.

PubMed

Solomon, Lawrence R

2016-05-01

Neuropathies often accompany vitamin B12 deficiency. Since many neuropathies are linked to oxidative stress and since B12 has both antioxidant and neurotrophic properties, B12 may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B12-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined. Retrospective review of 78 subjects with neurological abnormalities treated with B12 and evaluated by the measurement of B12 and the B12-dependent metabolites, methylmalonic acid (MMA), and homocysteine. Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B12-responsive macrocytosis. Pretherapy B12, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B12 therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable non-responders. At least one oxidant risk was present in 41 of the 46 responders with normal B12 levels (89%). Oral therapy was effective, but parenteral B12 improved responses in four subjects. B12-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B12-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B12 levels are normal. Since no predictors of responses to B12 therapy were identified, empiric trials with parenteral B12 should be considered in appropriate subjects.

Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study.

PubMed

Singh, Charu; Kawatra, Rahul; Gupta, Jaya; Awasthi, Vishnu; Dungana, Homnath

2016-01-01

True tinnitus is a phantom auditory perception arising from a source or trigger in the cochlea, brainstem, or at higher centers and has no detectable acoustic generator. The most accepted is the famous neurophysiologic model of Jastreboff, which stresses that tinnitus, is a subcortical perception and results from the processing of weak neural activity in the periphery. The aim of this study is to determine the role of Vitamin B12 in treatment of chronic tinnitus. In this randomized, double-blind pilot study, total 40 patients were enrolled, of which 20 in Group A (cases) received intramuscular therapy of 1 ml Vitamin B12 (2500 mcg) weekly for a period of 6 weeks and Group B (20) patients received placebo isotonic saline 01 ml intramuscular. The patients were subjected to Vitamin B12 assay and audiometry pre- and post-therapy. Of the total patients of tinnitus, 17 were Vitamin B12 deficient that is 42.5% showed deficiency when the normal levels were considered to be 250 pg/ml. A paired t-test showed that in Group A, patients with Vitamin B12 deficiency showed significant improvement in mean tinnitus severity index score and visual analog scale (VAS) after Vitamin B12 therapy. This pilot study highlights the significant prevalence of Vitamin B12 deficiency in North Indian population and improvement in tinnitus severity scores and VAS in cobalamin-deficient patients receiving intramuscular Vitamin B12 weekly for 6 weeks further provides a link between cobalamin deficiency and tinnitus thereby suggestive of a therapeutic role of B12 in cobalamin-deficient patients of tinnitus.

Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study

PubMed Central

Singh, Charu; Kawatra, Rahul; Gupta, Jaya; Awasthi, Vishnu; Dungana, Homnath

2016-01-01

True tinnitus is a phantom auditory perception arising from a source or trigger in the cochlea, brainstem, or at higher centers and has no detectable acoustic generator. The most accepted is the famous neurophysiologic model of Jastreboff, which stresses that tinnitus, is a subcortical perception and results from the processing of weak neural activity in the periphery. The aim of this study is to determine the role of Vitamin B12 in treatment of chronic tinnitus. In this randomized, double-blind pilot study, total 40 patients were enrolled, of which 20 in Group A (cases) received intramuscular therapy of 1 ml Vitamin B12 (2500 mcg) weekly for a period of 6 weeks and Group B (20) patients received placebo isotonic saline 01 ml intramuscular. The patients were subjected to Vitamin B12 assay and audiometry pre- and post-therapy. Of the total patients of tinnitus, 17 were Vitamin B12 deficient that is 42.5% showed deficiency when the normal levels were considered to be 250 pg/ml. A paired t-test showed that in Group A, patients with Vitamin B12 deficiency showed significant improvement in mean tinnitus severity index score and visual analog scale (VAS) after Vitamin B12 therapy. This pilot study highlights the significant prevalence of Vitamin B12 deficiency in North Indian population and improvement in tinnitus severity scores and VAS in cobalamin-deficient patients receiving intramuscular Vitamin B12 weekly for 6 weeks further provides a link between cobalamin deficiency and tinnitus thereby suggestive of a therapeutic role of B12 in cobalamin-deficient patients of tinnitus. PMID:26960786

[Clinical, biological and therapeutic profile of anemia by vitamin B12 deficiency in the department of hematology of Marrakech (Morocco)].

PubMed

Nafil, H; Tazi, I; Sifessalam, M; Bouchtia, M; Mahmal, L

2013-05-01

The aim of this study is to examine retrospectively the clinical, biological and treatment features of anemia by vitamin B12 deficiency in the Hematology department of CHU Mohamed VI Marrakech. We report the results of a retrospective study conducted during six years (2005-2010). It included all patients with anemia (with or without thrombocytopenia or leukopenia) associated with vitamin B12 levels <200 pg / ml. One hundred twenty one cases were analyzed. The average age of patients was 62 years (38-89 years) with a female predominance (sex ratio F/M: 1.3). The clinical symptomatology is dominated by pallor (97.5%), cardiovascular signs (46%) and digestive symptoms (34.7%). Neurological signs were noted in 17.3% of cases. The blood count showed anemia (hemoglobin: mean= 6.9 g/dl), macrocythemia (MCV: mean= 109 fl). Leukopenia was noted in 35 patients (29%), thrombocytopenia in 34 patients (28%) and pancytopenia in 21 patients (17,3%). The average vitamin B12 was 72 pg/ml. The causes of B12 deficiency are pernicious anemia (43%), food-cobalamin malabsorption (43%), and in 14% of cases no etiology was found. Gastritis was found in 82.7% of our patients and Helicobacter pylori (HP) infection in 72.7% of cases. Reticulocyte crisis was observed after parenteral administration of hydroxocobalamine within an average of 8 days and normalization of blood counts, in all patients, within an average of 51 days. In patients with HP infection, eradication therapy of HP was performed. The cure rate of the HP is 90%.

Vitamin B12–dependent taurine synthesis regulates growth and bone mass

PubMed Central

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

2014-01-01

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

Alcohol and B1 vitamin deficiency-related stillbirths.

PubMed

Bâ, Abdoulaye

2009-05-01

The present study attempts to determine whether prenatal thiamine (B1 vitamin) deficiency and prenatal alcohol exposure are risk factors for stillbirths. From conception to parturition, Wistar rat dams were exposed to the following treatments: (1) Rat dams consuming a thiamine-deficient diet; (2) 12% alcohol/water drinking mothers; (3) mothers drinking 12% alcohol/water + thiamine hydrochloride mixture. Appropriate pair-fed controls and ad libitum controls were assessed. Gestation outcome and fetal parameters, including spontaneous abortion, still-born fetuses, litter size and birth weight, were assessed from the dams of each experimental group. Both alcohol and thiamine deficiency during pregnancy increased fetal death (48.26%vs. 84.47%), reduced litter size (44.54%vs. 72.7%), respectively, and lowered birth weight. Thiamine administration reversed the effects of alcohol-induced fetal death, suggesting that a part of deleterious actions of alcohol on fetal death was mediated by thiamine deficiency. Prenatal thiamine deficiency increased singularly spontaneous abortion with abundant bleeding (40%), rising the occurrence of stillbirth. Such a pathology was not observed in alcohol group. The results indexed thiamine deficiency as a potent risk factor for stillbirths. The vitamin supply during pregnancy prevents stillbirths related to chronic alcoholism and different facets of malnutrition.

False-normal vitamin B12 results in a patient with pernicious anaemia.

PubMed

Wainwright, P; Narayanan, S; Cook, P

2015-12-01

Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms.

PubMed

Souirti, Zouhayr; Loukili, Mouna; Soudy, Imar D; Rtibi, Kaies; Özel, Aslihan; Limas-Nzouzi, Nicolas; El Ouezzani, Seloua; Eto, Bruno

2016-12-01

The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB 12 ) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B 12 -deficient patients (vit B 12 < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B 12 level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose-dependent manner with HB 12 . The apparent permeability of Hdrx was P app = 34.9 ± 4.6 × 10 -6 cm/s in the presence of 3 mg/mL (HB 12 B) compared to the control P app = 6.2 ± 0.7 × 10 -6 cm/s. (ii) Total transepithelial electrical conductance (G t ) increased in dose-dependent manner with HB 12 , G t = 161.5 ± 10.8 mS/cm² with HB 12 B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, G t = 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Vitamin B12 serostatus in Colombian children and adult women: results from a nationally representative survey.

PubMed

Herrán, Oscar F; Ward, Julia B; Villamor, Eduardo

2015-04-01

Vitamin B12 deficiency is associated with many adverse health outcomes and is highly prevalent worldwide. The present study assesses the prevalence of vitamin B12 deficiency and marginal deficiency in Colombian children and women and examines the sociodemographic correlates of serum vitamin B12 concentrations in these groups. Cross-sectional, nationally representative survey. Colombia. Children <18 years old (n 7243), pregnant women (n 1781), and non-pregnant women 18-49 years old (n 499). The overall prevalence of vitamin B12 deficiency (serum vitamin B12<148 pmol/l) and marginal deficiency (serum vitamin B12=148-221 pmol/l) was, respectively, 6.6 % (95 % CI 5.2%, 8.3%) and 22.5% (95% CI 21.1%, 23.9%). Pregnant women had the highest prevalence of deficiency (18.9 %; 95 % CI 16.6 %, 21.5 %) compared with non-pregnant adult women (18.5%; 95% CI 4.4%, 53.1%) and children (2.8 %; 95 % CI 2.3 % %, 3.3 %). In multivariable analyses among children, mean serum vitamin B12 was positively associated with female sex (12 pmol/l higher compared with males; P=0.004), secondary or higher education of the household head (12 pmol/l higher compared with primary or less; P=0.009) and food security (21 pmol/l higher compared with severe food insecurity; P=0.003). In multivariable analyses among pregnant women, mean serum vitamin B12 was positively associated with education of the household head and inversely associated with living in the National territories, Eastern or Pacific regions. The prevalence of vitamin B12 deficiency and marginal deficiency in Colombian women and children is substantial. The burden falls largely on adult women, those with lowest education and those living in the poorest, most rural regions of the country.

Clinical features of patients with homozygous complement C4A or C4B deficiency.

PubMed

Liesmaa, Inka; Paakkanen, Riitta; Järvinen, Asko; Valtonen, Ville; Lokki, Marja-Liisa

2018-01-01

Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%CI = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%CI = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%CI = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%CI = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%CI = 1.22-4.88, p = 0.010). This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

PubMed

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-03-28

To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

PubMed Central

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-01-01

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy

NutriPhone: vitamin B12 testing on your smartphone (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Seoho; O'Dell, Dakota; Hohenstein, Jessica; Colt, Susannah; Mehta, Saurabh; Erickson, David

2016-03-01

Vitamin B12 deficiency is the leading cause of cognitive decline in the elderly and is associated with increased risks of several acute and chronic conditions including anemia. The deficiency is prevalent among the world population, most of whom are unaware of their condition due to the lack of a simple diagnostics system. Recent advancements in the smartphone-enabled mobile health can help address this problem by making the deficiency tests more accessible. Previously, our group has demonstrated the NutriPhone, a smartphone platform for the accurate quantification of vitamin D levels. The NutriPhone technology comprises of a disposable test strip that performs a colorimetric reaction upon collecting a sample, a reusable accessory that interfaces with the smartphone camera, and a smartphone app that stores the algorithm for analyzing the test-strip reaction. In this work, we show that the NutriPhone can be expanded to measure vitamin B12 concentrations by developing a lateral flow assay for B12 that is compatible with our NutriPhone system. Our novel vitamin B12 assay incorporates blood sample processing and key reagent storage on-chip, which advances it into a sample-in-answer-out format that is suitable for point-of-care diagnostic applications. In order to enable the detection of pM levels of vitamin B12 levels, silver amplification of the initial signal is used within the total assay time of less than 15 minutes. We demonstrate the effectiveness of our NutriPhone system by deploying it in a resource-limited clinical setting in India where it is used to test tens of participants for vitamin B12 deficiency.

Vitamin B1 Deficiency Does not Affect the Liver Concentrations of the Other Seven Kinds of B-Group Vitamins in Rats

PubMed Central

Shibata, Katsumi; Shimizu, Atsushi; Fukuwatari, Tsutomu

2013-01-01

We aimed to determine the effects of vitamin B1 deficiency on vitamin contents of urine, liver, and blood. In the current study, rats were divided into 3 groups (n = 5, each group): the first was freely fed a complete diet (ad lib-fed control group); the second freely fed a vitamin B1-free diet (vitamin B1 deficient group); and the third pair-fed a complete diet with the same amounts of the vitamin B1 deficient group (pair-fed control group). The experimental period was for 15 days. The blood concentrations of vitamin B2, PLP, vitamin B12, folic acid, and biotin were lower in the pair-fed control than in the ad lib-fed control and those of nicotinamide and pantothenic acid were the same. We conclude that Vitamin B1 deficiency did not affect concentrations of the other B-group vitamins. PMID:23935367

Measurements of vitamin B12 in human blood serum using resonance Raman spectroscopy

NASA Astrophysics Data System (ADS)

Tsiminis, G.; Schartner, E. P.; Brooks, J. L.; Hutchinson, M. R.

2016-12-01

Vitamin B12 (cobalamin and its derivatives) deficiency has been identified as a potential modifiable risk factor for dementia and Alzheimer's disease. Chronic deficiency of vitamin B12 has been significantly associated with an increased risk of cognitive decline. An effective and efficient method for measuring vitamin B12 concentration in human blood would enable ongoing tracking and assessment of this potential modifiable risk factor. In this work we present an optical sensor based on resonance Raman spectroscopy for rapid measurements of vitamin B12 in human blood serum. The measurement takes less than a minute and requires minimum preparation (centrifuging) of the collected blood samples.

Serum vitamin B12 levels in young vegans who eat brown rice.

PubMed

Suzuki, H

1995-12-01

A nutritional analysis was conducted on the dietary intake of a group of 6 vegan children aged 7 to 14 who had been living on a vegan diet including brown rice for from 4 to 10 years, and on that of an age-matched control group. In addition, their serum vitamin B12 levels and other data (red blood cell count, hematocrit, hemoglobin, etc.) were determined in the laboratory. In vegans' diets, 2-4 g of nori (dried laver), which contained B12, were consumed daily. Not a single case of symptoms due to B12 deficiency was found. There were no statistically significant differences between the two groups with respect to any of the examination data, including B12 levels (p < 0.05). Therefore, consumption of nori may keep vegans from suffering B12 deficiency.

Vitamin B-12 supplementation of rural Mexican women changes biochemical B-12 status indicators but does not affect hematology or a bone turnover marker

USDA-ARS?s Scientific Manuscript database

Based on the high prevalence of low serum vitamin B-12 concentrations and low dietary intake of the vitamin in Latin American studies including research in Mexico, it appears that vitamin B-12 deficiency is common. Whether this is associated with adverse effects on human function is unknown. To eval...

Pancreatic SEC23B deficiency is sufficient to explain the perinatal lethality of germline SEC23B deficiency in mice

PubMed Central

Khoriaty, Rami; Everett, Lesley; Chase, Jennifer; Zhu, Guojing; Hoenerhoff, Mark; McKnight, Brooke; Vasievich, Matthew P.; Zhang, Bin; Tomberg, Kärt; Williams, John; Maillard, Ivan; Ginsburg, David

2016-01-01

In humans, loss of function mutations in SEC23B result in Congenital Dyserythropoietic Anemia type II (CDAII), a disease limited to defective erythroid development. Patients with two nonsense SEC23B mutations have not been reported, suggesting that complete SEC23B deficiency might be lethal. We previously reported that SEC23B-deficient mice die perinatally, exhibiting massive pancreatic degeneration and that mice with hematopoietic SEC23B deficiency do not exhibit CDAII. We now show that SEC23B deficiency restricted to the pancreas is sufficient to explain the lethality observed in mice with global SEC23B-deficiency. Immunohistochemical stains demonstrate an acinar cell defect but normal islet cells. Mammalian genomes contain two Sec23 paralogs, Sec23A and Sec23B. The encoded proteins share ~85% amino acid sequence identity. We generate mice with pancreatic SEC23A deficiency and demonstrate that these mice survive normally, exhibiting normal pancreatic weights and histology. Taken together, these data demonstrate that SEC23B but not SEC23A is essential for murine pancreatic development. We also demonstrate that two BAC transgenes spanning Sec23b rescue the lethality of mice homozygous for a Sec23b gene trap allele, excluding a passenger gene mutation as the cause of the pancreatic lethality, and indicating that the regulatory elements critical for Sec23b pancreatic function reside within the BAC transgenes. PMID:27297878

Vitamin B12 and folate levels in long-term vegans.

PubMed

Bar-Sella, P; Rakover, Y; Ratner, D

1990-06-01

Serum vitamin B12, serum folate and red blood cell (RBC) folate levels were examined among 36 strict vegans of 5-35 years' duration. Vitamin B12 levels among the vegans were generally lower than in a control population. Most of the vegans had vitamin B12 values less than 200 pg/ml. RBC folate levels were normal but serum folate levels among the vegans were higher than among the controls. None of the vegans had any hematologic evidence of vitamin B12 deficiency, however four of them had neurologic complaints. Long-standing vegans should be monitored for vitamin B12 levels.

Pernicious anemia presenting as catatonia: correlating vitamin B12 levels and catatonic symptoms.

PubMed

Bram, Damien; Bubrovszky, Maxime; Durand, Jean-Paul; Lefevre, Guillaume; Morell-Dubois, Sandrine; Vaiva, Guillaume

2015-01-01

Pernicious anemia has been associated with various psychiatric manifestations, such as depression, mania and psychosis. Psychiatric symptoms can sometimes occur without hematological and neurological abnormalities and can be prodromal of vitamin B12 deficiency. We report a case of autoimmune B12 deficiency presenting as catatonia without signs of anemia or macrocytosis, in which a correlation was found between the patient's B12 blood levels and catatonic symptoms over time. This catatonic episode was successfully treated with only lorazepam and adequate doses of cyanocobalamin. Copyright © 2015 Elsevier Inc. All rights reserved.

Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women.

PubMed

Hübner, Ulrich; Alwan, Ahmad; Jouma, Muhidin; Tabbaa, Mohammad; Schorr, Heike; Herrmann, Wolfgang

2008-01-01

Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid. A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined. Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 micromol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio. The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion.

Reversal of isolated 20q deletion with vitamin B12 replacement in a patient with pernicious anaemia.

PubMed

Cingam, Shashank Reddy; Koshy, Nebu; Veillon, Diana; Peddi, Prakash

2017-03-08

Severe vitamin B 12 deficiency is well known to cause morphological alterations in bone marrow. In rare instances, these myelodysplastic and megaloblastic changes can coexist with cytogenetic abnormalities. Here, we report a case of a 38-year-old African-American woman with pernicious anaemia, who was found to have an isolated 20q deletion and which resolved after vitamin B 12 replacement. We also discuss various mechanisms in which vitamin B 12 deficiency can lead to chromosomal abnormalities. A literature review is also performed to evaluate various other chromosomal aberrations associated with B 12 deficiency. 2017 BMJ Publishing Group Ltd.

High prevalence of suboptimal vitamin B12 status in young adult women of South Asian and European ethnicity.

PubMed

Quay, Teo A W; Schroder, Theresa H; Jeruszka-Bielak, Marta; Li, Wangyang; Devlin, Angela M; Barr, Susan I; Lamers, Yvonne

2015-12-01

Suboptimal vitamin B12 (B12) status has been associated with an increased risk of congenital anomalies, preterm birth, and childhood insulin resistance. South Asians - Canada's largest minority group - and women of reproductive age are vulnerable to B12 deficiency. This study aimed to assess the prevalence of and factors associated with B12 deficiency and suboptimal B12 status in a convenience sample of young adult women of South Asian and European descent in Metro Vancouver. We measured serum B12, holotranscobalamin, plasma methylmalonic acid, red blood cell and plasma folate, and hematologic parameters in 206 nonpregnant, healthy women aged 19-35 years. Categorization for B12 status adhered to serum B12 cutoffs for deficiency (<148 pmol/L) and suboptimal B12 status (148-220 pmol/L). We collected demographic, lifestyle, and dietary intake data and conducted genotyping for common genetic variants linked to B-vitamin metabolism. The prevalence of deficiency and suboptimal B12 status were 14% and 20%, respectively. Serum vitamin B12 concentrations were negatively associated with oral contraceptive use and first-generation immigrant status, and positively with dietary B12 intake and B12 supplement use. The prevalence of B12 inadequacy in this sample of highly educated women is higher than in the general Canadian population. In light of maternal and fetal health risks associated with B12 inadequacy in early-pregnancy, practitioners should consider monitoring B12 status before and during early pregnancy, especially in immigrants and women with low dietary B12 intakes including non-users of vitamin supplements.

Vitamin B12-Containing Plant Food Sources for Vegetarians

PubMed Central

Watanabe, Fumio; Yabuta, Yukinori; Bito, Tomohiro; Teng, Fei

2014-01-01

The usual dietary sources of Vitamin B12 are animal-derived foods, although a few plant-based foods contain substantial amounts of Vitamin B12. To prevent Vitamin B12 deficiency in high-risk populations such as vegetarians, it is necessary to identify plant-derived foods that contain high levels of Vitamin B12. A survey of naturally occurring plant-derived food sources with high Vitamin B12 contents suggested that dried purple laver (nori) is the most suitable Vitamin B12 source presently available for vegetarians. Furthermore, dried purple laver also contains high levels of other nutrients that are lacking in vegetarian diets, such as iron and n-3 polyunsaturated fatty acids. Dried purple laver is a natural plant product and it is suitable for most people in various vegetarian groups. PMID:24803097

Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial.

PubMed

Winkels, Renate M; Brouwer, Ingeborg A; Clarke, Robert; Katan, Martijn B; Verhoef, Petra

2008-08-01

Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries. Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status. The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherlands, where folic acid fortification is not taking place. Men and women aged 50-75 y were randomly assigned in this 12-wk double-blind, placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily (n = 72) or unfortified bread (n = 70). The consumption of fortified bread increased serum folate concentrations by 45% (mean: 6.3 nmol/L; 95% CI: 4.5, 8.1 nmol/L) and serum vitamin B-12 concentrations by 49% (mean: 102 pmol/L; 95% CI: 82, 122 pmol/L) relative to the placebo group. Fortified bread increased erythrocyte folate concentrations by 22% and holotranscobalamin concentrations by 35%; it decreased homocysteine concentrations by 13% and methylmalonic acid concentrations by 10%. Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations (<133 pmol/L) from 8% at enrollment to 0% after 12 wk. Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people. This trial was registered at clinicaltrials.gov as NCT00353353.

Vitamin B-12 concentrations in breast milk are low and are not associated with reported household hunger, recent animal source food or vitamin B-12 intake among women in rural Kenya

USDA-ARS?s Scientific Manuscript database

Background: Breastmilk vitamin B-12 concentration may be inadequate in mothers living in regions where animal source food consumption is low or infrequent. Vitamin B-12 deficiency causes megaloglastic anemia and impairs growth and development in children. Objective: To measure vitamin B-12 in breast...

Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an intervention trial.

PubMed

Naik, Sadanand; Bhide, Vijayshri; Babhulkar, Ashish; Mahalle, Namita; Parab, Sonali; Thakre, Ravi; Kulkarni, Mohan

2013-10-09

Asymptomatic Indian lacto vegetarians, who make up more than half of the Indian population in different geographic regions, have distinctly low vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but it seems that the amount is not enough to improve vitamin B-12 status or vitamin B-12 concentration in milk itself may be low. The aim of this study was to determine if daily milk consumption can improve vitamin B-12 status. Fifteen male and 36 female, young healthy post-graduate volunteers participated. Blood from ten participants (4 males and 6 females) was collected (day-1). They continued their regular diet for next fourteen days and on day-15, blood of all 51 participants was collected, plasma vitamin B-12 concentration was measured and were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored. All participants consumed 600 ml. of non-enriched buffalo milk (200 × 3) during the day along with their usual diet. Next day blood was collected for plasma holotranscobalamin II measurement. Subjects from deficient group continued to drink 400 ml of milk daily for next 14 days and blood was collected on day-30. Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk vitamin B-12 concentrations (day-15, 16, 30) were measured. Fifty seven per cent of the participants were vitamin B-12 deficient and 65% were hyperhomocysteinemic. No significant difference in biomarkers was observed when there was no intervention. Plasma holotranscobalamin II concentration increased from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group. Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations decreased from 31.9 to 24.9 μ mol/L (p < 0.0001 for both) 14 days after regular milk intake in vitamin B-12

Vitamin B-12 supplementation of rural Mexican women changes biochemical vitamin B-12 status indicators but does not affect hematology or a bone turnover marker.

PubMed

Shahab-Ferdows, Setareh; Anaya-Loyola, Miriam A; Vergara-Castañeda, Haydé; Rosado, Jorge L; Keyes, William R; Newman, John W; Miller, Joshua W; Allen, Lindsay H

2012-10-01

A high prevalence of low serum vitamin B-12 concentrations has been reported in studies and surveys in Latin America including Mexico, but the functional consequences are unknown. This randomized controlled trial assessed the response to a high-dose vitamin B-12 supplementation of women in rural Querétaro, Mexico. Participants aged 20-59 y were stratified at baseline to deficient, marginal, and adequate status groups (serum vitamin B-12, 75-148, 149-220, and >220 pmol/L, respectively), and each group was randomized to vitamin B-12 treatment (single dose of 1 mg i.m. then 500 μg/d orally for 3 mo, n = 70) or placebo (n = 62). Measures at baseline and 3 mo included: complete blood count, serum vitamin B-12, holotranscobalamin (holoTC), folate, ferritin, C-reactive protein (CRP), bone alkaline phosphatase, and methylmalonic acid (MMA) and plasma total homocysteine (tHcy). At baseline, 11% of the women were vitamin B-12 deficient and 22% had marginal status. HoloTC was low (<35 pmol/L) in 23% and correlated with serum vitamin B-12 (r = 0.7; P < 0.001). Elevated MMA (>271 nmol/L) and tHcy (>12 μmol/L) occurred in 21 and 31%, respectively, and correlated with serum vitamin B-12 (r = -0.28, P < 0.0007 and r = -0.20, P < 0.01, respectively). Supplementation increased serum vitamin B-12 and holoTC and lowered MMA and tHcy, normalizing all values except for elevated tHcy in 21% of the women. Supplementation did not affect hematology or bone-specific alkaline phosphatase. Vitamin B-12 supplementation normalized biochemical indicators of vitamin B-12 status in the treatment group but did not affect the functional outcomes measured.

Folate and vitamin B12 status of adolescent girls in northern Nigeria.

PubMed Central

VanderJagt, D. J.; Spelman, K.; Ambe, J.; Datta, P.; Blackwell, W.; Crossey, M.; Glew, R. H.

2000-01-01

The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12. PMID:10946529

Vitamin B supplementation for diabetic peripheral neuropathy.

PubMed

Jayabalan, Bhavani; Low, Lian Leng

2016-02-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

Vitamin B supplementation for diabetic peripheral neuropathy

PubMed Central

Jayabalan, Bhavani; Low, Lian Leng

2016-01-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID:26892473

Breast milk vitamin B-12 concentrations of Guatemalan women are correlated with maternal but not infant vitamin B–12 status at 12 months postpartum

USDA-ARS?s Scientific Manuscript database

In our previous studies one third of lactating Guatemalan women, infants and children had deficient or marginal serum vitamin B-12 concentrations. Relationships among maternal and infant status and breast milk vitamin B-12, however, have not been investigated in such populations. Our purpose was to ...

[Vitamin B12 levels in the patient population attending an urban health centre in Madrid].

PubMed

Camarero-Shelly, M

2018-04-01

Vitamin B 12 levels are usually measured in Primary Care when the patients have symptoms or risk factors associated with its deficiency, mostly in the elderly. However, no evidence has been found to support the recommendation of screening in the general population. The aim of this study is to assess the relevance of having extended the screening of vitamin B 12 deficiency to a younger population, after observing an increase in the prescription of this injected vitamin in a population under 65 years, by analysing the vitamin B 12 values obtained. A descriptive, retrospective, observational study was conducted on a sample consisting of 5,531 patients from Barajas Health Primary Centre, Madrid, between 2008 and 2012, and on whom a blood test was performed for any reason, with values of vitamin B 12 . A deficiency was found in 9.1% (SD 2.3) of the patients, of whom 49.4% were less than 65 years. The deficiencies were associated (P<.001, 95% CI) with age, dementia, changes in blood red cell counts, memory, and with the taking of metformin and proton pump inhibitors (P=.007). The prevalence of vitamin B 12 deficiency in our served population is similar in patients older and younger than 65 years. The extended screening was relevant. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Anemia and deficiencies of folate and vitamin B-6 are common and vary with season in Chinese women of childbearing age.

PubMed

Ronnenberg, A G; Goldman, M B; Aitken, I W; Xu, X

2000-11-01

Little is known about the micronutrient status of Chinese women of childbearing age. We assessed nonfasting plasma concentrations of folic acid, vitamin B-12, vitamin B-6 (as pyridoxal-5'-phosphate), hemoglobin (Hb), ferritin and transferrin receptor (TfR) in 563 nonpregnant textile workers aged 21-34 y from Anqing, China. All women had obtained permission to become pregnant and were participating in a prospective study of pregnancy outcomes. Mean (SD) plasma concentrations were 9.7 (4.1) nmol/L folic acid, 367 (128) pmol/L vitamin B-12, 40.2 (15.8) nmol/L vitamin B-6, 108 (12. 9) g/L Hb, 42.6 (34.2) microgram/L ferritin and 5.2 (2.7) mg/L TfR. Twenty-three percent of women had biochemical evidence of folic acid deficiency, 26% were deficient in vitamin B-6 and 10% had low vitamin B-12. Overall, 44% of women were deficient in at least one B vitamin. Although anemia (Hb < 120 g/L) was detected in 80% of women, only 17% had depleted iron stores (ferritin < 12 microgram/L); 11% had elevated TfR concentrations. Distinct seasonal trends were observed in the prevalence of moderate anemia (Hb < 100 g/L) and deficiencies of folic acid and vitamin B-6, with significantly lower concentrations of folate and Hb occurring in summer and lower concentrations of vitamin B-6 occurring in winter and spring than in other seasons. We conclude that deficiencies of folic acid, vitamin B-6 and iron were relatively common in this sample of Chinese women of childbearing age and were contributing to the high prevalence of anemia. Without appropriate supplementation, these deficiencies could jeopardize the women's health and increase their risk of adverse pregnancy outcomes.

Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study.

PubMed

Schmidt, C; Ahmad, T; Tulassay, Z; Baumgart, D C; Bokemeyer, B; Howaldt, S; Stallmach, A; Büning, C

2016-08-01

Ferric maltol was effective and well-tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12-week placebo-controlled trial. To perform a Phase 3 extension study evaluating long-term efficacy and safety with ferric maltol in inflammatory bowel disease patients in whom oral ferrous therapies had failed to correct iron deficiency anaemia. After 12 weeks of randomised, double-blind treatment, patients with iron deficiency anaemia and mild-to-moderate ulcerative colitis or Crohn's disease received open-label ferric maltol 30 mg b.d. for 52 weeks. 111 patients completed randomised treatment and 97 entered the open-label ferric maltol extension. In patients randomised to ferric maltol ('continued'; n = 50), mean ± s.d. haemoglobin increased by 3.07 ± 1.46 g/dL between baseline and Week 64. In patients randomised to placebo ('switch'; n = 47), haemoglobin increased by 2.19 ± 1.61 g/dL. Normal haemoglobin was achieved in high proportions of both continued and switch patients (89% and 83% at Week 64, respectively). Serum ferritin increased from 8.9 μg/L (baseline) to 26.0 μg/L (Week 12) in ferric maltol-treated patients, and to 57.4 μg/L amongst all patients at Week 64. In total, 80% of patients reported ≥1 adverse event by Week 64. Adverse events considered related to ferric maltol were recorded in 27/111 (24%) patients: 8/18 discontinuations due to adverse events were treatment-related. One patient was withdrawn due to increased ulcerative colitis activity. Normal haemoglobin was observed in ≥80% of patients from weeks 20-64 of long-term ferric maltol treatment, with concomitant increases in iron storage parameters. Ferric maltol was well-tolerated throughout this 64-week study. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Vitamin B-12-fortified toothpaste improves vitamin status in vegans: a 12-wk randomized placebo-controlled study.

PubMed

Siebert, Anne-Kathrin; Obeid, Rima; Weder, Stine; Awwad, Hussain M; Sputtek, Andreas; Geisel, Juergen; Keller, Markus

2017-03-01

Background: The oral application of vitamin B-12 may prevent its deficiency if the vitamin is absorbed via the mucosal barrier. Objectives: We studied the effect of the use of a vitamin B-12-fortified toothpaste on vitamin-status markers in vegans and assessed the efficiency of markers in the identification of vitamin-augmentation status. Design: In this 12-wk, double-blinded, randomized, placebo-controlled study, 76 vegans received either a placebo ( n = 34) or vitamin B-12 ( n = 42) toothpaste. Sixty-six subjects ( n = 30 in the placebo arm; n = 36 in the vitamin B-12 arm) completed the intervention. Serum and plasma concentrations of vitamin B-12, holotranscobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) were measured before and after the intervention. Results: Both postintervention concentrations of vitamin B-12 and holotranscobalamin and their changes over 12 wk were higher in the vitamin B-12 group (mean ± SD change: 81 ± 135 pmol/L for vitamin B-12 and 26 ± 34 pmol/L for holotranscobalamin) than in the placebo group (-27 ± 64 and -5 ± 17 pmol/L, respectively) after adjustment for baseline concentrations. Postintervention concentrations of MMA and their changes differed significantly between groups (MMA changes: -0.169 ± 0.340 compared with -0.036 ± 0.544 μmol/L in vitamin B-12 and placebo groups, respectively; P < 0.001). After adjustment for baseline tHcy, postintervention concentrations of tHcy tended to be lower ( P = 0.051), and the changes in tHcy (-0.7 ± 4.4 compared with 2.0 ± 5.6 μmol/L, respectively) were greater in the vitamin B-12 group than in the placebo group. Changes in vitamin B-12 markers were more prominent in vegans who reported that they had not taken vitamin B-12 supplements. Conclusion: Vitamin B-12 that is applied to the oral cavity via toothpaste enters the circulation and corrects the vitamin B-12 markers in the blood of vegans who are at higher risk of vitamin B-12 deficiency. This trial was registered

Low levels of vitamin B12 can persist in the early resettlement of refugees: symptoms, screening and monitoring.

PubMed

Benson, Jill; Phillips, Christine; Kay, Margaret; Hanifi, Hoda; Giri, Gauri; Leahy, Catherine; Lorimer, Michelle

2015-09-01

Many refugees have vitamin B12 (B12) deficiency. It has been assumed that deficiency would be predictable from macrocytosis or symptoms, and borderline levels would improve after a period of resettlement in countries rich with animal-source foods. We explored B12 levels and symptoms soon after the refugees' arrival and 4-8 months after settlement in Australia. Newly arrived refugees aged >18 years (n = 136) were tested for vitamin B12 and haematological indices. They also completed a language-validated questionnaire, which they repeated 4-8 months after arrival. B12 levels were reassessed in patients with levels ≤240 pmol at baseline. We found that 21 participants (15%) had low levels of B12 
(≤150 pmol/L) and 65 (48%) had borderline B12 levels 
(151-240 pmol/L). There was no relationship between B12 level and mean corpuscular volume, ferritin or symptoms. Borderline B12 levels persisted in 64% of participants at follow-up and deficiency developed in 11%. B12 levels cannot be predicted from macrocytosis or symptoms, and may not 'self-correct' after resettlement. Health assessments for newly arrived refugees should include B12 measurement and those with borderline levels should be followed up.

An appraisal of the value of vitamin B 12 in the prevention of motion sickness

NASA Astrophysics Data System (ADS)

Kohl, Randall L.; Lacey, Carol L.; Homick, Jerry L.

Unpublished reports have suggested that hydroxycobalamin (B 12, i.m.) prevents motion sickness. Some biomedical evidence supports this contention in that B 12 influences the metabolism of histidine and choline; dietary precursors to neurotransmitters with established roles in motion sickness. Susceptibility to motion sickness was evaluated after B 12 (1000 μg, i.m.). Subjects initially completed vestibular function and motion sickness susceptibility tests to establish normal vestibular function. The experimental motion stressor was a modified coriolis sickness susceptibility test. Subjects executed standardized head movements at successively higher RPM until a malaise III endpoint was reached. Following two baseline tests with this motion stressor, subjects received a B 12 injection, a second injection two weeks later, and a final motion sickness test three weeks later. No significant differences in susceptibility were noted after B 12. Hematological parameters revealed no B 12 deficiency before injection. The possibility that patients with B 12 deficiencies are more susceptible to motion sickness cannot be ruled out.

Oral administration of Bifidobacterium breve B-3 modifies metabolic functions in adults with obese tendencies in a randomised controlled trial.

PubMed

Minami, Jun-Ichi; Kondo, Shizuki; Yanagisawa, Naotake; Odamaki, Toshitaka; Xiao, Jin-Zhong; Abe, Fumiaki; Nakajima, Shigeru; Hamamoto, Yukie; Saitoh, Sanae; Shimoda, Taeko

2015-01-01

Accumulating evidence suggests an association between gut microbiota and the development of obesity, raising the possibility of probiotic administration as a therapeutic approach. Bifidobacterium breve B-3 was found to exhibit an anti-obesity effect on high-fat diet-induced obesity mice. In the present study, a randomised, double-blind, placebo-controlled trial was conducted to evaluate the effect of the consumption of B. breve B-3 on body compositions and blood parameters in adults with a tendency for obesity. After a 4-week run-in period, the participants were randomised to receive either placebo or a B-3 capsule (approximately 5 × 10(10) colony-forming units of B-3/d) daily for 12 weeks. A significantly lowered fat mass was observed in the B-3 group compared with the placebo group at week 12. Improvements were observed for some blood parameters related to liver functions and inflammation, such as γ-glutamyltranspeptidase and high-sensitivity C-reactive protein. Significant correlations were found between the changed values of some blood parameters and the changed fat mass in the B-3 group. These results suggest the beneficial potential of B. breve B-3 in improving metabolic disorders.

Restoring balance to B cells in ADA deficiency.

PubMed

Luning Prak, Eline T

2012-06-01

It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.

The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study

USDA-ARS?s Scientific Manuscript database

Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed parti...

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

PubMed Central

Rizzo, Gianluca; Laganà, Antonio Simone; Rapisarda, Agnese Maria Chiara; La Ferrera, Gioacchina Maria Grazia; Buscema, Massimo; Rossetti, Paola; Nigro, Angela; Muscia, Vincenzo; Valenti, Gaetano; Sapia, Fabrizio; Sarpietro, Giuseppe; Zigarelli, Micol; Vitale, Salvatore Giovanni

2016-01-01

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism. PMID:27916823

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation.

PubMed

Rizzo, Gianluca; Laganà, Antonio Simone; Rapisarda, Agnese Maria Chiara; La Ferrera, Gioacchina Maria Grazia; Buscema, Massimo; Rossetti, Paola; Nigro, Angela; Muscia, Vincenzo; Valenti, Gaetano; Sapia, Fabrizio; Sarpietro, Giuseppe; Zigarelli, Micol; Vitale, Salvatore Giovanni

2016-11-29

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.

Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay.

PubMed

Merrigan, Stephen D; Owen, William E; Straseski, Joely A

2015-01-01

Vitamin B12 (cobalamin) is a necessary cofactor in methionine and succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as 30% in the elderly population. Ten to thirty percent of circulating cobalamin is bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter cells and is therefore considered the bioactive form. The objective of our study was to evaluate the analytical performance of a high-throughput, automated holoTC assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to other available methods. Manufacturer-specified limits of blank (LoB), detection (LoD), and quantitation (LoQ), imprecision, interference, and linearity were evaluated for the ARCHITECT HoloTC assay. Residual de-identified serum samples were used to compare the ARCHITECT HoloTC assay with the automated AxSYM Active-B12 (Holotranscobalamin) assay (Abbott Diagnostics) and the manual Active-B12 (Holotranscobalamin) Enzyme Immunoassay (EIA) (Axis-Shield Diagnostics, Dundee, Scotland, UK). Manufacturer's claims of LoB, LoD, LoQ, imprecision, interference, and linearity to the highest point tested (113.4 pmol/L) were verified for the ARCHITECT HoloTC assay. Method comparison of the ARCHITECT HoloTC to the AxSYM HoloTC produced the following Deming regression statistics: (ARCHITECT(HoloTc)) = 0.941 (AxSYM(HoloTC)) + 1.2 pmol/L, S(y/x) = 6.4, r = 0.947 (n = 98). Comparison to the Active-B12 EIA produced: (ARCHITECT(HoloTC)) = 1.105 (EIA(Active-B12)) - 6.8 pmol/L, S(y/x) = 11.0, r = 0.950 (n = 221). This assay performed acceptably for LoB, LoD, LoQ, imprecision, interference, linearity and method comparison to the predicate device (AxSYM). An additional comparison to a manual Active-B12 EIA method performed similarly, with minor exceptions. This study determined that the ARCHITECT HoloTC assay is suitable for routine clinical use, which provides a high-throughput alternative for automated testing of this emerging marker of cobalamin

Effect of Pre-treatment Nutritional Status, Folate and Vitamin B12 Levels on Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia.

PubMed

Tandon, Sneha; Moulik, Nirmalya Roy; Kumar, Archana; Mahdi, Abbas Ali; Kumar, Ashutosh

2015-05-01

To evaluate pre-treatment undernutrition, and folate and B12 deficiency in children with acute lymphoblastic leukemia, and their correlation with complications and outcome of induction chemotherapy. Observational study. Tertiary care teaching hospital in Northern India. 50 children with acute lymphoblastic leukemia. Children were assessed for nutritional status (Weight for age Z-score, serum albumin, folate and B12) at presentation, and were followed-up during induction for bone marrow response, counts and outcome. Folate and B12 were repeated twice at monthly intervals after induction. Univariate and multivariate analyses were done to determine the association of nutritional parameters with the outcome variables. Baseline undernutrition was observed in 66%, hypo-albuminemia in 32.6%, folate deficiency in 41.3% and B12 deficiency in 36.9% of included children. Significant decline in folate levels was noted on serial assays during chemotherapy (P=0.001). Folate deficient children had higher risk for delayed marrow recovery and counts on day 14 (P=0.007 and P=0.001). Hypoalbuminemia (P=0.04), B12 deficiency (P=0.001) and folate (P=0.03) deficiency were associated with toxic deaths during induction. Baseline nutritional deficiencies negatively influence the outcome and occurrence of complications during induction chemotherapy in children with acute lymphoblastic leukemia.

Vitamin Deficiency Anemia

MedlinePlus

... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

Early biomarker response and patient preferences to oral and intramuscular vitamin B12 substitution in primary care: a randomised parallel-group trial.

PubMed

Metaxas, Corina; Mathis, Deborah; Jeger, Cyrill; Hersberger, Kurt Eduard; Arnet, Isabelle; Walter, Philipp

2017-04-19

Vitamin B12 (VB12) deficiency can be treated with oral high-dose substitution or intramuscular (i.m.) injection of VB12. Whenever alternative routes of administration exist, patient preferences should be considered when choosing the treatment. We aimed to assess outpatient preferences towards oral or IM VB12 substitution and confirm noninferiority of early biomarker response with oral treatment, in a typical primary care population. Prospective randomised nonblinded parallel-group trial. Patients were recruited by their general practitioner and randomly assigned to oral or IM treatment. Group O-oral was given 28 tablets of 1000 µg cyanocobalamin in a monthly punch card fitted with an electronic monitoring system. Group I-IM received four, weekly injections of 1000 µg hydroxocobalamin. Blood samples were drawn before the first administration and after 1, 2 and 4 weeks of treatment, and analysed for VB12, holotranscobalamin (HoloTc), homocysteine (Hcy) and methylmalonic acid (MMA). For group O-oral, treatment adher-ence and percentage of days with 2 dosing events were calcu-lated. Before and after 28 days of treatment, patients were asked to fill in a questionnaire about their preference for the therapy options and associated factors. Between November 2013 and December 2015, 37 patients (age: 49.5 ± 18.5 years; women: 60.5%) were recruited for oral (19) or IM (18) treatment. Baseline values with 95% confidence intervals for serum VB12, HoloTc, Hcy and MMA were 158 pmol/l [145-172], 49.0 pmol/l [40.4-57.5], 14.8 µmol/l [12.0-17.7] and 304 nmol/l [219-390], respective-ly, in group O-oral and 164 pmol/l [154-174], 50.1 pmol/l [38.7-61.6], 13.0 µmol/l [11.0-15.1] and 321 nmol/l [215-427], respectively, in group I-IM (not significant). After 1 month of treatment, levels of VB12 and HoloTc showed a significant increase compared with baseline (group O-oral: VB12 354 pmol/l [298-410] and HoloTc 156 pmol/l [116-196]; group I-IM: VB12 2796 pmol/l [1277-4314] and

Attenuation of acoustic and tactile startle responses of vitamin B-6 deficient rats.

PubMed

Schaeffer, M C

1987-01-01

Vitamin B-6 deficient rats exhibit changes in behavior, sensory function, and other nervous system abnormalities such as convulsive seizures and motor disturbances. Sensorimotor reactivity was evaluated quantitatively by measuring auditory and tactile startle responses in 12 week old female Long-Evans rats fed a diet devoid of added vitamin B-6 (DEF) or a control diet, either ad lib (AL-CON) or pair-fed to deficient rats (PF-CON). Deficiency was confirmed with a tryptophan-load test administered to a separate group of rats fed simultaneously according to the same protocol. At week 18, body weight and feed efficiency were different among groups (p less than 0.001), and were lowest in DEF. Amplitude of response to both acoustic and tactile stimuli was depressed in DEF compared to both control groups, which generally did not differ in response. This effect was seen most dramatically in responses to the acoustic stimulus (p = 0.034), and especially to the first presentation (p = 0.017). Latency to maximum response was not affected by diet. Possible mechanisms for this nervous system abnormality, not previously reported in vitamin B-6 deficiency, are discussed.

Strain Background Modifies Phenotypes in the ATP8B1-Deficient Mouse

PubMed Central

Vargas, Julie C.; Xu, Hongmei; Groen, Annamiek; Paulusma, Coen C.; Grenert, James P.; Pawlikowska, Ludmila; Sen, Saunak; Elferink, Ronald P. J. Oude; Bull, Laura N.

2010-01-01

Background Mutations in ATP8B1 (FIC1) underlie cases of cholestatic disease, ranging from chronic and progressive (progressive familial intrahepatic cholestasis) to intermittent (benign recurrent intrahepatic cholestasis). The ATP8B1-deficient mouse serves as an animal model of human ATP8B1 deficiency. Methodology/Principal Findings We investigated the effect of genetic background on phenotypes of ATP8B1-deficient and wild-type mice, using C57Bl/6 (B6), 129, and (B6-129) F1 strain backgrounds. B6 background resulted in greater abnormalities in ATP8B1-deficient mice than did 129 and/or F1 background. ATP8B1-deficient pups of B6 background gained less weight. In adult ATP8B1-deficient mice at baseline, those of B6 background had lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibited higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers. ATP8B1-deficient phenotypes in mice of F1 and 129 backgrounds are usually similar, suggesting that susceptibility to manifestations of ATP8B1 deficiency may be recessive. We also detected differences in hepatobiliary phenotypes between wild-type mice of differing strains. Conclusions/Significance Our results indicate that the ATP8B1-deficient mouse in a B6 background may be a better model of human ATP8B1 deficiency and highlight the importance of informed background strain selection for mouse models of liver disease. PMID:20126555

28 CFR 12.23 - Deficient registration statement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Deficient registration statement. 12.23 Section 12.23 Judicial Administration DEPARTMENT OF JUSTICE REGISTRATION OF CERTAIN PERSONS HAVING KNOWLEDGE OF FOREIGN ESPIONAGE, COUNTERESPIONAGE, OR SABOTAGE MATTERS UNDER THE ACT OF AUGUST 1, 1956 § 12...

28 CFR 12.23 - Deficient registration statement.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Deficient registration statement. 12.23 Section 12.23 Judicial Administration DEPARTMENT OF JUSTICE REGISTRATION OF CERTAIN PERSONS HAVING KNOWLEDGE OF FOREIGN ESPIONAGE, COUNTERESPIONAGE, OR SABOTAGE MATTERS UNDER THE ACT OF AUGUST 1, 1956 § 12...

28 CFR 12.23 - Deficient registration statement.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Deficient registration statement. 12.23 Section 12.23 Judicial Administration DEPARTMENT OF JUSTICE REGISTRATION OF CERTAIN PERSONS HAVING KNOWLEDGE OF FOREIGN ESPIONAGE, COUNTERESPIONAGE, OR SABOTAGE MATTERS UNDER THE ACT OF AUGUST 1, 1956 § 12...

28 CFR 12.23 - Deficient registration statement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Deficient registration statement. 12.23 Section 12.23 Judicial Administration DEPARTMENT OF JUSTICE REGISTRATION OF CERTAIN PERSONS HAVING KNOWLEDGE OF FOREIGN ESPIONAGE, COUNTERESPIONAGE, OR SABOTAGE MATTERS UNDER THE ACT OF AUGUST 1, 1956 § 12...

28 CFR 12.23 - Deficient registration statement.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Deficient registration statement. 12.23 Section 12.23 Judicial Administration DEPARTMENT OF JUSTICE REGISTRATION OF CERTAIN PERSONS HAVING KNOWLEDGE OF FOREIGN ESPIONAGE, COUNTERESPIONAGE, OR SABOTAGE MATTERS UNDER THE ACT OF AUGUST 1, 1956 § 12...

Total serum homocysteine as an indicator of vitamin B12 and folate status

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

Chu, R.C.; Hall, C.A.

1988-10-01

Presented is a modification of an assay for total serum homocysteine (Hcy) in which the Hcy plus radioactive adenosine is converted enzymatically to labeled S-adenosylhomocysteine (AdoHcy). The modifications included a commerical source for the AdoHcy hydrolase, adenosine labeled with either /sup 14/C or /sup 3/H, and separation of the AdoHcy by thin layer chromatography. The assay was sensitive to 25 pmol. Hcy levels in sera from 18 controls ranged from 6.9 to 12.1 mumol/L with a mean of 9.1 and a SD of 1.5 mumol/L. The total serum Hcy was increased in vitamin B12 and folate deficiency. The level wasmore » high in congenital defects of vitamin B12 metabolism, blocking the methylation of Hcy regardless of the serum vitamin B12 levels, but was normal in the absence of tissue deficiency even if the serum vitamin B12 levels were low. The procedure has been found practical in two years of use and requires only 0.1 mL of serum.« less

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

Medical intelligence in Sweden. Vitamin B12: oral compared with parenteral?

PubMed

Nilsson, M; Norberg, B; Hultdin, J; Sandström, H; Westman, G; Lökk, J

2005-03-01

Sweden is the only country in which oral high dose vitamin B12 has gained widespread use in the treatment of deficiency states. The aim of the study was to describe prescribing patterns and sales statistics of vitamin B12 tablets and injections in Sweden 1990-2000.Design, setting, and sources: Official statistics of cobalamin prescriptions and sales were used. The use of vitamin B12 increased in Sweden 1990-2000, mainly because of an increase in the use of oral high dose vitamin B12 therapy. The experience, in statistical terms a "total investigation", comprised 1,000,000 patient years for tablets and 750,000 patient years for injections. During 2000, 13% of residents aged 70 and over were treated with vitamin B12, two of three with the tablet preparation. Most patients in Sweden requiring vitamin B12 therapy have transferred from parenteral to oral high dose vitamin B12 since 1964, when the oral preparation was introduced. The findings suggest that many patients in other post-industrial societies may also be suitable for oral vitamin B12 treatment.

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.

Maternal micronutrient deficiency leads to alteration in the kidney proteome in rat pups.

PubMed

Ahmad, Shadab; Basak, Trayambak; Anand Kumar, K; Bhardwaj, Gourav; Lalitha, A; Yadav, Dilip K; Chandak, Giriraj Ratan; Raghunath, Manchala; Sengupta, Shantanu

2015-09-08

Maternal nutritional deficiency significantly perturbs the offspring's physiology predisposing them to metabolic diseases during adulthood. Vitamin B12 and folate are two such micronutrients, whose deficiency leads to elevated homocysteine levels. We earlier generated B12 and/or folate deficient rat models and using high-throughput proteomic approach, showed that maternal vitamin B12 deficiency modulates carbohydrate and lipid metabolism in the liver of pups through regulation of PPAR signaling pathway. In this study, using similar approach, we identified 26 differentially expressed proteins in the kidney of pups born to mothers fed with vitamin B12 deficient diet while only four proteins were identified in the folate deficient group. Importantly, proteins like calreticulin, cofilin 1 and nucleoside diphosphate kinase B that are involved in the functioning of the kidney were upregulated in B12 deficient group. Our results hint towards a larger effect of vitamin B12 deficiency compared to that of folate presumably due to greater elevation of homocysteine in vitamin B12 deficient group. In view of widespread vitamin B12 and folate deficiency and its association with several diseases like anemia, cardiovascular and renal diseases, our results may have large implications for kidney diseases in populations deficient in vitamin B12 especially in vegetarians and the elderly people.This article is part of a Special Issue entitled: Proteomics in India. Copyright © 2015 Elsevier B.V. All rights reserved.

Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial.

PubMed

Thacher, Tom D; Fischer, Philip R; Pettifor, John M

2014-09-01

To determine whether children with calcium-deficiency rickets have a better response to treatment with vitamin D and calcium than with calcium alone. Randomised controlled trial. Jos University Teaching Hospital, Jos, Nigeria. Nigerian children with active rickets treated with calcium carbonate as limestone (approximately 938 mg elemental calcium twice daily) were, in addition, randomised to receive either oral vitamin D2 50,000 IU (Ca+D, n=44) or placebo (Ca, n=28) monthly for 24 weeks. Achievement of a 10-point radiographic severity score ≤1.5 and serum alkaline phosphatase ≤350 U/L. The median (range) age of enrolled children was 46 (15-102) months, and baseline characteristics were similar in the two groups. Mean (±SD) 25-hydroxyvitamin D (25(OH)D) was 30.2±13.2 nmol/L at baseline, and 29 (43%) had values <30 nmol/L. Baseline alkaline phosphatase and radiographic scores were unrelated to vitamin D status. Of the 68 children (94% of original cohort) who completed 24 weeks of treatment, 29 (67%) in the Ca+D group and 11 (44%) in the Ca group achieved the primary outcome (p=0.06). Baseline 25(OH)D did not alter treatment group effects (p=0.99 for interaction). At the end of 24 weeks, 25(OH)D values were 55.4±17.0 nmol/L and 37.9±20.0 nmol/L in the Ca+D and Ca groups, respectively, (p<0.001). In the Ca+D and Ca groups, the final 25(OH)D concentration was greater in those who achieved the primary outcome (56.4±17.2 nmol/L) than in those who did not (37.7±18.5 nmol/L, p<0.001). In children with calcium-deficiency rickets, there is a trend for vitamin D to improve the response to treatment with calcium carbonate as limestone, independent of baseline 25(OH)D concentrations. ClinicalTrials.gov NCT00949832. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate123

PubMed Central

Miller, Joshua W; Garrod, Marjorie G; Allen, Lindsay H; Haan, Mary N

2009-01-01

Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid and higher odds ratios for cognitive impairment and anemia than the combination of low vitamin B-12 and nonelevated folate. These findings await confirmation in other populations. Objective: The purpose was to compare metabolic indicators of vitamin B-12 status, cognitive function, and depressive symptoms among elderly Latinos with elevated and nonelevated plasma folate. Design: Cross-sectional data were analyzed for 1535 subjects (age: ≥60 y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or ≥148 pmol/L) and folate (≤ or >45.3 nmol/L). Homocysteine, methylmalonic acid, holotranscobalamin, ratio of holotranscobalamin to vitamin B-12, Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were compared between the groups. Results: Individuals with low vitamin B-12 and elevated folate (n = 22) had the highest concentrations of homocysteine and methylmalonic acid and the lowest concentration of holotranscobalamin and ratio of holotranscobalamin to vitamin B-12 when compared with all other groups (P ≤ 0.003). No differences in Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were observed between the low vitamin B-12 and elevated-folate group compared with other groups. Conclusions: Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the potential costs, risks, and benefits of folic acid and vitamin B-12 fortification programs. PMID:19726595

Vitamin B12 concentration and its association with sociodemographic factors in Colombian children: Findings from the 2010 National Nutrition Survey.

PubMed

Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Martínez-Torres, Javier; Meneses-Echávez, José Francisco; Lobelo, Felipe

2016-02-01

Rapid changes in dietary patterns, economic development, and urbanization in low- to middle-income countries are fueling complex malnutrition states that need better characterization using population-level data. The aim of this study was to describe the key findings related to vitamin B12 status to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. We analyzed cross-sectional data from 6910 Colombian children between the ages of 5 and 12. Serum vitamin B12 concentrations were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. Of the children assessed, 2.8% had vitamin B12 deficiency, defined as levels <200 pg/mL, and 18.1% had marginal vitamin B12 deficiency, defined as levels between 200 and 300 pg/mL. A multivariate logistic regression analysis revealed increased risks for vitamin B12 deficiency among children ages ≥9 y and for those living in the eastern, western, and southern regions of the country. No significant associations were found for ethnic groups, socioeconomic status, or urbanity levels. Being 11 y of age (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.56-3.00; P = 0.0001), living in the west (Pacific) region of the country (OR, 3.92; 95% CI, 3.14-4.90; P = 0.0001), and being male (OR, 1.41; 95% CI, 1.20-1.65; P = 0.0001) were the factors most strongly associated with an increased risk for vitamin B12 deficiency. Compared with data from other Latin American countries, Colombian children have a lower prevalence of vitamin B12 deficiency; however the prevalence of marginal deficiency is substantial. Continued surveillance and implementation of interventions to improve dietary patterns among the high-risk groups identified should be considered. Copyright © 2016 Elsevier Inc. All rights reserved.

Considering the case for vitamin B12 fortification of flour

USDA-ARS?s Scientific Manuscript database

Reasons to fortify flour with vitamin B12 are considered, which include the high prevalence of depletion and deficiency of this vitamin that occurs in persons of all ages in resource-poor countries and in elderly in wealthier countries, as well as the adverse functional consequences of poor vitamin ...

Combined vitamin B-12 and balanced protein-energy supplementation affect homocysteine remethylation in the methionine cycle in pregnant south Indian women of low vitamin B-12 status

USDA-ARS?s Scientific Manuscript database

Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy, and may affect epigenetic modifications of the fetal genome. The objective of this randomized, partially open-labeled intervention trial was...

FKBP12 deficiency reduces strength deficits after eccentric contraction-induced muscle injury

PubMed Central

Corona, Benjamin T.; Rouviere, Clement; Hamilton, Susan L.; Ingalls, Christopher P.

2008-01-01

Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction uncoupling. FKBP12 is a 12-kDa binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca2+ release channel [ryanodine receptor (RyR1)] and plays an important role in excitation-contraction coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (tibialis anterior and extensor digitorum longus muscles) strength in skeletal muscle-specific FKBP12-deficient and wild-type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the tibialis anterior muscle was assessed after injury. Body weight and peak isometric and eccentric torques were lower in FKBP12-deficient mice compared with WT mice. There were no differences between FKBP12-deficient and WT mice in preinjury peak isometric and eccentric torques when normalized to body weight, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12-deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice, despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12-deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice. PMID:18511525

Interventions with vitamins B6, B12 and C in pregnancy.

PubMed

Dror, Daphna K; Allen, Lindsay H

2012-07-01

The water-soluble vitamins B6, B12 and C play important roles in maternal health as well as fetal development and physiology during gestation. This systematic review evaluates the risks and benefits of interventions with vitamins B6, B12 and C during pregnancy on maternal, neonatal and child health and nutrition outcomes. Relevant publications were identified by searching PubMed, Popline and Web of Science databases. Meta-analyses were conducted for outcomes where results from at least three controlled trials were available. Potential benefits of vitamin B6 supplementation were reduction in nausea and vomiting, improvement in dental health, and treatment of some cases of anaemia. In meta-analysis based on three small studies, vitamin B6 supplementation had a significant positive effect on birthweight (d = 217 g [95% confidence interval (CI) 130, 304]). Interventions with vitamin C alone or combined with vitamin E did not systematically reduce the incidence of pre-eclampsia, premature rupture of membranes, or other adverse pregnancy outcomes. In meta-analyses, vitamins C and E increased the risk of pregnancy-related hypertension (relative risk 1.10 [95% CI 1.02, 1.19]). Effects of vitamin B6 or C intervention on other neonatal outcomes, including preterm birth, low birthweight, and perinatal morbidity and mortality, were not significant. Data on child health outcomes were lacking. Despite the prevalence of vitamin B12 deficiency amongst populations with limited intake of animal source foods, no intervention trials have evaluated vitamin B12 supplementation before or during pregnancy. In conclusion, existing evidence does not justify vitamin C supplementation during pregnancy. Additional studies are needed to confirm positive effects of vitamin B6 supplementation on infant birthweight and other outcomes. While vitamin B12 supplementation may reduce the incidence of neural tube defects in the offspring based on theoretical considerations, research is needed to support

Efficacy of a microencapsulated iron pyrophosphate-fortified fruit juice: a randomised, double-blind, placebo-controlled study in Spanish iron-deficient women.

PubMed

Blanco-Rojo, Ruth; Pérez-Granados, Ana M; Toxqui, Laura; González-Vizcayno, Carmen; Delgado, Marco A; Vaquero, M Pilar

2011-06-01

Fe-deficiency anaemia is a worldwide health problem. We studied the influence of consuming an Fe-fortified fruit juice on Fe status in menstruating women. A randomised, double-blind, placebo-controlled study of 16 weeks of duration was performed. Subjects were randomised into two groups: the P group (n 58) or the F group (n 64), and consumed, as a supplement to their usual diet, 500 ml/d of a placebo fruit juice or an Fe-fortified fruit juice, respectively. The Fe-fortified fruit juice, containing microencapsulated iron pyrophosphate, provided 18 mg Fe/d (100 % of the RDA). At baseline and monthly, dietary intake, body weight and Fe parameters were determined: total erythrocytes, haematocrit, mean corpuscular volume (MCV), red blood cell distribution width (RDW), Hb, serum Fe, serum ferritin, serum transferrin, transferrin saturation, soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZnPP). The fruit juice consumption involved increased intake of carbohydrates and vitamin C, and increased BMI within normal limits. Ferritin was higher in the F group after week 4 (P < 0·05) and became 80 % higher than in the P group after week 16 (P < 0·001), and transferrin decreased in the F group compared with the P group after week 4 (P < 0·001). RDW was higher at weeks 4 and 8 in the F group compared with the P group (P < 0·05). Transferrin saturation increased after week 8, and haematocrit, MCV and Hb increased after week 12, in the F group compared with the P group. Serum Fe did not change. sTfR and ZnPP decreased in the F group at week 16 (P < 0·05). Iron pyrophosphate-fortified fruit juice improves Fe status and may be used to prevent Fe-deficiency anaemia.

[Polyneuropathy caused by vitamin B12 deficiency secondary to chronic atrophic gastritis and giardiasis].

PubMed

Brieva, L; Ara, J R; Bertol, V; Canellas, A; del Agua, C

1998-06-01

In chronic atrophic gastritis atrophy of the stomach glands leads to intrinsic factor deficit, with consequent failure to absorb vitamin B12 and gastric achylia, which predisposes to Giardia infection which in itself leads to depletion of vitamin B12. We describe the case of a patient with peripheral and central nervous system pathology due to lack of vitamin B12 secondary to the combined effect of these two disorders. A 54 year old woman consulted us for paraesthesia and weakness of the legs which had been progressive for the previous two years. She presented with tactile hypoaesthesia, hypoparaesthesia, distal hyperreflexia and dysymmetry of the legs, ataxic-spastic gait and a positive Romberg sign. The investigations carried out showed the serum vitamin B12 level to be 3 pg/ml (N: 180-900), hemoglobin 13 g/dl and MCV 111 fl with MCHC 348/dl; neurophysiological studies: compatible with demyelinating motor polyneuropathy. Schilling test: deficit of absorption of vitamin B12 which was corrected on administration of intrinsic factor; gastroscopy; atrophic gastritis which confirmed the morbid anatomy findings. There was also flora containing Helicobacter and massive Giardia infection. Replacement and antibiotic therapy was followed by complete remission of the clinical picture. We emphasize the excellent clinical response to treatment in spite of the time elapsed since onset of symptoms.

Aberrant antibody affinity selection in SHIP-deficient B cells.

PubMed

Leung, Wai-Hang; Tarasenko, Tatiana; Biesova, Zuzana; Kole, Hemanta; Walsh, Elizabeth R; Bolland, Silvia

2013-02-01

The strength of the Ag receptor signal influences development and negative selection of B cells, and it might also affect B-cell survival and selection in the GC. Here, we have used mice with B-cell-specific deletion of the 5'-inositol phosphatase SHIP as a model to study affinity selection in cells that are hyperresponsive to Ag and cytokine receptor stimulation. In the absence of SHIP, B cells have lower thresholds for Ag- and interferon (IFN)-induced activation, resulting in augmented negative selection in the BM and enhanced B-cell maturation in the periphery. Despite a tendency to spontaneously downregulate surface IgM expression, SHIP deficiency does not alter anergy induction in response to soluble hen-egg lysozyme Ag in the MDA4 transgenic model. SHIP-deficient B cells spontaneously produce isotype-switched antibodies; however, they are poor responders in immunization and infection models. While SHIP-deficient B cells form GCs and undergo mutation, they are not properly selected for high-affinity antibodies. These results illustrate the importance of negative regulation of B-cell responses, as lower thresholds for B-cell activation promote survival of low affinity and deleterious receptors to the detriment of optimal Ab affinity maturation. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Clinical hematological symptoms of vitamin B12 deficiency in old age : Summarized overview of this year's symposium of the Working Group "Anemia in the Aged" on the occasion of the annual conference of the German Geriatric Society (DGG) in Frankfurt].

PubMed

Röhrig, Gabriele; Gütgemann, Ines; Kolb, Gerald; Leischker, Andreas

2018-05-23

The interdisciplinary symposium of the working group "anemia in the aged" on the occasion of the annual conference of the German Society of Geriatrics focused this year on vitamin B 12 deficiency in aged patients. Experts from hematopathology, clinical geriatrics and geriatric hematology presented the case of a 78-year-old woman and an interdisciplinary discussion was held on the epidemiology, clinical aspects as well as diagnostic and therapeutic steps. This article reviews the symposium on vitamin B 12 deficiency in the aged in the context of the currently available literature.

NutriPhone: a mobile platform for low-cost point-of-care quantification of vitamin B12 concentrations

PubMed Central

Lee, Seoho; O’Dell, Dakota; Hohenstein, Jess; Colt, Susannah; Mehta, Saurabh; Erickson, David

2016-01-01

Vitamin B12 is necessary for formation of red blood cells, DNA synthesis, neural myelination, brain development, and growth. Vitamin B12 deficiency is often asymptomatic early in its course; however, once it manifests, particularly with neurological symptoms, reversal by dietary changes or supplementation becomes less effective. Access to easy, low cost, and personalized nutritional diagnostics could enable individuals to better understand their own deficiencies as well as track the effects of dietary changes. In this work, we present the NutriPhone, a mobile platform for the analysis of blood vitamin B12 levels in 15 minutes. The NutriPhone technology comprises of a smartphone accessory, an app, and a competitive-type lateral flow test strip that quantifies vitamin B12 levels. To achieve the detection of sub-nmol/L physiological levels of vitamin B12, our assay incorporates an innovative “spacer pad” for increasing the duration of the key competitive binding reaction and uses silver amplification of the initial signal. We demonstrate the efficacy of our NutriPhone system by quantifying physiologically relevant levels of vitamin B12 and performing human trials where it was used to accurately evaluate blood vitamin B12 status of 12 participants from just a drop (~40 μl) of finger prick blood. PMID:27301282

NutriPhone: a mobile platform for low-cost point-of-care quantification of vitamin B12 concentrations.

PubMed

Lee, Seoho; O'Dell, Dakota; Hohenstein, Jess; Colt, Susannah; Mehta, Saurabh; Erickson, David

2016-06-15

Vitamin B12 is necessary for formation of red blood cells, DNA synthesis, neural myelination, brain development, and growth. Vitamin B12 deficiency is often asymptomatic early in its course; however, once it manifests, particularly with neurological symptoms, reversal by dietary changes or supplementation becomes less effective. Access to easy, low cost, and personalized nutritional diagnostics could enable individuals to better understand their own deficiencies as well as track the effects of dietary changes. In this work, we present the NutriPhone, a mobile platform for the analysis of blood vitamin B12 levels in 15 minutes. The NutriPhone technology comprises of a smartphone accessory, an app, and a competitive-type lateral flow test strip that quantifies vitamin B12 levels. To achieve the detection of sub-nmol/L physiological levels of vitamin B12, our assay incorporates an innovative "spacer pad" for increasing the duration of the key competitive binding reaction and uses silver amplification of the initial signal. We demonstrate the efficacy of our NutriPhone system by quantifying physiologically relevant levels of vitamin B12 and performing human trials where it was used to accurately evaluate blood vitamin B12 status of 12 participants from just a drop (~40 μl) of finger prick blood.

Folate, vitamin B12, and vitamin B6 status of a group of high socioeconomic status women in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.

PubMed

Fayyaz, Faiqa; Wang, Flora; Jacobs, René L; O'Connor, Deborah L; Bell, Rhonda C; Field, Catherine J

2014-12-01

Folic acid supplementation and food fortification policies have improved folate status in North American women of child bearing age. Recent studies have reported the possible inadequacy of vitamin B12 and B6 in the etiology of neural tube defects in folate-fortified populations. The aims of this study were to describe folate status and its relationship to supplementation and to assess vitamin B12 and B6 status in a cohort of pregnant women. Supplement intake data were collected in each trimester from the first cohort (n = 599) of the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Red blood cell folate (RBCF) and plasma folate, holotranscobalamin, and pyridoxal 5-phosphate were measured. Overt folate deficiency was rare (3%) but 24% of women in their first trimester had suboptimal RBCF concentration (<906 nmol·L(-1)). The proportion of the cohort in this category declined substantially in second (9%) and third (7%) trimesters. High RBCF (>1360 nmol·L(-1)) was observed in approximately half of the women during each pregnancy trimester. Vitamin B12 and B6 deficiencies were rare (<1% of the cohort). Women consuming folic acid supplements above the upper level had significantly higher RBCF and plasma folate concentrations. In conclusion, the prevalence of vitamin B12 and B6 deficiency was very low. A quarter of the women had suboptimal folate status in the first trimester of pregnancy and over half the women had abnormally high RBCF, suggesting that supplementation during pregnancy is not appropriate in a cohort of women considered to be healthy and a low risk for nutritional deficiencies.

Heat Shock Protein B1-Deficient Mice Display Impaired Wound Healing

PubMed Central

McNamee, Kay; Przybycien, Paulina M.; Lu, Xin; Williams, Richard O.; Bou-Gharios, George; Saklatvala, Jeremy; Dean, Jonathan L. E.

2013-01-01

There is large literature describing in vitro experiments on heat shock protein (hsp)B1 but understanding of its function in vivo is limited to studies in mice overexpressing human hspB1 protein. Experiments in cells have shown that hspB1 has chaperone activity, a cytoprotective role, regulates inflammatory gene expression, and drives cell proliferation. To investigate the function of the protein in vivo we generated hspB1-deficient mice. HspB1-deficient fibroblasts display increased expression of the pro-inflammatory cytokine, interleukin-6, compared to wild-type cells, but reduced proliferation. HspB1-deficient fibroblasts exhibit reduced entry into S phase and increased expression of cyclin-dependent kinase inhibitors p27kip1 and p21waf1. The expression of hspB1 protein and mRNA is also controlled by the cell cycle. To investigate the physiological function of hspB1 in regulating inflammation and cell proliferation we used an excisional cutaneous wound healing model. There was a significant impairment in the rate of healing of wounds in hspB1-deficient mice, characterised by reduced re-epithelialisation and collagen deposition but also increased inflammation. HspB1 deficiency augments neutrophil infiltration in wounds, driven by increased chemokine (C-X-C motif) ligand 1 expression. This appears to be a general mechanism as similar results were obtained in the air-pouch and peritonitis models of acute inflammation. PMID:24143227

Does Abiotic Stress Cause Functional B Vitamin Deficiency in Plants?1[OPEN

PubMed Central

Beaudoin, Guillaume A.; Gregory, Jesse F.

2016-01-01

B vitamins are the precursors of essential metabolic cofactors but are prone to destruction under stress conditions. It is therefore a priori reasonable that stressed plants suffer B vitamin deficiencies and that certain stress symptoms are metabolic knock-on effects of these deficiencies. Given the logic of these arguments, and the existence of data to support them, it is a shock to realize that the roles of B vitamins in plant abiotic stress have had minimal attention in the literature (100-fold less than hormones) and continue to be overlooked. In this article, we therefore aim to explain the connections among B vitamins, enzyme cofactors, and stress conditions in plants. We first outline the chemistry and biochemistry of B vitamins and explore the concept of vitamin deficiency with the help of information from mammals. We then summarize classical and recent evidence for stress-induced vitamin deficiencies and for plant responses that counter these deficiencies. Lastly, we consider potential implications for agriculture. PMID:27807106

The effect of vitamin C deficiency and chronic ultraviolet-B exposure on corneal ultrastructure: a preliminary investigation

PubMed Central

Hayes, Sally; Cafaro, Thamara A.; Boguslawska, Patrycja J.; Kamma-Lorger, Christina S.; Boote, Craig; Harris, Jonathan; Young, Robert; Hiller, Jennifer; Terrill, Nicholas; Meek, Keith M.

2011-01-01

Purpose In the visually debilitating condition of climatic droplet keratopathy, corneal transparency is progressively lost. Although the precise cause of the disease and the mechanism by which it progresses are not known, a lifetime exposure to high solar radiation and a vitamin C–deficient diet may be involved in its development. This study examines the effect of dietary ascorbate levels and ultraviolet (UV)-B exposure on corneal stromal structure. Methods Eight guinea pigs were divided into four treatment groups (A, B, C, and D). For 15 weeks, Groups A and C were fed an ascorbate-rich diet (2 mg/100 g bodyweight/day), while Groups B and D received an ascorbate-deficient diet (0.07 mg/100 g bodyweight/day). For the last 12 weeks of the study, Groups C and D also experienced chronic UVB exposure (0.12 J/cm2 for 40 min/day). Following euthanasia, the corneas were enucleated and their stromal ultrastructure examined using X-ray scattering and electron microscopy. Results UVB exposure resulted in an increased corneal thickness (p<0.001), but this was not accompanied by a widespread expansion of the collagen fibrillar array, and in the case of ascorbate-deficient animals, stromal thickening was associated with the compaction of collagen fibrils (p<0.01). Neither UVB exposure nor ascorbic acid deficiency caused any change in the average diameter or D-periodicity of the stromal collagen fibrils. Conclusions UVB-induced changes in the corneal ultrastructure were most pronounced in animals fed an ascorbic acid–deficient diet. This suggests that ascorbic acid may play a vital role in protecting the corneal stroma from the harmful effects of UVB. PMID:22171156

An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.

PubMed

Gupta, Kamesh; Jain, Anand; Rohatgi, Anurag

A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12<150pg/ml and possible B12 deficiency as <220pg/ml. In our study, we found a negative correlation between duration of metformin use and Vitamin B12 levels(r=-0.40). The mean Vitamin B12 levels seen in our study was 212.3pg/mL. There is a positive correlation between the duration of metformin therapy and peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Vitamin B12 assays compared by use of patients sera with low vitamin B12 content

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

Sheridan, B.L.; Pearce, L.C.

1985-05-01

The authors compared four radioisotope dilution (RD) methods and a microbiological assay for measuring concentrations of vitamin B12 in a selected panel of serum samples from patients known to be deficient in the vitamin. Low (less than 100 ng/L) and borderline (100-180 ng/L) results were similar between methods, but use of the manufacturers recommended ranges for borderline results would have changed the diagnostic classifications for 22 of 38 samples. Results of all the RD methods inter-correlated well, but less so with the microbiological assay. Borderline, nondiagnostic results were common to all methods, and no apparent advantage was gained from usingmore » the microbiological assay.« less

Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123

PubMed Central

Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M

2011-01-01

Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. PMID:21653798

Assessment of Vitamin B12 and Its Correlation with Dental Caries and Gingival Diseases in 10- to 14-year-old Children: A Cross-sectional Study.

PubMed

M Hugar, Shivayogi; S Dhariwal, Neha; Majeed, Andleeb; Badakar, Chandrashekhar; Gokhale, Niraj; Mistry, Laresh

2017-01-01

To assess the level of vitamin B 12 and correlate it with dental caries [decayed, missing, and filled permanent teeth (DMFT) score] and gingival diseases [plaque index (PI) and gingival index (GI)]. Healthy children according to the inclusion criteria were selected by the computerized randomization method from a school to assess the vitamin B 12 levels using Centaur/ Versace machine. Blood samples were collected to assess vitamin B 12 levels using automated analyzer. Oral examination was done by a single calibrated dentist. A thorough oral examination was carried out and the DMFT, PI, and GI scores of all the children were recorded and assessed. Data were analyzed using Karl Pearson's correlation test. Vitamin B 12 levels were deficient in 64% of the children. In boys, vitamin B 12 deficiency was found in about 76.2%, whereas, in girls it was 57.1%, which was not statistically significant. The vitamin B 12 deficient children showed a significantly high DMFT scores than the children with normal vitamin B 12 levels. The Pearson's correlation was -0.614 for DMFT, PI value -0.663, and GI value of -0.477. The negative correlation stated that there was a reverse relation between these indices and vitamin B 12 . In children with systemic vitamin B 12 deficiency, there is increased dental caries prevalence and associated gingival problems. Hugar SM, Dhariwal NS, Majeed A, Badakar C, Gokhale N, Mistry L. Assessment of Vitamin B 12 and Its Correlation with Dental Caries and Gingival Diseases in 10- to 14-year-old Children: A Cross-sectional Study. Int J Clin Pediatr Dent 2017;10(2):142-146.

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated periphreal nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of..

USDA-ARS?s Scientific Manuscript database

Since 2005 the National Feeding Program for the Elderly (PACAM) in Chile has provided a B12 fortified milk drink (1.7 µg B12/d) which is insufficient to ensure B12 adequacy in many individuals. The objective was to evaluate effects of adding 1 mg B12/d to PACAM vs 1 mg B12/d as a pill with PACAM on ...

Connective tissue integrity is lost in vitamin B-6-deficient chicks

NASA Technical Reports Server (NTRS)

Masse, P. G.; Yamauchi, M.; Mahuren, J. D.; Coburn, S. P.; Muniz, O. E.; Howell, D. S.

1995-01-01

The objective of the present investigation was to characterize further the connective tissue disorder produced by pyridoxine (vitamin B-6) deficiency, as previously evidenced by electron microscopy. Following the second post-natal week, fast growing male chicks were deprived of pyridoxine for a 1-mo period. Six weeks post-natally, blood concentrations in the experimental deficiency group had declined to deficiency levels as registered by low concentrations of pyridoxal phosphate (coenzyme form) in erythrocytes, but did not reach levels associated with neurological symptoms. Light microscopic study showed abnormalities in the extracellular matrix of the connective tissues. Collagen cross-links and the aldehyde contents were not significantly lower in cartilage and tendon collagens of vitamin B-6-deficient animals than in age-matched controls; also, their proteoglycan degrading protease and collagenase activities measured in articular cartilages were not greater. Thus, proteolysis was an unlikely alternative mechanism to account for the loss of connective tissue integrity. These results point to the need for further investigation into adhesive properties of collagen associated proteoglycans or other proteins in vitamin B-6-deficient connective tissue.

[Folate metabolism--epigenetic role of choline and vitamin B12 during pregnancy].

PubMed

Drews, Krzysztof

2015-12-01

Adequate choline intake during pregnancy is essential for proper fetal development. Nowadays studies suggest that even in high income countries regular pregnant women diet does not provide the satisfactory amount of choline. Choline demand during pregnancy is high and it seems to exceed present choline intake recommendations. Moreover lactation period also demands choline supplementation because of its high concentration in female milk. Numerous studies on animal model proved correlation between choline supplementation during pregnancy and proper fetal cognitive function development. Despite increased synthesis in maternal liver during pregnancy choline demand is much higher than common dietary uptake. Nowadays studies as to the nutritional recommendations during pregnancy concern also vitamin B12 supplementation. Vitamin B12 deficiency may be an important risk factor of neural tube defects development. Presented article contains a review of data on proper choline and vitamin B12 uptake during pregnancy and lactation and potential results of choline and vitamin B12 poor maternal status.

Assessment of Vitamin B12 and Its Correlation with Dental Caries and Gingival Diseases in 10- to 14-year-old Children: A Cross-sectional Study

PubMed Central

S Dhariwal, Neha; Majeed, Andleeb; Badakar, Chandrashekhar; Gokhale, Niraj; Mistry, Laresh

2017-01-01

Aim To assess the level of vitamin B12 and correlate it with dental caries [decayed, missing, and filled permanent teeth (DMFT) score] and gingival diseases [plaque index (PI) and gingival index (GI)]. Design Healthy children according to the inclusion criteria were selected by the computerized randomization method from a school to assess the vitamin B12 levels using Centaur/ Versace machine. Materials and methods Blood samples were collected to assess vitamin B12 levels using automated analyzer. Oral examination was done by a single calibrated dentist. A thorough oral examination was carried out and the DMFT, PI, and GI scores of all the children were recorded and assessed. Data were analyzed using Karl Pearson’s correlation test. Results Vitamin B12 levels were deficient in 64% of the children. In boys, vitamin B12 deficiency was found in about 76.2%, whereas, in girls it was 57.1%, which was not statistically significant. The vitamin B12 deficient children showed a significantly high DMFT scores than the children with normal vitamin B12 levels. The Pearson’s correlation was -0.614 for DMFT, PI value -0.663, and GI value of -0.477. The negative correlation stated that there was a reverse relation between these indices and vitamin B12. Conclusion In children with systemic vitamin B12 deficiency, there is increased dental caries prevalence and associated gingival problems. How to cite this article Hugar SM, Dhariwal NS, Majeed A, Badakar C, Gokhale N, Mistry L. Assessment of Vitamin B12 and Its Correlation with Dental Caries and Gingival Diseases in 10- to 14-year-old Children: A Cross-sectional Study. Int J Clin Pediatr Dent 2017;10(2):142-146. PMID:28890613

Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians, and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study

PubMed Central

Gilsing, Anne MJ; Crowe, Francesca L; Lloyd-Wright, Zouë; Sanders, Thomas AB; Appleby, Paul N; Allen, Naomi E; Key, Timothy J

2010-01-01

Background/Objectives Vegans and to a lesser extent vegetarians have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet. Subjects/Methods A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort. Results Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate in vegetarians (182, 95% CI: 175-189 pmol/l), and lowest in vegans (122, 95% CI: 117-127 pmol/l). Fifty-two percent of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 < 118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate in vegetarians, and lowest in omnivores, but only two men (both omnivores) were categorised as folate deficient (defined as serum folate < 6.3 nmol/l). Conclusion Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorised as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency. PMID:20648045

Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study.

PubMed

Gilsing, A M J; Crowe, F L; Lloyd-Wright, Z; Sanders, T A B; Appleby, P N; Allen, N E; Key, T J

2010-09-01

Vegans, and to a lesser extent vegetarians, have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet. A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort. Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate among vegetarians (182, 95% CI: 175-189 pmol/l) and lowest among vegans (122, 95% CI: 117-127 pmol/l). In all, 52% of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 <118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate among vegetarians and lowest among omnivores, but only two men (both omnivores) were categorized as folate deficient (defined as serum folate <6.3 nmol/l). Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency.

Effectiveness of the National Program of Complementary Feeding for older adults in Chile on vitamin B12 status in older adults; secondary outcome analysis from the CENEX Study (ISRCTN48153354)

PubMed Central

2013-01-01

Background Older people are at increased risk of vitamin B12 deficiency and the provision of fortified foods may be an effective way to ensure good vitamin B12 status in later life. Aim To evaluate the effectiveness of a vitamin B12 fortified food provided by a national program of complementary food for older people on plasma vitamin B12 levels. Subjects and methods A random sub-sample of 351 subjects aged 65-67y from a large cluster randomised controlled trial provided blood samples at baseline and after 24 months of intervention. The intervention arm (10 clusters 186 participants) received a vitamin B12 fortified food designed to deliver 1.4 μg/day, while the control arm did not receive complementary food (10 clusters, 165 participants). Serum vitamin B12 and folate levels determined by radioimmunoassay were used to estimate the effect of intervention on vitamin B12 levels, adjusting for baseline levels and sex. Results Attrition at 24 months was 16.7% and 23.6% in the intervention and control arms respectively (p = 0.07). Over 24 months of intervention, mean (95% CI) serum vitamin B12 decreased from 392 (359–425) pmol/dL to 357 (300–414) pmol/dL (p < 0.07) in the intervention arm and from 395 (350–440) pmol/dL to 351 (308–395) pmol/dL in the control arm. There was no significant effect of the intervention on folate status. Discussion Our findings suggest that foods fortified with 1.4 μg/daily vitamin B12 as provided by Chile’s national programme for older people are insufficient to ensure adequate vitamin B12 levels in this population. Chile has a long and successful experience with nutrition intervention programs; however, the country’s changing demographic and nutritional profiles require a constant adjustment of the programs. PMID:24016218

Choline and betaine ameliorate liver lipid accumulation induced by vitamin B6 deficiency in rats.

PubMed

Kitagawa, Erina; Yamamoto, Tatsuya; Fujishita, Mayuko; Ota, Yuki; Yamamoto, Kohei; Nakagawa, Tomoyuki; Hayakawa, Takashi

2017-02-01

We investigated the efficacy of supplementing the diet with choline or betaine in ameliorating lipid accumulation induced by vitamin B 6 (B 6 ) deficiency in rat liver. Male Wistar rats were fed a control, B 6 -deficient, choline-supplemented (2, 4, or 6 g choline bitartrate/kg diet) B 6 -deficient diet or betaine-supplemented (1, 2, or 4 g betaine anhydrous/kg diet) B 6 -deficient diet for 35 d; all diets contained 9 g L-methionine (Met)/kg diet. Choline or betaine supplementation attenuated liver lipid deposition and restored plasma lipid profiles to control levels. These treatments restored the disruptions in Met metabolism and the phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio induced by B 6 deficiency in liver microsomes. These results suggest that choline and betaine ameliorated liver lipid accumulation induced by B 6 deficiency via recovery of Met metabolism and very low-density lipoprotein secretion by restoring the supply of PC derived from PE.

Vitamin B12 supplementation improves heart rate variability in healthy elderly Indian subjects.

PubMed

Sucharita, S; Thomas, T; Antony, B; Vaz, M

2012-05-21

While vitamin B(12) deficiency is global, data in elderly Indians are lacking. The problem in India is likely to be higher because of vegetarianism and malabsorption related to gastro-intestinal parasites. Autonomic dysfunction is known to occur much earlier in pernicious anemia. However, what is not known is whether these changes are reflected in healthy elderly individuals. This study assessed cardiac sympathetic and parasympathetic activity using heart rate variability (HRV) in healthy elderly individuals of low and high vitamin B(12) status and evaluated the effect of vitamin B(12) supplementation in those with low vitamin B(12) status. 140 elderly subjects aged ≥60 years were screened; 47 healthy subjects were assessed. They underwent blood sampling, anthropometry, HRV and nerve conduction assessment. Subjects were classified based on vitamin B(12) level (148 pmol/L) into deplete vitamin B(12) and replete vitamin B(12) groups. Elderly subjects with low vitamin B(12) status underwent cyanocobalamin supplementation (100 μg) for 3 months. Low frequency (LF) HRV in absolute units was significantly lower in the low vitamin B(12) group. Following supplementation, LF HRV in absolute units and total power rose significantly as compared to pre-supplementation values for the entire supplemented group. In conclusion, elderly with lower vitamin B(12) status have reduced low frequency HRV suggestive of sympathetic involvement. Supplementation with vitamin B(12) for 3 months results in a significant increase in low frequency HRV to values comparable with unsupplemented, but vitamin B(12) replete elderly. Copyright © 2012 Elsevier B.V. All rights reserved.

Screening and diagnosis of micronutrient deficiencies before and after bariatric surgery

PubMed Central

Gudzune, Kimberly A.; Huizinga, Mary M.; Chang, Hsien-Yen; Asamoah, Vivian; Gadgil, Meghana; Clark, Jeanne M.

2013-01-01

Introduction Micronutrient deficiencies are key concerns after bariatric surgery. We describe the prevalence of perioperative testing and diagnosis of micronutrient deficiencies among a cohort of insured bariatric surgery patients. Methods We used claims data from seven health insurers to identify bariatric surgery patients from 2002–2008. Our outcomes were perioperative claims for vitamin D, B12, folate, and iron testing and diagnosed deficiencies. We analyzed results by bariatric surgery type: Roux-en-Y gastric bypass (RYGB), restrictive, and malabsorptive. We calculated the prevalence of testing and deficiency diagnosis, and performed multivariate logistic regression to determine the association with surgery type. Results Of 21,345 eligible patients, 84% underwent RYGB. The pre-surgical testing prevalence for all micronutrients was <25%. The testing prevalence during the first 12 months after surgery varied: vitamin D (12%), vitamin B12 (60%), folate (47%) and iron (49%), and declined during 13–24 and 25–36 months. The deficiency prevalence during 0–12 months post-survey varied: vitamin D (34%), vitamin B12 (20%), folate (13%), and iron (10%). The odds of vitamin B12, folate, and iron deficiency during 0–12 months were significantly lower for restrictive as compared to RYGB, but were not different during 13–24 and 25–36 months post-surgery. The odds of vitamin D deficiency were significantly greater for malabsorptive as compared to RYGB during all post-surgical periods. Conclusion Many patients did not receive micronutrient testing pre- or post-surgery, yet deficiencies were relatively common among those tested. These results highlight the need for surgeons and primary care providers to test all bariatric surgery patients for micronutrient deficiencies. PMID:23515975

A comparative study on the B12N12, Al12N12, B12P12 and Al12P12 fullerene-like cages.

PubMed

Beheshtian, Javad; Bagheri, Zargham; Kamfiroozi, Mohammad; Ahmadi, Ali

2012-06-01

The stability, geometry and electronic structure of the title nanoclusters were compared by using density functional theory (DFT) calculations. Their electrical property analysis showed that the relative magnitude of the HOMO-LUMO gaps (eV) that are average values from the calculated results with five different DFT functionals is as follows: B12N12(7:02)>Al12N12(4.09)>B12P12(3.80)>Al12P12(3.39). Computing the standard enthalpy and the Gibbs free energy of formation, it was found that the B(12)N(12) structure is thermodynamically stable at 298 K and 1 atmosphere of pressure, while the Al(12)N(12) structure may be stable at low temperatures. Due to positive values of change of enthalpy and entropy of formation for both the B(12)P(12) and Al(12)P(12) clusters, it seems that their formation from the consisting atoms is not spontaneous at any temperature.

Active B12: a rapid, automated assay for holotranscobalamin on the Abbott AxSYM analyzer.

PubMed

Brady, Jeff; Wilson, Lesley; McGregor, Lynda; Valente, Edward; Orning, Lars

2008-03-01

Conventional tests for vitamin B(12) deficiency measure total serum vitamin B12, whereas only that portion of vitamin B12 carried by transcobalamin (holotranscobalamin) is metabolically active. Measurement of holotranscobalamin (holoTC) may be more diagnostically accurate for detecting B(12) deficiency that requires therapy. We developed an automated assay for holoTC that can be used on the Abbott AxSYM immunoassay analyzer. AxSYM Active B12 is a 2-step sandwich microparticle enzyme immunoassay. In step 1, a holoTC-specific antibody immobilized onto latex microparticles captures holoTC in samples of serum or plasma. In step 2, the captured holoTC is detected with a conjugate of alkaline phosphatase and antiTC antibody. Neither apoTC nor haptocorrin exhibited detectable cross-reactivity. The detection limit was < or = 0.1 pmol/L. Within-run and total imprecision (CV ranges) were 3.4%-5.1% and 6.3%-8.5%, respectively. Assay CVs were < 20% from at least 3 pmol/L to 107 pmol/L. With diluted serum samples, measured concentrations were 104%-114% of the expected values in the working range of the assay. No interference from bilirubin, hemoglobin, triglycerides, erythrocytes, rheumatoid factor, or total protein was detected at expected (abnormal) concentrations. A comparison of the AxSYM Active B12 assay with a commercial RIA for holoTC yielded the regression equation: AxSYM = 0.98RIA + 4.7 pmol/L (S(y x), 11.4 pmol/L; n = 204). Assay throughput was 45 tests/h. A 95% reference interval of 19-134 pmol/L holoTC was established with samples from 292 healthy individuals. The AxSYM Active B12 assay allows rapid, precise, sensitive, specific, and automated measurement of human holoTC in serum and plasma.

Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations.

PubMed

Qian, Bingjun; Shen, Shanqi; Zhang, Jianhua; Jing, Pu

2017-01-01

The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF- γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN- γ . Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

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.

Vitamin B12 status and the effects of vitamin B12 supplementation during the first year of life of spring calves from pasture-fed dairy herds.

PubMed

Grace, N D; Knowles, S O; Nortjé, R

2014-09-01

during the transition to a pasture-based diet. Supplementation increased concentrations of vitamin B12 in serum but did not improve liveweight gains. Under this calf rearing system, vitamin B12 deficiency is unlikely to occur prior to weaning, and vitamin B12 supplementation is unlikely to increase growth rates of grazing calves when concentrations of vitamin B12 in serum are > 90 pmol/L.

Myeloid Kdm6b deficiency results in advanced atherosclerosis.

PubMed

Neele, Annette E; Gijbels, Marion J J; van der Velden, Saskia; Hoeksema, Marten A; Boshuizen, Marieke C S; Prange, Koen H M; Chen, Hung-Jen; Van den Bossche, Jan; van Roomen, Cindy P P A; Shami, Annelie; Levels, Johannes H M; Kroon, Jeffrey; Lucas, Tina; Dimmeler, Stefanie; Lutgens, Esther; de Winther, Menno P J

2018-06-01

Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells. Given the importance of these cells in atherosclerosis, we now studied the effect of myeloid Kdm6b on disease progression. Bone marrow of myeloid Kdm6b deficient (Kdm6b del ) mice or wild type littermates (Kdm6b wt ) was transplanted to lethally irradiated Ldlr -/- mice fed a high fat diet for 9 weeks to induce atherosclerosis. Lesion size was similar in Kdm6b wt and Kdm6b del transplanted mice. However, lesions of Kdm6b del mice contained more collagen and were more necrotic. Pathway analysis on peritoneal foam cells showed that the pathway involved in leukocyte chemotaxis was most significantly upregulated. Although macrophage and neutrophil content was similar after 9 weeks of high fat diet feeding, the relative increase in collagen content and necrosis revealed that atherosclerotic lesions in Kdm6b del mice progress faster. Myeloid Kdm6b deficiency results in more advanced atherosclerosis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods

USDA-ARS?s Scientific Manuscript database

The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous ...

The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial.

PubMed

Strand, Tor A; Ulak, Manjeswori; Chandyo, Ram K; Kvestad, Ingrid; Hysing, Mari; Shrestha, Merina; Basnet, Sudha; Ranjitkar, Suman; Shrestha, Laxman; Shrestha, Prakash S

2017-04-21

Vitamin B 12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B 12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B 12 on the neurodevelopment and growth of young children in Nepal. We are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6-11 months old (length for age less than -1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B 12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study. If vitamin B 12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.

The impact of vegan diet on B-12 status in healthy omnivores: five-year prospective study.

PubMed

Mądry, Edyta; Lisowska, Aleksandra; Grebowiec, Philip; Walkowiak, Jarosław

2012-04-02

There are no long-term prospective studies assessing the impact of the vegan diet on vitamin B-12 (B-12) status. Many vegans take B-12 supplements irregularly or refuse to adopt them at all, considering them to be "unnatural" products. The use of B-12 fortified food may be an alternative. Therefore, we aimed to estimate the long-term effect of a vegan diet on serum B-12 concentrations in healthy omnivore adults, comparing the influence of natural products consumption and B-12 fortified food. A five year prospective study was carried out comprising 20 omnivore healthy adult subjects, who moved to strict vegan diet for 5 years. Ten volunteers followed vegan diet based entirely on natural products, while the remaining ten subjects consumed food fortified in B-12. In all subjects serum vitamin B-12 concentration was determined before and 6, 12, 24 and 60 months after the implementation of the diet. A significant decrease (p < 0.0002) of serum B-12 concentrations in the whole studied group was noted after 60 months of vegan diet. However, observed changes were in fact limited to the subgroup consuming exclusively natural products (p < 0.0001). Transition from omnivore to vegan diet is associated with the risk of vitamin B-12 deficiency. B-12 fortified products might constitute a valuable alternative in vegans refusing to take vitamin supplements.

Correlations between maternal, breast milk, and infant vitamin B12 concentrations among mother-infant dyads in Vancouver, Canada and Pry Veng, Cambodia: an exploratory analysis

USDA-ARS?s Scientific Manuscript database

Vitamin B12 plays an essential role in fetal and infant development. In regions where animal source food consumption is low and perinatal supplementation is uncommon, infants are at risk of vitamin B12 deficiency. In this secondary analysis, we measured total vitamin B12 concentrations in maternal a...

Fermentation of 1,2-Propanediol and 1,2-Ethanediol by Some Genera of Enterobacteriaceae, Involving Coenzyme B12-Dependent Diol Dehydratase

PubMed Central

Toraya, Tetsuo; Honda, Susumu; Fukui, Saburo

1979-01-01

Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724 was able to grow anaerobically on 1,2-propanediol and 1,2-ethanediol as carbon and energy sources. Whole cells of the bacterium grown anaerobically on 1,2-propanediol or on glycerol catalyzed conversion of 1,2-diols and aldehydes to the corresponding acids and alcohols. Glucose-grown cells also converted aldehydes, but not 1,2-diols, to acids and alcohols. The presence of activities of coenzyme B12-dependent diol dehydratase, alcohol dehydrogenase, coenzyme-A-dependent aldehyde dehydrogenase, phosphotransacetylase, and acetate kinase was demonstrated with crude extracts of 1,2-propanediol-grown cells. The dependence of the levels of these enzymes on growth substrates, together with cofactor requirements in in vitro conversion of these substrates, indicates that 1,2-diols are fermented to the corresponding acids and alcohols via aldehydes, acyl-coenzyme A, and acyl phosphates. This metabolic pathway for 1,2-diol fermentation was also suggested in some other genera of Enterobacteriaceae which were able to grow anaerobically on 1,2-propanediol. When the bacteria were cultivated in a 1,2-propanediol medium not supplemented with cobalt ion, the coenzyme B12-dependent conversion of 1,2-diols to aldehydes was the rate-limiting step in this fermentation. This was because the intracellular concentration of coenzyme B12 was very low in the cells grown in cobalt-deficient medium, since the apoprotein of diol dehydratase was markedly induced in the cells grown in the 1,2-propanediol medium. Better cell yields were obtained when the bacteria were grown anaerobically on 1,2-propanediol. Evidence is presented that aerobically grown cells have a different metabolic pathway for utilizing 1,2-propanediol. PMID:378959

Vitamin B12 intake and status in early pregnancy among urban South Indian women

PubMed Central

Samuel, Tinu Mary; Duggan, Christopher; Thomas, Tinku; Bosch, Ronald; Rajendran, Ramya; Virtanen, Suvi M; Srinivasan, Krishnamachari; Kurpad, Anura V

2015-01-01

Aim To evaluate the vitamin B12 status of South Indian women in early pregnancy and its relationship with sociodemographic, anthropometry and dietary intake. Methods Cross-sectional study among 366 pregnant urban South Indian women ≤14 weeks of gestation with outcome variables defined as low vitamin B12 blood concentration (<150 pmol/L) and impaired vitamin B12 status [low vitamin B12 plus elevated methylmalonic acid (MMA) >0.26 μmol/L)]. Results Low plasma vitamin B12 concentration was observed in 51.1% of the women, while 42.4% had impaired B12 status. Elevated MMA, elevated homocysteine ( >10 μmol/L) and low erythrocyte folate (<283 nmol/L) was observed among 75.8%, 43.3% and 22.2% of women, respectively. The median (25th, 75th percentile) dietary intake of vitamin B12 was 1.25 (0.86, 1.96) μg/day. Lower maternal body weight was associated with higher vitamin B12 concentration [prevalence ratios (PR) (95% CI) 0.57 (0.39, 0.84)). The predictors of impaired vitamin B12 status were non-use of yoghurt [PR (95%CI) 1.63 (1.03, 2.58)], non-use of fish [PR (95% CI) 1.32 (1.01, 1.71)] and primiparity [PR (95% CI) 1.41 (1.05, 1.90)]. Conclusion A high prevalence of vitamin B12 deficiency in early pregnancy among urban South Indian women was related to primiparity and to a low consumption of yoghurt and fish. PMID:23344013

Nutritional Deficiencies in Chinese Patients Undergoing Gastric Bypass and Sleeve Gastrectomy: Prevalence and Predictors.

PubMed

Guan, Bingsheng; Yang, Jingge; Chen, Yanya; Yang, Wah; Wang, Cunchuan

2018-05-12

Nutritional deficiencies have been reported in bariatric surgery patients with inconsistent results. However, scarce data exist for Chinese patients. We aimed to assess nutritional deficiencies in Chinese patients undergoing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), and to identify predictors of postoperative nutritional status. A retrospective review of a prospectively collected database was conducted in the patients undergoing RYGB and SG in our hospital between June 2013 and January 2017. Anthropometric data and nutritional data were collected before surgery, at 6 and 12 months postoperatively. This study enrolled 269 patients (120 RYGB, 149 SG). Nutritional deficiencies were common in Chinese bariatric candidates, with vitamin D deficiency the most serious (78.8%), followed by vitamin B1 (39.2%), vitamin B6 (28.0%), folate (26.8%), vitamin C (18.0%) albumin (13.4%), transferrin (11.6%), and phosphorus (11.5%). Despite postoperative routine multivitamin and calcium supplements, nutritional deficiencies were still obvious for RYGB and SG patients. The prevalence of hemoglobin and vitamin B12 deficiencies increased remarkably in the RYGB group; the levels of hemoglobin, globin, vitamin B12, and ferritin decreased significantly (P < 0.05). Preoperative hemoglobin, vitamin B12, and ferritin levels were independently associated with postoperative decrease, respectively. Deficiencies of vitamin D, vitamin B1, vitamin B6, vitamin C, and albumin before surgery were predictors for deficiencies 1 year after surgery, respectively. Nutritional deficiencies are common in Chinese bariatric surgery candidates. Similar deficiencies were also seen after RYGB and SG. Routine evaluation and related corrections of preoperative nutritional abnormity could contribute to postoperative nutrient balance.

Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. a study protocol [ISRCTN 02694183

PubMed Central

2011-01-01

Background Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. Less is known about subclinical vitamin B12 deficiency and concurrent neuroconduction and cognitive impairment. A Programme of Complementary Feeding for the Older Population (PACAM) in Chile delivers 2 complementary fortified foods that provide approximately 1.4 μg/day of vitamin B12 (2.4 μg/day elderly RDA). The aim of the present study is to assess whether supplementation with vitamin B12 will improve neuroconduction and cognitive function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of clinical deficiency. Methods We designed a cluster double-blind placebo-controlled trial involving community dwelling people aged 70-79 living in Santiago, Chile. We randomized 15 clusters (health centers) involving 300 people (20 per cluster). Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk-PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food and a placebo pill. The study has been designed as an 18 month follow up period. The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum levels of vitamin B12, neuroconduction and cognitive function. Conclusions In view of the high prevalence of vitamin B12 deficiency in later life, the present study has potential public health interest because since it will measure the impact of the existing program of complementary feeding as compared to two options that provide higher vitamin B12 intakes that might potentially may contribute in preserving neurophysiologic and cognitive function and thus improve quality of life for older people in Chile

C. elegans MRP-5 Exports Vitamin B12 from Mother to Offspring to Support Embryonic Development.

PubMed

Na, Huimin; Ponomarova, Olga; Giese, Gabrielle E; Walhout, Albertha J M

2018-03-20

Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short-chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of offspring. However, the mechanism for exporting vitamin B12 from the mother to the offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that the injection of vitamin B12 into the gonad of mrp-5 deficient mothers rescues embryonic lethality in the offspring. Altogether, our findings identify a maternal mechanism for the transit of an essential vitamin to support the development of the next generation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats.

PubMed

Kulkarni, Asmita; Dangat, Kamini; Kale, Anvita; Sable, Pratiksha; Chavan-Gautam, Preeti; Joshi, Sadhana

2011-03-10

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12) are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12) deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12) deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12) lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.

Variation in the Phenotypic Expression of B-Glucuronidase Deficiency

ERIC Educational Resources Information Center

Beaudet, Arthur L.; And Others

1975-01-01

Presented are case studies of two children, 2-and 14 years-old, with widely differing manifestations of B-glucuronidase deficiency: one child was severly retarded with multiple anomalies, the other child exhibited milder symptoms with cardiovasculor involvement. (CL)

Haematinic Deficiency and Macrocytosis in Middle-Aged and Older Adults

PubMed Central

Harrington, Janas; Cadogan, Sharon; Honari, Bahman; Perera, Kanthi; Fitzgerald, Anthony P.; Perry, Ivan J.; Cahill, Mary R.

2013-01-01

Objective To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults. Methods A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT). Results The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). Conclusions Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland

Nuclear carbonic anhydrase 6B associates with PRMT5 to epigenetically promote IL-12 expression in innate response.

PubMed

Xu, Jia; Xu, Xiaoqing; Wang, Bingjing; Ma, Yuanwu; Zhang, Lianfeng; Xu, Henan; Hu, Ye; Wu, Jiacheng; Cao, Xuetao

2017-08-08

Interleukin-12 (IL-12) is critical for induction of protective immunity against intracellular bacterial infection. However, the mechanisms for efficient induction of IL-12 in innate response remain poorly understood. Here we report that the B type of carbonic anhydrase 6 ( Car6-b , which encoded CA-VI B) is essential for host defense against Listeria monocytogenes (LM) infection by epigenetically promoting IL-12 expression independent of its carbonic anhydrase activity. Deficiency of Car6-b attenuated IL-12 production upon LM infection both in vitro and in vivo. Car6 -/- mice were more susceptible to LM infection with less production of IL-12. Mechanistically, the nuclear localized CA-VI B selectively promotes IL-12 expression by interaction with protein arginine N -methyltransferase 5 (PRMT5), which reduces symmetric dimethylation of histone H3 arginine 8 modification (H3R8me2s) at Il12 promoters to facilitate chromatin accessibility, selectively enhancing c-Rel binding to the Il12b promoter. Our findings add insights to the epigenetic regulation of IL-12 induction in innate immunity.

FAD-induced in vitro activation of glutathione reductase in the lens of B2 deficient rats.

PubMed

Ono, S; Hirano, H

1984-04-01

We studied the FAD-induced in vitro stimulation of lenticular glutathione reductase in riboflavin-deficient rats. The stimulatory effect of FAD on lenticular glutathione reductase in rats fed a B2-deficient diet for 4 weeks was remarkably higher than in paired control rats fed a B2-supplemented basal diet and control rats had ad libitum access to a B2-supplemented basal diet. The in vitro FAD stimulation effect on rat lenticular glutathione reductase represents a sensitive indicator of the B2 deficient status.

Vitamin B-12 Concentrations in Breast Milk Are Low and Are Not Associated with Reported Household Hunger, Recent Animal-Source Food, or Vitamin B-12 Intake in Women in Rural Kenya.

PubMed

Williams, Anne M; Chantry, Caroline J; Young, Sera L; Achando, Beryl S; Allen, Lindsay H; Arnold, Benjamin F; Colford, John M; Dentz, Holly N; Hampel, Daniela; Kiprotich, Marion C; Lin, Audrie; Null, Clair A; Nyambane, Geoffrey M; Shahab-Ferdows, Setti; Stewart, Christine P

2016-05-01

Breast milk vitamin B-12 concentration may be inadequate in regions in which animal-source food consumption is low or infrequent. Vitamin B-12 deficiency causes megaloblastic anemia and impairs growth and development in children. We measured vitamin B-12 in breast milk and examined its associations with household hunger, recent animal-source food consumption, and vitamin B-12 intake. In a cross-sectional substudy nested within a cluster-randomized trial assessing water, sanitation, hygiene, and nutrition interventions in Kenya, we sampled 286 women 1-6 mo postpartum. Mothers hand-expressed breast milk 1 min into a feeding after 90 min observed nonbreastfeeding. The Household Hunger Scale was used to measure hunger, food intake in the previous week was measured with the use of a food-frequency questionnaire (FFQ), and vitamin B-12 intake was estimated by using 24-h dietary recall. An animal-source food score was based on 10 items from the FFQ (range: 0-70). Breast milk vitamin B-12 concentration was measured with the use of a solid-phase competitive chemiluminescent enzyme immunoassay and was modeled with linear regression. Generalized estimating equations were used to account for correlated observations at the cluster level. Median (IQR) vitamin B-12 intake was 1.5 μg/d (0.3, 9.7 μg/d), and 60% of women consumed <2.4 μg/d, the estimated average requirement during lactation. Median (IQR) breast milk vitamin B-12 concentration was 113 pmol/L (61, 199 pmol/L); 89% had concentrations <310 pmol/L, the estimated adequate concentration. Moderate or severe hunger prevalence was 27%; the animal-source food score ranged from 0 to 30 item-d/wk. Hunger and recent animal-source food and vitamin B-12 intake were not associated with breast milk vitamin B-12 concentrations. Maternal age was negatively associated with breast milk vitamin B-12 concentrations. Most lactating Kenyan women consumed less than the estimated average requirement of vitamin B-12 and had low breast milk

Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significa...

PKK deficiency in B cells prevents lupus development in Sle lupus mice

PubMed Central

Oleksyn, D.; Zhao, J.; Vosoughi, A.; Zhao, JC.; Misra, R; Pentland, AP; Ryan, D.; Anolik, J.; Ritchlin, C.; Looney, J.; Anandarajah, AP.; Schwartz, G.; Calvi, LM; Georger, M; Mohan, C.; Sanz, I.; Chen, L

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B- lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment. PMID:28274793

Severe osteogenesis imperfecta in cyclophilin B-deficient mice.

PubMed

Choi, Jae Won; Sutor, Shari L; Lindquist, Lonn; Evans, Glenda L; Madden, Benjamin J; Bergen, H Robert; Hefferan, Theresa E; Yaszemski, Michael J; Bram, Richard J

2009-12-01

Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of CypB in this complex has been a complete mystery. To study the role of mammalian CypB, we generated mice lacking this protein. Early in life, Ppib-/- mice developed kyphosis and severe osteoporosis. Collagen fibrils in Ppib-/- mice had abnormal morphology, further consistent with an OI phenotype. In vitro studies revealed that in CypB-deficient fibroblasts, procollagen did not localize properly to the golgi. We found that levels of P3H1 were substantially reduced in Ppib-/- cells, while CRTAP was unaffected by loss of CypB. Conversely, knockdown of either P3H1 or CRTAP did not affect cellular levels of CypB, but prevented its interaction with collagen in vitro. Furthermore, knockdown of CRTAP also caused depletion of cellular P3H1. Consistent with these changes, post translational prolyl-3-hydroxylation of type I collagen by P3H1 was essentially absent in CypB-deficient cells and tissues from CypB-knockout mice. These data provide significant new mechanistic insight into the pathophysiology of OI and reveal how the members of the P3H1/CRTAP/CypB complex interact to direct proper formation of collagen and bone.

B61 Mod 12 Life Extension Program Tailkit Assembly (B61 Mod 12 LEP TKA)

DTIC Science & Technology

2013-12-01

Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-468 B61 Mod 12 Life Extension Program Tailkit Assembly ( B61 Mod 12 LEP TKA...REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE B61 Mod 12 Life Extension Program Tailkit Assembly ( B61 Mod 12 LEP...REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 B61 Mod 12

Zinc deficiency induces vascular pro-inflammatory parameters associated with NF-kappaB and PPAR signaling.

PubMed

Shen, Huiyun; Oesterling, Elizabeth; Stromberg, Arnold; Toborek, Michal; MacDonald, Ruth; Hennig, Bernhard

2008-10-01

Marginal intake of dietary zinc can be associated with increased risk of cardiovascular diseases. In the current study we hypothesized that vascular dysfunction and associated inflammatory events are activated during a zinc deficient state. We tested this hypothesis using both vascular endothelial cells and mice lacking the functional LDL-receptor gene. Zinc deficiency increased oxidative stress and NF-kappaB DNA binding activity, and induced COX-2 and E-selectin gene expression, as well as monocyte adhesion in cultured endothelial cells. The NF-kappaB inhibitor CAPE significantly reduced the zinc deficiency-induced COX-2 expression, suggesting regulation through NF-kappaB signaling. PPAR can inhibit NF-kappaB signaling, and our previous data have shown that PPAR transactivation activity requires adequate zinc. Zinc deficiency down-regulated PPARalpha expression in cultured endothelial cells. Furthermore, the PPARgamma agonist rosiglitazone was unable to inhibit the adhesion of monocytes to endothelial cells during zinc deficiency, an event which could be reversed by zinc supplementation. Our in vivo data support the importance of PPAR dysregulation during zinc deficiency. For example, rosiglitazone induced inflammatory genes (e.g., MCP-1) only during zinc deficiency, and adequate zinc was required for rosiglitazone to down-regulate pro-inflammatory markers such as iNOS. In addition, rosiglitazone increased IkappaBalpha protein expression only in zinc adequate mice. Finally, plasma data from LDL-R-deficient mice suggest an overall pro-inflammatory environment during zinc deficiency and support the concept that zinc is required for proper anti-inflammatory or protective functions of PPAR. These studies suggest that zinc nutrition can markedly modulate mechanisms of the pathology of inflammatory diseases such as atherosclerosis.

Proton Pump Inhibitors Intake and Iron and Vitamin B12 Status: A Prospective Comparative Study with a Follow up of 12 Months

PubMed Central

Qorraj-Bytyqi, Hasime; Hoxha, Rexhep; Sadiku, Shemsedin; Bajraktari, Ismet H.; Sopjani, Mentor; Thaçi, Kujtim; Thaçi, Shpetim; Bahtiri, Elton

2018-01-01

BACKGROUND: Proton pump inhibitors (PPIs) represent the most widely prescribed antisecretory agents, but their prolonged use, may influence iron and vitamin B12 status, which could have important implications for clinical practice. AIM: We undertook this study aiming to investigate the association between PPIs use for 12 months and potential changes in iron and vitamin B12 status, as well as whether this potential association varies among four specific PPI drugs used in the study. METHODS: A total of 250 adult subjects were recruited into this study, of which 200 subjects were PPIs users while 50 subjects belonged to the control group. Serum iron, ferritin, vitamin B12, and homocysteine (Hcy) levels were measured before the start of the study and after 12 months. Mann - Whitney U test and Kruskal - Wallis test was used to compare the baseline characteristics of the study groups, while Wilcoxon test was used to analyse post - pre differences. RESULTS: Statistical analysis showed significant changes within PPIs group and specific PPIs subgroups between the two-time points in serum ferritin and vitamin B12 levels, respectively, while no significant changes in serum iron and homocysteine levels were shown. However, subsequent diagnosis of hypoferremia and hypovitaminosis B12 in the whole study sample at 12 months was established in only 3.8% and 2.9% of the subjects, respectively. CONCLUSION: PPIs use for 12 months did not result in clinically significant iron and/or vitamin B12 deficiency; thus, these findings argue routine screening under normal circumstances, although monitoring in elderly and malnourished may be of precious value. PMID:29610598

Intramuscular glucocorticoid injection versus placebo injection in hip osteoarthritis: a 12-week blinded randomised controlled trial.

PubMed

Dorleijn, Desirée M J; Luijsterburg, Pim A J; Reijman, Max; Kloppenburg, Margreet; Verhaar, Jan A N; Bindels, Patrick J E; Bos, Pieter Koen; Bierma-Zeinstra, Sita M A

2018-06-01

Guidelines recommend intra-articular glucocorticoid injection in patients with painful hip osteoarthritis. However, intra-articular hip injection is an invasive procedure. The efficacy of systemic glucocorticoid treatment for pain reduction in hip osteoarthritis is unknown. This randomised, double-blind, trial assessed effectiveness in hip pain reduction of an intramuscular glucocorticoid injection compared with a placebo injection in patients with hip osteoarthritis. Patients with painful hip osteoarthritis were randomised to either 40 mg triamcinolone acetate or placebo with an intramuscular injection into the gluteus muscle. The primary outcomes were severity of hip pain at rest, during walking (0-10) and WOMAC pain at 2-week postinjection. We used linear mixed models for repeated measurements at 2, 4, 6 and 12 weeks for the intention-to-treat data analysis. Of the 107 patients randomised, 106 could be analysed (52 in the glucocorticoid group, 54 in the placebo group). At 2-week follow-up, compared with placebo injection, the intramuscular glucocorticoid injection showed a significant and clinically relevant difference in hip pain reduction at rest (difference -1.3, 95% CI -2.3 to -0.3). This effect persisted for the entire 12-week follow-up. For hip pain during walking, the effect was present at 4-week, 6-week and 12-week follow-ups, and for WOMAC pain the effect was present at 6-week and 12-week follow-up. An intramuscular glucocorticoid injection showed effectiveness in patients with hip osteoarthritis on one of the three primary outcomes at 2-week postinjection. All primary outcomes showed effectiveness from 4 to 6 weeks, up to a 12-week follow-up. NTR2966. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Low plasma vitamin B-12 is associated with a lower pregnancy-associated rise in plasma free choline in Canadian pregnant women and lower postnatal growth rates in their male infants.

PubMed

Wu, Brian Tf; Innis, Sheila M; Mulder, Kelly A; Dyer, Roger A; King, D Janette

2013-11-01

Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 deficiency increases choline use for homocysteine methylation. We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants. Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference. The proportion of women with a plasma total vitamin B-12 concentration <148 pmol/L (deficient) or 148-220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (>220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P < 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient. This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition.

CD22 x Siglec-G double-deficient mice have massively increased B1 cell numbers and develop systemic autoimmunity.

PubMed

Jellusova, Julia; Wellmann, Ute; Amann, Kerstin; Winkler, Thomas H; Nitschke, Lars

2010-04-01

CD22 and Siglec-G are inhibitory coreceptors for BCR-mediated signaling. Although CD22-deficient mice show increased calcium signaling in their conventional B2 cells and a quite normal B cell maturation, Siglec-G-deficient mice have increased calcium mobilization just in B1 cells and show a large expansion of the B1 cell population. Neither CD22-deficient, nor Siglec-G-deficient mice on a pure C57BL/6 or BALB/c background, respectively, develop autoimmunity. Using Siglec-G x CD22 double-deficient mice, we addressed whether Siglec-G and CD22 have redundant functions. Siglec-G x CD22 double-deficient mice show elevated calcium responses in both B1 cells and B2 cells, increased serum IgM levels and an enlarged population of B1 cells. The enlargement of B1 cell numbers is even higher than in Siglecg(-/-) mice. This expansion seems to happen at the expense of B2 cells, which are reduced in absolute cell numbers, but show an activated phenotype. Furthermore, Siglec-G x CD22 double-deficient mice show a diminished immune response to both thymus-dependent and thymus-independent type II Ags. In contrast, B cells from Siglec-G x CD22 double-deficient mice exhibit a hyperproliferative response to stimulation with several TLR ligands. Aged Siglec-G x CD22 double-deficient mice spontaneously develop anti-DNA and antinuclear autoantibodies. These resulted in a moderate form of immune complex glomerulonephritis. These results show that Siglec-G and CD22 have partly compensatory functions and together are crucial in maintaining the B cell tolerance.

17 CFR 210.12-12B - Open option contracts written.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Open option contracts written. 210.12-12B Section 210.12-12B Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... § 210.12-12B Open option contracts written. [For management investment companies only] Col. A Col. B Col...

Serum folate, vitamin B-12 and cognitive function in middle and older age: The HAPIEE study.

PubMed

Horvat, Pia; Gardiner, Julian; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Schöttker, Ben; Pikhart, Hynek; Peasey, Anne; Jansen, Eugene; Bobak, Martin

2016-04-01

Nutrient status of B vitamins, particularly folate and vitamin B-12, may be related to cognitive ageing but epidemiological evidence remains inconclusive. The aim of this study was to estimate the association of serum folate and vitamin B-12 concentrations with cognitive function in middle-aged and older adults from three Central and Eastern European populations. Men and women aged 45-69 at baseline participating in the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) study were recruited in Krakow (Poland), Kaunas (Lithuania) and six urban centres in the Czech Republic. Tests of immediate and delayed recall, verbal fluency and letter search were administered at baseline and repeated in 2006-2008. Serum concentrations of biomarkers at baseline were measured in a sub-sample of participants. Associations of vitamin quartiles with baseline (n=4166) and follow-up (n=2739) cognitive domain-specific z-scores were estimated using multiple linear regression. After adjusting for confounders, folate was positively associated with letter search and vitamin B-12 with word recall in cross-sectional analyses. In prospective analyses, participants in the highest quartile of folate had higher verbal fluency (p<0.01) and immediate recall (p<0.05) scores compared to those in the bottom quartile. In addition, participants in the highest quartile of vitamin B-12 had significantly higher verbal fluency scores (β=0.12; 95% CI=0.02, 0.21). Folate and vitamin B-12 were positively associated with performance in some but not all cognitive domains in older Central and Eastern Europeans. These findings do not lend unequivocal support to potential importance of folate and vitamin B-12 status for cognitive function in older age. Long-term longitudinal studies and randomised trials are required before drawing conclusions on the role of these vitamins in cognitive decline. Copyright © 2016. Published by Elsevier Inc.

Assay for vitamin B12 absorption and method of making labeled vitamin B12

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

Anderson, Peter J; Dueker, Stephen; Miller, Joshua

2012-06-19

The invention provides methods for labeling vitamin B12 with .sup.14C, .sup.13C, tritium, and deuterium. When radioisotopes are used, the invention provides for methods of labeling B12 with high specific activity. The invention also provides labeled vitamin B12 compositions made in accordance with the invention.

A randomised, placebo-controlled trial assessing the efficacy of an oral B group vitamin in preventing the development of chemotherapy-induced peripheral neuropathy (CIPN).

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul; Linnane, Anthony W; Vitetta, Luis

2017-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect resulting from neurotoxic chemotherapeutic agents. This study aimed to assess the efficacy and safety of an oral B group vitamin compared to placebo, in preventing the incidence of CIPN in cancer patients undergoing neurotoxic chemotherapy. A pilot, randomised, placebo-controlled trial was conducted. Newly diagnosed cancer patients prescribed with taxanes, oxaliplatin or vincristine were invited to participate. A total of 71 participants (female 68 %, male 32 %) were enrolled into the study and randomised to the B group vitamin (n = 38) arm or placebo (n = 33). The data from 47 participants were eligible for analysis (B group vitamins n = 27, placebo n = 22). The primary outcome measure was the total neuropathy score assessed by an independent neurologist. Secondary outcome measures included serum vitamin B levels, quality of life, pain inventory and the patient neurotoxicity questionnaires. Outcome measures were conducted at baseline, 12, 24 and 36 weeks. The total neuropathy score (TNS) demonstrated that a B group vitamin did not significantly reduce the incidence of CIPN compared to placebo (p = 0.73). Statistical significance was achieved for patient perceived sensory peripheral neuropathy (12 weeks p = 0.03; 24 weeks p = 0.005; 36 weeks p = 0.021). The risk estimate for the Patient Neurotoxicity Questionnaire (PNQ) was also statistically significant (OR = 5.78, 95 % CI = 1.63-20.5). The European Organisation of Research and Treatment of Cancer (EORTC) quality of life, total pain score and pain interference showed no significance (p = 0.46, p = 0.9, p = 0.37 respectively). A trend was observed indicating that vitamin B12 may reduce the onset and severity of CIPN. An oral B group vitamin as an adjunct to neurotoxic chemotherapy regimens was not superior to placebo (p > 0.05) for the prevention of CIPN. Patients taking the B group vitamin perceived a

Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis.

PubMed

Pan, Yun; Liu, Ya; Guo, Haizhuo; Jabir, Majid Sakhi; Liu, Xuanchen; Cui, Weiwei; Li, Dong

2017-04-13

Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn's disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.

PubMed

Rathod, Richa S; Khaire, Amrita A; Kale, Anvita A; Joshi, Sadhana R

2015-01-01

In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function. © 2015 International Union of Biochemistry and Molecular Biology.

Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice

PubMed Central

Kaifu, Tomonori; Nakahara, Jin; Inui, Masanori; Mishima, Kenichi; Momiyama, Toshihiko; Kaji, Mitsuji; Sugahara, Akiko; Koito, Hisami; Ujike-Asai, Azusa; Nakamura, Akira; Kanazawa, Kiyoshi; Tan-Takeuchi, Kyoko; Iwasaki, Katsunori; Yokoyama, Wayne M.; Kudo, Akira; Fujiwara, Michihiro; Asou, Hiroaki; Takai, Toshiyuki

2003-01-01

Deletions in the DAP12 gene in humans result in Nasu-Hakola disease, characterized by a combination of bone fractures and psychotic symptoms similar to schizophrenia, rapidly progressing to presenile dementia. However, it is not known why these disorders develop upon deficiency in DAP12, an immunoreceptor signal activator protein initially identified in the immune system. Here we show that DAP12-deficient (DAP12–/–) mice develop an increased bone mass (osteopetrosis) and a reduction of myelin (hypomyelinosis) accentuated in the thalamus. In vitro osteoclast induction from DAP12–/– bone marrow cells yielded immature cells with attenuated bone resorption activity. Moreover, immature oligodendrocytes were arrested in the vicinity of the thalamus, suggesting that the primary defects in DAP12–/– mice are the developmental arrest of osteoclasts and oligodendrocytes. In addition, the mutant mice also showed synaptic degeneration, impaired prepulse inhibition, which is commonly observed in several neuropsychiatric diseases in humans including schizophrenia, and aberrant electrophysiological profiles in the thalami. These results provide a molecular basis for a unique combination of skeletal and psychotic characteristics of Nasu-Hakola disease as well as for schizophrenia and presenile dementia. PMID:12569157

Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

PubMed

Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

2007-01-01

B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition.

Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12)-Defective Mice Is Subject to Maternal Influences.

PubMed

Mottram, Lynda; Speak, Anneliese O; Selek, Reza M; Cambridge, Emma L; McIntyre, Zoe; Kane, Leanne; Mukhopadhyay, Subhankar; Grove, Carolyn; Colin, Amy; Brandt, Cordelia; Duque-Correa, Maria A; Forbester, Jessica; Nguyen, Tu Anh Pham; Hale, Christine; Vasilliou, George S; Arends, Mark J; Wren, Brendan W; Dougan, Gordon; Clare, Simon

2016-06-21

Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif), a protein essential for the absorption of vitamin B12/cobalamin (Cbl), have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Gif(tm1a/tm1a) mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1) mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2) equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility. Malnutrition continues to be a major public health problem in countries with weak infrastructures. In communities with a high prevalence of poor diet, malnourishment and infectious disease can impact vulnerable individuals such as pregnant women and children. Here, we describe a highly flexible murine model for monitoring maternal and environmental influences of vitamin B12 metabolism. We also demonstrate the potential importance of vitamin B12 in controlling susceptibility to bacterial pathogens such as C. rodentium and S Typhimurium. We postulate that this model, along with similarly vitamin deficient mice, could be used to further explore the mechanisms associated with micronutrients and susceptibility to diseases, thereby increasing our understanding of disease in the malnourished. Copyright © 2016 Mottram et al.

Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization

PubMed Central

Draves, Kevin E.; Young, Lucy B.; Bryan, Marianne A.; Dresch, Christiane; Diamond, Michael S.; Gale, Michael

2017-01-01

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike μMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient μMT mice, but unlike μMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in μMT mice. Thus, the immature B cells present in BAFFR-/- and not μMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals. PMID:29176765

17 CFR 210.12-12B - Open option contracts written.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Open option contracts written. 210.12-12B Section 210.12-12B Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... AND CONSERVATION ACT OF 1975 For Management Investment Companies § 210.12-12B Open option contracts...

Infant feeding bottle design, growth and behaviour: results from a randomised trial

PubMed Central

2012-01-01

Background Whether the design of an anti-vacuum infant feeding bottle influences infant milk intake, growth or behavior is unknown, and was the subject of this randomized trial. Methods Subjects 63 (36 male) healthy, exclusively formula-fed term infants. Intervention Randomisation to use Bottle A (n = 31), one-way air valve: Philips Avent) versus Bottle B (n = 32), internal venting system: Dr Browns). 74 breast-fed reference infants were recruited, with randomisation (n = 24) to bottle A (n = 11) or B (n = 13) if bottle-feeding was subsequently introduced. Randomisation stratified by gender and parity; computer-based telephone randomisation by independent clinical trials unit. Setting Infant home. Primary outcome measure infant weight gain to 4 weeks. Secondary outcomes (i) milk intake (ii) infant behaviour measured at 2 weeks (validated 3-day diary); (iii) risk of infection; (iv) continuation of breastfeeding following introduction of mixed feeding. Results Number analysed for primary outcome Bottle A n = 29, Bottle B n = 25. Primary outcome There was no significant difference in weight gain between randomised groups (0-4 weeks Bottle A 0.74 (SD 1.2) SDS versus bottle B 0.51 (0.39), mean difference 0.23 (95% CI -0.31 to 0.77). Secondary outcomes Infants using bottle A had significantly less reported fussing (mean 46 versus 74 minutes/day, p < 0.05) than those using bottle B. There was no significant difference in any other outcome measure. Breast-fed reference group There were no significant differences in primary or secondary outcomes between breast-fed and formula fed infants. The likelyhood of breastfeeding at 3 months was not significantly different in infants subsequently randomised to bottle A or B. Conclusion Bottle design may have short-term effects on infant behaviour which merit further investigation. No significant effects were seen on milk intake or growth; confidence in these findings is limited by the small sample size and this needs confirmation in

17 CFR 210.12-12B - Open option contracts written.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Open option contracts written. 210.12-12B Section 210.12-12B Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... AND CONSERVATION ACT OF 1975 Form and Content of Schedules § 210.12-12B Open option contracts written...

17 CFR 210.12-12B - Open option contracts written.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Open option contracts written. 210.12-12B Section 210.12-12B Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... AND CONSERVATION ACT OF 1975 Form and Content of Schedules § 210.12-12B Open option contracts written...

Vitamin B12 deficiency-induced neuropathy secondary to prolonged recreational use of nitrous oxide.

PubMed

Egan, William; Steinberg, Eric; Rose, Jeremy

2018-05-24

A 24-year-old female, otherwise healthy, presented to the Emergency Department (ED) with difficulty walking and bilateral leg pain. The patient was a recreational nitrous oxide (NO 2 ) user, also known as "whippets" or simply nitrous. Neurologic examination demonstrated an unsteady gait and positive Romberg sign along with normal deep tendon reflexes and normal muscle strength in upper and lower extremities. Laboratory results demonstrated macrocytic erythropoiesis, reduced B 12 , elevated homocysteine, and elevated methylmalonic acid. Outpatient MRI later demonstrated degeneration of the posterior spinal column. The patient was empirically treated in the ED with intramuscular B 12 and admitted to the evaluation unit for pain control and Physical Therapy (PT) evaluation. Emergency Medicine (EM) physicians should be aware of this condition because NO 2 is used both recreationally and in medicine. With the popularity of recreational nitrous oxide, many emergency patients have experience with this drug. As in our case report, the toxic effects can be profound and mimic other emergent conditions like stroke. Emergency physicians should have a higher index of suspicion for the toxic effects of this common drug. Elderly, vegetarians and patients with Irritable Bowel Disease are at higher risk and may even experience toxicity from nitrous oxide used therapeutically during routine anesthesia. Copyright © 2018 Elsevier Inc. All rights reserved.

Treatment of depression: time to consider folic acid and vitamin B12.

PubMed

Coppen, Alec; Bolander-Gouaille, Christina

2005-01-01

We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily

Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment.

PubMed

Köbe, Theresa; Witte, A Veronica; Schnelle, Ariane; Grittner, Ulrike; Tesky, Valentina A; Pantel, Johannes; Schuchardt, Jan Philipp; Hahn, Andreas; Bohlken, Jens; Rujescu, Dan; Flöel, Agnes

2016-04-01

Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear. We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI). In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n= 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure. MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P= 0.014) and recognition performance (P= 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P= 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects. Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. This trial was registered at clinicaltrials.gov as NCT01219244. © 2016

Serum homocysteine, folate, vitamin B12 and total antioxidant status in vegetarian children.

PubMed

Ambroszkiewicz, J; Klemarczyk, W; Chełchowska, M; Gajewska, J; Laskowska-Klita, T

2006-01-01

The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth.

Natural Versus Synthetic Vitamin B Complexes in Human

ClinicalTrials.gov

2018-04-12

Healthy; Thiamine and Niacin Deficiency States; Pyridoxine Deficiency; Folic Acid Deficiency Anemia, Dietary; Vitamin B 12 Deficiency; Peroxidase; Defect; Polyphenols; Oxidative Stress; Homocystine; Metabolic Disorder

Cyp1b1 deletion and retinol deficiency coordinately suppress mouse liver lipogenic genes and hepcidin expression during post-natal development

PubMed Central

Maguire, Meghan; Larsen, Michele Campaigne; Foong, Yee Hoon; Tanumihardjo, Sherry; Jefcoate, Colin R.

2018-01-01

Cyp1b1 deletion and gestational vitamin A deficiency (GVAD) redirect adult liver gene expression. A matched sufficient pre- and post-natal diet, which has high carbohydrate and normal iron content (LF12), increased inflammatory gene expression markers in adult livers that were suppressed by GVAD and Cyp1b1 deletion. At birth on the LF12 diet, Cyp1b1 deletion and GVAD each suppress liver expression of the iron suppressor, hepcidin (Hepc), while increasing stellate cell activation markers and suppressing post-natal increases in lipogenesis. Hepc was less suppressed in Cyp1b1−/− pups with a standard breeder diet, but was restored by iron supplementation of the LF12 diet. Conclusions The LF12 diet delivered low post-natal iron and attenuated Hepc. Hepc decreases in Cyp1b1−/− and GVAD mice resulted in stellate activation and lipogenesis suppression. Endothelial BMP6, a Hepc stimulant, is a potential coordinator and Cyp1b1 target. These neonatal changes in Cyp1b1−/− mice link to diminished adult obesity and liver inflammation. PMID:28583802

Improved metabolic phenotype of hypothalamic PTP1B-deficiency is dependent upon the leptin receptor.

PubMed

Tsou, Ryan C; Rak, Kimberly S; Zimmer, Derek J; Bence, Kendra K

2014-06-01

Protein tyrosine phosphatase 1B (PTP1B) is a known regulator of central metabolic signaling, and mice with whole brain-, leptin receptor (LepRb) expressing cell-, or proopiomelanocortin neuron-specific PTP1B-deficiency are lean, leptin hypersensitive, and display improved glucose homeostasis. However, whether the metabolic effects of central PTP1B-deficiency are due to action within the hypothalamus remains unclear. Moreover, whether or not these effects are exclusively due to enhanced leptin signaling is unknown. Here we report that mice with hypothalamic PTP1B-deficiency (Nkx2.1-PTP1B(-/-)) display decreased body weight and adiposity on high-fat diet with no associated improvements in glucose tolerance. Consistent with previous reports, we find that hypothalamic deletion of the LepRb in mice (Nkx2.1-LepRb(-/-)) results in extreme hyperphagia and obesity. Interestingly, deletion of hypothalamic PTP1B and LepRb (Nkx2.1-PTP1B(-/-):LepRb(-/-)) does not rescue the hyperphagia or obesity of Nkx2.1-LepRb(-/-) mice, suggesting that hypothalamic PTP1B contributes to the central control of energy balance through a leptin receptor-dependent pathway.

Micronutrient Deficiencies Are Common in 6- to 8-Year-Old Children of Rural Nepal, with Prevalence Estimates Modestly Affected by Inflammation12

PubMed Central

Schulze, Kerry J.; Christian, Parul; Wu, Lee S.-F.; Arguello, Margia; Cui, Hongjie; Nanayakkara-Bind, Ashika; Stewart, Christine P.; Khatry, Subarna K.; LeClerq, Steven; West, Keith P.

2014-01-01

Subclinical micronutrient deficiencies remain a hidden aspect of malnutrition for which comprehensive data are lacking in school-aged children. We assessed the micronutrient status of Nepalese children, aged 6 to 8 y, born to mothers who participated in a community-based antenatal micronutrient supplementation trial from 1999 to 2001. Of 3305 participants, plasma indicators were assessed in a random sample of 1000 children. Results revealed deficiencies of vitamins A (retinol <0.70 μmol/L, 8.5%), D (25-hydroxyvitamin D <50 nmol/L, 17.2%), E (α-tocopherol <9.3 μmol/L, 17.9%), K (decarboxy prothombin >2 μg/L, 20%), B-12 (cobalamin <150 pmol/L, 18.1%), B-6 [pyridoxal-5′-phosphate (PLP) <20 nmol/L, 43.1%], and β-carotene (41.5% <0.09 μmol/L), with little folate deficiency (6.2% <13.6 nmol/L). Deficiencies of iron [ferritin <15 μg/L, 10.7%; transferrin receptor (TfR) >8.3 mg/L, 40.1%; TfR:ferritin >500 μg/μg, 14.3%], iodine (thyroglobulin >40 μg/L, 11.4%), and selenium (plasma selenium <0.89 μmol/L, 59.0%) were observed, whereas copper deficiency was nearly absent (plasma copper <11.8 μmol/L, 0.7%). Hemoglobin was not assessed. Among all children, 91.7% experienced at least 1 micronutrient deficiency, and 64.7% experienced multiple deficiencies. Inflammation (α-1 acid glycoprotein >1 g/L, C-reactive protein >5 mg/L, or both) was present in 31.6% of children, affecting the prevalence of deficiency as assessed by retinol, β-carotene, PLP, ferritin, TfR, selenium, copper, or having any or multiple deficiencies. For any nutrient, population deficiency prevalence estimates were altered by ≤5.4% by the presence of inflammation, suggesting that the majority of deficiencies exist regardless of inflammation. Multiple micronutrient deficiencies coexist in school-aged children in rural Nepal, meriting more comprehensive strategies for their assessment and prevention. PMID:24744314

Multiple micronutrient-fortified rice affects physical performance and plasma vitamin B-12 and homocysteine concentrations of Indian school children.

PubMed

Thankachan, Prashanth; Rah, Jee Hyun; Thomas, Tinku; Selvam, Sumithra; Amalrajan, Vani; Srinivasan, Krishnamachari; Steiger, Georg; Kurpad, Anura V

2012-05-01

Fortifying rice with multiple micronutrients could be a promising strategy for combat micronutrient deficiencies in developing countries. We determined the efficacy of extruded rice grains fortified with multiple micronutrients on the prevalence of anemia, micronutrient status, and physical and cognitive performance in 6- to 12-y-old, low-income school children in Bangalore, India. In a randomized, double-blind, controlled trial, 258 children were assigned to 1 of 3 intervention groups to receive rice-based lunch meals fortified with multiple micronutrients with either low-iron (6.25 mg) or high-iron (12.5 mg) concentrations or identical meals with unfortified rice. The meals were provided 6 d/wk for 6 mo. Anthropometric, biochemical, physical performance, and cognitive assessments were taken at baseline and endpoint. At baseline, study groups were comparable, with 61% of the children being anemic. However, only <10% were deficient in iron, vitamin A, and zinc. After 6 mo, plasma vitamin B-12 and homocysteine concentrations (both P < 0.001) as well as physical performance (P < 0.05) significantly improved in the intervention arms. No between-group differences were observed in hemoglobin concentration, anemia, and deficiencies of other micronutrients or cognitive function after 6 mo, but paired analyses revealed a small reduction in anemia prevalence in children in the low-iron group. The fortified rice was efficacious in improving vitamin B-12 status and physical performance in Indian school children.

The effect of Helicobacter pylori on vitamin B 12 blood levels in chronic renal failure patients: a single blind control trial.

PubMed

Khedmat, Hossein; Amini, Mohsen; Karbasi, Ashraf; Azizi, Reza

2013-07-01

Helicobacter pylori (HP) is a common infection worldwide and has been associated with severe morbidity. The level of vitamin B 12 in HP-infected chronic kidney disease (CKD) patients is reported to be lower than in the general population. The present study has been designed to evaluate the vitamin B 12 level in HP-infected CKD patients. We assessed the serum levels of vitamin B 12 in 50 CKD patients with positive HP serology, one and three months after the eradication of HP infection. There were significant differences between the serum levels of vitamin B 12 in the study patients before (806.98 ± 466.82) and after (760.36 ± 433.93) eradication treatment (P <0.001). We conclude that our study suggests the correlation between vitamin B 12 deficiency in CKD patients and the HP infection status.

INTERFERON α ACTIVATES NF-κ B IN JAK1-DEFICIENT CELLS THROUGH A TYK2-DEPENDENT PATHWAY

PubMed Central

Yang, Chuan He; Murti, Aruna; Valentine, William J.; Du, Ziyun; Pfeffer, Lawrence M.

2005-01-01

In addition to activating members of the STAT transcription factor family, IFN α/β activates the NF-κ B transcription factor. To determine the role of the JAK-STAT pathway in NF-κ B activation by IFN, we examined NF-κ B activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH) IFN activates STAT1, STAT2 and STAT3, as well as NF-κB complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells IFN induces NF-κB activation and NF-κB dependent gene transcription, but does not activate these STAT proteins and has no effect on STAT-dependent gene transcription. Expression of a catalytically-inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, abrogates NF-κB activation by IFN. Moreover, IFN does not promote NF-κB activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-κB signaling pathway. In the IFN signaling pathway leading to STAT activation both JAK1 and TYK2 are essential, while NF-κB activation requires only TYK2. PMID:15883164

Vitamin B12-Loaded Buccoadhesive Films as a Noninvasive Supplement in Vitamin B12 Deficiency: In Vitro Evaluation and In Vivo Comparative Study With Intramuscular Injection.

PubMed

Mohamad, Soad A; Sarhan, Hatem A; Abdelkader, Hamdy; Mansour, Heba F

2017-07-01

This study aimed to formulate and evaluate vitamin B12-loaded buccal mucoadhesive hydrogel films. Various film formulations were prepared using chitosan and polyvinyl alcohol. The prepared films were characterized for thickness, weight variation, drug content, percentage moisture uptake and moisture content, surface pH, mechanical properties, in vitro release, and mucoadhesion. Vitamin B12 bioavailability from the optimized formulation was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neuroton ® I.M. injection was used for comparison. The films had acceptable mechanical and mucoadhesion properties. The percentages of moisture content of the optimized formulation were 3.2 ± 0.95, whereas the percentage drug released was 98.59 ± 1.41% at the end of 40 min. FTIR revealed the incidence of drug/polymer interaction. Differential scanning calorimetry revealed the possibility of the dispersion of cyanocobalamin in a molecular state with complete amorphization in the polymers. The estimated AUC 0-8h showed 1.5-fold increases in the bioavailability of cyanocobalamin from the optimized formulation compared with the marketed I.M. injection. These findings warrant that vitamin B12 buccal film formulation can be considered as an effective alternative portal with noninvasive and more convenient characteristics compared with the I.M. injection dosage form. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Deficiency of the Cyclin-Dependent Kinase Inhibitor, CDKN1B, Results in Overgrowth and Neurodevelopmental Delay

PubMed Central

Grey, William; Izatt, Louise; Sahraoui, Wafa; Ng, Yiu-Ming; Ogilvie, Caroline; Hulse, Anthony; Tse, Eric; Holic, Roman; Yu, Veronica

2013-01-01

Germline mutations in the cyclin-dependent kinase inhibitor, CDKN1B, have been described in patients with multiple endocrine neoplasia (MEN), a cancer predisposition syndrome with adult onset neoplasia and no additional phenotypes. Here, we describe the first human case of CDKN1B deficiency, which recapitulates features of the murine CDKN1B knockout mouse model, including gigantism and neurodevelopmental defects. Decreased mRNA and protein expression of CDKN1B were confirmed in the proband's peripheral blood, which is not seen in MEN syndrome patients. We ascribed the decreased protein level to a maternally derived deletion on chromosome 12p13 encompassing the CDKN1B locus (which reduced mRNA expression) and a de novo allelic variant (c.-73G>A) in the CDKN1B promoter (which reduced protein translation). We propose a recessive model where decreased dosage of CDKN1B during development in humans results in a neuronal phenotype akin to that described in mice, placing CDKN1B as a candidate gene involved in developmental delay. PMID:23505216

Vitamin B6 deficiency: a potential cause of refractory seizures in adults.

PubMed

Gerlach, Anthony T; Thomas, Sheela; Stawicki, Stanislaw P; Whitmill, Melissa L; Steinberg, Steven M; Cook, Charles H

2011-03-01

In children, vitamin B(6) (pyridoxine) deficiency has been described as a cause of seizures that are refractory to conventional antiepileptic medications. We describe the clinical presentation of 3 adults with refractory seizures (later diagnosed with vitamin B(6) deficiency) that resolved after pyridoxine treatment. Case series. Tertiary care surgical intensive care unit. In the first case, a 54-year-old male with history of alcoholic cirrhosis developed new-onset seizures refractory to phenytoin and levetiracetam 8 days after liver transplantation. In the second case, a 59-year-old male with hepatitis C infection developed intracranial hemorrhage and new-onset seizures refractory to phenytoin, levetiracetam, and pentobarbital. The third patient is a 78-year-old male with a history of alcohol dependence who was admitted for an intraventricular bleed and developed new onset of refractory seizures. Intravenous pyridoxine followed by oral pyridoxine. In all 3 cases, seizures persisted despite escalation of conventional antiepileptic medications but resolved within 2 days of pyridoxine supplementation. In each case, low serum pyridoxal 5'-phosphate concentrations normalized with pyroxidine administration. Although refractory seizures caused by vitamin B(6) deficiency are rare in adults, it should be considered in critically ill adult patients with refractory seizures.

The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled Trial

PubMed Central

Chandyo, Ram K; Ulak, Manjeswori; Kvestad, Ingrid; Shrestha, Merina; Ranjitkar, Suman; Basnet, Sudha; Hysing, Mari; Shrestha, Laxman

2017-01-01

Introduction Vitamin B12 is crucial for normal cell division and differentiation, and necessary for the development and myelination of the central nervous system. Pregnant mothers in resource poor settings are at risk for poor vitamin B12 status. Poor vitamin B12 status in infancy is linked to poor growth and neurodevelopment. Brain development starts from conception, and pregnancy is a period of rapid growth and development for the brain. Methods and analysis The study is an individually randomised double-blind placebo controlled trial in 800 pregnant Nepalese women randomised in a 1:1 ratio. A daily dose of 50 µg of vitamin B12 or placebo is given to women from early pregnancy, not later than week 15, until 6 months after birth. Weekly visits are conducted in order to record compliance, growth and morbidity. The primary outcomes are scores on the cognitive, language and motor subscales of the Bayley Scales of Infant and Toddler Development, Third Edition, measured at 6 and 12 months of age, and growth (length and weight) measured at 6 and 12 months of age. Ethics and dissemination National Health and Research Council, Nepal (NHRC 253/2016) and Regional Committee for Medical and Health Research Ethics of Western Norway (2016/1620/REK vest) have approved the study. Investigators who have contributed to the conceptualising, conducting, as well as being involved in the data analyses and manuscript writing will be eligible for authorship and be responsible to share outcomes with different stakeholders through publications and workshops. The results from this study may support new dietary guidelines for Nepalese and possibly South Asian pregnant women that can lead to improved pregnancy outcomes, neurodevelopment and cognitive functioning in children. Trial registration number Universal Trial Number: U1111-1183-4093. Trial registration: clinicaltrials.gov: NCT03071666. Protocol date: version 1.2, 1 June 2017. PMID:28851784

Antisense oligonucleotide reduction of apoB-ameliorated atherosclerosis in LDL receptor-deficient mice[S

PubMed Central

Mullick, Adam E.; Fu, Wuxia; Graham, Mark J.; Lee, Richard G.; Witchell, Donna; Bell, Thomas A.; Whipple, Charles P.; Crooke, Rosanne M.

2011-01-01

Chronic elevations of plasma apolipoprotein B (apoB) are strongly associated with cardiovascular disease. We have previously demonstrated that inhibition of hepatic apoB mRNA using antisense oligonucleotides (ASO) results in reductions of apoB, VLDL, and LDL in several preclinical animal models and humans. In this study, we evaluated the anti-atherogenic effects of a murine-specific apoB ASO (ISIS 147764) in hypercholesterolemic LDLr deficient (LDLr−/−) mice. ISIS 147764 was administered weekly at 25-100 mg/kg for 10-12 weeks and produced dose-dependent reductions of hepatic apoB mRNA and plasma LDL by 60-90%. No effects on these parameters were seen in mice receiving control ASOs. ApoB ASO treatment also produced dose-dependent reductions of aortic en face and sinus atherosclerosis from 50-90%, with high-dose treatment displaying less disease than the saline-treated, chow-fed LDLr−/− mice. No changes in intestinal cholesterol absorption were seen with apoB ASO treatment, suggesting that the cholesterol-lowering pharmacology of 147764 was primarily due to inhibition of hepatic apoB synthesis and secretion. In summary, ASO-mediated suppression of apoB mRNA expression profoundly reduced plasma lipids and atherogenesis in LDLr−/− mice, leading to the hypothesis that apoB inhibition in humans with impaired LDLr activity may produce similar effects. PMID:21343632

IL-12Rβ1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

PubMed Central

Bustamante, Jacinta; Feinberg, Jacqueline; Samarina, Arina; Grant, Audrey V.; Janniere, Lucile; El Hafidi, Naima; Hassani, Amal; Nolan, Daniel; Najib, Jilali; Camcioglu, Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Tanir, Gonul; Aytekin, Caner; Keser, Melike; Somer, Ayper; Aksu, Guside; Kutukculer, Necil; Mansouri, Davood; Mahdaviani, Alireza; Mamishi, Setareh; Alcais, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

2011-01-01

Background and Objectives In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. Methods and Principal Findings We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. Significance This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity. PMID:21533230

Vitamin B-12 status is not associated with plasma homocysteine in parents and their preschool children: lacto-ovo, lacto, and ovo vegetarians and omnivores.

PubMed

Yen, Chin-En; Yen, Chi-Hua; Cheng, Chien-Hsiang; Huang, Yi-Chia

2010-02-01

Vegetarians may be at risk of certain nutrient deficiencies, particularly vitamin B-12. Vitamin B-12 deficiency may increase plasma homocysteine concentration and thus may potentially increase the risk of cardiovascular disease in vegetarians. The purpose of this study was to assess and compare plasma homocysteine and vitamin B-12 status in vegetarian and omnivorous preschool children and their parents. In addition, the association between parents' and children's homocysteine and vitamin B-12 concentration was also examined. Fifty-six omnivores (28 preschool children and one of their parents), 34 lacto-ovo vegetarians (16 parents and 18 children), 5 ovo vegetarians (2 parents and 3 children), 1 lacto vegetarian parent, and 2 vegan parents were enrolled in this study. The mean age of preschool children was 5.1 +/- 1.3 years and that of their parent was 35.4 +/- 4.2 years. Nutrient intakes were recorded using 3-day dietary records. Fasting venous blood samples were obtained to measure serum creatinine, high-sensitivity C-reactive protein, hematological parameters, plasma homocysteine, serum folate, and vitamin B-12 concentrations. There was no significant difference in dietary folate intake between vegetarian and omnivores within parent and child groups. The mean plasma homocysteine level of vegetarian parents and their children was in the physiological range, and they had slightly but not significantly higher plasma homocysteine levels than omnivores. Omnivorous parents and their children had significantly higher vitamin B-12 intake than vegetarian participants but similar serum vitamin B-12 concentrations. Plasma homocysteine concentration was significantly and negatively associated with only serum folate levels (beta = -0.15) and dietary vitamin B-12 intake (beta = -0.05) in the omnivorous parents after adjusting for age, gender, body mass index, and serum creatinine. Vegetarian parents and their preschool children had a lower vitamin B-12 intake than omnivorous

Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations.

PubMed

Manchanda, Ranjit; Burnell, Matthew; Loggenberg, Kelly; Desai, Rakshit; Wardle, Jane; Sanderson, Saskia C; Gessler, Sue; Side, Lucy; Balogun, Nyala; Kumar, Ajith; Dorkins, Huw; Wallis, Yvonne; Chapman, Cyril; Tomlinson, Ian; Taylor, Rohan; Jacobs, Chris; Legood, Rosa; Raikou, Maria; McGuire, Alistair; Beller, Uziel; Menon, Usha; Jacobs, Ian

2016-07-01

Newer approaches to genetic counselling are required for population-based testing. We compare traditional face-to-face genetic counselling with a DVD-assisted approach for population-based BRCA1/2 testing. A cluster-randomised non-inferiority trial in the London Ashkenazi Jewish population. Ashkenazi Jewish men/women >18 years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches. 936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD-C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=-0.07; lower 97.5% CI=-0.41), counselling satisfaction (d=-0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=-3%; lower/upper 97.5% CI -7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p<0.005)). 98% people

Wiskott-Aldrich syndrome protein deficiency in B cells results in impaired peripheral homeostasis

PubMed Central

Meyer-Bahlburg, Almut; Becker-Herman, Shirly; Humblet-Baron, Stephanie; Khim, Socheath; Weber, Michele; Bouma, Gerben; Thrasher, Adrian J.; Batista, Facundo D.

2008-01-01

To more precisely identify the B-cell phenotype in Wiskott-Aldrich syndrome (WAS), we used 3 distinct murine in vivo models to define the cell intrinsic requirements for WAS protein (WASp) in central versus peripheral B-cell development. Whereas WASp is dispensable for early bone marrow B-cell development, WASp deficiency results in a marked reduction in each of the major mature peripheral B-cell subsets, exerting the greatest impact on marginal zone and B1a B cells. Using in vivo bromodeoxyuridine labeling and in vitro functional assays, we show that these deficits reflect altered peripheral homeostasis, partially resulting from an impairment in integrin function, rather than a developmental defect. Consistent with these observations, we also show that: (1) WASp expression levels increase with cell maturity, peaking in those subsets exhibiting the greatest sensitivity to WASp deficiency; (2) WASp+ murine B cells exhibit a marked selective advantage beginning at the late transitional B-cell stage; and (3) a similar in vivo selective advantage is manifest by mature WASp+ human B cells. Together, our data provide a better understanding of the clinical phenotype of WAS and suggest that gene therapy might be a useful approach to rescue altered B-cell homeostasis in this disease. PMID:18687984

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

Delayed Language Development Due to Infantile Thiamine Deficiency

ERIC Educational Resources Information Center

Fattal-Valevski, Aviva; Azouri-Fattal, Iris; Greenstein, Yoram J.; Guindy, Michal; Blau, Ayala; Zelnik, Nathanel

2009-01-01

The aim of this study was to investigate the language development of 20 children who had been exposed to thiamine (vitamin B[subscript 1]) deficiency in infancy due to feeding with soy-based formula that was accidentally deficient of thiamine. In this case-control study, 20 children (12 males, eight females; mean age 31.8 mo [SD 4.1], range 24-39…

Epidemiological survey of vitamin deficiencies in older Thai adults: implications for national policy planning.

PubMed

Assantachai, Prasert; Lekhakula, Somsong

2007-01-01

To examine the prevalence and risk factors of vitamin deficiencies among older Thai adults. The cross-sectional study was conducted in four rural communities, one from each of the four main regions of Thailand. In total, 2336 subjects aged 60 years and over were recruited. Anthropometric variables, demographic data, blood glucose and lipid profile, albumin, globulin and blood levels of vitamin A, beta-carotene, folic acid, vitamin B12, vitamin C, vitamin E and vitamin B1 were all measured. The prevalence of vitamin deficiencies was 0.6% for vitamin B12, 6.1% for vitamin A, 9.9% for vitamin C, 30.1% for vitamin B1, 38.8% for erythrocyte folate, 55.5% for vitamin E and 83.0% for beta-carotene. Male gender was a common risk factor for at least three vitamin deficiencies, i.e. beta-carotene, folate and vitamin E. Being a manual worker was a common risk factor of beta-carotene and vitamin B1 deficiency. Poor income was found as a risk factor only in erythrocyte folate deficiency while increasing age was a significant factor only in vitamin C deficiency. The prevalence of vitamin deficiencies among older Thai people was quite different from that found in Western countries, reflecting different socio-economic backgrounds. Vitamin deficiency was not only from poor food intake but also from the dietary habit of monotonous food consumption in older people. Some common associated factors of atherosclerosis were also significantly related to folate and vitamin E deficiencies.

Li2 B12 and Li3 B12 : Prediction of the Smallest Tubular and Cage-like Boron Structures.

PubMed

Dong, Xue; Jalife, Said; Vásquez-Espinal, Alejandro; Ravell, Estefanía; Pan, Sudip; Cabellos, José Luis; Liang, Wei-Yan; Cui, Zhong-Hua; Merino, Gabriel

2018-04-16

An intriguing structural transition from the quasi-planar form of B 12 cluster upon the interaction with lithium atoms is reported. High-level computations show that the lowest energy structures of LiB 12 , Li 2 B 12 , and Li 3 B 12 have quasi-planar (C s ), tubular (D 6d ), and cage-like (C s ) geometries, respectively. The energetic cost of distorting the B 12 quasi-planar fragment is overcompensated by an enhanced electrostatic interaction between the Li cations and the tubular or cage-like B 12 fragments, which is the main reason of such drastic structural changes, resulting in the smallest tubular (Li 2 B 12 ) and cage-like (Li 3 B 12 ) boron structures reported to date. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

B61 Mod 12 Life Extension Program Tailkit Assembly (B61 Mod 12 LEP TKA)

DTIC Science & Technology

2015-12-01

Selected Acquisition Report ( SAR ) RCS: DD-A&T(Q&A)823-468 B61 Mod 12 Life Extension Program Tailkit Assembly (B61 Mod 12 LEP TKA) As of FY 2017... SAR March 23, 2016 10:38:20 UNCLASSIFIED 2 Table of Contents Common Acronyms and Abbreviations for MDAP Programs 3 Program Information...Unit Cost B61 Mod 12 LEP TKA December 2015 SAR March 23, 2016 10:38:20 UNCLASSIFIED 3 PB - President’s Budget PE - Program Element PEO - Program

Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

PubMed

Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

2015-08-01

Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

18 CFR 1b.12 - Transcripts.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any, of...

18 CFR 1b.12 - Transcripts.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any, of...

18 CFR 1b.12 - Transcripts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any, of...

18 CFR 1b.12 - Transcripts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Transcripts. 1b.12 Section 1b.12 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.12 Transcripts. Transcripts, if any, of...

The coexistence of other micronutrient deficiencies in anaemic adolescent schoolgirls in rural Bangladesh.

PubMed

Ahmed, F; Khan, M R; Banu, C P; Qazi, M R; Akhtaruzzaman, M

2008-03-01

To investigate the prevalence of selected micronutrient deficiencies amongst anaemic adolescent schoolgirls in rural Bangladesh and to examine their relationship with haemoglobin (Hb) levels. A cross-sectional study. Girls' high schools in rural areas of Dhaka District in Bangladesh. Three hundred and ten anaemic adolescent girls aged 14-18 years from eight schools participated in the study. Information on personal characteristics and food habits were collected by interview. Parents were asked about their socio-economic conditions. Anthropometric data and blood samples were collected following the interview. Twenty-eight per cent of the girls had depleted iron stores (serum ferritin <12.0 microg/l), 25% had folic acid deficiency (red blood cell folic acid <317 nmol/l), 89% had vitamin B(2) (erythrocyte glutathione reductase activity coefficient > or =1.4) and 7% had vitamin B(12) deficiencies (serum vitamin B(12) <150 pmol/l). Although the prevalence of vitamins A and C deficiency was very low, a significant proportion had low vitamin A (serum retinol between 0.70 and <1.05 micromol/l) and vitamin C status (plasma ascorbic acid between 11.4-23.0 micromol/l). Frequency of consumption of meat, serum ferritin and vitamin B(2) status were found to be strongly related to Hb by multiple regression analysis. For 1 microg/l change in serum ferritin, there was a 0.13 g/l change in Hb when adjusted for other factors. There is coexistence of micronutrient deficiencies among anaemic adolescent girls in rural Bangladesh, although they do not suffer from energy deficiency. Of all micronutrients, only iron and vitamin B(2) concentrations were found to be related to the Hb concentration.

45 CFR 5b.12 - Contractors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Contractors. 5b.12 Section 5b.12 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.12 Contractors. (a) All contracts entered into on or after September 27, 1975 which require a contractor to maintain...

34 CFR 5b.12 - Contractors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Contractors. 5b.12 Section 5b.12 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.12 Contractors. (a) All contracts entered into on or after September 27, 1975 which require a contractor to maintain or on behalf of the...

Informing disinvestment with limited evidence: cobalamin deficiency in the fatigued.

PubMed

Mnatzaganian, George; Karnon, Jonathan; Moss, John R; Elshaug, Adam G; Metz, Michael; Frank, Oliver R; Hiller, Janet E

2015-01-01

Health technology reassessment and disinvestment can be difficult due to uncertainties regarding available evidence. Pathology testing to investigate cobalamin (vitamin B12) deficiency is a strong case in point. We conducted a 3-month economic evaluation of five strategies for diagnosing and treating cobalamin deficiency in adult patients hypothetically presenting with new unexplained fatigue in the primary care setting. The first consultation per patient was considered. Screening tests other than serum cobalamin were not included. A cost-effectiveness analysis was undertaken using a decision tree to represent the diagnostic / treatment pathways, with relevant cost and utility scores assigned to different stages in the evaluation process. Input parameter values were estimated from published evidence, supplemented by expert opinion, with sensitivity analysis undertaken to represent parameter uncertainty. Ordering serum vitamin B12 to assess cobalamin deficiency among patients with unexplained fatigue was not cost-effective in any patient population, irrespective of pretest prevalence of this deficiency. For patients with a pretest prevalence above 1 percent, treating all with oral vitamin B12 supplements without testing was most cost-effective, whereas watchful waiting with symptoms monitoring was most cost-effective for patients with lower pretest prevalence probabilities. Substantial evidence gaps exist for parameter estimation: questionable cobalamin deficiency levels in the fatigued; debatable treatment methods; unknown natural history of the condition. Despite this, we reveal a robust path for disinvestment decision making in the face of a paradox between the evidence required to inform disinvestment compared with its paucity in informing initial funding decisions.

Vitamin B-12 status and neurologic function in older people: a cross-sectional analysis of baseline trial data from the Older People and Enhanced Neurological Function (OPEN) study.

PubMed

Miles, Lisa M; Allen, Elizabeth; Mills, Kerry; Clarke, Robert; Uauy, Ricardo; Dangour, Alan D

2016-09-01

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status. We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer. In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function. This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be

12 CFR 204.6 - Charges for reserve deficiencies.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... (a) Deficiencies in a depository institution's required reserve balance, after application of the... authorized to assess charges for deficiencies in required reserves at a rate of 1 percentage point per year... involved, permit a depository institution to eliminate deficiencies in its required reserve balance by...

Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis.

PubMed

Chang, Julia Yu-Fong; Wang, Yi-Ping; Wu, Yang-Che; Wu, Yu-Hsueh; Tseng, Chih-Huang; Sun, Andy

2016-10-01

Erosive oral lichen planus (EOLP) patients with desquamative gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic. This study assessed hematinic deficiencies and anemia statuses in antigastric parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA + /DG + /EOLP patients). The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and serum GPCA levels in 92 GPCA + /DG + /EOLP patients and 184 age- and sex-matched healthy controls were measured and compared between the two groups. We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of 92 GPCA + /DG + /EOLP patients had hemoglobin (men < 13 g/dL and women < 12 g/dL), iron (< 60 μg/dL), and vitamin B12 (< 200 pg/mL) deficiencies, respectively. Moreover, 37 (40.2%) of 92 GPCA + /DG + /EOLP patients had an abnormally high blood homocysteine level (> 12.1μM). GPCA + /DG + /EOLP patients had a significantly higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally high blood homocysteine level than healthy control individuals (all p < 0.001). Of 27 anemic GPCA + /DG + /EOLP patients, 13 (48.2%) had pernicious anemia, five (18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA + /DG + /EOLP patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had pernicious anemia. We conclude that GPCA + /DG + /EOLP patients may have vitamin B12 deficiency, iron deficiency, and an abnormally high blood homocysteine level. In addition to pernicious anemia, GPCA + /DG + /EOLP patients may sometimes have normocytic anemia or iron deficiency anemia. Copyright © 2016. Published by Elsevier B.V.

Vitamin B12 and folate during pregnancy and offspring motor, mental and social development at 2 years of age.

PubMed

Bhate, V K; Joshi, S M; Ladkat, R S; Deshmukh, U S; Lubree, H G; Katre, P A; Bhat, D S; Rush, E C; Yajnik, C S

2012-04-01

Insufficiency of vitamin B12 (B12) and folate during pregnancy can result in low concentrations in the fetus and have adverse effects on brain development. We investigated the relationship between maternal B12 and folate nutrition during pregnancy and offspring motor, mental and social development at two years of age (2 y). Mothers (n = 123) and their offspring (62 girls, 61 boys) from rural and middle-class urban communities in and around Pune city were followed through pregnancy up to 2 y. Maternal B12 and folate concentrations were measured at 28 and 34 weeks of gestation. At 2 y, the Developmental Assessment Scale for Indian Infants was used to determine motor and mental developmental quotients and the Vineland Social Maturity Scale for the social developmental quotient. Overall, 62% of the mothers had low B12 levels (<150 pmol/l) and one mother was folate deficient during pregnancy. Maternal B12 at 28 and 34 weeks of gestation was associated with offspring B12 at 2 y (r = 0.29, r = 0.32, P < 0.001), but folate was not associated with offspring folate. At 2 y, motor development was associated with maternal folate at 28 and 34 weeks of gestation. Mental and social development quotients were associated positively with head circumference and negatively with birth weight. In addition, pregnancy B12 and folate were positively associated with mental and social development quotients. Maternal B12 and folate during intrauterine life may favorably influence brain development and function. Pregnancy provides a window of opportunity to enhance fetal psychomotor (motor and mental) development.

Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity.

PubMed

Mori, Marcelo A; Araújo, Ronaldo C; Reis, Felipe C G; Sgai, Daniela G; Fonseca, Raphael G; Barros, Carlos C; Merino, Vanessa F; Passadore, Mariana; Barbosa, Ana M; Ferrari, Bernard; Carayon, Pierre; Castro, Charlles H M; Shimuta, Suma I; Luz, Jacqueline; Bascands, Jean-Loup; Schanstra, Joost P; Even, Patrick C; Oliveira, Suzana M; Bader, Michael; Pesquero, João B

2008-06-01

Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown. Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity. Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet. Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.

Plasma zinc, vitamin B(12) and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh.

PubMed

Shamim, Abu Ahmed; Kabir, Alamgir; Merrill, Rebecca D; Ali, Hasmot; Rashid, Mahbubur; Schulze, Kerry; Labrique, Alain; West, Keith P; Christian, Parul

2013-08-01

The objective of the current analysis was to explore the association of multiple micronutrients with Hb concentration among pregnant women in a South Asian setting, a topic that has not been adequately explored. Sociodemographic, anthropometric and micronutrient status (plasma ferritin, transferrin receptor, retinol, a- and g-tocopherol, folate, vitamin B12, Zn) and Hb concentration were assessed at early pregnancy. The biochemical sub-study was nested within a double-blind, placebo-controlled, community-based vitamin A and b-carotene supplementation trial in rural north-western Bangladesh (JiVitA). All assessments were conducted before trial supplementation was initiated. A systematic sample of 285 women was selected from those enrolled in the biochemical sub-study. Seventeen per cent of women were mildly anaemic; moderate and severe anaemia was uncommon (2.1 %). a-Tocopherol, vitamin B12 and Zn deficiencies were common (43.5%, 19.7% and 14.7%, respectively); however, vitamin A, folate and Fe deficiencies were comparatively rare (7.4%, 2.8% and ,1%,respectively). Plasma Zn, vitamin B12 and a-tocopherol were positively associated and plasma g-tocopherol was negatively associated with Hb (P < 0.05) after adjustment for gestational age, inflammation status, season and nutritional status measured by mid-upper arm circumference. Among pregnant women in rural Bangladesh with minimal Fe deficiency, plasma Zn, vitamin B12, and a- and g-tocopherol concentrations were associated with Hb concentration. Appreciating the influence on Hb of micronutrients in addition to those with known associations with anaemia, such as Fe, folate, and vitamin A, is important when addressing anaemia in similar settings.

Metabolomic Analysis Reveals Extended Metabolic Consequences of Marginal Vitamin B-6 Deficiency in Healthy Human Subjects

PubMed Central

Lamers, Yvonne; Bandyopadhyay, Nirmalya; Chi, Yueh-Yun; Lee, Kichen; Kim, Steven; da Silva, Vanessa; Hove, Nikolas; Ranka, Sanjay; Kahveci, Tamer; Muller, Keith E.; Stevens, Robert D.; Newgard, Christopher B.; Stacpoole, Peter W.; Jones, Dean P.

2013-01-01

Marginal deficiency of vitamin B-6 is common among segments of the population worldwide. Because pyridoxal 5′-phosphate (PLP) serves as a coenzyme in the metabolism of amino acids, carbohydrates, organic acids, and neurotransmitters, as well as in aspects of one-carbon metabolism, vitamin B-6 deficiency could have many effects. Healthy men and women (age: 20-40 y; n = 23) were fed a 2-day controlled, nutritionally adequate diet followed by a 28-day low-vitamin B-6 diet (<0.5 mg/d) to induce marginal deficiency, as reflected by a decline of plasma PLP from 52.6±14.1 (mean ± SD) to 21.5±4.6 nmol/L (P<0.0001) and increased cystathionine from 131±65 to 199±56 nmol/L (P<0.001). Fasting plasma samples obtained before and after vitamin B6 restriction were analyzed by 1H-NMR with and without filtration and by targeted quantitative analysis by mass spectrometry (MS). Multilevel partial least squares-discriminant analysis and S-plots of NMR spectra showed that NMR is effective in classifying samples according to vitamin B-6 status and identified discriminating features. NMR spectral features of selected metabolites indicated that vitamin B-6 restriction significantly increased the ratios of glutamine/glutamate and 2-oxoglutarate/glutamate (P<0.001) and tended to increase concentrations of acetate, pyruvate, and trimethylamine-N-oxide (adjusted P<0.05). Tandem MS showed significantly greater plasma proline after vitamin B-6 restriction (adjusted P<0.05), but there were no effects on the profile of 14 other amino acids and 45 acylcarnitines. These findings demonstrate that marginal vitamin B-6 deficiency has widespread metabolic perturbations and illustrate the utility of metabolomics in evaluating complex effects of altered vitamin B-6 intake. PMID:23776431

Geological investigations in the U12b.03 and U12b.04 tunnels, Nevada Test Site

USGS Publications Warehouse

Diment, W.H.; Wilmarth, V. R.; McKeown, F.A.; Dickey, D.D.; Hinrichs, E.N.; Botinelly, T.; Roach, C.H.; Byers, F.M.; Hawley, C.C.; Izett, G.A.; Clebsch, Alfred

1959-01-01

The U12b.03 and .04 tunnels are part of the U12b (Rainier) tunnel complex that was driven northwestward from the steep east slope of Rainier Mesa (a prominent topographic feature in the northwest part of the Test Site (fig . 2)). The U12b.03 tunnel trends north from a point about 980 feet from the portal of the U12b tunnel (fig. 3). The U12b.03 tunnel consists of 620 feet of tunnel, two alcoves, and a shot chamber. The tunnel is irregular, ranging from 6 to 10 feet in width, and 6 to 9 feet in height. The shot chamber at the north end of the tunnel is 22 feet on each sidee The vertical and minimum cover over the shot chamber are 610 and 510 feet, respectively.

Identification of boron-deficiency-responsive microRNAs in Citrus sinensis roots by Illumina sequencing

PubMed Central

2014-01-01

Background Boron (B)-deficiency is a widespread problem in many crops, including Citrus. MicroRNAs (miRNAs) play important roles in nutrient deficiencies. However, little is known on B-deficiency-responsive miRNAs in plants. In this study, we first identified miRNAs and their expression pattern in B-deficient Citrus sinensis roots by Illumina sequencing in order to identify miRNAs that might be involved in the tolerance of plants to B-deficiency. Results We isolated 52 (40 known and 12 novel) up-regulated and 82 (72 known and 10 novel) down-regulated miRNAs from B-deficient roots, demonstrating remarkable metabolic flexibility of roots, which might contribute to the tolerance of plants to B-deficiency. A model for the possible roles of miRNAs in the tolerance of roots to B-deficiency was proposed. miRNAs might regulate the adaptations of roots to B-deficiency through following several aspects: (a) inactivating reactive oxygen species (ROS) signaling and scavenging through up-regulating miR474 and down-regulating miR782 and miR843; (b) increasing lateral root number by lowering miR5023 expression and maintaining a certain phenotype favorable for B-deficiency-tolerance by increasing miR394 expression; (c) enhancing cell transport by decreasing the transcripts of miR830, miR5266 and miR3465; (d) improving osmoprotection (miR474) and regulating other metabolic reactions (miR5023 and miR821). Other miRNAs such as miR472 and miR2118 in roots increased in response to B-deficiency, thus decreasing the expression of their target genes, which are involved in disease resistance, and hence, the disease resistance of roots. Conclusions Our work demonstrates the possible roles of miRNAs and related mechanisms in the response of plant roots to B-deficiency. PMID:24885979

Vitamin B6 deficient plants display increased sensitivity to high light and photo-oxidative stress

PubMed Central

Havaux, Michel; Ksas, Brigitte; Szewczyk, Agnieszka; Rumeau, Dominique; Franck, Fabrice; Caffarri, Stefano; Triantaphylidès, Christian

2009-01-01

Background Vitamin B6 is a collective term for a group of six interconvertible compounds: pyridoxine, pyridoxal, pyridoxamine and their phosphorylated derivatives. Vitamin B6 plays essential roles as a cofactor in a range of biochemical reactions. In addition, vitamin B6 is able to quench reactive oxygen species in vitro, and exogenously applied vitamin B6 protects plant cells against cell death induced by singlet oxygen (1O2). These results raise the important question as to whether plants employ vitamin B6 as an antioxidant to protect themselves against reactive oxygen species. Results The pdx1.3 mutation affects the vitamin B6 biosynthesis enzyme, pyridoxal synthase (PDX1), and leads to a reduction of the vitamin B6 concentration in Arabidopsis thaliana leaves. Although leaves of the pdx1.3 Arabidopsis mutant contained less chlorophyll than wild-type leaves, we found that vitamin B6 deficiency did not significantly impact photosynthetic performance or shoot and root growth. Chlorophyll loss was associated with an increase in the chlorophyll a/b ratio and a selective decrease in the abundance of several PSII antenna proteins (Lhcb1/2, Lhcb6). These changes were strongly dependent on light intensity, with high light amplifying the difference between pdx1.3 and the wild type. When leaf discs were exposed to exogenous 1O2, lipid peroxidation in pdx1.3 was increased relative to the wild type; this effect was not observed with superoxide or hydrogen peroxide. When leaf discs or whole plants were exposed to excess light energy, 1O2-mediated lipid peroxidation was enhanced in leaves of the pdx1.3 mutant relative to the wild type. High light also caused an increased level of 1O2 in vitamin B6-deficient leaves. Combining the pdx1.3 mutation with mutations affecting the level of 'classical' quenchers of 1O2 (zeaxanthin, tocopherols) resulted in a highly photosensitive phenotype. Conclusion This study demonstrates that vitamin B6 has a function in the in vivo antioxidant

The effects of vitamin B12 supplementation in pregnancy and postpartum on growth and neurodevelopment in early childhood: Study Protocol for a Randomized Placebo Controlled Trial.

PubMed

Chandyo, Ram K; Ulak, Manjeswori; Kvestad, Ingrid; Shrestha, Merina; Ranjitkar, Suman; Basnet, Sudha; Hysing, Mari; Shrestha, Laxman; Strand, Tor A

2017-08-29

Vitamin B 12 is crucial for normal cell division and differentiation, and necessary for the development and myelination of the central nervous system. Pregnant mothers in resource poor settings are at risk for poor vitamin B 12 status. Poor vitamin B 12 status in infancy is linked to poor growth and neurodevelopment. Brain development starts from conception, and pregnancy is a period of rapid growth and development for the brain. The study is an individually randomised double-blind placebo controlled trial in 800 pregnant Nepalese women randomised in a 1:1 ratio. A daily dose of 50 µg of vitamin B 12 or placebo is given to women from early pregnancy, not later than week 15, until 6 months after birth. Weekly visits are conducted in order to record compliance, growth and morbidity. The primary outcomes are scores on the cognitive, language and motor subscales of the Bayley Scales of Infant and Toddler Development, Third Edition, measured at 6 and 12 months of age, and growth (length and weight) measured at 6 and 12 months of age. National Health and Research Council, Nepal (NHRC 253/2016) and Regional Committee for Medical and Health Research Ethics of Western Norway (2016/1620/REK vest) have approved the study. Investigators who have contributed to the conceptualising, conducting, as well as being involved in the data analyses and manuscript writing will be eligible for authorship and be responsible to share outcomes with different stakeholders through publications and workshops. The results from this study may support new dietary guidelines for Nepalese and possibly South Asian pregnant women that can lead to improved pregnancy outcomes, neurodevelopment and cognitive functioning in children. Universal Trial Number: U1111-1183-4093. clinicaltrials.gov: NCT03071666. Protocol date: version 1.2, 1 June 2017. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted

21 CFR 184.1945 - Vitamin B12.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin B12. 184.1945 Section 184.1945 Food and... Substances Affirmed as GRAS § 184.1945 Vitamin B12. (a) Vitamin B12, also known as cyanocobalamin (C63H88Co... is used in food at levels not to exceed current good manufacturing practice. Vitamin B12 also may be...

Clinical features of Candidiasis in patients with inherited interleukin 12 receptor β1 deficiency.

PubMed

Ouederni, Monia; Sanal, Ozden; Ikinciogullari, Aydan; Tezcan, Ilhan; Dogu, Figen; Sologuren, Ithaisa; Pedraza-Sánchez, Sigifredo; Keser, Melike; Tanir, Gonul; Nieuwhof, Chris; Colino, Elena; Kumararatne, Dinakantha; Levy, Jacov; Kutukculer, Necil; Aytekin, Caner; Herrera-Ramos, Estefanía; Bhatti, Micah; Karaca, Neslihan; Barbouche, Ridha; Broides, Arnon; Goudouris, Ekaterini; Franco, José Luis; Parvaneh, Nima; Reisli, Ismail; Strickler, Alexis; Shcherbina, Anna; Somer, Ayper; Segal, Anthony; Angel-Moreno, Alfonso; Lezana-Fernandez, José Luis; Bejaoui, Mohamed; Bobadilla-Del Valle, Miriam; Kachboura, Salem; Sentongo, Timothy; Ben-Mustapha, Imen; Bustamante, Jacinta; Picard, Capucine; Puel, Anne; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent; Rodríguez-Gallego, Carlos

2014-01-01

Interleukin 12Rβ1 (IL-12Rβ1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

Clinical Features of Candidiasis in Patients With Inherited Interleukin 12 Receptor β1 Deficiency

PubMed Central

Ouederni, Monia; Sanal, Ozden; Ikincioğullari, Aydan; Tezcan, Ilhan; Dogu, Figen; Sologuren, Ithaisa; Pedraza-Sánchez, Sigifredo; Keser, Melike; Tanir, Gonul; Nieuwhof, Chris; Colino, Elena; Kumararatne, Dinakantha; Levy, Jacov; Kutukculer, Necil; Aytekin, Caner; Herrera-Ramos, Estefanía; Bhatti, Micah; Karaca, Neslihan; Barbouche, Ridha; Broides, Arnon; Goudouris, Ekaterini; Franco, José Luis; Parvaneh, Nima; Reisli, Ismail; Strickler, Alexis; Shcherbina, Anna; Somer, Ayper; Segal, Anthony; Angel-Moreno, Alfonso; Lezana-Fernandez, José Luis; Bejaoui, Mohamed; Bobadilla-Del Valle, Miriam; Kachboura, Salem; Sentongo, Timothy; Ben-Mustapha, Imen; Bustamante, Jacinta; Picard, Capucine; Puel, Anne; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent; Rodríguez-Gallego, Carlos

2014-01-01

Background. Interleukin 12Rβ1 (IL-12Rβ1)–deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12–dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23–dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency. Results. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. Conclusions. Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients. PMID:24186907

Degradation of vitamin B12 in dietary supplements.

PubMed

Yamada, Keiko; Shimodaira, Michiko; Chida, Seiko; Yamada, Noriko; Matsushima, Norio; Fukuda, Morimichi; Yamada, Shoji

2008-01-01

Beverages and solid dietary supplements rich in various added vitamins and minerals have recently become available. It seems reasonable to consider that the intake of these foods is convenient for easy ingestion of nutrients, but problems caused by blending different nutrients in high concentrations have arisen. We focused on vitamin B12 (B12) among vitamins and determined the B12 contents of beverages and solid dietary supplements purchased from a retail shop. The B12 contents of three of five beverages were less than stated on the labels. On the other hand, certain beverages unexpectedly contained much more B12 than stated on the labels. In these beverages the amount of B12 decreased rapidly with time, whereas B12 content was lower than stated on the label in only one of four solid dietary supplements. The content of B12 was affected by storage time, light exposure, temperature and vitamin C. From experimental analysis with a competitive binding assay method employing a ACS Chemiluminescent B12 kit, examining differential binding by intrinsic factors and spectral analysis of B12, it was determined that some of the B12 might have been converted into B12 analogues or small degradation products by multinutrient interaction during storage.