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Sample records for periconceptional folic acid

  1. Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus–associated birth defects

    PubMed Central

    Correa, Adolfo; Gilboa, Suzanne M.; Botto, Lorenzo D.; Moore, Cynthia A.; Hobbs, Charlotte A.; Cleves, Mario A.; Riehle-Colarusso, Tiffany J.; Waller, D. Kim; Reece, E. Albert

    2016-01-01

    OBJECTIVE The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. STUDY DESIGN The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. RESULTS The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. CONCLUSION The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus. PMID:22284962

  2. Periconceptional folic acid supplementation and the risk of preterm births in China: a large prospective cohort study

    PubMed Central

    Li, Zhiwen; Ye, Rongwei; Zhang, Le; Li, Hongtian; Liu, Jianmeng; Ren, Aiguo

    2014-01-01

    Background: Folic acid-containing multivitamins have been associated with a reduced risk of preterm birth. We examined whether periconceptional use of folic acid alone reduced this risk. Methods: Data were derived from a large population-based cohort study conducted in China to evaluate the prevention of neural tube defects with folic acid supplementation. The sample comprised 207 936 singleton live births delivered at gestational ages of 20–42 weeks to women from two provinces in southern China. Healthcare workers recorded folic acid intake prospectively each month. Gestational age calculation was based on the first day of the last menstrual period. Preterm births were categorized into three clinical subtypes: iatrogenic preterm birth, preterm premature rupture of membranes (PPROM) and spontaneous preterm birth. Logistic regression was used to evaluate the association between folic acid use and the risk of preterm birth, adjusting for potential confounders. Results: The incidence of preterm birth was significantly lower among folic acid users (5.28%) than among non-users (6.10%). Folic acid use showed a 14% risk reduction for preterm birth overall [adjusted risk ratio (RR) = 0.86, 95% confidence interval (CI) 0.82–0.90]. This association was strongest for spontaneous preterm birth (adjusted RR = 0.81, 95% CI 0.78–0.86) and was not significant for iatrogenic preterm birth (adjusted RR = 0.97, 95% CI 0.88–1.07) or PPROM (adjusted RR = 1.07, 95% CI 0.93–1.23). Conclusions: Daily intake of 400 μg folic acid alone during the periconceptional period was associated with a reduced risk of spontaneous preterm birth. PMID:24603317

  3. A Mixed-Method Study to Determine the Benefits of Periconceptional Folic Acid Supplementation and Effects of Folic Acid Deficiency in Mothers on Birth Outcomes

    PubMed Central

    Murthy, Gudlavalleti Venkata S; Kolli, Sunanda Reddy; Neogi, Sutapa B; Singh, Samiksha; John, Neena; N., Srinivas; Ramani, Sudha; Shamanna, BR; Doyle, Pat; Kinra, Sanjay; Ness, Andy; Pallepogula, Dinesh Raj; Pant, Hira B; Babbar, Smiksha; Reddy, Raghunath; Singh, Rachna

    2016-01-01

    Background Evidence from high income countries shows mothers who are supplemented with folic acid in their periconceptional period and early pregnancy have significantly reduced adverse outcomes like birth defects. However, in India there is a paucity of data on association of birth defects and folic acid supplementation. We identified a few important questions to be answered using separate scientific methods and then planned to triangulate the information. Objective In this paper, we describe the protocol of our study that aims to determine the association of folic acid and pregnancy outcomes like neural tube defects (NTDs) and orofacial clefts (OFCs). We decided to fill the gaps in knowledge from India to determine public health consequences of folic acid deficiency and factors influencing dietary and periconceptional consumption of folic acid. Methods The proposed study will be carried out in five stages and will examine the questions related to folic acid deficiency across selected locations in South and North India. The study will be carried out over a period of 4 years through the hierarchical evidence-based approach. At first a systematic review was conducted to pool the current birth prevalence of NTDs and orofacial clefts OFCs in India. To investigate the population prevalence, we plan to use the key informant method to determine prevalence of NTDs and OFCs. To determine the normal serum estimates of folic acid, iron, and vitamin B12 among Indian women (15-35 years), we will conduct a population-based, cross-sectional study. We will further strengthen the evidence of association between OFCs and folic acid by conducting a hospital-based, case-control study across three locations of India. Lastly, using qualitative methods we will understand community and health workers perspective on factors that decide the intake of folic acid supplements. Results This study will provide evidence on the community prevalence of birth defects and prevalence folic acid and

  4. Periconceptional folic acid fortification for the risk of gestational hypertension and pre-eclampsia: a meta-analysis of prospective studies.

    PubMed

    Yang, Xiaorong; Chen, Hui; Du, Yihui; Wang, Shuting; Wang, Zhiping

    2016-10-01

    Published literatures report controversial results about the association of folic acid-containing multivitamins with gestational hypertension and pre-eclampsia. A comprehensive search was performed to identify related prospective studies to assess the effect of folic acid fortification on gestational hypertension and pre-eclampsia. The Q test and I(2) statistic were used to examine between-study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Eleven studies conformed to the criteria. Pooled results indicated that folic acid fortification alone was not associated with the occurrence of gestational hypertension [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.98-1.09, P = 0.267] and pre-eclampsia (RR = 0.99, 95% CI: 0.90-1.08, P = 0.738). However, supplementation of multivitamins containing folic acid could prevent gestational hypertension (RR = 0.57, 95% CI: 0.43-0.76, P < 0.001) and pre-eclampsia (RR = 0.64, 95% CI: 0.48-0.84, P = 0.001). The difference between folic acid fortification alone and multivitamins containing folic acid was significant. This meta-analysis suggests that periconceptional multivitamin supplementation with appropriate dose, not folic acid alone, is an appropriate recommendation for pregnant women. The effect should be further confirmed by conducting large-scale randomised controlled trials.

  5. Folic Acid

    MedlinePlus

    Folic acid is a B vitamin. It helps the body make healthy new cells. Everyone needs folic acid. For women who may get pregnant, it is really important. Getting enough folic acid before and during pregnancy can prevent major birth ...

  6. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  7. Effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intrauterine and early life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use and periconceptional folic acid supplementation. The effect of maternal and postweaning folic acid supplementation on colorectal cancer risk ...

  8. [Women's knowledge of folic acid].

    PubMed

    Salgues, Mathilde; Damase-Michel, Christine; Montastruc, Jean-Louis; Lacroix, Isabelle

    2016-10-27

    Many trials have shown that folic acid supplementation before and during pregnancy reduces the risk of neural tube defects in general population. We investigated the knowledge of folic acid in women of child-bearing age. Women of child-bearing age were interviewed by 20 pharmacists living in Haute-Garonne between January and February 2014. One hundred ninety-six women were included in the present study. Out of them, 36% of women never heard of folic acid and 82% were not aware of its benefits. Knowledge was higher in older women, women in a couple and women with higher educational level (P<10(-2)). This study underlines that women are not enough aware of benefits of folic acid during pregnancy. Moreover, previous studies have shown that French women have low use of folic acid during peri-conceptional period. Information of general population will be required for a better prevention of folic acid-preventable NTDs.

  9. Peri-conceptional supplementation of folic acid-knowledge and practices of pregnant women and health providers

    PubMed Central

    Saxena, Vartika; Naithani, Manisha; Kumari, Ranjeeta; Singh, Richa; Das, Pranoti

    2016-01-01

    Context: Neural tube defects (NTDs) are one of the most common congenital anomalies. NTDs are preventable if folic acid (FA) is supplemented before and during conception. Knowledge and supplementation of FA by pregnant women as well as it's timely provision by health providers is crucial in reducing the burden of NTDs in the community. Aim: To study the knowledge and supplementation of FA by pregnant women and it's prescription/provision by health providers. Settings and Design: A cross-sectional study was conducted in the block Doiwala, District Dehradun, Uttarakhand. Subjects and Methods: A total of 400 pregnant women and 121 government health providers (5 medical officers, 25 auxiliary nurse midwives [ANMs], and 91 accredited social health activists [ASHAs]) were interviewed on predesigned, pretested questionnaire by study/field investigator. Statistical Analysis Used: Proportion of different variables calculated and Chi-square test with Yates correction was applied. Results: Of 400, 73.50% of women had heard of FA. Overall, knowledge scores suggested intermediate to low level of knowledge about FA. Totally 94.25% of women had planned pregnancies; however, only 4.75% of women reported FA supplementation before conception. This indicates that if these women would have been properly counseled and prescribed FA, they might have taken it. About 60% of medical officers, 4% of ANMs, and 3.3% of ASHAs knew FA deficiency as one of the causes of NTD. None of the health providers reported to be prescribing/counseling FA to pregnant women. FA was out of supply on the block at the time of the study. Conclusions: Knowledge and supplementation practices related with FA are poor. PMID:27843847

  10. Folic Acid

    MedlinePlus

    ... folic acid can hide signs that you lack vitamin B12, which can cause nerve damage. 10 Do I ... Rosenberg, I.H., et al. (2007). Folate and vitamin B12 status in relation to anemia, macrocytosis and cognitive ...

  11. Folic Acid and Pregnancy

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Folic Acid and Pregnancy KidsHealth > For Parents > Folic Acid and ... before conception and during early pregnancy . About Folic Acid Folic acid, sometimes called folate, is a B ...

  12. Facts about Folic Acid

    MedlinePlus

    ... Information For... Media Policy Makers Facts About Folic Acid Language: English Español (Spanish) Recommend on Facebook Tweet ... of the baby's brain and spine. About folic acid Folic acid is a B vitamin. Our bodies ...

  13. Periconceptional folic acid supplementation and vitamin B12 status in a cohort of Chinese early pregnancy women with the risk of adverse pregnancy outcomes

    PubMed Central

    Yang, Ting; Gu, Yan; Wei, Xiaoping; Liang, Xiaohua; Chen, Jie; Liu, Youxue; Zhang, Ting; Li, Tingyu

    2017-01-01

    Maternal folate and vitamin B12 deficiency predict poor pregnancy outcome. To improve pregnancy outcomes in rural area of China, we investigate rural women’s folic acid supplementation (FAS) status and the associations between maternal vitamin B status during the first trimester and subsequent adverse pregnancy outcomes. We collected the questionnaire information and drew 5 ml of blood from 309 early pregnant rural women. The birth outcomes were retrieved from medical records after delivery. Out of the total, 257 had taken FAS, including 50 before conception (group A) and 207 during the first trimester (group B). The concentration of plasma folate and the RBC folate supplementation groups were obviously higher than that of no-supplementation group (group N, p<0.01). The mean vitamin B12 levels in FAS group were significantly higher than those in groups N and B (p<0.05). Women who delivered SGA or premature infants had reduced plasma folate levels (p<0.05) compared with controls. The multiple linear regression models revealed that RBC folate levels affected the infant birth weight (p<0.01) and birth length (p<0.05). In conclusion, FAS can significantly improve plasma folate and RBC folate levels in childbearing-age women and reduce the risk of subsequent adverse pregnancy outcomes. PMID:28366994

  14. Folic Acid Quiz

    MedlinePlus

    ... About Us Information For... Media Policy Makers Folic Acid Quiz Language: English Español (Spanish) Recommend on Facebook ... button beside the question. Good Luck! 1. Folic acid is: A a B vitamin B a form ...

  15. Folic Acid and Pregnancy

    MedlinePlus

    ... Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development (Birth to 3 Years) Feeding Your 1- to 3-Month-Old Feeding Your 4- to 7-Month-Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old Folic Acid ... > For Parents > Folic Acid and Pregnancy A A A What's ...

  16. Folic acid - test

    MedlinePlus

    ... folic acid before and during pregnancy helps prevent neural tube defects, such as spina bifida. Women who ... take more if they have a history of neural tube defects in earlier pregnancies. Ask your provider ...

  17. Neural Tube Defects, Folic Acid and Methylation

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  18. Neural tube defects, folic acid and methylation.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J

    2013-09-17

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

  19. Circulating folic acid in plasma: relation to folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated co...

  20. Folic Acid Questions and Answers

    MedlinePlus

    ... Controls NCBDDD Cancel Submit Search The CDC Folic Acid Note: Javascript is disabled or is not supported ... please visit this page: About CDC.gov . Folic Acid Homepage Facts Quiz Frequently Asked Questions General Information ...

  1. Folic acid, methylation and neural tube closure in humans.

    PubMed

    Blom, Henk J

    2009-04-01

    This review provides a brief description of folate use and folic acid metabolism in relation to neural tube defect (NTD) risk. First, a meta-analysis of reduction in NTD recurrence and occurrence risk with periconceptional folic acid supplementation is presented. Second, an overview of the complex folate metabolism is given. Third, SNPs for genes involved in folate and homocysteine metabolism that have been studied in relation to NTD riskare discussed. Fourth, the questions whether folate receptor autoantibodies or hampered methylation are mechanisms underlying NTDs are briefly discussed.

  2. Folic acid food fortification-its history, effect, concerns, and future directions.

    PubMed

    Crider, Krista S; Bailey, Lynn B; Berry, Robert J

    2011-03-01

    Periconceptional intake of folic acid is known to reduce a woman's risk of having an infant affected by a neural tube birth defect (NTD). National programs to mandate fortification of food with folic acid have reduced the prevalence of NTDs worldwide. Uncertainty surrounding possible unintended consequences has led to concerns about higher folic acid intake and food fortification programs. This uncertainty emphasizes the need to continually monitor fortification programs for accurate measures of their effect and the ability to address concerns as they arise. This review highlights the history, effect, concerns, and future directions of folic acid food fortification programs.

  3. Neural tube defects and maternal folate intake among pregnancies conceived after folic acid fortification in the United States.

    PubMed

    Mosley, Bridget S; Cleves, Mario A; Siega-Riz, Anna Maria; Shaw, Gary M; Canfield, Mark A; Waller, D Kim; Werler, Martha M; Hobbs, Charlotte A

    2009-01-01

    Rates of neural tube defects have decreased since folic acid fortification of the food supply in the United States. The authors' objective was to evaluate the associations between neural tube defects and maternal folic acid intake among pregnancies conceived after fortification. This is a multicenter, case-control study that uses data from the National Birth Defects Prevention Study, 1998-2003. Logistic regression was used to compute crude and adjusted odds ratios between cases and controls assessing maternal periconceptional use of folic acid and intake of dietary folic acid. Among 180 anencephalic cases, 385 spina bifida cases, and 3, 963 controls, 21.1%, 25.2%, and 26.1%, respectively, reported periconceptional use of folic acid supplements. Periconceptional supplement use did not reduce the risk of having a pregnancy affected by a neural tube defect. Maternal intake of dietary folate was not significantly associated with neural tube defects. In this study conducted among pregnancies conceived after mandatory folic acid fortification, the authors found little evidence of an association between neural tube defects and maternal folic acid intake. A possible explanation is that folic acid fortification reduced the occurrence of folic acid-sensitive neural tube defects. Further investigation is warranted to possibly identify women who remain at increased risk of preventable neural tube defects.

  4. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks.

    PubMed

    Czeizel, Andrew E; Bártfai, Zoltán; Bánhidy, Ferenc

    2011-08-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate ('folate').

  5. [Folic acid use by pregnant women in Israel for preventing neural tube defects].

    PubMed

    Gil, Z; Aran, A; Friedman, O; Beni-Adani, L; Constantini, S

    2000-12-01

    Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women. Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p = 0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p > 0.05). Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p = 0.038). Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

  6. [Folic acid intake in daily food rations of 20-25 years old women from Wroclaw and assessment of knowledge about its importance for health].

    PubMed

    Wyka, Joanna; Mikołajczak, Jolanta

    2007-01-01

    The mean folic acid content in the diets of 50 young women from Wroclaw was 282 mcg and complied in 70.5% of recommended intake in prophylactic of neural tube defects. Only 8% of women used peri-conceptional folate supplementation every day. In the examined group low knowledge about importance of folic acid in health was noticed. Educational interventions are required to inform women at childbearing age of the benefits resulting from supplementation of diet with folic acid.

  7. Fatal Folic Acid Toxicity in Humans.

    PubMed

    Devnath, Gerard Pradeep; Kumaran, Senthil; Rajiv, R; Shaha, Kusa Kumar; Nagaraj, Ashok

    2017-03-06

    Folic acid is B-9 vitamin. Folic acid is prescribed commonly for pregnant women to prevent neural tube defects in the fetus, patients under chemotherapy, pernicious anemia and to reduce the risk of stroke and cardiovascular disease. Acute or chronic ingestion of a large dose of folic acid generally manifests as neurological complications, which are reversible. In this present case, a 23-year-old pregnant woman committed suicide by consuming folic acid tablets and succumbed to death within 36 h. Postmortem toxicological analysis detected folic acid in viscera. Death following acute consumption of folic acid is rare and has been not reported in the literature, to the best of our knowledge.

  8. Getting folic acid nutrition right

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The two articles in this issue of the journal provide some definitive answers to questions relating to folic acid exposure and folate nutritional status of the US population in the post-fortification era, and, by implication, pose other questions. Most convincingly, these reports, which are based la...

  9. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Folic acid test system. 862.1295 Section 862.1295....1295 Folic acid test system. (a) Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis...

  10. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Folic acid test system. 862.1295 Section 862.1295....1295 Folic acid test system. (a) Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis...

  11. Awareness and intake of folic acid for the prevention of neural tube defects among Lebanese women of childbearing age.

    PubMed

    Nasr Hage, Claudine; Jalloul, Maya; Sabbah, Mohamad; Adib, Salim M

    2012-01-01

    Since the early 1990s, international recommendations have promoted folic acid supplementation during the periconception period as an effective way of preventing neural tube defects (NTDs). However, the adoption of this recommendation remains insufficient. To assess the awareness and actual intake of folic acid among married Lebanese women aged 18-45 years, a cross-sectional study was conducted among 600 women selected from all five administrative districts in Lebanon, using a multistage cluster sampling procedure. An anonymous questionnaire was completed which covered measures of knowledge and use of folate supplements, as well as demographic, socioeconomic and obstetrical factors. Sixty percent of surveyed women (60%; n = 360) had heard about folic acid. Doctors were the most frequent source of information (61.1%) but only 24.7% of women have been told of the correct period during which folic acid supplementation was useful. Overall, only 6.2% had taken folic acid tablets during the adequate period. Younger age, higher education level and stability/sufficiency of income appeared to be significant predictors of awareness among Lebanese women. Actual folic acid intake was significantly associated with younger age, higher number of pregnancies, planning the last pregnancy and having had that last one after 1990. In Lebanon, the level of folic acid awareness and adequate intake remain relatively low. Several approaches should be used to promote folic acid intake including awareness campaigns, and routine counseling by primary health care physicians on folic acid during preconception visits.

  12. Impact of folic acid supplementation on single- and double-stranded RNA degradation in human colostrum and mature milk.

    PubMed

    Kocic, Gordana; Bjelakovic, Ljiljana; Bjelakovic, Bojko; Jevtoci-Stoimenov, Tatjana; Sokolovic, Dusan; Cvetkovic, Tatjana; Kocic, Hristina; Stojanovic, Svetlana; Langerholc, Tomaz; Jonovic, Marina

    2014-07-01

    Sufficient intake of folic acid is necessary for normal embryogenesis, fetal, and neonatal development. Folic acid facilitates nucleic acid internalization, and protects cellular DNA from nuclease degradation. Human milk contains enzymes, antimicrobial proteins, and antibodies, along with macrophages, that protect against infections and allergies. However, little to no information is available on the effects of folic acid supplementation on degradation of nucleic acids in human milk. In the present study, we aimed to determine the RNase activity (free and inhibitor-bound) in colostrum and mature milk, following folic acid supplementation. The study design included a total of 59 women, 27 of whom received 400 μg of folic acid daily periconceptionally and after. Folic acid supplementation increased the free RNase and polyadenylase activity following lactation. However, the increased RNase activity was not due to de novo enzyme synthesis, as the inhibitor-bound (latent) RNase activity was significantly lower and disappeared after one month. Folic acid reduced RNase activity by using double-stranded RNA as substrate. Data suggests that folic acid supplementation may improve viral RNAs degradation and mRNA degradation, but not dsRNA degradation, preserving in this way the antiviral defense.

  13. Folic acid and birth defect prevention

    MedlinePlus

    ... Women who have had a baby with a neural tube defect may need a higher dose of folic acid. If you have had a baby with a neural tube defect, you should take 400 micrograms of folic acid every day, even when you are not planning ...

  14. Folic Acid Production by Engineered Ashbya gossypii.

    PubMed

    Serrano-Amatriain, Cristina; Ledesma-Amaro, Rodrigo; López-Nicolás, Rubén; Ros, Gaspar; Jiménez, Alberto; Revuelta, José Luis

    2016-10-28

    Folic acid (vitamin B9) is the common name of a number of chemically related compounds (folates), which play a central role as cofactors in one-carbon transfer reactions. Folates are involved in the biosynthesis and metabolism of nucleotides and amino acids, as well as supplying methyl groups to a broad range of substrates, such as hormones, DNA, proteins, and lipids, as part of the methyl cycle. Humans and animals cannot synthesize folic acid and, therefore, need them in the diet. Folic acid deficiency is an important and underestimated problem of micronutrient malnutrition affecting billions of people worldwide. Therefore, the addition of folic acid as food additive has become mandatory in many countries thus contributing to a growing demand of the vitamin. At present, folic acid is exclusively produced by chemical synthesis despite its associated environmental burdens. In this work, we have metabolically engineered the industrial fungus Ashbya gossypii in order to explore its potential as a natural producer of folic acid. Overexpression of FOL genes greatly enhanced the synthesis of folates and identified GTP cyclohydrolase I as the limiting step. Metabolic flux redirection from competing pathways also stimulated folic acid production. Finally, combinatorial engineering synergistically increased the production of different bioactive forms of the folic vitamin. Overall, strains were constructed which produce 146-fold (6595µg/L) more vitamin than the wild-type and by far represents the highest yield reported.

  15. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Folic acid (folacin). 172.345 Section 172.345 Food... Special Dietary and Nutritional Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No. 59-30-3... following prescribed conditions: (a) Folic acid is the chemical N- amino]benzoyl]-L-glutamic acid. (b)...

  16. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Folic acid (folacin). 172.345 Section 172.345 Food... Special Dietary and Nutritional Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No. 59-30-3... following prescribed conditions: (a) Folic acid is the chemical N- amino]benzoyl]-L-glutamic acid. (b)...

  17. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Folic acid (folacin). 172.345 Section 172.345 Food... Special Dietary and Nutritional Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No. 59-30-3... following prescribed conditions: (a) Folic acid is the chemical N- amino]benzoyl]-L-glutamic acid. (b)...

  18. [A two-faced vitamin : Folic acid - prevention or promotion of colon cancer?

    PubMed

    Weißenborn, Anke; Ehlers, Anke; Hirsch-Ernst, Karen-I; Lampen, Alfonso; Niemann, Birgit

    2017-03-01

    In the late 1930s, it was discovered that liver and yeast extracts can be used to correct certain cases of megaloblastic anemia in pregnancy. The factor responsible for this was isolated from spinach leaves in the 1940s, and referred to as folate, a term derived from the Latin word folium for leaf. Folate is considered an essential nutrient for human beings. Folic acid, the synthetic form of the vitamin, is used in dietary supplements, medicines and fortified foods. Since the 1980s, it has been recommended that women who plan to become pregnant and pregnant women during the first trimester of pregnancy take folic acid supplements. This recommendation was based on studies that revealed that periconceptional folic acid supplementation can reduce the risk for neural tube defects (NTDs). Many countries later implemented folic acid fortification programs. The resulting population-wide increase of folic acid intakes led to significant reductions in NTD rates. However, a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada. On the basis of currently available data from experimental and human studies it can be concluded that the association between folate/folic acid and cancer is rather complex: Folate intake in the range of the dietary reference intake (DRI) is associated with a reduced risk for cancer in healthy populations, whereas high intakes of folic acid might result in an increased risk for cancer incidence or progression in persons with precancerous lesions and under certain conditions. Since no adverse effects have been observed in association with the intake of dietary folate, research activities that aim at investigating cause and effect relationships focus on folic acid.

  19. Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects.

    PubMed

    Czeizel, Andrew E; Dudás, Istvan; Vereczkey, Attila; Bánhidy, Ferenc

    2013-11-21

    Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin's statement: "An ounce of prevention is better than a pound of care".

  20. Folic acid in early pregnancy: a public health success story.

    PubMed

    Obican, Sarah G; Finnell, Richard H; Mills, James L; Shaw, Gary M; Scialli, Anthony R

    2010-11-01

    Folate is a water-soluble B vitamin that must be obtained in the diet or through supplementation. For >50 yr, it has been known that folate plays an integral role in embryonic development. In mice, inactivation of genes in the folate pathway results in malformations of the neural tube, heart, and craniofacial structures. It has been shown that diets and blood levels of women who had a fetus with a neural tube defect are low for several micronutrients, particularly folate. Periconceptional use of folic acid containing supplements decreased recurrent neural tube defects in the offspring of women with a previously affected child and the occurrence of a neural tube defect and possibly other birth defects in the offspring of women with no prior history. Based on these findings, the U.S. Public Health Service recommended that all women at risk take folic acid supplements, but many did not. Mandatory food fortification programs were introduced in numerous countries, including the United States, to improve folate nutritional status and have resulted in a major decrease in neural tube defect prevalence. The success story of folate represents the cooperation of embryologists, experimentalists, epidemiologists, public health scientists, and policymakers.

  1. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Folic acid (folacin). 172.345 Section 172.345 Food... Additives § 172.345 Folic acid (folacin). Folic acid (CAS Reg. No. 59-30-3), also known as folacin or folate...) Folic acid is the chemical N- amino]benzoyl]-L-glutamic acid. (b) Folic acid meets the specifications...

  2. Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis.

    PubMed

    Xiao, Wen-Lin; Wu, Min; Shi, Bing

    2006-11-01

    It's clear that environmental factors play a role in the aetiology of orofacial clefting (OFC) and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Periconceptional folic acid supplementation may reduce the risk of OFC. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methylenetetrahydrofolate, the predominant circulating form of folic acid. To determine the effect of MTHFR gene mutation on murine embryonic palatal mesenchymal (MEPM) cells and the interaction with folic acid supplement, we used RNAi study in the primary cultures of MEPM cells. The cells of MTHFR gene silencing grew slower and the apoptosis cell number was more than the cells of control. Supplement with 20 microg/ml folic acid was the best to preventing teratogenic effect of MTHFR gene silencing. By flow cytometry analysis of cell cycle, results were shown that the MEPM cells were retarded in G(0)/G(1) after MTHFR gene silencing. While using 20 microg/ml folic acid supplements could make cell transit the G(1)/S restriction point and the cells growth was close to normal level.

  3. When folic acid fails: Insights from 20 years of neural tube defect surveillance in South Carolina.

    PubMed

    Bupp, Caleb P; Sarasua, Sara M; Dean, Jane H; Stevenson, Roger E

    2015-10-01

    Neural tube defects (NTDs) are the most common of the severe malformations of the brain and spinal cord. Increased maternal intake of folic acid (FA) during the periconceptional period is known to reduce NTD risk. Data from 1046 NTD cases in South Carolina were gathered over 20 years of surveillance. It was possible to determine maternal periconceptional FA use in 615 NTD-affected pregnancies. In 163 occurrent (26.9%) and two recurrent (22%) NTD cases, the mothers reported periconceptional FA use. These women were older and more likely to be white. Maternal periconceptional FA usage was reported in 40.4% of cases of spina bifida with other anomalies but in only 25.2% of isolated spina bifida cases (P = 0.02). This enrichment for associated anomalies was not noted among cases of anencephaly or of encephalocele. Among the 563 subsequent pregnancies to mothers with previous NTD-affected pregnancies, those taking FA had a 0.4% NTD recurrence rate, but the recurrence without FA was 8.5%. NTDs with other associated findings were less likely to be prevented by FA, suggesting there is a background NTD rate that cannot be further reduced by FA. Nonetheless, the majority (73.9%) of NTDs in pregnancies in which the mothers reported periconceptional FA use were isolated NTDs of usual types. Cases in which FA failed in prevention of NTDs provide potential areas for further study into the causation of NTDs. The measures and techniques implemented in South Carolina can serve as an effective and successful model for prevention of NTD occurrence and recurrence.

  4. Arnold Chiari malformation with spina bifida: a lost opportunity of folic Acid supplementation.

    PubMed

    Ganesh, Deepa; Sagayaraj, Benjamin M; Barua, Ravi Kumar; Sharma, Nidhi; Ranga, Upasana

    2014-12-01

    In Arnold Chiari (kee-AHR-ee) II malformation elongated cerebellar tonsils are displaced inferiorly through the Foramen Magnum into the upper cervical spinal canal. It is a complex anomaly with skull, dura, brain, spine and cord manifestations. Meningomyelocele is seen in all cases. We present a case of type II Arnold Chiari Malformation diagnosed in utero in a pregnant lady .There was no periconceptional folic acid supplementation. As the role of the Methylene Tetra Hydro Folate Reductase gene polymorphism in neural tube defects is becoming evident, a simple opportunity as folic acid supplementation should not be missed. Folate supplementation as fortification of cereal grains will also prevent other conditions like congenital heart defects, urinary tract anomalies, orofacial defects, limb defects and pyloric stenosis.

  5. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid.

    PubMed

    Heseker, Helmut B; Mason, Joel B; Selhub, Jacob; Rosenberg, Irwin H; Jacques, Paul F

    2009-07-01

    Some countries have introduced mandatory folic acid fortification, whereas others support periconceptional supplementation of women in childbearing age. Several European countries are considering whether to adopt a fortification policy. Projections of the possible beneficial effects of increased folic acid intake assume that the measure will result in a considerable reduction in neural-tube defects (NTD) in the target population. Therefore, the objective of the present study is to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of NTD. Countries with mandatory fortification achieved a significant increase in folate intake and a significant decline in the prevalence of NTD. This was also true for supplementation trials. However, the prevalence of NTD at birth declined to approximately five cases at birth per 10 000 births and seven to eight cases at birth or abortion per 10 000 births. This decline was independent of the amount of folic acid administered and apparently reveals a 'floor effect' for folic acid-preventable NTD. This clearly shows that not all cases of NTD are preventable by increasing the folate intake. The relative decline depends on the initial NTD rate. Countries with NTD prevalence close to the observed floor may have much smaller reductions in NTD rates with folic acid fortification. Additionally, potential adverse effects of fortification on other vulnerable population groups have to be seriously considered. Policy decisions concerning national mandatory fortification programmes must take into account realistically projected benefits as well as the evidence of risks to all vulnerable groups.

  6. Effect of folic acid on zinc absorption

    SciTech Connect

    Wada, L.; Keating, S.; King, J.C.; Stokstad, E.L.R.

    1986-03-05

    The effect of folic acid on zinc uptake was studied in the human and in the rat. The serum zinc response to a 25 mg oral dose or zinc was measured with and without a 10 mg dose of folic acid. Serum zinc levels were measured prior to the oral dose of zinc and at hourly intervals up to 4 hours after the dose. When zinc was given along, the increases in serum zinc from baseline at hours 1, 2, 3 and 4 were 92, 118, 92 and 66 ..mu..g/dl, respectively. When both zinc and folic acid were given, the increases in serum zinc at hours 1, 2, 3 and 4 were 100, 140, 110 and 75 ..mu..g/dl, respectively. When the increases in serum zinc were plotted against time, there was no significant difference between the areas under the two curves. The everted jejunal sac from the rat was used to study the effect of folate on zinc transport using 100 ..mu..M zinc in the mucosal buffer. The addition of folic acid at levels up to 10/sup -3/M had no significant effect on zinc transport to the serosal side solution or on uptake by the intestinal mucosa. This in vivo study with humans and in vitro study with rat intestine does not support a direct adverse effect of folic acid on zinc absorption.

  7. [Folic acid and prevention of neural tube closure defects: the question is not solved yet].

    PubMed

    Vidailhet, M; Bocquet, A; Bresson, J-L; Briend, A; Chouraqui, J-P; Dupont, C; Darmaun, D; Frelut, M-L; Ghisolfi, J; Girardet, J-P; Goulet, O; Putet, G; Rieu, D; Rigo, J; Turck, D

    2008-07-01

    Between 1981 and 1996, several interventional studies proved the efficacy of periconceptional folic acid supplementation in the prevention of neural tube closure defects (NTCD), first in women at risk (with a previous case of NTCD) and also in women of the general population in age to become pregnant. The poor observance of this supplementation led several countries (USA, Canada, Chile...) to decide mandatory folic acid fortification of cereals, which permitted a 30% (USA) to 46% (Canada) reduction in the incidence of NTCD. Moreover, this benefit was accompanied by a diminished incidence of several other malformations and of stroke and coronary accidents in elderly people. However, several papers drew attention to an increased risk of colorectal and breast cancer in relation with high blood folate levels and the use of folic acid supplements. A controlled interventional study showed a higher rate of recurrence of colic adenomas and a higher percentage of advanced adenomas in subjects receiving 1mg/day of folic acid. A recent study demonstrated an abrupt reversal of the downward trend in colorectal cancer 1 year after the beginning of cereal folic acid fortification in the USA and Canada. Two studies also reported impaired cognitive functions in elder persons with defective vitamin B(12) status. Taken in aggregate, these studies question the wisdom of a nationwide, mandatory, folic acid fortification of cereals. As of today, despite their limited preventive efficacy, a safe approach is to keep our current French recommendations and to increase the awareness of all caregivers, so as to improve the observance of these recommendations.

  8. Folic Acid Supplements: Can They Slow Cognitive Decline?

    MedlinePlus

    ... slow cognitive decline? I've heard that folic acid supplements can improve cognitive function in older adults. ... those with Alzheimer's disease also benefit from folic acid? Answers from Paul Y. Takahashi, M.D. There's ...

  9. Folic Acid Supplementation and Preterm Birth: Results from Observational Studies

    PubMed Central

    Franchi, Massimo

    2014-01-01

    Introduction. Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. Aim of the Study. The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. Materials and Methods. We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. Results. The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB. PMID:24724083

  10. Contemporary Issues Surrounding Folic Acid Fortification Initiatives

    PubMed Central

    Choi, Jeong-Hwa; Yates, Zoe; Veysey, Martin; Heo, Young-Ran; Lucock, Mark

    2014-01-01

    The impact of folate on health and disease, particularly pregnancy complications and congenital malformations, has been extensively studied. Mandatory folic acid fortification therefore has been implemented in multiple countries, resulting in a reduction in the occurrence of neural tube defects. However, emerging evidence suggests increased folate intake may also be associated with unexpected adverse effects. This literature review focuses on contemporary issues of concern, and possible underlying mechanisms as well as giving consideration the future direction of mandatory folic acid fortification. Folate fortification has been associated with the presence of unmetabolized folic acid (PteGlu) in blood, masking of vitamin B12 deficiency, increased dosage for anti-cancer medication, photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the pathoaetiology of colorectal cancer. Increased folate intake has also been associated with twin birth and insulin resistance in offspring, and altered epigenetic mechanisms of inheritance. Although limited data exists to elucidate potential mechanisms underlying these issues, elevated blood folate level due to the excess use of PteGlu without consideration of an individual’s specific phenotypic traits (e.g. genetic background and undiagnosed disease) may be relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to inhibition of dihydrofolate reductase and other enzymes. Concerns notwithstanding, folic acid fortification has achieved enormous advances in public health. It therefore seems prudent to target and carefully monitor high risk groups, and to conduct well focused further research to better understand and to minimize any risk of mandatory folic acid fortification. PMID:25580388

  11. Contemporary issues surrounding folic Acid fortification initiatives.

    PubMed

    Choi, Jeong-Hwa; Yates, Zoe; Veysey, Martin; Heo, Young-Ran; Lucock, Mark

    2014-12-01

    The impact of folate on health and disease, particularly pregnancy complications and congenital malformations, has been extensively studied. Mandatory folic acid fortification therefore has been implemented in multiple countries, resulting in a reduction in the occurrence of neural tube defects. However, emerging evidence suggests increased folate intake may also be associated with unexpected adverse effects. This literature review focuses on contemporary issues of concern, and possible underlying mechanisms as well as giving consideration the future direction of mandatory folic acid fortification. Folate fortification has been associated with the presence of unmetabolized folic acid (PteGlu) in blood, masking of vitamin B12 deficiency, increased dosage for anti-cancer medication, photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the pathoaetiology of colorectal cancer. Increased folate intake has also been associated with twin birth and insulin resistance in offspring, and altered epigenetic mechanisms of inheritance. Although limited data exists to elucidate potential mechanisms underlying these issues, elevated blood folate level due to the excess use of PteGlu without consideration of an individual's specific phenotypic traits (e.g. genetic background and undiagnosed disease) may be relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to inhibition of dihydrofolate reductase and other enzymes. Concerns notwithstanding, folic acid fortification has achieved enormous advances in public health. It therefore seems prudent to target and carefully monitor high risk groups, and to conduct well focused further research to better understand and to minimize any risk of mandatory folic acid fortification.

  12. Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread

    PubMed Central

    Dugbaza, Jacinta; Cunningham, Judy

    2012-01-01

    Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population's folic acid intake from fortified foods. Food Standards Australia New Zealand's (FSANZ) custom-built dietary modelling program (DIAMOND) was used for the estimates. The mean amount of folic acid found in white bread was 200 μg/100 g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159 μg per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid. PMID:22957218

  13. New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children – A Systematic Review

    PubMed Central

    Sun, Wen; Asztalos, Elizabeth; Moddemann, Diane; Zwaigenbaum, Lonnie; Walker, Mark; Wen, Shi Wu

    2016-01-01

    It has been conclusively established that folic acid supplementation prior to and during early pregnancy (up to 12 weeks of gestation) can prevent neural tube defects (NTDs). We hypothesized that folate effects may extend from neuro-structural defects to alterations in neuro-behavioural and emotional skills including autism spectrum disorders (ASDs) and other developmental disorders. The objective of this review was to comprehensively evaluate evidence on the impact of folic acid on neurodevelopment other than NTDs. We conducted an online search of relevant literature compiled by the National Library of Medicine from Medline and EMBASE (searched on Dec 31, 2014: http://www.ncbi.nlm.nih.gov/entrez/query/fcgi and http://www.elsevier.com/online-tools/embase). We first created 3 files (search restricted to English literature) using the following key words: 1) folate or folic acid (171322 papers identified by this search); 2) maternal or pregnancy or pregnant or gestation or gestational or prenatal or antenatal or periconception or periconceptional (1349219 papers identified by this search); and 3) autism or autism spectrum disorders or developmental delay or development or neurodevelopment or mental or cognitive or language or personal-social or gross motor or fine motor or behaviour or intellectual or intelligence or Bayley Scale (8268145 papers identified by this search). We then merged the 3 files and reviewed the papers that addressed these three issues simultaneously. A total of 22 original papers that examined the association between folic acid supplementation in human pregnancy and neurodevelopment/autism were identified after the screening, with 15 studies showing a beneficial effect of folic acid supplementation on neurodevelopment/autism, 6 studies showed no statistically significant difference, while one study showed a harmful effect in > 5 mg folic acid supplementation/day during pregnancy. Folic acid supplementation in pregnancy may have beneficial effects

  14. Knowledge of Health Professionals on Folic Acid Use and Their Prescribing Practice in Bahir Dar City Administration, Northwest Ethiopia: Cross-Sectional Study

    PubMed Central

    Demilew, Yeshalem Mulugeta; Asres Nigussie, Azezu

    2017-01-01

    Background Taking folic acid supplement during periconception period is effective to prevent neural tube defects. Unfortunately, a minority of Ethiopian women took folic acid supplement during this period. Low consumption of folic acid might be correlated with knowledge and prescribing practice of health professionals. Therefore, this study was conducted to assess knowledge and prescribing practice of health professionals. Methods Institution based cross-sectional quantitative study supplemented by qualitative approach using thematic content analysis of in-depth interview was conducted. A total of 424 health professionals were selected by simple random sampling technique. A convenience sampling technique was used to generate the qualitative data. Bivariable and multivariable logistic regression analysis were used to identify factors associated with knowledge of health professionals. Result About 47.7% of health professionals had sufficient knowledge and 9.7% of them had prescribed folic acid to women during periconception period. Age, having work experience in ANC clinic, and being a general practitioner were independent predictors for knowledge of health professionals. Lack of guideline to use as a reference, refreshment training and clear direction from health bureau, time constraint, differing patient priorities, and competing topics were some of the reasons for insufficient knowledge and poor practice. Conclusion The majority of the health professionals had insufficient knowledge and poor prescribing practice on folic acid during periconception period. Lack of guideline to be used as a reference, refreshment training and clear direction from health bureau, time constraint, differing patient priorities, and competing topics were some of the reasons for low level of knowledge and poor prescribing practice. Thus, guideline to use as a reference, refreshment training, incorporate the topic in the curriculum of health professionals and supportive supervision should

  15. Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study

    PubMed Central

    2013-01-01

    Background Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). Methods The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999–2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4–5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). Results The median total folate intake was 266 μg/d (interquartile range IQR 154–543) in the overall population and 540 μg/d (IQR 369–651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and

  16. Reaction of folic acid with single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Ellison, Mark D.; Chorney, Matthew

    2016-10-01

    The oxygen-containing functional groups on oxidized single-walled carbon nanotubes (SWNTs) are used to covalently bond folic acid molecules to the SWNTs. Infrared spectroscopy confirms intact molecular binding to the SWNTs through the formation of an amide bond between a carboxylic acid group on an SWNT and the primary amine group of folic acid. The folic acid-functionalized SWNTs are readily dispersible in water and phosphate-buffered saline, and the dispersions are stable for a period of two weeks or longer. These folic acid-functionalized SWNTs offer potential for use as biocompatible SWNTs.

  17. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis

    PubMed Central

    Crider, Krista S; Cordero, Amy M; Qi, Yan Ping; Mulinare, Joseph; Dowling, Nicole F; Berry, Robert J

    2016-01-01

    Background Childhood asthma has become a critical public health problem because of its high morbidity and increasing prevalence. The impact of nutrition and other exposures during pregnancy on long-term health and development of children has been of increasing interest. Objective We performed a systematic review and meta-analysis of the association of folate and folic acid intake during pregnancy and risk of asthma and other allergic outcomes in children. Design We performed a systematic search of 8 electronic databases for articles that examined the association between prenatal folate or folic acid exposure and risk of asthma and other allergic outcomes (eg, allergy, eczema, and atopic dermatitis) in childhood. We performed a meta-analysis by using a random-effects model to derive a summary risk estimate of studies with similar exposure timing, exposure assessment, and outcomes. Results Our meta-analysis provided no evidence of an association between maternal folic acid supplement use (compared with no use) in the prepregnancy period through the first trimester and asthma in childhood (summary risk estimate: 1.01; 95% CI: 0.78, 1.30). Because of substantial heterogeneity in exposures and outcomes, it was not possible to generate summary measures for other folate indicators (eg, blood folate concentrations) and asthma or allergy-related outcomes; however, the preponderance of primary risk estimates was not elevated. Conclusions Our findings do not support an association between periconceptional folic acid supplementation and increased risk of asthma in children. However, because of the limited number and types of studies in the literature, additional research is needed. PMID:24004895

  18. Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates.

    PubMed

    Cal, Pedro M S D; Frade, Raquel F M; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M P

    2014-05-25

    Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.

  19. Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study.

    PubMed

    Bergman, J E H; Otten, E; Verheij, J B G M; de Walle, H E K

    2016-01-01

    Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception.

  20. Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: The Folic Acid Clinical Trial Study

    PubMed Central

    Champagne, Josee; Rennicks White, Ruth; Coyle, Doug; Fraser, William; Smith, Graeme; Fergusson, Dean; Walker, Mark C.

    2013-01-01

    Preeclampsia (PE) is hypertension with proteinuria that develops during pregnancy and affects at least 5% of pregnancies. The Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia: the Folic Acid Clinical Trial (FACT) aims to recruit 3,656 high risk women to evaluate a new prevention strategy for PE: supplementation of folic acid throughout pregnancy. Pregnant women with increased risk of developing PE presenting to a trial participating center between 80/7 and 166/7 weeks of gestation are randomized in a 1 : 1 ratio to folic acid 4.0 mg or placebo after written consent is obtained. Intent-to-treat population will be analyzed. The FACT study was funded by the Canadian Institutes of Health Research in 2009, and regulatory approval from Health Canada was obtained in 2010. A web-based randomization system and electronic data collection system provide the platform for participating centers to randomize their eligible participants and enter data in real time. To date we have twenty participating Canadian centers, of which eighteen are actively recruiting, and seven participating Australian centers, of which two are actively recruiting. Recruitment in Argentina, UK, Netherlands, Brazil, West Indies, and United States is expected to begin by the second or third quarter of 2013. This trial is registered with NCT01355159. PMID:24349782

  1. Folic Acid Determination Using Electrochemical Sensors

    PubMed Central

    Mirmoghtadaie, Leila; Shamaeizadeh, Nahal; Mirzanasiri, Nooshin

    2015-01-01

    Folic acid (FA) is a water soluble vitamin that exists in many natural species. The lack of FA causes some deficiencies in the human body, so finding a simple and sensitive method for determining the FA is important. One of the modern techniques which overcome the disadvantages of conventional determination methods is the sensors. Possibility of miniaturization, the development of microfabricated electrochemical (EC) sensors has resulted in high sensitivity, portability, improved performance and spatial resolution, low power consumption, and the opportunity for integration with other technologies made Micro-Electrical-Mechanical Systems-based EC sensors suitable to identify low concentration analytes and microorganisms in a variety of mediums. PMID:26605021

  2. Folic Acid Determination Using Electrochemical Sensors.

    PubMed

    Mirmoghtadaie, Leila; Shamaeizadeh, Nahal; Mirzanasiri, Nooshin

    2015-01-01

    Folic acid (FA) is a water soluble vitamin that exists in many natural species. The lack of FA causes some deficiencies in the human body, so finding a simple and sensitive method for determining the FA is important. One of the modern techniques which overcome the disadvantages of conventional determination methods is the sensors. Possibility of miniaturization, the development of microfabricated electrochemical (EC) sensors has resulted in high sensitivity, portability, improved performance and spatial resolution, low power consumption, and the opportunity for integration with other technologies made Micro-Electrical-Mechanical Systems-based EC sensors suitable to identify low concentration analytes and microorganisms in a variety of mediums.

  3. Folic acid: to fortify or not to fortify? An examination of selected national policies towards mandatory folic acid fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many national authorities are reviewing their policy towards mandatory folic acid fortification of staple foods in response to epidemiological evidence of the relationship between folic acid and neural tube defects (NTDs). However, there are scientific, ethical and technical challenges associated wi...

  4. New Guidelines Reaffirm Prenatal Folic Acid to Curb Birth Defects

    MedlinePlus

    ... that folic acid supplements reduce the risk of neural tube defects. As it advised in 2009, the independent ... acid to prevent these potentially fatal birth defects. Neural tube defects occur when the brain or spinal cord ...

  5. Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes

    PubMed Central

    Joseph, K.S.; Luo, Wei; León, Juan Andrés; Lisonkova, Sarka; Van den Hof, Michiel; Evans, Jane; Lim, Ken; Little, Julian; Sauve, Reg; Kramer, Michael S.

    2016-01-01

    Background: Previous studies have yielded inconsistent results for the effects of periconceptional multivitamins containing folic acid and of folic acid food fortification on congenital heart defects (CHDs). Methods: We carried out a population-based cohort study (N=5 901 701) of all live births and stillbirths (including late-pregnancy terminations) delivered at ≥20 weeks’ gestation in Canada (except Québec and Manitoba) from 1990 to 2011. CHD cases were diagnosed at birth and in infancy (n=72 591). We compared prevalence rates and temporal trends in CHD subtypes before and after 1998 (the year that fortification was mandated). An ecological study based on 22 calendar years, 14 geographic areas, and Poisson regression analysis was used to quantify the effect of folic acid food fortification on nonchromosomal CHD subtypes (n=66 980) after controlling for changes in maternal age, prepregnancy diabetes mellitus, preterm preeclampsia, multiple birth, and termination of pregnancy. Results: The overall birth prevalence rate of CHDs was 12.3 per 1000 total births. Rates of most CHD subtypes decreased between 1990 and 2011 except for atrial septal defects, which increased significantly. Folic acid food fortification was associated with lower rates of conotruncal defects (adjusted rate ratio [aRR], 0.73, 95% confidence interval [CI], 0.62–0.85), coarctation of the aorta (aRR, 0.77; 95% CI, 0.61–0.96), ventricular septal defects (aRR, 0.85; 95% CI, 0.75–0.96), and atrial septal defects (aRR, 0.82; 95% CI, 0.69–0.95) but not severe nonconotruncal heart defects (aRR, 0.81; 95% CI, 0.65–1.03) and other heart or circulatory system abnormalities (aRR, 0.98; 95% CI, 0.89–1.11). ConclusionS: The association between food fortification with folic acid and a reduction in the birth prevalence of specific CHDs provides modest evidence for additional benefit from this intervention. PMID:27572879

  6. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects.

    PubMed

    Liu, Shiliang; West, Roy; Randell, Edward; Longerich, Linda; O'connor, Kathleen Steel; Scott, Helen; Crowley, Marian; Lam, Angeline; Prabhakaran, Victor; McCourt, Catherine

    2004-09-27

    BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19-44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991-93 and 1994-97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76-1.34). The rates of NTDs fell by 78% (95% CI 65%-86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991-1997 to 0.96 per 1,000 births during 1998-2001 (RR 0.22, 95% CI 0.14-0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19-44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19-44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education

  7. Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience

    PubMed Central

    El-Shabrawi, Mortada H.; Kamal, Naglaa Mohamed; Elhusseini, Mona Abbas; Hussein, Laila; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim; Azab, Ahmed Abelfattah; Salama, Mostafa Abdelazim; Kassab, Muna; Krawinkel, Michael

    2015-01-01

    Abstract Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period. PMID:26376380

  8. Folic Acid Intake and Neural Tube Defects: Two Egyptian Centers Experience.

    PubMed

    El-Shabrawi, Mortada H; Kamal, Naglaa Mohamed; Elhusseini, Mona Abbas; Hussein, Laila; Abdallah, Enas Abdallah Ali; Ali, Yahia Zakaria Abdelalim; Azab, Ahmed Abelfattah; Salama, Mostafa Abdelazim; Kassab, Muna; Krawinkel, Michael

    2015-09-01

    Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt. A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire. Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors. The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period.

  9. Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants.

    PubMed

    Harris, Muriel J

    2009-04-01

    Almost 30 years after the initial study by Richard W. Smithells and coworkers, it is still unknown how maternal periconceptional folic acid supplementation prevents human neural tube defects (NTDs). In this article, questions about human NTD prevention are considered in relation to three groups of mouse models: NTD mutants that respond to folate, NTD mutants and strains that do not respond to folate, and mutants involving folate-pathway genes. Of the 200 mouse NTD mutants, only a few have been tested with folate; half respond and half do not. Among responsive mutants, folic acid supplementation reduces exencephaly and/or spina bifida aperta frequency in the Sp(2H), Sp, Cd, Cited2, Cart1, and Gcn5 mutants. Prevention ranges from 35 to 85%. The responsive Sp(2H) (Pax3) mutant has abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate-pathway genes do not cause NTDs, except for 30% exencephaly in folate-treated Folr1. Among folate-pathway mutants, neural tube closure is normal in Cbs, Folr2, Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1, Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in the ability to respond to folic acid and also to heterogeneity in genetic cause of NTDs that can be prevented by folic acid.

  10. Avidity Mechanism of Dendrimer–Folic Acid Conjugates

    PubMed Central

    2015-01-01

    Multivalent conjugation of folic acid has been employed to target cells overexpressing folate receptors. Such polymer conjugates have been previously demonstrated to have high avidity to folate binding protein. However, the lack of a monovalent folic acid–polymer material has prevented a full binding analysis of these conjugates, as multivalent binding mechanisms and polymer-mass mechanisms are convoluted in samples with broad distributions of folic acid-to-dendrimer ratios. In this work, the synthesis of a monovalent folic acid–dendrimer conjugate allowed the elucidation of the mechanism for increased binding between the folic acid–polymer conjugate and a folate binding protein surface. The increased avidity is due to a folate-keyed interaction between the dendrimer and protein surfaces that fits into the general framework of slow-onset, tight-binding mechanisms of ligand/protein interactions. PMID:24725205

  11. Folate/Folic Acid Knowledge, Intake, and Self-Efficacy of College-Aged Women: Impact of Text Messaging and Availability of a Folic Acid-Containing Supplement

    ERIC Educational Resources Information Center

    Rampersaud, Gail C.; Sokolow, Andrew; Gruspe, Abigail; Colee, James C.; Kauwell, Gail P. A.

    2016-01-01

    Objective: To evaluate the impact of educational text messages (TMs) on folate/folic acid knowledge and consumption among college-aged women, and to evaluate the impact of providing folic acid supplements on folate/folic acid intake among college-aged women. Participants: A total of 162 women (18-24 years) recruited from a university. Methods: The…

  12. Folic acid, neurodegenerative and neuropsychiatric disease.

    PubMed

    Kronenberg, Golo; Colla, Michael; Endres, Matthias

    2009-04-01

    Folic acid plays an important role in neuroplasticity and in the maintenance of neuronal integrity. Folate is a co-factor in one-carbon metabolism during which it promotes the regeneration of methionine from homocysteine, a highly reactive sulfur-containing amino acid. Methionine may then be converted to S-adenosylmethionine (SAM), the principal methyl donor in most biosynthetic methylation reactions. On the cellular level, folate deficiency and hyperhomocysteinemia exert multiple detrimental effects. These include induction of DNA damage, uracil misincorporation into DNA and altered patterns of DNA methylation. Low folate status and elevated homocysteine increase the generation of reactive oxygen species and contribute to excitotoxicity and mitochondrial dysfunction which may lead to apoptosis. Strong epidemiological and experimental evidence links derangements of one-carbon metabolism to vascular, neurodegenerative and neuropsychiatric disease, including most prominently cerebral ischemia, Alzheimer's dementia and depression. Although firm evidence from controlled clinical trials is largely lacking, B-vitamin supplementation and homocysteine reduction may have a role especially in the primary prevention of stroke and dementia as well as as an adjunct to antidepressant pharmacotherapy.

  13. Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

    PubMed

    Kondo, Atsuo; Morota, Nobuhito; Date, Hiroaki; Yoshifuji, Kazuhisa; Morishima, Toshibumi; Miyazato, Minoru; Shirane, Reizo; Sakai, Hideki; Pooh, Kyong Hon; Watanabe, Tomoyuki

    2015-07-14

    The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan.

  14. More Folic Acid in Pregnancy May Protect Kids from High Blood Pressure

    MedlinePlus

    ... medlineplus.gov/news/fullstory_163990.html More Folic Acid in Pregnancy May Protect Kids From High Blood ... WEDNESDAY, March 8, 2017 (HealthDay News) -- Higher folic acid levels during pregnancy may reduce the risk of ...

  15. 21 CFR 172.345 - Folic acid (folacin).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... acid meets the specifications of the “Food Chemicals Codex,” 4th ed. (1996), pp. 157-158, which is... chapter. (f) Folic acid may be added to a medical food, as defined in section 5(b)(3) of the Orphan...

  16. Maternal Folic Acid Supplementation during Pregnancy and Early Childhood Asthma

    PubMed Central

    Veeranki, Sreenivas P.; Gebretsadik, Tebeb; Mitchel, Edward F.; Tylavsky, Frances A.; Hartert, Tina V.; Cooper, William O.; Dupont, William D; Dorris, Stacy L.; Hartman, Terryl J.; Carroll, Kecia N.

    2016-01-01

    Background Asthma is one of the most common chronic childhood diseases. While folic acid supplementation around conception helps prevent neural tube defects, an animal model suggests it may be a risk factor for respiratory diseases; although epidemiologic studies have had conflicting results. We investigated the timing of folic acid-containing prescription filling during pregnancy and child asthma. Methods In a retrospective cohort study of 104,428 children, born 1996–2005, and their mothers enrolled in Tennessee Medicaid, we investigated the association of filling folic acid-containing prescriptions during pregnancy and childhood asthma at age 4.5–6 years. We categorized women into exposure groups based on prescription-filling centered around the first trimester: no folic acid prescription exposure, exposure in first trimester only, exposure after first trimester, and exposure in first trimester and beyond. We defined asthma using asthma-specific healthcare visits and medication fills. Using logistic regression models, we investigated the relationship adjusting for potential confounders. Results Overall 15% of children had asthma. Compared with children born to women with no folic acid prescription exposure, children born to women with exposures in the first trimester only or first trimester and later had increased relative odds of asthma [adjusted odds ratios (OR) 1.2, 95% confidence interval (CI) 1.1–1.3] and 1.2, 95% CI 1.2–1.3]; no association was seen in children born to women exposed after the first trimester. Conclusion Timing of folic acid-containing prescription filling during pregnancy was associated with childhood asthma. Our findings contribute to understanding of the role of prenatal nutritional supplements on child respiratory health. PMID:26360371

  17. Benefits and risks of folic acid to the nervous system

    PubMed Central

    Reynolds, E

    2002-01-01

    During three decades of neurological practice I have witnessed a remarkable change in attitudes to the benefits and risks of folic acid therapy in nervous system disorders. In the 1960s all that was known and taught was that folic acid was harmful to the nervous system, especially in precipitating or exacerbating the neurological complications of vitamin B12 deficiency. So deeply held was this view that the possibility of neuropsychological benefits from this vitamin was initially viewed with considerable scepticism.1 PMID:11971038

  18. Excessive folic acid intake and relation to adverse health outcome.

    PubMed

    Selhub, Jacob; Rosenberg, Irwin H

    2016-07-01

    The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that "high folic acid intake has not reliably been shown to be associated with negative healeffects". In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young. Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that

  19. Efficacy of adding folic acid to foods.

    PubMed

    Fajardo, Violeta; Varela-Moreiras, Gregorio

    2012-06-01

    In the past, food fortification along with nutritional education and the decrease in food costs relative to income have proven successful in eliminating common nutritional deficiencies. These deficiencies such as goiter, rickets, beriberi, and pellagra have been replaced with an entirely new set of "emergent deficiencies" that were not previously considered a problem [e.g., folate and neural tube defects (NTDs)]. In addition, the different nutrition surveys in so-called affluent countries have identified "shortfalls" of nutrients specific to various age groups and/or physiological status. Complex, multiple-etiology diseases, such as atherosclerosis, diabetes, cancer, and obesity have emerged. Food fortification has proven an effective tool for tackling nutritional deficiencies in populations; but today a more reasonable approach is to use food fortification as a means to support but not replace dietary improvement strategies (i. e. nutritional education campaigns). Folic acid (FA) is a potential relevant factor in the prevention of a number of pathologies. The evidence linking FA to NTD prevention led to the introduction of public health strategies to increase folate intakes: pharmacological supplementation, mandatory or voluntary fortification of staple foods with FA, and the advice to increase the intake of folate-rich foods. It is quite contradictory to observe that, regardless of these findings, there is only limited information on food folate and FA content. Data in Food Composition Tables and Databases are scarce or incomplete. Fortification of staple foods with FA has added difficulty to this task. Globally, the decision to fortify products is left up to individual food manufacturers. Voluntary fortification is a common practice in many countries. Therefore, the "worldwide map of vitamin fortification" may be analyzed. It is important to examine if fortification today really answers to vitamin requirements at different ages and/or physiological states. The

  20. 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.

  1. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  3. 21 CFR 862.1295 - Folic acid test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Folic acid test system. 862.1295 Section 862.1295 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  4. Physicians' Knowledge of Alcohol, Tobacco and Folic Acid in Pregnancy

    ERIC Educational Resources Information Center

    Lefebvre, L. G.; Ordean, A.; Midmer, D.; Kahan, M.; Tolomiczenko, G.

    2007-01-01

    Objective: To assess: (1) physicians' knowledge and clinical confidence regarding problematic substance use in pregnancy compared to folic acid, and (2) physicians' desire for education in this area and their preferred learning modalities tools. Design: Self-administered survey. Setting: "Family Medicine Forum 2004" in Toronto, Canada.…

  5. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    PubMed

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  6. Folic acid-Functionalized Nanoparticles for Enhanced Oral Drug Delivery

    PubMed Central

    Roger, Emilie; Kalscheuer, Stephen; Kirtane, Ameya; Guru, Bharath Raja; Grill, Alex E.; Whittum-Hudson, Judith; Panyam, Jayanth

    2012-01-01

    The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (Papp) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid-functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability. PMID:22670575

  7. A Village-Based Intervention: Promoting Folic Acid Use among Rural Chinese Women

    PubMed Central

    Lin, Qian; Yang, Lina; Li, Fang; Qin, Hong; Li, Mingzhi; Chen, Jihua; Deng, Jing; Hu, Xiangying

    2017-01-01

    Background: Folic acid supplementation is effective in reducing the risk of neural tube defects (NTDs). However, the use of folic acid is low among rural women in China. Nutrition education can provide information about folic acid and encourage its use. The primary objective of this study was to test the effectiveness of a village-based nutrition intervention on folic acid use among rural women. Methods: Sixty villages were randomly selected using multiple-stage sampling and were divided into control and intervention groups. The intervention included nutritional education at village clinics, written materials, and text messages (SMS). Folic acid use knowledge and behavior was assessed at baseline and after the intervention. Results: Self-reported compliance with folic acid supplement use increased from 17.0%–29.2% at baseline to 41.7%–59.2% one year post-intervention. During the same period, the folic acid knowledge score in the intervention group increased from 3.07 to 3.65, significantly higher than the control group (3.11 to 3.35). Multivariate binary logistic regression showed that the women who received folic acid education and SMS intervention were more likely to comply with folic acid supplement recommendations. Conclusions: The results indicated that an integrated village-based folic acid education intervention may be an effective way of promoting folic acid use for the prevention of NTDs in rural women. PMID:28230798

  8. Folic acid supplementation during pregnancy protects against lipopolysaccharide-induced neural tube defects in mice.

    PubMed

    Zhao, Mei; Chen, Yuan-Hua; Chen, Xue; Dong, Xu-Ting; Zhou, Jun; Wang, Hua; Wu, Shu-Xian; Zhang, Cheng; Xu, De-Xiang

    2014-01-13

    Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20 μg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg/d) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-κB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti-oxidative effects.

  9. Association Between Preconception Counseling and Folic Acid Supplementation Before Pregnancy and Reasons for Non-Use.

    PubMed

    Bixenstine, Paul J; Cheng, Tina L; Cheng, Diana; Connor, Katherine A; Mistry, Kamila B

    2015-09-01

    To examine the relationship between folic acid preconception counseling (PCC) and folic acid use and reasons for non-use among women with a recent live birth. We analyzed Maryland Pregnancy Risk Assessment Monitoring System (PRAMS) survey responses from 2009 to 2011 (n = 4,426, response rate = 67%). Multivariable weighted logistic regression models were used to explore associations between folic acid PCC receipt and folic acid use and reasons for non-use. Approximately 30% of women reported daily folic acid use the month before pregnancy, with lower rates among those who were <30, non-white, or unmarried; received WIC during pregnancy; had suffered a stressful event prepregnancy; smoked prepregnancy; had a previous live birth; or had an unintended pregnancy (all p < 0.05). The most common reasons for folic acid non-use were "not planning pregnancy" (61%) and "didn't think needed to take" (41%). Folic acid PCC receipt was reported by 27% of women and was associated with three times the odds of folic acid use (adjusted odds ratio [aOR] 3.15, 95% CI 2.47-4.03) and half the odds of reporting "didn't think needed to take" (aOR 0.47, 95% CI 0.28-0.78) as a reason for non-use. Less than one-third of recent Maryland mothers reported using folic acid daily before pregnancy and only 27% reported receiving folic acid PCC. However, folic acid PCC was associated with increased folic acid use and decreased reporting that women did not think they needed to take folic acid. Our data support initiatives to promote provision of folic acid PCC to all women of childbearing age.

  10. Synthesis of an indole analog of folic acid

    SciTech Connect

    Shengeliya, M.S.; Avramenko, V.G.; Kuleshova, L.N.; Ershova, Yu.A.; Chernov, V.A.; Surorov, N.N.

    1987-06-01

    The authors study the replacement of the p-aminobenzoic acid (PABA) moiety. The authors synthesized an indole analog of folic acid, namely dimethyl N-(5-(2'-amino-4'-oxo-6'-pteridinyl)methylaminoindol-2-yl)glutamate. The physicochemical properties and the chemical shifts in the PMR spectra of the compounds obtained are shown. The examination of the compound for antitumor activity was carried out using rats and mice.

  11. Folic acid-CdTe quantum dot conjugates and their applications for cancer cell targeting

    SciTech Connect

    Suriamoorthy, Preethi; Zhang, Xing; Hao, Guiyang; Joly, Alan G.; Singh, S.; Hossu, Marius; Sun, Xiankai; Chen, Wei

    2010-12-01

    In this study, we report the preparation,luminescence, and targeting properties of folic acid- CdTe quantum dot conjugates. Water-soluble CdTe quantum dots were synthesized and conjugated with folic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide chemistry. The in-fluence of folic acid on the luminescence properties of CdTe quantum dots was investigated, and no energy transfer between them was observed. To investigate the efficiency of folic acid-CdTe nanoconjugates for tumor targeting, pure CdTe quantum dots and folic acid-coated CdTe quantum dots were incubated with human naso- pharyngeal epidermal carcinoma cell line with positive expressing folic acid receptors (KB cells) and lung cancer cells without expression of folic acid receptors (A549 cells). For the cancer cells with positive folate receptors (KB cells), the uptake for CdTe quantum dots is very low, but for folic acid-CdTe nanoconjugates, the uptake is very high. For the lung cancer cells without folate receptors (A549 cells), the uptake for folic acid- CdTe nanoconjugates is also very low. The results indicate that folic acid is an effective targeting molecule for tumor cells with overexpressed folate receptors.

  12. Controlled release of insulin from folic acid-insulin complex nanoparticles.

    PubMed

    Gupta, Rajat; Mohanty, Sanat

    2017-03-03

    Associative interactions between folic acid and proteins are well known. This work leverages these interactions to engineer folic acid nanoparticles for controlled release of insulin during diabetes therapy. The insulin-loaded folic acid nanoformulation is synthesized during this study to achieve better insulin loading and encapsulation than previous strategies. The maximum insulin loading in the FA particles was kept at 6mg with less than 10% insulin loss during the synthesis process which is significantly better compare to previous strategies. The folic acid nanoparticles of 50-150nm size are further characterized in the present study. The release behaviour of insulin from the nanoparticles has been studied to quantify released insulin and folic acid with time using high performance liquid chromatography. Insulin release results suggest that more than 90% of the insulin is encapsulated and released within 24h from folic acid nanoparticles. The analysis of folic acid release along with insulin release indicates that the particles are formed by folic acid-insulin complexation at the molecular level. The release of insulin from nanoparticles is controllable with the change in the crosslinking salt concentration as well as the amount of folic acid loaded during particle synthesis. These results prove that folic acid nanocarriers are capable to control the release of therapeutic proteins.

  13. Preventive Effects of Folic Acid Supplementation on Adverse Maternal and Fetal Outcomes

    PubMed Central

    Kim, Min Woo; Ahn, Ki Hoon; Ryu, Ki-Jin; Hong, Soon-Cheol; Lee, Ji Sung; Nava-Ocampo, Alejandro A.; Oh, Min-Jeong; Kim, Hai-Joong

    2014-01-01

    Although there is accumulating evidence regarding the additional protective effect of folic acid against adverse pregnancy outcomes other than neural tube defects, these effects have not been elucidated in detail. We evaluated whether folic acid supplementation is associated with favorable maternal and fetal outcomes. This was a secondary analysis of 215 pregnant women who were enrolled in our prior study. With additional data from telephone interviews regarding prenatal folic acid supplementation, existing demographic, maternal and fetal data were statistically analyzed. The concentration of folic acid in maternal blood was significantly higher following folic acid supplementation (24.6 ng/mL vs.11.8 ng/mL). In contrast, homocysteine level in maternal blood decreased with folic acid supplementation (5.5 µmol/mL vs. 6.8 µmol/mL). The rates of both preeclampsia (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.09–0.76) and small for gestational age (SGA; 9.2% vs. 20.0%; OR, 0.42; 95% CI, 0.18–0.99) were lower in the folic acid supplementation group than those in the control group. Other pregnancy outcomes had no association with folic acid supplementation. The findings indicate that folic acid supplementation may help to prevent preeclampsia and SGA. Further studies are warranted to elucidate the favorable effects of folic acid supplementation on pregnancy outcomes. PMID:24842467

  14. Folic acid improve developmental toxicity induced by aluminum sulphates.

    PubMed

    Yassa, Heba A; George, Safaa M; Mohamed, Heba K

    2017-03-01

    Aluminum sulphate has a significant toxic effects for humans. Aluminum is one of the most abundant metal on the Earth crust. The purpose of this study is to evaluate the effects of short term exposure to aluminum sulphate on the bone development of the fetuses in rats, and if folic acid has a protective role upon that effects or not. Forty female rats were used, ten per group, GI served as negative control (receive nothing except normal feeding and water), GII served as positive control (receive water by gastric gavage), GIII treated with aluminum sulphate orally by gastric gavage and GIV treated with aluminum sulphate with folic acid. Mating occurred and known by presence of vaginal plug in the female rats. Rats were killed on day 18 of gestation.

  15. Imaging Pancreatic Cancer with Folic Acid Terminated Luminescent Silicon Nanocrystals

    NASA Astrophysics Data System (ADS)

    Erogbogbo, Folarin; Swihart, Mark T.

    2010-10-01

    Quantum dots have great potential for visualization of medically relevant targets such as cancer. However, potential toxicity, stemming from the use of heavy metal based semidonductor materials, has been a major impediment to use of quantum dots in vivo. Silicon is an inherently non-toxic element. By combining the unique optical properties of silicon quantum dots with fundamentals of cancer biology, we can develop probes that safely target and enable the visualization of cancer cells. Many cancer cells overexpress folate receptors, making the folate receptors a suitable target for cancer imaging evaluations. Here, we report the synthesis of folic acid coated silicon quantum dots for targeting pancreatic cancer cells. Folic acid on the silicon quantum dots improves selectivity and may decrease possible negative side effects. This demonstration adds to the evidence that silicon can be sucessfully used for biological imaging.

  16. Carbamazepine and folic acid in trigeminal neuralgia patients.

    PubMed Central

    al-Musaed, A A; Zakrzewska, J M; Bain, B J

    1992-01-01

    The effect of carbamazepine monotherapy on the red cell folate level of 133 patients with trigeminal neuralgia was evaluated. The patient group had a significantly lower mean value of red cell folate levels compared with 110 controls. No significant correlation was found between the red cell folate levels and the mean cell volume or haemoglobin values in either the carbamazepine or control group. In addition no significant correlation was found between the red cell folate levels and drug dosage. Administration of folic acid supplements raised the mean value of red cell folate significantly. Dietary folate intake was assessed in 43 trigeminal neuralgia patients and 33 matched control patients and there was no significant difference between the groups. Patients taking carbamazepine should be advised on a well-balanced diet rich in folate as opposed to being given a routine prescription of folic acid. PMID:1548649

  17. Folic acid conjugated ferritins as photosensitizer carriers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zhen, Zipeng; Tang, Wei; Zhang, Weizhong; Xie, Jin

    2015-06-01

    We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis.We coupled folic acid as a tumour targeting ligand to the surface of ferritins and loaded them with ZnF16Pc. The resulting nanoconjugates can efficiently hone in on 4T1 tumours in vivo, and, with photoirradiation, leading to suppressed tumour growth and tumour metastasis. Electronic supplementary information (ESI) available: Details of experiments and ex vivo imaging results. See DOI: 10.1039/c5nr01833a

  18. Folic acid and autism: What do we know?

    PubMed

    Castro, Kamila; Klein, Luciana da Silveira; Baronio, Diego; Gottfried, Carmem; Riesgo, Rudimar; Perry, Ingrid Schweigert

    2016-09-01

    Autism spectrum disorders (ASD) consist in a range of neurodevelopmental conditions that share common features with autism, such as impairments in communication and social interaction, repetitive behaviors, stereotypies, and a limited repertoire of interests and activities. Some studies have reported that folic acid supplementation could be associated with a higher incidence of autism, and therefore, we aimed to conduct a systematic review of studies involving relationships between this molecule and ASD. The MEDLINE database was searched for studies written in English which evaluated the relationship between autism and folate. The initial search yielded 60 potentially relevant articles, of which 11 met the inclusion criteria. The agreement between reviewers was κ = 0.808. The articles included in the present study addressed topics related to the prescription of vitamins, the association between folic acid intake/supplementation during pregnancy and the incidence of autism, food intake, and/or nutrient supplementation in children/adolescents with autism, the evaluation of serum nutrient levels, and nutritional interventions targeting ASD. Regarding our main issue, namely the effect of folic acid supplementation, especially in pregnancy, the few and contradictory studies present inconsistent conclusions. Epidemiological associations are not reproduced in most of the other types of studies. Although some studies have reported lower folate levels in patients with ASD, the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed.

  19. [Folate and folic acid intake estimation and food enrichment requirements].

    PubMed

    Olivares Martínez, Ana Belén; Ros Berruezo, Gaspar; Bernal Cava, M José; Martínez Graciá, Carmen; Periago Castón, M Jesús

    2005-03-01

    The term "folate" is a generic way to name the different forms derived from folic acid, one of the B vitamins (specifically B9 vitamin). They are essential in the metabolism when they act as cofactors in the transfer reactions of one carbon. However, only plants and microorganisms are able to synthesize them de novo, in such a way that both animals and human beings have to intake them through their diet. Folic acid is widely spread in nature, mainly in vegetables, liver ans cereals. However, nowadays, the lack of folates in the diet is one of the most common nutritional deficiencies in the world, and it has serious consequences on human health. There is evidence that even in developed countries folate intake is usually low; and even, is some cases, below optima levels. The authorities in several countries have adapted different norms related to folic acid, fortifying staple food such as dairy products or cereals, mandatory (U.S.A., Canada or Chile) or voluntary (most of the European countries).

  20. Folic acid utilisation related to sulfa drug resistance in Saccharomyces cerevisiae.

    PubMed

    Bayly, A M; Berglez, J M; Patel, O; Castelli, L A; Hankins, E G; Coloe, P; Hopkins Sibley, C; Macreadie, I G

    2001-11-13

    Saccharomyces cerevisiae mutants deficient in folate synthesis have been constructed and employed to study the utilisation of exogenous folates in yeast. One mutant specifically lacked dihydropteroate synthase while the second lacked dihydrofolate synthase. Exogenous folinic acid restored optimal growth to both strains. Folic acid did not generally rescue growth but spontaneous isolates capable of utilising folic acid were selected. The folic acid synthesis pathway in the folate utilising isolates was restored via transformation with FOL1 or FOL3 expression plasmids and transformants were tested for resistance to sulfamethoxazole (SMX). The presence of elevated levels of folic acid led to greatly reduced SMX sensitivity regardless of whether strains were folate utilisers or not.

  1. A relationship between vitamin B sub 12 , folic acid, ascorbic acid, and mercury uptake and methylation

    SciTech Connect

    Zorn, N.E.; Smith, J.T. )

    1990-01-01

    Ingestion of megadoses of certain vitamins appears to influence the in vivo methylation of mercuric chloride in guinea pigs. The addition of megadoses of vitamin B{sub 12} fed either singularly or in combination with folic acid resulted in increased methylmercury concentrations in the liver. Moreover, percent methylmercury levels were significantly increased with B{sub 12} treatment in the liver (B{sub 12} only and B{sub 12}/folic acid) and brain (B{sub 12}/vitamin C). Incorporation of high levels of folic acid into the dietary regime also increased the methylmercury concentration particularly in the liver and hair tissues. The addition of vitamin C in the diet, particularly in combination with B{sub 12} (brain) or folic acid (muscle) resulted in increased methylmercury levels in these tissues and percent methylmercury values with B{sub 12} in the muscle and brain tissue.

  2. Detection of folic acid protein in human serum using reduced graphene oxide electrodes modified by folic-acid.

    PubMed

    He, Lijie; Wang, Qian; Mandler, Daniel; Li, Musen; Boukherroub, Rabah; Szunerits, Sabine

    2016-01-15

    The detection of disease markers is considered an important step for early diagnosis of cancer. We design in this work a novel electrochemical sensing platform for the sensitive and selective detection of folic acid protein (FP). The platform is fabricated by electrophoretic deposition (EPD) of reduced graphene oxide (rGO) onto a gold electrode and post-functionalization of rGO with folic acid. Upon FP binding, a significant current decrease can be measured using differential pulse voltammetry (DPV). Using this scheme, a detection limit of 1pM is achieved. Importantly, the method also allows the detection of FP in serum being thus an appealing approach for the sensitive detection of biomarkers in clinical samples.

  3. Locating the binding sites of folic acid with milk α- and β-caseins.

    PubMed

    Bourassa, P; Tajmir-Riahi, H A

    2012-01-12

    We located the binding sites of folic acid with milk α- and β-caseins at physiological conditions, using constant protein concentration and various folic acid contents. FTIR, UV-visible, and fluorescence spectroscopic methods as well as molecular modeling were used to analyze folic acid binding sites, the binding constant, and the effect of folic acid interaction on the stability and conformation of caseins. Structural analysis showed that folic acid binds caseins via both hydrophilic and hydrophobic contacts with overall binding constants of K(folic acid-α-caseins) = 4.8 (±0.6) × 10(4) M(-1) and K(folic acid-β-caseins) = 7.0 (±0.9) × 10(4) M(-1). The number of bound acid molecules per protein was 1.5 (±0.4) for α-casein and 1.4 (±0.3) for β-casein complexes. Molecular modeling showed different binding sites for folic acid on α- and β-caseins. The participation of several amino acids in folic acid-protein complexes was observed, which was stabilized by hydrogen bonding network and the free binding energy of -7.7 kcal/mol (acid-α-casein) and -8.1 kcal/mol (acid-β-casein). Folic acid complexation altered protein secondary structure by the reduction of α-helix from 35% (free α-casein) to 33% (acid-complex) and 32% (free β-casein) to 26% (acid-complex) indicating a partial protein destabilization. Caseins might act as carriers for transportation of folic acid to target molecules.

  4. Use of high doses of folic acid supplements in pregnant women in Spain: an INMA cohort study

    PubMed Central

    Navarrete-Muñoz, Eva María; Valera-Gran, Desirée; García de la Hera, Manoli; Gimenez-Monzo, Daniel; Morales, Eva; Julvez, Jordi; Riaño, Isolina; Tardón, Adonina; Ibarluzea, Jesus; Santa-Marina, Loreto; Murcia, Mario; Rebagliato, Marisa; Vioque, Jesus

    2015-01-01

    Objectives We examined the use of low (<400 μg/day, including no use) and high folic acid supplement (FAS) dosages (≥1000 μg/day) among pregnant women in Spain, and explored factors associated with the use of these non-recommended dosages. Design Population-based cohort study. Setting Spain. Participants We analysed data from 2332 pregnant women of the INMA study, a prospective mother-child cohort study in Spain. Main outcome measures We assessed usual dietary folate and the use of FAS from preconception to the 3rd month (first period) and from the 4th to the 7th month (second period), using a validated food frequency questionnaire. We used multinomial logistic regression to estimate relative risk ratios (RRRs). Results Over a half of the women used low dosages of FAS in the first and second period while 29% and 17% took high dosages of FAS, respectively. In the first period, tobacco smoking (RRR=1.63), alcohol intake (RRR=1.40), multiparous (RRR=1.44), unplanned pregnancy (RRR=4.20) and previous spontaneous abortion (RRR=0.58, lower use of high FAS dosages among those with previous abortions) were significantly associated with low FAS dosages. Alcohol consumption (RRR=1.42), unplanned pregnancy (RRR=2.66) and previous spontaneous abortion (RRR=0.68) were associated with high dosage use. In the second period, only tobacco smoking was significantly associated with high FAS dosage use (RRR=0.67). Conclusions A high proportion of pregnant women did not reach the recommended dosages of FAS in periconception and a considerable proportion also used FAS dosages ≥1000 μg/day. Action should be planned by the Health Care System and health professionals to improve the appropriate periconceptional use of FAS, taking into consideration the associated factors. PMID:26603248

  5. More folic acid, the five questions: why, who, when, how much, and how.

    PubMed

    Mastroiacovo, Pierpaolo; Leoncini, Emanuele

    2011-01-01

    In recent years, a number of studies have been performed to evaluate the possible health benefits of an increased intake of folic acid (FA) on human health. However, the only well-documented benefit emerging from randomized controlled trials, nonrandomized interventions trials, and observational studies is the risk reduction of neural tube defects (NTDs). NTDs are congenital malformations that include anencephaly, encephalocele, and spina bifida caused by the failure of fusion of the neural tube that normally closes between 22nd and 28th day since conception (on an average 40-42th day after the first day of last menstrual period). The occurrence of NTDs varies among population between 0.8 and 3 per 1,000, and it is estimated that 324,000 pregnancies are affected every year worldwide. More FA can decrease the NTDs risk up to 0.6 per 1,000 births. Other malformations as congenital heart defects, cleft lip, and limb deficiencies can be most probably also reduced. To decrease the NTDs risk, it is recommended that all women capable of becoming pregnant should have more FA. The goal is that every woman could start her pregnancy with an optimal folate status, estimated today to be as more than 906 nmol/L of red blood cell folate concentration. More FA can be obtained through a strict Mediterranean pattern of nutrition and healthy life style, fortified food, supplements. Women and health authorities can choose the most appropriate strategy. Monitoring folate status of women during the periconceptional period is an essential way to evaluate the success of the preferred strategy.

  6. Multivitamin and Iron Supplementation to Prevent Periconceptional Anemia in Rural Tanzanian Women: A Randomized, Controlled Trial

    PubMed Central

    Gunaratna, Nilupa S.; Masanja, Honorati; Mrema, Sigilbert; Levira, Francis; Spiegelman, Donna; Hertzmark, Ellen; Saronga, Naomi; Irema, Kahema; Shuma, Mary; Elisaria, Ester; Fawzi, Wafaie

    2015-01-01

    Objective Women’s nutritional status during conception and early pregnancy can influence maternal and infant outcomes. This study examined the efficacy of pre-pregnancy supplementation with iron and multivitamins to reduce the prevalence of anemia during the periconceptional period among rural Tanzanian women and adolescent girls. Design A double-blind, randomized controlled trial was conducted in which participants were individually randomized to receive daily oral supplements of folic acid alone, folic acid and iron, or folic acid, iron, and vitamins A, B-complex, C, and E at approximately single recommended dietary allowance (RDA) doses for six months. Setting Rural Rufiji District, Tanzania. Subjects Non-pregnant women and adolescent girls aged 15–29 years (n = 802). Results The study arms were comparable in demographic and socioeconomic characteristics, food security, nutritional status, pregnancy history, and compliance with the regimen (p>0.05). In total, 561 participants (70%) completed the study and were included in the intention-to-treat analysis. Hemoglobin levels were not different across treatments (median: 11.1 g/dL, Q1-Q3: 10.0–12.4 g/dL, p = 0.65). However, compared with the folic acid arm (28%), there was a significant reduction in the risk of hypochromic microcytic anemia in the folic acid and iron arm (17%, RR: 0.61, 95% CI: 0.42–0.90, p = 0.01) and the folic acid, iron, and multivitamin arm (19%, RR: 0.66, 95% CI: 0.45–0.96, p = 0.03). Inverse probability of treatment weighting (IPTW) to adjust for potential selection bias due to loss to follow-up did not materially change these results. The effect of the regimens was not modified by frequency of household meat consumption, baseline underweight status, parity, breastfeeding status, or level of compliance (in all cases, p for interaction>0.2). Conclusions Daily oral supplementation with iron and folic acid among women and adolescents prior to pregnancy reduces risk of anemia. The

  7. Preliminary data on changes in neural tube defect prevalence rates after folic acid fortification in South America.

    PubMed

    Castilla, Eduardo E; Orioli, Iêda M; Lopez-Camelo, Jorge S; Dutra, Maria da Graça; Nazer-Herrera, Julio

    2003-12-01

    Several South American countries are fortifying wheat flour with folic acid. However, only Chile started in 2000 to add 2.2 mg/kg, providing 360 microg daily per capita, an acceptable dosage for preventing the occurrence of some neural tube defect (NTD) cases. ECLAMC (Spanish acronym for the Latin American Collaborative Study of Congenital Malformations) routinely monitoring birth defects in South America since 1976, surveyed the impact of this fortification. Data from 361,374 births occurred in 43 South American hospitals, distributed in five different countries, active throughout the 1999-2001 triennium, were selected from the ECLAMC network. Birth prevalence rates for three different congenital anomalies with similar expected prevalence rates, were surveyed by the Cumulative Sum Method (CUSUM) method. They were NTD, oral clefts (OC), and Down syndrome (DS). Expected values were derived from observations made in 1999, and CUSUM was applied to the consecutive series of 24 months covering years 2000 and 2001. Only one of three congenital anomaly types, NTDs, in only one of five sampled out countries, Chile, showed a significant decrease, of 31%, during the 2000-2001 biennium, corresponding to the birth of the periconceptionally fortified infants. The level of significance (P < 0.001) was reached in the 20th month after fortification started, corresponding to August 2001. This is the first observation of a significant decrease in the occurrence of NTD after folic acid food fortification in a population little influenced by confounders common in the developed world as pre-existing secular decreasing trends, and partially unregistered induced abortions.

  8. Role of folic acid in nitric oxide bioavailability and vascular endothelial function.

    PubMed

    Stanhewicz, Anna E; Kenney, W Larry

    2017-01-01

    Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk.

  9. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine.

    PubMed

    Naithani, Manisha; Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus.

  10. Assessment of Folic Acid Supplementation in Pregnant Women by Estimation of Serum Levels of Tetrahydrofolic Acid, Dihydrofolate Reductase, and Homocysteine

    PubMed Central

    Saxena, Vartika; Mirza, Anissa Atif; Kumari, Ranjeeta; Sharma, Kapil; Bharadwaj, Jyoti

    2016-01-01

    Background. Status of folic acid use in pregnant women of the hilly regions in North India was little known. This study was carried out to assess the folic acid use and estimate folate metabolites in pregnant women of this region. Materials and Methods. This cross-sectional study is comprised of 76 pregnant women, whose folic acid supplementation was assessed by a questionnaire and serum levels of homocysteine, tetrahydrofolic acid (THFA), and dihydrofolate reductase (DHFR) were estimated using Enzyme Linked Immunoassays. Results. The study data revealed awareness of folic acid use during pregnancy was present in 46.1% and 23.7% were taking folic acid supplements. The study depicted that there was no statistically significant difference between serum levels of THFA and DHFR in pregnant women with and without folic acid supplements (p = 0.790). Hyperhomocysteinemia was present in 15.78% of the participants. Conclusion. Less awareness about folic acid supplementation and low use of folic acid by pregnant women were observed in this region. Sufficient dietary ingestion may suffice for the escalated requirements in pregnancy, but since this cannot be ensured, hence folic acid supplementation should be made as an integral part of education and reproductive health programs for its better metabolic use, growth, and development of fetus. PMID:27064332

  11. High dose folic acid supplementation in women with epilepsy: are we sure it is safe?

    PubMed

    Asadi-Pooya, Ali A

    2015-04-01

    Most experts agree that folic acid supplementation is a key preconception intervention, particularly in women with epilepsy who take anti-epileptic drugs (AEDs). Primary prevention of neural tube defect through folic acid supplementation results in reduction of risk in an otherwise healthy population. The current folic acid supplementation recommendation is that all women of childbearing potential be supplemented with at least 0.4 mg of folic acid daily prior to conception and during pregnancy. It is recommended that all women with epilepsy and of childbearing potential be supplemented with folic acid daily prior to conception and during pregnancy. However, considering the potential significant drug-drug interactions between high doses of folic acid and some AEDs in patients with epilepsy and also with the emerging evidence from animal studies that high levels of folic acid throughout gestation may have adverse effects on fetal brain development, it is not suggested to advocate high dose folic acid supplementation in women with epilepsy until more information is available about its appropriate, safe and optimal dosing.

  12. [Change in the sensitivity to methotrexate of neoplastic cells cultivated in the presence of folic acid].

    PubMed

    Leĭpunskaia, I L; Svet-Moldavskiĭ, G I

    1976-01-01

    Cultivation of tumour L-cells in the presence of increasing folic acid concentrations led to the rise in the resistance of these cells population to metotrexate. With the subsequent cultivation, when the folic acid concentration was not increased the population of such cells became more sensitive to metotrexate even in comparison with the initial L-cells.

  13. Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

  14. Awareness and Use of Folic Acid among Women in the Lower Mississippi Delta

    ERIC Educational Resources Information Center

    Robbins, James M.; Hopkins, Sarah E.; Mosley, Bridget S.; Casey, Patrick H.; Cleves, Mario A.; Hobbs, Charlotte A.

    2006-01-01

    Context: National and state efforts to increase folic acid awareness and use may not be reaching large segments of the population. Purpose: This study examines folic acid awareness and use among women of childbearing age in a representative, economically at-risk rural sample and identifies factors that influence awareness and use. Methods: A…

  15. Multivitamins, Folic Acid and Birth Defects: Knowledge, Beliefs and Behaviors of Hispanic Women in North Carolina

    ERIC Educational Resources Information Center

    deRosset, Leslie; Mullenix, Amy; Zhang, Lei

    2009-01-01

    Background: Consumption of folic acid prior to conception can prevent up to 70% of neural tube defect (NTD)-affected pregnancies. In 1992, the U.S. Public Health Service (USPHS) issued a recommendation that all women of childbearing age capable of becoming pregnant consume 400 [mu]g of folic acid daily to reduce their risk for a NTD-affected…

  16. Impact of Periconceptional Use of Nitrosatable Drugs on the Risk of Neural Tube Defects.

    PubMed

    Benedum, Corey M; Yazdy, Mahsa M; Mitchell, Allen A; Werler, Martha M

    2015-10-15

    Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly acidic conditions, form N-nitroso compounds that have been found to be teratogenic in animal models. Using data from the Slone Epidemiology Center Birth Defects Study collected from 1998 to 2012, we compared maternal periconceptional NSD use between 334 neural tube defect cases and 7,619 nonmalformed controls. We categorized NSDs according to their functional group (secondary amine, tertiary amine, and amide). With logistic regression models, we estimated adjusted odds ratios and 95% confidence intervals. Neural tube defect risk was associated with maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95% confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95% CI: 1.2, 2.5) amines; an association was observed for amides, but the 95% confidence interval included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine group, elevated adjusted odds ratios were observed for 3 drugs but were null for the remaining medications. Increases in risk were observed for both strata of folic acid intake (<400 µg/day, ≥400 µg/day), with a slightly higher risk in the ≥400-µg/day stratum. Our findings support previously reported positive associations between neural tube defects and periconceptional exposure to NSDs containing a secondary or tertiary amine or amide.

  17. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance among American seniors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folate deficiency has serious consequences for the fetus. Folic acid fortification of food addresses this problem. However, clinical consequences of vitamin B-12 deficiency may be worsened by high folic acid intakes, perhaps as a direct result of unmetabolized folic acid, which does not occur natura...

  18. [Fortification of food with folic acid diminishes the number of neural tube defects].

    PubMed

    Brouwer, I A

    2008-01-26

    A recent study from a research group from Quebec showed a strong decrease in the number of births affected by a neural tube defect since folic acid fortification was introduced in Canada. The prevalence decreased from 1.58 neural tube defects per 1000 births before the introduction of folic acid fortification to 0.86 per 1000 births in the period of complete fortification. Although folic acid fortification of staple food is probably the most effective way to decrease the incidence of neural tube defects, more knowledge about possible health risks should be obtained before fortification is introduced. More research is needed to determine which population groups are at risk of possible negative effects of folic acid fortification and at which level of fortification. Until then, it is important to generate more attention and publicity in order to increase awareness and knowledge concerning folic acid and to promote its use before and after conception.

  19. Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks

    PubMed Central

    Moussa, Hind N; Hosseini Nasab, Susan; Haidar, Ziad A; Blackwell, Sean C; Sibai, Baha M

    2016-01-01

    The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4–5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks. PMID:28031963

  20. Intestinal transport of zinc and folic acid: a mutual inhibitory effect

    SciTech Connect

    Ghishan, F.K.; Said, H.M.; Wilson, P.C.; Murrell, J.E.; Greene, H.L.

    1986-02-01

    Recent observations suggest an inverse relationship between folic acid intake and zinc nutriture and indicate an interaction between folic acid and zinc at the intestinal level. To define that interaction, we designed in vivo and in vitro transport studies in which folic acid transport in the presence of zinc, as well as zinc transport in the presence of folic acid was examined. These studies show that zinc transport is significantly decreased when folate is present in the intestinal lumen. Similarly folic acid transport is significantly decreased with the presence of zinc. To determine whether this intestinal inhibition is secondary to zinc and folate-forming complexes, charcoal-binding studies were performed. These studies indicate that zinc and folate from complexes at pH 2.0, but that at pH 6.0, these complexes dissolve. Therefore, our studies suggest that under normal physiological conditions a mutual inhibition between folate and zinc exists at the site of intestinal transport.

  1. Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks.

    PubMed

    Moussa, Hind N; Hosseini Nasab, Susan; Haidar, Ziad A; Blackwell, Sean C; Sibai, Baha M

    2016-06-01

    The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4-5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks.

  2. The risk of menstrual abnormalities after preconceptional use of folic acid or a folic acid-containing multivitamin in Chinese women.

    PubMed

    Shen, Lianlian; Chu, Zhiping; Yang, Jian; Wang, Yubang

    2016-01-01

    The associations of preconceptional folic acid use with menstruation-related changes were examined by a retrospective study through 219 questionnaires. The kind of folic acid (alone or with other vitamins), the using time and frequency, the menstrual regularity, the cycle length before and after use, and other menstruation-related changes after use were obtained. Two hundred of 219 participants were users, and menstruation-related changes occurred in 32 women, with abnormalities of involvement being longer cycles (increase of 3-20 days, 7.7 ± 4.8 days), shorter cycles (decrease of 3-7 days, 5.7 ± 2.3 days), irregular cycles, less blood loss, bleeding or spotting between cycles, and algomenorrhea. Seventeen women stopped using folic acid or folic acid-containing multivitamin, and sixteen of the seventeen women experienced at least one menstruation before conception. Fifteen of sixteen women found complete recovery, indicating the high possibility that these changes were attributed to the use of folic acid or folic acid-containing multivitamin.

  3. Association of low potassium diet and folic acid deficiency in patients with CKD

    PubMed Central

    Hassan, Kamal

    2015-01-01

    Background Most of the folic acid sources are rich also in potassium. Patients with chronic kidney disease (CKD) usually receive a low potassium diet. We investigated the possibility of an association between low potassium diet and folic acid deficiency. Methods In total, 128 CKD patients participated in this cross-sectional study. Sixty-four patients with CKD grades 1 and 2 were on an unrestricted potassium diet when enrolled in the study, and 64 patients with CKD grades 3 and 4 had received instructions to restrict their intake of potassium at least 6 months before enrollment in the study. Subjects were evaluated for daily intake of folic acid (DIFA), daily intake of potassium (DIK), and serum folic acid levels (SFA). Results DIFA correlated with the estimated glomerular filtration rate, the DIK, and the SFA (P<0.001). SFA correlated with the estimated glomerular filtration rate (P<0.001). Mean DIFA and mean SFA were lower among patients with CKD grades 3 and 4 than among those with CKD grades 1 and 2 (P<0.001). The mean DIFA in patients with folic acid deficiency was lower than that in those with SFA ≥7.1 nmol/L (P<0.001). There was lower SFA and threefold greater frequency of folic acid deficiency among patients with CKD grades 3 and 4 who had received instructions to restrict their intake of potassium than among patients with CKD grades 1 and 2 who were on an unrestricted potassium diet. Conclusion A potassium-restricted diet offered to patients with CKD grades 3 and 4 may be associated with folic acid deficiency. Serum levels of folic acid should be investigated before starting potassium restriction in patients with CKD grades 3 and 4, in order to identify individuals with folic acid deficiency or with marginal serum levels who should receive folic acid replacement therapy. PMID:26056461

  4. Zein nanoparticles as delivery systems for covalently linked and physically entrapped folic acid

    NASA Astrophysics Data System (ADS)

    Chuacharoen, Thanida; Sabliov, Cristina M.

    2017-02-01

    Zein nanoparticles covalently linked to folic acid were hypothesized to sustain the release of the folic acid in addition to targeting cancer cells overexpressing folate-binding receptors, whereas zein nanoparticles with physically entrapped folic acid would only be able to control the release of the bioactive without targeting of cancer cells. The two types of particles, folic acid covalently linked zein nanoparticles (ZN-FA nps) and zein nanoparticles with entrapped folic acid (ZN(FA) nps), were synthesized and the covalent link between folic acid and zein was assessed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (1H NMR). Their size, polydispersity index, zeta potential, morphology, and loading capacity were evaluated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometric technique. The release studies of the folic acid preformed in phosphate-buffered saline (PBS) at 37 °C for 7 days concluded that the release of the loaded folic acid was sustained over 7 days for both systems. The cytotoxicity was investigated using a methyl thiazolyl tetrazolium (MTT) assay, and the results showed that zein nanoparticles were biocompatible to HeLa (an overexpressing folate receptor cells) and A549 (a deficient folate receptor cells) cells, which have different levels of folate receptors on surface and both folic acid nanoparticle systems were able to diminish the adverse toxic effect of folic acid to cells. The increased uptake of ZN-FA nps relative to ZN(FA) nps supported the use of ZN-FA nps as targeting nanoagents to cells overexpressing folate receptors.

  5. Malaria in the Era of Food Fortification With Folic Acid.

    PubMed

    Nzila, Alexis; Okombo, John; Hyde, John

    2016-06-01

    Food fortified with folic acid has been available for consumption in North America for over a decade. This strategy has led to an increase in folate levels in the general population and, more importantly, a significant decrease in the incidence of neural tube defects. However, this increase in folate intake has been associated with a greater risk of cancer disease. Many African countries are now embracing this concept; however, because folate promotes malaria parasite division, as it does in cancer cells, there is a possibility of malaria exacerbation if folate intake is increased. A precedent for such a concern is the now compelling evidence showing that an increase in iron intake can lead to a higher malaria risk; as a result, mass administration of iron in malaria-endemic areas is not recommended. In this article, we review work on the effect of folate on malaria parasites. Although this topic has received little research attention, the available data suggest that the increase in folate concentration could be associated with an increase in malaria infection. Thus, the introduction of food fortification with folic acid in malaria-endemic areas should be attended by precautionary programs to monitor the risk of malaria.

  6. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    PubMed

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  7. Folic acid fortification of grain: an economic analysis.

    PubMed Central

    Romano, P S; Waitzman, N J; Scheffler, R M; Pi, R D

    1995-01-01

    OBJECTIVES. The purpose of this study was to compare the economic costs and benefits of fortifying grain with folic acid to prevent neural tube defects. METHODS. A cost-benefit analysis based on the US population, using the human capital approach to estimate the costs associated with preventable neural tube defects, was conducted. RESULTS. Under a range of assumptions about discount rates, baseline folate intake, the effectiveness of folate in preventing neural tube defects, the threshold dose that minimizes risk, and the cost of surveillance, fortification would likely yield a net economic benefit. The best estimate of this benefit is $94 million with low-level (140 micrograms [mcg] per 100 g grain) fortification and $252 million with high-level (350 mcg/100 g) fortification. The benefit-to-cost ratio is estimated at 4.3:1 for low-level and 6.1:1 for high-level fortification. CONCLUSIONS. By averting costly birth defects, folic acid fortification of grain in the United States may yield a substantial economic benefit. We may have underestimated net benefits because of unmeasured costs of neural tube defects and unmeasured benefits of higher folate intake. We may have overestimated net benefits if the cost of neurologic sequelae related to delayed diagnosis of vitamin B12 deficiency exceeds our projection. PMID:7733427

  8. Soy protein/soy polysaccharide complex nanogels: folic acid loading, protection, and controlled delivery.

    PubMed

    Ding, Xuzhe; Yao, Ping

    2013-07-09

    In this study, we developed a facile approach to produce nanogels via self-assembly of folic acid, soy protein, and soy polysaccharide. High-pressure homogenization was introduced to break down the original aggregates of soy protein, which benefits the binding of soy protein with soy polysaccharide and folic acid at pH 4.0. After a heat treatment that causes the soy protein denaturation and gelation, folic acid-loaded soy protein/soy polysaccharide complex nanogels were fabricated. The nanogels have a polysaccharide surface that makes the nanogels dispersible in acidic conditions where folic acid is insoluble and soy protein forms precipitates after heating. More importantly, the protein and polysaccharide can inhibit the reactions between dissolved oxygen and folic acid during UV irradiation. After the preparation and storage of the nanogels in the presence of heat, oxygen, and light in acidic conditions, most of the folic acid molecules in the nanogels remain in their natural structure and can be released rapidly at neutral pH, that is, in the intestine. Because most food and beverages are acidic, the nanogels are a suitable delivery system of folic acid in food and beverages.

  9. [Risk factors for prevalence of folic acid deficiency in Chinese lactating women in 2013].

    PubMed

    Bi, Y; Duan, Y F; Wang, J; Yu, D M; Yang, X G; Yin, S A; Yang, Z Y

    2016-12-06

    Objective: The study aimed to assess the folic acid status of lactating women in China and to analyze factors related to folic acid deficiency in these subjects. Methods: The data on lactating women were extracted from the Chinese National Nutrition and Health Surveillance in 2013. By a multi-stage stratified cluster random sampling method, 10 331 lactating women were selected for the study. The lactating women, 0-24 months postpartum, were from 55 sites in 30 provinces of China, excluding the Tibet Autonomous Region. A standard questionnaire was used to obtain general information and dietary intake during the previous one month period was collected using a food frequency questionnaire. A total of 20% of the total number of lactating women were randomly selected to analyze serum folic acid. Finally, 1 894 lactating women, with questionnaire results and serum folic acid data, were included in the study. Serum folic acid concentrations were analyzed using an electro-chemiluminescence immunoassay method. Folic acid deficiency was defined as a serum folic acid level <2 ng/ml. A multiple logistic regression analysis was used to analyze the factors associated with folic acid deficiency in these women. Results: After excluding abnormal values, 1 894 lactating women were included in the study. Based on our findings, the prevalence of folate deficiency was 3.0% (56/1 894) in lactating women in China. The prevalence of folic acid deficiency was 0.3% (1/388), 1.3% (7/550), 6.0% (38/639) and 3.2% (10/317) in larger, medium or small cities, general rural counties and poor rural counties, respectively. The prevalence of folic acid deficiency was 6.3% (17/269) and 2.4% (39/1 623) for minority and Han ethnic groups, respectively, and was 6.3% (52/823) and 0.4% (4/1 071) for subjects in northern and southern areas of China, respectively. Binary unconditionally logistic regression was used to analyze the factors associated with folic acid deficiency in the lactating women. The

  10. Abnormal O-GlcNAcylation of Pax3 Occurring from Hyperglycemia-Induced Neural Tube Defects Is Ameliorated by Carnosine But Not Folic Acid in Chicken Embryos.

    PubMed

    Tan, Rui-Rong; Li, Yi-Fang; Zhang, Shi-Jie; Huang, Wen-Shan; Tsoi, Bun; Hu, Dan; Wan, Xin; Yang, Xuesong; Wang, Qi; Kurihara, Hiroshi; He, Rong-Rong

    2017-01-01

    Neural tube defects (NTDs) are among the most common of the embryonic abnormalities associated with hyperglycemic gestation. In this study, the molecular mechanisms of embryonic neurogenesis influenced by hyperglycemia was investigated using chicken embryo models. High-concentration glucose was administered into chicken eggs and resulted in increased plasma and brain tissue glucose, and suppressed expression of glucose transporters (GLUTs). The rate of NTD positively correlated with hyperglycemia. Furthermore, abnormally increased O-GlcNAcylation, a nutritionally responsive modification, of the key neural tube marker Pax3 protein led to the loss of this protein. This loss was not observed in a folate-deficiency NTD induced by methotrexate. Carnosine, an endogenous dipeptide, showed significant recovery effects on neural tube development. In contrast, folic acid, a well-known periconceptional agent, surprisingly showed relatively minimal effect. Higher expression levels of the Pax3 protein were found in the carnosine-treated groups, while lower expression levels were found in folic acid groups. Furthermore, the abnormal O-GlcNAcylation of the Pax3 protein was restored by carnosine. These results suggest new insights into using endogenous nutrients for the protection of embryonic neurodevelopment affected by diabetes gestation. The abnormal excessive O-GlcNAcylation of Pax3 may be responsible for the neural tube defects associated with hyperglycemia.

  11. Folic acid and the decline in neural tube defects in Arkansas.

    PubMed

    Mosley, Bridget S; Hobbs, Charlotte A; Flowers, Bettye S; Smith, Veronica; Robbins, James M

    2007-04-01

    Folic acid has been shown to reduce the risk of pregnancies affected by neural tube defects (NTDs) by as much as 70%. Cereal grains sold in the U.S. have been fortified with folic acid since 1998. The Arkansas Reproductive Health Monitoring System and the Arkansas Folic Acid Coalition have encouraged use of folic acid and monitored the impact of increased consumption of folic acid among Arkansans. NTDs in Arkansas have declined 40% since intervention programs were implemented. The greatest decline has been observed among white and Hispanic women. Efforts to encourage folic acid consumption should continue to target Arkansas women. NTDs include anencephaly and spina bifida. These birth defects result from incomplete closure of the fetal neural tube during the first month of pregnancy. Infants with anencephaly are born without all or most of their brain and die within a few days of life. Infants with spina bifida have varying degrees of impairment ranging from little noticeable disability to severe, lifelong disability. Folic acid, when taken in supplement form has been shown to reduce the risk of a pregnancy affected by a neural tube defect by as much as 70%. As a result of this finding, the U.S. Federal Drug Administration mandated that cereal grains sold in this country be fortified with at least 140 mcg of folic acid per 100 grams of grain by January 1, 1998. Prior to mandatory fortification, the March of Dimes and the U.S. Public Health Service released statements encouraging all women of reproductive age who are capable of becoming pregnant to take 400 mcg 'of synthetic folic acid daily. The Arkansas Reproductive Health Monitoring System (ARHMS) has monitored rates of NTDs in Arkansas since 1980. ARHMS is the lead agency of the Arkansas Folic Acid Coalition whose mission is to encourage folic acid use among all Arkansas women of reproductive age. In this report, we summarize efforts by ARHMS and the Arkansas Folic Acid Coalition to increase the awareness and

  12. Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update.

    PubMed

    Chitayat, David; Matsui, Doreen; Amitai, Yona; Kennedy, Deborah; Vohra, Sunita; Rieder, Michael; Koren, Gideon

    2016-02-01

    During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid-sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4-1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3- to 5-fold higher in Northern China and 3-fold higher in India. A recent population-based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with known genetic variations in

  13. Assessment of different folic acid supplementation doses for low-birth-weight infants

    PubMed Central

    Çelik, Fatma Çakmak; Aygün, Canan; Gülten, Sedat; Bedir, Abdulkerim; Çetinoğlu, Erhan; Küçüködük, Şükrü; Bek, Yüksel

    2016-01-01

    Aim The adequacy of 50 mcg folic acid supplementation given to low-birth-weight babies was investigated. The folate levels of the mothers and infants, and breastmilk, and the optimum dose for folic acid supplementation were also investigated. Material and Methods After obtaining blood from 141 low-birth-weight infants on the 1st day of life for serum and red cell folate levels, the infants were randomly allocated into three groups according to the folic acid supplement dose. Forty-six infants were given 25 μg/d folic acid, 39 were given 50 μg/d folic acid, and 44 were given 75 μg/d folic acid. Folic acid could not be given to 12 infants. Follow-up blood samples were obtained at the end of folic acid supplementation. Maternal samples for red cell and serum folate levels and breast milk folate levels were obtained within the first 48 hours and the samples for measuring breastmilk folate level were obtained on the 3rd day postnatally. The feeding modes of the infants, maternal folic acid intake, and details of neonate intensive care unit course were recorded. Results The mean birth weight and gestational age of the infants were found as 1788.2±478.4 g and 33.5±2.9 weeks, respectively. The mean serum and red cell folate levels on admission were found as 21.2±12.2 ng/mL and 922.7±460.7 ng/mL, respectively. The mean maternal serum and red cell folate levels and the mean breast milk folate levels were found as 12.3±7.5 ng/mL, 845.5±301.4 ng/mL, and 30.6±33.0 ng/m, respectively. The breast milk folate levels of mothers who were supplemented with folic acid during pregnancy were significantly higher compared with mothers who were not supplemented with folic acid (p<0.001). Infants who were supplemented with folic acid had higher follow-up serum folate levels compared with the basal level in all groups, but there was no statistically significant difference between the groups. Conclusion This study showed that the folic acid doses of 25, 50, and 75 μcg/d affected

  14. Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update

    PubMed Central

    Chitayat, David; Matsui, Doreen; Amitai, Yona; Kennedy, Deborah; Vohra, Sunita; Rieder, Michael

    2015-01-01

    Abstract During the last decade critical new information has been published pertaining to folic acid supplementation in the prevention of neural tube defects (NTDs) and other folic acid–sensitive congenital malformations. These new data have important implications for women, their families, and health care professionals. We performed a review looking for the optimal dosage of folic acid that should be given to women of reproductive age who are planning or not avoiding conception to propose updated guidelines and thus help health care providers and patients. In addition to fortification of dietary staples with folic acid, women of reproductive age should supplement before conception with 0.4‐1.0 mg of folic acid daily as part of their multivitamins. In the United States all enriched rice is also fortified with folic acid at 0.7 mg per pound of raw rice. However, this is not the case in many countries, and it has been estimated that only 1% of industrially milled rice is fortified with folic acid. In countries where rice is the main staple (eg, China), this does not allow effective folate fortification. Whereas the incidence of NTDs is around 1/1000 in the United States, it is 3‐ to 5‐fold higher in Northern China and 3‐fold higher in India. A recent population‐based US study estimated that the reduction in NTD rates by folic acid is more modest than previously predicted. The potential of NTD prevention by folic acid is underutilized due to low adherence with folic acid supplementation, and calls for revising the policy of supplementation have been raised. We identified groups of women of reproductive age who may benefit from higher daily doses of folic acid, and this should be considered in current practice. These include women who have had previous pregnancies with NTDs, those who did not plan their pregnancy and hence did not supplement, and women with low intake or impaired adherence to daily folic acid supplementation. In addition, women with

  15. Blood folic acid, vitamin B12, and homocysteine levels in pregnant women with fetal growth restriction.

    PubMed

    Jiang, H L; Cao, L Q; Chen, H Y

    2016-12-19

    Deficiencies in nutrients such as folic acid and vitamin B12 may play a role in fetal growth restriction (FGR). However, whether folic acid, vitamin B12, or homocysteine is associated with FGR in Chinese populations remains unclear. This study investigated the relationship between these nutrient deficiencies and FGR in pregnant Chinese women. We selected 116 mother and infant pairs, and categorized the neonates into the FGR, appropriate for gestational age, and large for gestational age groups. Birth weight, body length, head circumference, body mass index (BMI), and Rohrer's body index of the newborns were measured. Serum folic acid, vitamin B12, and homocysteine levels were measured in mothers during the first three days of their hospital stay. Results showed that the FGR group exhibited reduced folic acid and vitamin B12 levels and elevated homocysteine levels than those in the other two groups. Folic acid and vitamin B12 levels were positively correlated with birth weight, head circumference, and BMI, whereas homocysteine level was negatively correlated with these variables. The FGR ratio in the folic acid and vitamin B12 deficiency group was higher than that in the sufficiency group (χ(2) = 4.717 and 4.437, P = 0.029 and 0.035, respectively). In addition, elevated homocysteine was associated with FGR (χ(2) = 5.366, P = 0.021). In conclusion, we found that folic acid and vitamin B12 deficiency was associated with elevated homocysteine levels, which may increase susceptibility to FGR.

  16. Alx3-deficient mice exhibit folic acid-resistant craniofacial midline and neural tube closure defects.

    PubMed

    Lakhwani, Sita; García-Sanz, Patricia; Vallejo, Mario

    2010-08-15

    Neural tube closure defects are among the most frequent congenital malformations in humans. Supplemental maternal intake of folic acid before and during pregnancy reduces their incidence significantly, but the mechanism underlying this preventive effect is unknown. As a number of genes that cause neural tube closure defects encode transcriptional regulators in mice, one possibility is that folic acid could induce the expression of transcription factors to compensate for the primary genetic defect. We report that folic acid is required in mouse embryos for the specific expression of the homeodomain gene Alx3 in the head mesenchyme, an important tissue for cranial neural tube closure. Alx3-deficient mice exhibit increased failure of cranial neural tube closure and increased cell death in the craniofacial region, two effects that are also observed in wild type embryos developing in the absence of folic acid. Folic acid cannot prevent these defects in Alx3-deficient embryos, indicating that one mechanism of folic acid action is through induced expression of Alx3. Thus, Alx3 emerges as a candidate gene for human neural tube defects and reveals the existence of induced transcription factor gene expression as a previously unknown mechanism by which folic acid prevents neural tube closure defects.

  17. Oral folic acid supplementation decreases palate and/or lip cleft occurrence in Pug and Chihuahua puppies and elevates folic acid blood levels in pregnant bitches.

    PubMed

    Domosławska, A; Jurczak, A; Janowski, T

    2013-01-01

    The aim of this study was to compare the frequency of the occurrence of lip and/or palate cleft (CL/CP) in new-borns of two breeds, Pugs and Chihuahuas, and to measure the folic acid blood levels in bitches during gestations both with and without folic acid oral supplementation. Bitches of 13 Pugs and 17 Chihuahuas with CL/CP cases were used in the study. In trial 1, the animals of the experimental group (n=25) were given additional folic acid from the onset of heat till the 40th day of gestation. The females of the control group (n=12) were fed a traditional diet. From all the animals blood was collected at the onset of heat, 14 days later and on the 30th day of the gestation to estimate folic acid concentration. In trial 2, the prevalence of CP/CL cases in litters from pregnancies before and after supplementation was compared. The percentage of puppies with CL/CP after supplementation decreased in both Pugs and Chihuahua puppies (10.86% and 15.78% vs. 4.76% and 4.8% respectively). On Day 0, the concentrations of folic acid were at a low physiological level (around 8 ng/ml) in all the animals. In bitches of the experimental group the blood level of folic acid on day 14th and 30th of the treatment showed an increase in both breeds (13.65 +/- 4.27 ng/ml in Pugs, 10.79 +/- 2.84 ng/ml in Chihuahuas, and 14.94 +/- 3.22 ng/ml in Pugs, 12.95 +/- 3.58 in Chihuahuas, respectively) while in the control group, this level decreased with time of gestation both in Pugs and in Chihuahuas (around 6 ng/ml). Folic acid supplementation seems to be a simple, effective preventive method to reduce the risk of CL/CP, especially in the predisposed breeds.

  18. The Effects of Periconceptional Risk Factor Exposure and Micronutrient Supplementation on Birth Defects in Shaanxi Province in Western China

    PubMed Central

    Yang, Wenfang; Zeng, Lingxia; Cheng, Yue; Chen, Zhijun; Wang, Xiang; Li, Xu; Yan, Hong

    2012-01-01

    Objectives 1) To understand the current prevalence and main types of birth defects, 2) assess the periconceptional exposure of factors associated with birth defects in Shaanxi Province, and 3) provide scientific evidence for local governments to formulate services for the primary prevention of birth defects. Methods We sampled 16,541 households from 128 townships in 16 counties/districts in Shaanxi province using a multi-stage random sampling method. Among them, 10,544 women who had live born or stillborn infants with gestational age ≥28 weeks between 2008 and 2009 were interviewed using a structured questionnaire designed to collect information about periconceptional risk factor exposure, health care service utilization, and micronutrient supplements. Logistic regression was performed to assess the risk factors associated with birth defects and adjustments were made for imbalanced social-demographic characteristics between case and control groups. Results The prevalence of congenital birth defect in Shaanxi province was 14.3/1000 births. The environment risk factors associated with birth defects include unhealthy lifestyle (Alcohol, odds ratio (OR): 3.60, 95% confidence interval (CI) 1.64−7.91; Smoking, OR: 1.32, 95% CI: 0.99−1.75; Drink strong tea, OR: 1.81, 95% CI: 1.27−2.59), exposure to heavy pollution (OR: 1.53, 95% CI: 1.01−2.30), maternal diseases (OR: 1.77, 95% CI: 1.35−2.33), drug use (OR: 2.11, 95% CI: 1.51−2.95), maternal chemical pesticide exposure (OR: 2.30, 95% CI: 1.16−4.57), and adverse pregnancy history (OR: 10.10, 95% CI: 7.55−13.53). Periconceptional folic acid or multiple micronutrients including folic acid supplementation, was associated with a reduced rate of birth defects (OR: 0.54, 95% CI: 0.29−0.998). Conclusions Health care service utilization, unhealthy lifestyle factors, and environment risk factors seem to be associated with birth defects in Shaanxi province. Governmental agencies should focus on effective primary

  19. High folic acid intake reduces natural killer cell cytotoxicity in aged mice.

    PubMed

    Sawaengsri, Hathairat; Wang, Junpeng; Reginaldo, Christina; Steluti, Josiane; Wu, Dayong; Meydani, Simin Nikbin; Selhub, Jacob; Paul, Ligi

    2016-04-01

    Presence of unmetabolized folic acid in plasma, which is indicative of folic acid intake beyond the metabolic capacity of the body, is associated with reduced natural killer (NK) cell cytotoxicity in postmenopausal women ≥50years. NK cells are cytotoxic lymphocytes that are part of the innate immune system critical for surveillance and defense against virus-infected and cancer cells. We determined if a high folic acid diet can result in reduced NK cell cytotoxicity in an aged mouse model. Female C57BL/6 mice (16-month-old) were fed an AIN-93M diet with the recommended daily allowance (1× RDA, control) or 20× RDA (high) folic acid for 3months. NK cytotoxicity was lower in splenocytes from mice fed a high folic acid diet when compared to mice on control diet (P<.04). The lower NK cell cytotoxicity in high folic acid fed mice could be due to their lower mature cytotoxic/naïve NK cell ratio (P=.03) when compared to the control mice. Splenocytes from mice on high folic acid diet produced less interleukin (IL)-10 when stimulated with lipopolysaccharide (P<.05). The difference in NK cell cytotoxicity between dietary groups was abolished when the splenocytes were supplemented with exogenous IL-10 prior to assessment of the NK cytotoxicity, suggesting that the reduced NK cell cytotoxicity of the high folic acid group was at least partially due to reduced IL-10 production. This study demonstrates a causal relationship between high folic acid intake and reduced NK cell cytotoxicity and provides some insights into the potential mechanisms behind this relationship.

  20. Folate status of young Canadian women after folic acid fortification of grain products.

    PubMed

    Shuaibi, Aysheh M; House, James D; Sevenhuysen, Gustaaf P

    2008-12-01

    Women of childbearing age are advised to consume folic acid-containing supplements. Whether this remains necessary after folic acid fortification of the food supply in North America has yet to be determined. The objectives of this study were to assess folate intakes and the contribution of folic acid to the diets of women of childbearing age in the post-folic acid fortification era. Using a cross-sectional study design, fasting blood samples were obtained from 95 women (aged 18 to 25 years), and the samples were analyzed for serum and red blood cell folate, as well for total homocysteine. Dietary and supplemental folate intakes were assessed. The biochemical evidence showed that no women were folate deficient, but only 14% reached red blood cell folate concentrations associated with significant reductions in neural tube defect risk. Mean dietary intake of food folic acid was 96+/-64 microg/day, supplemental folic acid was 94+/-189 microg/day, natural folate was 314+/-134 microg/day, and the total intake, as dietary folate equivalents, was 646+/-368 microg dietary folate equivalents/day. Therefore, intakes of folic acid from fortified foods are within the level originally predicted for the fortification efforts; however, only 17% of participants met the special recommendation for women capable of becoming pregnant (400 microg folic acid daily from supplements, fortified foods, or both in addition to consuming food folate from a varied diet). These data suggest that women of childbearing age are achieving positive folate status in the postfortification era, but it may not be sufficient to achieve red blood cell folate concentrations associated with a significant reduction in neural tube defect risk. Even with food fortification, women of childbearing age should be advised to take a folic acid-containing supplement on a daily basis.

  1. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    PubMed

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola.

  2. Assessment of the value of a competitive protein binding radioassay of folic acid in the detection of folic acid deficiency.

    PubMed Central

    Bain, B J; Wickramasinghe, S N; Broom, G N; Litwinczuk, R A; Sims, J

    1984-01-01

    The diagnostic value of the Becton Dickinson Radioassay Kit (125I) for the the assay of red cell folate has been investigated. The assay was acceptable with regards to precision but was non-linear with changing packed cell volume. Sensitivity of the assay was satisfactory, with 24 of 25 folate deficient patients giving red cell folate values which fell below the reference range. Specificity of the assay in the detection of folate deficiency was less satisfactory. As with microbiological assays, a considerable proportion of vitamin B12 deficient patients had low red cell folate values. In addition, low concentrations were found in 12% of patients who were unlikely to be deficient in either vitamin B12 or folic acid. PMID:6470170

  3. Folic acid supplementation attenuates hyperhomocysteinemia-induced preeclampsia-like symptoms in rats☆

    PubMed Central

    Wang, Jun; Cui, Yan; Ge, Jing; Ma, Meijing

    2012-01-01

    Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly. To establish a hyperhomocysteinemic pregnant rat model, 2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation. Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction. Results showed that systolic blood pressure, proteinuria/creatinine ratio, and plasma homocysteine levels in the hyperhomocysteinemic pregnant rats increased significantly, and that body weight and brain weight of rat pups significantly decreased. Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups. These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia- induced preeclampsia in pregnant rats without influencing brain development of rat pups. PMID:25624824

  4. Rhodamine-6G can photosensitize folic acid decomposition through electron transfer

    NASA Astrophysics Data System (ADS)

    Hirakawa, Kazutaka; Ito, Hiroki

    2015-05-01

    Rhodamine-6G photosensitized folic acid decomposition in aqueous solution, and its quantum yield in the presence of 10 μM folic acid was 9.9 × 10-6. A possible mechanism of this photodecomposition is direct oxidation through an electron transfer from folic acid to rhodamine-6G. The fluorescence lifetime of rhodamine-6G was slightly decreased by folic acid, suggesting electron transfer in the excited singlet state of rhodamine-6G. The quenching rate coefficient estimated from the Stern-Volmer plot of the fluorescence quenching supported that this electron transfer proceeds as a diffusion-controlled reaction. The quantum yields of the electron transfer and the following reaction could be determined.

  5. Encapsulation of folic acid in food hydrocolloids through nanospray drying and electrospraying for nutraceutical applications.

    PubMed

    Pérez-Masiá, Rocío; López-Nicolás, Rubén; Periago, Maria Jesús; Ros, Gaspar; Lagaron, Jose M; López-Rubio, Amparo

    2015-02-01

    In this work, two different technologies (electrospraying and nanospray drying) were evaluated for the encapsulation of folic acid using both a whey protein concentrate (WPC) matrix and a commercial resistant starch. The morphology of the capsules, molecular organization of the matrices upon encapsulation, encapsulation efficiency, and stability of the folic acid within the capsules under different storage conditions and upon thermal exposure were studied. Results showed that spherical nano-, submicro- and microcapsules were obtained through both techniques, although electrospraying led to smaller capsule sizes and to an enhanced control over their size distribution. Greater encapsulation efficiency was observed using WPC as encapsulating matrix, probably related to interactions between the protein and folic acid which favoured the incorporation of the bioactive. The best results in terms of bioactive stabilization in the different conditions assayed were also obtained for the WPC capsules, although both materials and encapsulation techniques led to improved folic acid stability, especially under dry conditions.

  6. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...

  7. Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

    PubMed Central

    Tian, Tian; Bai, Dong; Li, Wen; Huang, Guo-Wei; Liu, Huan

    2016-01-01

    Alzheimer’s disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component—presenilin 1 (PS1)—in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression. PMID:27618097

  8. Folic acid supplementation during early pregnancy and the risk of gestational hypertension and preeclampsia.

    PubMed

    Li, Zhiwen; Ye, Rongwei; Zhang, Le; Li, Hongtian; Liu, Jianmeng; Ren, Aiguo

    2013-04-01

    Emerging evidence has suggested that folic acid-containing multivitamins may markedly reduce the risk of gestational hypertension or preeclampsia. We examined whether maternal supplementation with folic acid alone during early pregnancy can prevent the occurrence of gestational hypertension and preeclampsia. The data are from a large population-based cohort study established to evaluate the effectiveness of the campaign to prevent neural tube defects with folic acid supplementation in China. We selected participants who were registered in 2 southern provinces, had exact information on folic acid use, and were not affected by chronic hypertension or diabetes mellitus before 20 weeks gestation. A logistic regression model was used to adjust for the effects of the main potential confounders, including age, body mass index, education, occupation, parity, and multiple births. The study size had 99.9% power (α=0.05) to detect a decrease of 10% over the unexposed rate of 9.4% for gestational hypertension. Among the 193 554 women (47.9% took folic acid, 52.1% did not), the overall incidence of gestational hypertension and preeclampsia was 9.5% and 2.5%, respectively. The incidence of gestational hypertension and preeclampsia was 9.7% and 2.5% for women who took folic acid, and 9.4% and 2.4% for women who did not use it. The adjusted risk ratio associated with folic acid use was 1.08 (95% confidence interval, 1.04-1.11) for gestational hypertension and 1.11 (95% confidence interval, 1.04-1.18) for preeclampsia. Our findings suggest that daily consumption of 400 μg folic acid alone during early pregnancy cannot prevent the occurrence of gestational hypertension and preeclampsia.

  9. Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice.

    PubMed

    Tian, Tian; Bai, Dong; Li, Wen; Huang, Guo-Wei; Liu, Huan

    2016-09-09

    Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component-presenilin 1 (PS1)-in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression.

  10. Folic acid and safflower oil supplementation interacts and protects embryos from maternal diabetes-induced damage.

    PubMed

    Higa, R; Kurtz, M; Mazzucco, M B; Musikant, D; White, V; Jawerbaum, A

    2012-05-01

    Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.

  11. Pros and cons of increasing folic acid and vitamin B12 intake by fortification.

    PubMed

    Allen, Lindsay H

    2012-01-01

    There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects. The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes briefly data on neural tube defect reduction and other benefits of folic acid fortification as these have been reviewed in more detail elsewhere. More attention is drawn to questions that have been raised about the possible adverse effects of folic acid fortification including the incidence of colorectal cancer and immune function. The main question addressed here is whether folic acid fortification can exacerbate the adverse effects of vitamin B12 deficiency. Most analyses of this question have been conducted in wealthier countries based on data from elderly populations - which have the highest prevalence of vitamin B12 deficiency. However, of potentially greater concern is the increasingly common practice of folic acid fortification in developing countries, where folate status is probably often adequate even prior to fortification, and vitamin B12 depletion or deficiency is common. To add to this information, data from a group of Chilean elderly with a range of vitamin B12 status and exposed to high levels of folic acid fortification will be presented.

  12. The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism

    PubMed Central

    Liang, Shuang; Zhou, Yuanpeng; Wang, Huijun; Qian, Yanyan; Ma, Duan; Tian, Weidong; Persaud-Sharma, Vishwani; Yu, Chen; Ren, Yunyun; Zhou, Shufeng; Li, Xiaotian

    2014-01-01

    Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r = 0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P = 0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid. PMID:24524080

  13. [The effect of folic acid fortification on the reduction of neural tube defects].

    PubMed

    Santos, Leonor Maria Pacheco; Pereira, Michelle Zanon

    2007-01-01

    Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic.

  14. Maternal Folic Acid Supplementation during Pregnancy and Childhood Allergic Disease Outcomes: A Question of Timing?

    PubMed Central

    McStay, Catrina L.; Prescott, Susan L.; Bower, Carol; Palmer, Debra J.

    2017-01-01

    Since the early 1990s, maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy, to reduce the risk of infant neural tube defects. In addition, many countries have also implemented the folic acid fortification of staple foods, in order to promote sufficient intakes amongst women of a childbearing age, based on concerns surrounding variable dietary and supplementation practices. As many women continue to take folic acid supplements beyond the recommended first trimester, there has been an overall increase in folate intakes, particularly in countries with mandatory fortification. This has raised questions on the consequences for the developing fetus, given that folic acid, a methyl donor, has the potential to epigenetically modify gene expression. In animal studies, folic acid has been shown to promote an allergic phenotype in the offspring, through changes in DNA methylation. Human population studies have also described associations between folate status in pregnancy and the risk of subsequent childhood allergic disease. In this review, we address the question of whether ongoing maternal folic acid supplementation after neural tube closure, could be contributing to the rise in early life allergic diseases. PMID:28208798

  15. Development of electrochemical folic acid sensor based on hydroxyapatite nanoparticles

    NASA Astrophysics Data System (ADS)

    Kanchana, P.; Sekar, C.

    2015-02-01

    We report the synthesis of hydroxyapatite (HA) nanoparticles (NPs) by a simple microwave irradiation method and its application as sensing element for the precise determination of folic acid (FA) by electrochemical method. The structure and composition of the HA NPs characterized using XRD, FTIR, Raman and XPS. SEM and EDX studies confirmed the formation of elongated spherical shaped HA NPs with an average particle size of about 34 nm. The HA NPs thin film on glassy carbon electrode (GCE) were deposited by drop casting method. Electrocatalytic behavior of FA in the physiological pH 7.0 was investigated by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and chronoamperometry. The fabricated HA/GCE exhibited a linear calibration plot over a wide FA concentration ranging from 1.0 × 10-7 to 3.5 × 10-4 M with the detection limit of 75 nM. In addition, the HA NPs modified GCE showed good selectivity toward the determination of FA even in the presence of a 100-fold excess of ascorbic acid (AA) and 1000-fold excess of other common interferents. The fabricated biosensor exhibits good sensitivity and stability, and was successfully applied for the determination of FA in pharmaceutical samples.

  16. Characteristics of U.S. Adults with Usual Daily Folic Acid Intake above the Tolerable Upper Intake Level: National Health and Nutrition Examination Survey, 2003-2010.

    PubMed

    Orozco, Angela M; Yeung, Lorraine F; Guo, Jing; Carriquiry, Alicia; Berry, Robert J

    2016-04-01

    The Food and Drug Administration mandated that by 1998, all enriched cereal grain products (ECGP) be fortified with folic acid in order to prevent the occurrence of neural tube defects. The Institute of Medicine established the tolerable upper intake level (UL) for folic acid (1000 µg/day for adults) in 1998. We characterized U.S. adults with usual daily folic acid intake exceeding the UL. Using NHANES 2003-2010 data, we estimated the percentage of 18,321 non-pregnant adults with usual daily folic acid intake exceeding the UL, and among them, we calculated the weighted percentage by sex, age, race/ethnicity, sources of folic acid intake, supplement use and median usual daily folic acid intakes. Overall, 2.7% (standard error 0.6%) of participants had usual daily intake exceeding the UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5% took supplements containing folic acid. When stratified by sex and age groups among those with usual daily folic acid intake exceeding the UL, 20.8% were women aged 19-39 years. Those with usual daily intake exceeding the folic acid UL were more likely to be female, non-Hispanic white, supplement users or to have at least one chronic medical condition compared to those not exceeding the folic acid UL. Among those with usual daily folic acid intake exceeding the UL who also took supplements, 86.6% took on average >400 µg of folic acid/day from supplements. Everyone with usual daily folic acid intake exceeding the UL consumed folic acid from multiple sources. No one in our study population had usual daily folic acid intake exceeding the UL through consumption of mandatorily-fortified enriched cereal grain products alone. Voluntary consumption of supplements containing folic acid is the main factor associated with usual daily intake exceeding the folic acid UL.

  17. Association between serum folic acid level and erectile dysfunction.

    PubMed

    Karabakan, M; Erkmen, A E; Guzel, O; Aktas, B K; Bozkurt, A; Akdemir, S

    2016-06-01

    This study measured the serum folic acid (FA) level in patients with erectile dysfunction (ED) and evaluated the possible association between the serum FA level and erectile function. The study divided 120 patients with ED into 3 groups of 40 patients each: those with severe, moderate and mild ED. Forty healthy men served as controls. Fasting serum samples were obtained, and the total testosterone, cholesterol and FA levels were measured using chemiluminescent immunoassays. There were no significant differences in the mean age, mean body mass index or mean serum total testosterone and cholesterol levels among the three ED groups and controls (P > 0.05). The mean serum FA concentrations were 7.2 ± 3.7, 7.1 ± 3.2, 10.2 ± 4.6 and 10.7 ± 4.6 ng ml(-1) in the severe, moderate and mild ED and control groups respectively. The mean serum FA concentration was significantly higher in the control group than in the severe and moderate ED groups (both P < 0.001), but not the mild ED group (P = 0.95). Considering the significant differences in the serum FA levels between the control and ED groups, serum FA deficiency might reflect the severity of ED.

  18. Does folic acid supplementation prevent or promote colorectal cancer? Results from model-based predictions.

    PubMed

    Luebeck, E Georg; Moolgavkar, Suresh H; Liu, Amy Y; Boynton, Alanna; Ulrich, Cornelia M

    2008-06-01

    Folate is essential for nucleotide synthesis, DNA replication, and methyl group supply. Low-folate status has been associated with increased risks of several cancer types, suggesting a chemopreventive role of folate. However, recent findings on giving folic acid to patients with a history of colorectal polyps raise concerns about the efficacy and safety of folate supplementation and the long-term health effects of folate fortification. Results suggest that undetected precursor lesions may progress under folic acid supplementation, consistent with the role of folate role in nucleotide synthesis and cell proliferation. To better understand the possible trade-offs between the protective effects due to decreased mutation rates and possibly concomitant detrimental effects due to increased cell proliferation of folic acid, we used a biologically based mathematical model of colorectal carcinogenesis. We predict changes in cancer risk based on timing of treatment start and the potential effect of folic acid on cell proliferation and mutation rates. Changes in colorectal cancer risk in response to folic acid supplementation are likely a complex function of treatment start, duration, and effect on cell proliferation and mutations rates. Predicted colorectal cancer incidence rates under supplementation are mostly higher than rates without folic acid supplementation unless supplementation is initiated early in life (before age 20 years). To the extent to which this model predicts reality, it indicates that the effect on cancer risk when starting folic acid supplementation late in life is small, yet mostly detrimental. Experimental studies are needed to provide direct evidence for this dual role of folate in colorectal cancer and to validate and improve the model predictions.

  19. Effect of folic acid supplementation on homocysteine concentration and association with training in handball players

    PubMed Central

    2013-01-01

    Background Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. Objective The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. Design A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. Results Bivariate analysis showed a significant negative correlation (P < 0.01) between Hcy and folic acid concentrations (r = −0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. Conclusion Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid

  20. Folic acid supplementation increases cutaneous vasodilator sensitivity to sympathetic nerve activity in older adults.

    PubMed

    Stanhewicz, Anna E; Greaney, Jody L; Alexander, Lacy M; Kenney, W Larry

    2017-02-22

    During heat stress, blunted increases in skin sympathetic nervous system activity (SSNA) and reductions in end-organ vascular responsiveness contribute to the age-related reduction in reflex cutaneous vasodilation. In older adults, folic acid supplementation improves the cutaneous vascular conductance (CVC) response to passive heating; however, the influence of folic acid supplementation on SSNA:CVC transduction is unknown. Fourteen older adults (66±1yrs, 8M/6F) ingested folic acid (5mg·day(-1)) or placebo for 6 weeks in a randomized, double-blind, crossover design. In protocol 1, esophageal temperature (Tes) was increased by 1.0ºC (water-perfused suit) while SSNA (peroneal microneurography) and red cell flux in the innervated dermatome (laser Doppler flowmetry; dorsum of the foot) were continuously measured. In protocol 2, two intradermal microdialysis fibers were placed in the skin of the lateral calf for graded infusions of acetylcholine (ACh; 10(-10) to 10(-1)M) with and without nitric oxide synthase (NOS) blockade (20mM L-NAME). Folic acid improved reflex vasodilation (46±4% vs. 31±3 %CVCmax for placebo; P<0.001) without affecting the increase in SSNA (Δ506±104% vs. Δ415±73% for placebo; NS). Folic acid increased the slope of the SSNA:CVC relation (0.08±0.02 vs. 0.05±0.01 for placebo; P<0.05) and extended the response range. Folic acid augmented ACh-induced vasodilation (83±3% vs. 66±4 %CVCmax for placebo; P=0.002); however there was no difference between treatments at the NOS-inhibited site (53±4% vs. 52±4% CVCmax for placebo; NS). These data demonstrate that folic acid supplementation enhances reflex vasodilation by increasing the sensitivity of skin arterioles to central sympathetic nerve outflow during hyperthermia in aged human subjects.

  1. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    PubMed

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

  2. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing.

    PubMed

    Scaglione, Francesco; Panzavolta, Giscardo

    2014-05-01

    1. Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism. Mammals cannot synthesize folate and depend on supplementation to maintain normal levels. Low folate status may be caused by low dietary intake, poor absorption of ingested folate and alteration of folate metabolism due to genetic defects or drug interactions. 2. Folate deficiency has been linked with an increased risk of neural tube defects, cardiovascular disease, cancer and cognitive dysfunction. Most countries have established recommended intakes of folate through folic acid supplements or fortified foods. External supplementation of folate may occur as folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF). 3. Naturally occurring 5-MTHF has important advantages over synthetic folic acid - it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects. Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency, reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism. Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation. 4. We review the evidence for the use of 5-MTHF in preventing folate deficiency.

  3. [Study of Reaction Dynamics between Bovine Serum Albumin and Folic Acid by Stopped-Flow/Fluorescence].

    PubMed

    Ye, San-xian; Luo, Yun-jing; Qiao, Shu-liang; Li, Li; Liu, Cai-hong; Shi, Jian-long; An, Xue-jing

    2016-01-01

    As a kind of coenzyme of one-carbon enzymes in vivo, folic acid belongs to B vitamins, which can interact with other vitamins and has great significance for converting among amino acids, dividing growth of cells and protein synthesis reactions. Half-life, concentration and reaction rate constant of drugs are important parameters in pharmacokinetic study. In this paper, by utilizing fluorescence spectrophotometer and stopped-flow spectrum analyzer, reaction kinetic parameters between bovine serum albumin(BSA) and folic acid in a bionic system have been investigated, which provide references for parameters of drug metabolism related to folic acid. By using Stern-Volmer equation dealing with fluorescence quenching experiments data, we concluded that under 25, 30, and 37 degrees C, the static quenching constants of folic acid to intrinsic fluorescence from bovine serum albumin were 2.455 x 10(10), 4.900 x 10(10) and 6.427 x 10(10) L x mol(-1) x s(-1) respectively; The results of kinetic reaction rate have shown that the reaction rate of BSA and folic acid are greater than 100 mol x L(-1) x s(-1) at different temperatures, pH and buffering media, illustrating that the quenching mechanism between BSA and folic acid is to form composite static quenching process. Reaction concentration of bovine serum albumin and its initial concentration were equal to the secondary reaction formula, and the correlation coefficient was 0.998 7, while the half-life (t1/2) was 0.059 s at physiological temperature. With the increase of folic acid concentration, the apparent rate constant of this reaction had a linear increasing trend, the BSA fluorescence quenching rate constant catalyzed by folic acid was 3.174 x 10(5) mol x L(-1) x s(-1). Furthermore, with different buffer, the apparent rate constant and reaction rate constant of BSA interacting with folic acid were detected to explore the influence on the reaction under physiological medium, which is of great significance to determine the

  4. Effect of folic acid and zinc sulphate on endocrine parameters and seminal antioxidant level after varicocelectomy.

    PubMed

    Nematollahi-Mahani, S N; Azizollahi, G H; Baneshi, M R; Safari, Z; Azizollahi, S

    2014-04-01

    Varicocele is among the most common problems which may lead to male infertility. Spermatogenesis is impaired as a consequence of this vascular defect, through mechanisms that are not well described. This study aimed to evaluate serum hormonal level (inhibin B, FSH and testosterone) and seminal plasma antioxidant defence levels after folic acid and zinc sulphate administration in varicocelectomised patients. Participants were randomly allocated to four experimental groups. Our randomisation schedule was as follows: zinc sulphate/folic acid, folic acid, zinc sulphate and placebo. The patients underwent varicocelectomy, before which a blood and semen sample were obtained and also three and six months after varicocelectomy for evaluation of blood hormonal level (FSH, testosterone, inhibin B) and seminal oxidative stress status (nitric oxide, superoxide dismutase, total antioxidant capacity). Patients in different groups took orally one capsule per day after dinner following varicocelectomy for 6 months. A significant rise in peripheral blood inhibin B and seminal plasma activity was detected in the zinc sulphate/folic acid group after 6 months. The present clinical trial indicates a change in the hormonal status of varicocelectomised patients following long-term administration of zinc sulphate and folic acid.

  5. Evaluation of Surfactants-Assisted Folic Acid-Loaded Pectin Submicrospheres: Characterization and Hemocompatibility Assay.

    PubMed

    Varuna Kumara, J B; Ravikumara, N R; Madhusudhan, Basavaraj

    2016-10-01

    Folic acid is used for preventing and treating multiple diseases and disorders, administered in the form of oral supplements. The present research work was aimed to study the influence of two non-ionic surfactants Poloxamer and Tween 80 (Polysorbate 80) on pectin submicrospheres formulations. Typical natural polymer pectin was used to encapsulate folic acid by cross linking method. The resultant submicrospheres contributed to improve the aqueous solubility to enhance the bioavailability of folic acid. During investigation, it was observed that pectin polymers influenced kinetics of the rate of reaction more intensively than the surfactants. The physical phenomenon caused the change in their size, shape and chemistry of pectin polymers transforming into submicrospheres in aqueous condition. The characteristic differences of submicrospheres were assessed by scanning electron microscopy, differential scanning calorimetry and Fourier-transform infrared spectroscopy. The average diameters of the submicrospheres ranged between 250 and 500 nm. The encapsulation efficiency of submicrospheres ranged between 80 and 96 %. The characteristic swelling behavior of lyophilized submicrospheres was influenced by the ratio of pectin polymers and folic acid used in the formulations. The submicrospheres systems exhibited controlled release of folic acid due to the pH-dependent solubility of pectin polymers in aqueous medium. The submicrospheres showed good haemocompatibility suggesting them to be promising candidates for oral delivery.

  6. Tailoring folic acid and methotrexate-attributed quantum dots for integrated cancer cell imaging and therapy

    NASA Astrophysics Data System (ADS)

    Fahmi, Mochamad Zakki; Chang, Jia-Yaw

    2016-03-01

    Potential application of folic acid and methotrexate-attributed AgInS2-ZnS quantum dots on both detection and therapeutic of cancer cell were intensively investigated on this study. In the initial step, the bright luminescent of QDs, with % QY up to 55.3, were synthesized with one-pot two-step process resulting narrow particle distribution and successfully transferred to water phase without significant effect on optical properties. The water-soluble AgInS2-ZnS quantum dots (QDs) encapsulated with oleylamine have been successfully prepared by ultrasonication assisting. Several aspect including QDs characterization, pH stability, ionic strength, and bonding properties were investigated to reach desired condition of water-soluble AgInS2-ZnS QDs. Folic acid was further conjugated to QDs for HeLa and MCF7 cancer cell imaging to performs the targeting capability. Moreover, folic acid is efficiently internalized into cell through the receptor-mediated endocytosis even when conjugated with a wide variety of molecules. Confocal imaging characterization further informs folic acid-conjugated AgInS2-ZnS QDs could most specific targeted to the human cervical (HeLa) cells. The therapeutic feature of QDs on HeLa cancer cell was conjugated by attributing methotrexate on the QDs, instead of folic acid, and the design could improve on inhibiting the cancer cell viability as well as its fluorescent intensity.

  7. Quantum dot-folic acid conjugates as potential photosensitizers in photodynamic therapy of cancer.

    PubMed

    Morosini, Vincent; Bastogne, Thierry; Frochot, Céline; Schneider, Raphaël; François, Aurélie; Guillemin, François; Barberi-Heyob, Muriel

    2011-05-01

    This study examined the in vitro potential of bioconjugated quantum dots (QDs) as photosensitizers for photodynamic therapy (PDT). According to our previous approaches using photosensitizers, folic acid appears to be an optimal targeting ligand for selective delivery of attached therapeutic agents to cancer tissues. We synthesized hydrophilic near infrared emitting CdTe(S)-type QDs conjugated with folic acid using different spacers. Photodynamic efficiency of QDs conjugated or not with folic acid was evaluated on KB cells, acting as a positive control due to their overexpression of FR-α, and HT-29 cells lacking FR-α, as negative control. A design of experiments was suggested as a rational solution to evaluate the impacts of each experimental factor (QD type and concentration, light fluence and excitation wavelength, time of contact before irradiation and cell phenotype). We demonstrated that, for concentrations lower than 10 nM, QDs displayed practically no cytotoxic effect without light exposure for both cell lines. Whereas QDs at 2.1 nM displayed a weak photodynamic activity, a concentration of 8 nM significantly enhanced the photodynamic efficiency characterized by a light dose-dependent response. A statistically significant difference in photodynamic efficiency between KB and HT-29 cells was evidenced in the case of folic acid-conjugated QDs. Optimal conditions led to an enhanced photocytotoxicity response, allowing us to validate the ability of QDs to generate a photodynamic effect and of folic acid-conjugated QDs for targeted PDT.

  8. Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction

    PubMed Central

    Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.

    2012-01-01

    Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention. PMID:21715240

  9. A new perspective on neural tube defects: folic acid and microRNA misexpression.

    PubMed

    Shookhoff, J M; Gallicano, G Ian

    2010-05-01

    Neural tube defects (NTDs) are the second most common birth defects in the United States. It is well known that folic acid supplementation decreases about 70% of all NTDs, although the mechanism by which this occurs is still relatively unknown. The current theory is that folic acid deficiency ultimately leads to depletion of the methyl pool, leaving critical genes unmethylated, and, in turn, their improper expression leads to failure of normal neural tube development. Recently, new studies in human cell lines have shown that folic acid deficiency and DNA hypomethylation can lead to misexpression of microRNAs (miRNAs). Misexpression of critical miRNAs during neural development may lead to a subtle effect on neural gene regulation, causing the sometimes mild to severely debilitating range of phenotypes exhibited in NTDs. This review seeks to cohesively integrate current information regarding folic acid deficiency, methylation cycles, neural development, and miRNAs to propose a potential model of NTD formation. In addition, we have examined the relevant gene pathways and miRNAs that are predicted to affect them, and based on our investigation, we have devised a basic template of experiments for exploring the idea that miRNA misregulation may be linked to folic acid deficiency and NTDs.

  10. [Evaluation of folate substitution in women with epilepsy. Determination of erythrocyte folic acid concentrations].

    PubMed

    Bauer, J; Bös, M; Rück, J; Stoffel-Wagner, B

    2011-04-01

    Insufficient maternal folate concentrations appear to be a fetal risk factor for neural tube defects (NTD). Erythrocyte folate concentrations are widely accepted as an indicator of tissue folate storage. We retrospectively evaluated erythrocyte folate concentrations to examine if a recommended daily dosage of 5 mg folic acid is sufficient to balance the impact of antiepileptic drugs (AED) on folate metabolism in women with epilepsy. Data of 48 women (mean age 30.3 years) with idiopathic epilepsy with generalized seizures (n=12) or symptomatic epilepsy with focal seizures (n=36) were available, 43 women submitted to further analysis and 30 women received AED monotherapy. Duration of folic acid supplementation varied between 0.5 and 12 months. The daily dosage of folic acid ranged from 0.4 to 15 mg and 32 women received 5 mg/day. Erythrocyte folate concentrations ranged from 282 to 1596 ng/ml (mean 780 ng/ml). In 29 out of the 32 women (90.6%) on 5 mg folic acid per day, red cell folate was ≥400 ng/ml. In previous studies the risk for NTD was estimated to be 0.8‰ if red cell folate was ≥400 ng/ml. Our results suggest that 5 mg/day folic acid as preconception supplementation in women with epilepsy is effective to balance the impact of AEDs on folate metabolism in women with epilepsy.

  11. Nucleotide precursors prevent folic acid-resistant neural tube defects in the mouse.

    PubMed

    Leung, Kit-Yi; De Castro, Sandra C P; Savery, Dawn; Copp, Andrew J; Greene, Nicholas D E

    2013-09-01

    Closure of the neural tube during embryogenesis is a crucial step in development of the central nervous system. Failure of this process results in neural tube defects, including spina bifida and anencephaly, which are among the most common birth defects worldwide. Maternal use of folic acid supplements reduces risk of neural tube defects but a proportion of cases are not preventable. Folic acid is thought to act through folate one-carbon metabolism, which transfers one-carbon units for methylation reactions and nucleotide biosynthesis. Hence suboptimal performance of the intervening reactions could limit the efficacy of folic acid. We hypothesized that direct supplementation with nucleotides, downstream of folate metabolism, has the potential to support neural tube closure. Therefore, in a mouse model that exhibits folic acid-resistant neural tube defects, we tested the effect of specific combinations of pyrimidine and purine nucleotide precursors and observed a significant protective effect. Labelling in whole embryo culture showed that nucleotides are taken up by the neurulating embryo and incorporated into genomic DNA. Furthermore, the mitotic index was elevated in neural folds and hindgut of treated embryos, consistent with a proposed mechanism of neural tube defect prevention through stimulation of cellular proliferation. These findings may provide an impetus for future investigations of supplemental nucleotides as a means to prevent a greater proportion of human neural tube defects than can be achieved by folic acid alone.

  12. Optimization of folic acid nano-emulsification and encapsulation by maltodextrin-whey protein double emulsions.

    PubMed

    Assadpour, Elham; Maghsoudlou, Yahya; Jafari, Seid-Mahdi; Ghorbani, Mohammad; Aalami, Mehran

    2016-05-01

    Due to susceptibility of folic acid like many other vitamins to environmental and processing conditions, it is necessary to protect it by highly efficient methods such as micro/nano-encapsulation. Our aim was to prepare and optimize real water in oil nano-emulsions containing folic acid by a low energy (spontaneous) emulsification technique so that the final product could be encapsulated within maltodextrin-whey protein double emulsions. A non ionic surfactant (Span 80) was used for making nano-emulsions at three dispersed phase/surfactant ratios of 0.2, 0.6, and 1.0. Folic acid content was 1.0, 2.0, and 3.0mg/mL of dispersed phase by a volume fraction of 5.0, 8.5, and 12%. The final optimum nano-emulsion formulation with 12% dispersed phase, a water to surfactant ratio of 0.9 and folic acid content of 3mg/mL in dispersed phase was encapsulated within maltodextrin-whey protein double emulsions. It was found that the emulsification time for preparing nano-emulsions was between 4 to 16 h based on formulation variables. Droplet size decreased at higher surfactant contents and final nano-emulsions had a droplet size<100 nm. Shear viscosity was higher for those formulations containing more surfactant. Our results revealed that spontaneous method could be used successfully for preparing stable W/O nano-emulsions containing folic acid.

  13. Folic Acid Supplementation Is Suboptimal in a National Cohort of Older Veterans Receiving Low Dose Oral Methotrexate

    PubMed Central

    Tonner, Chris; Miao, Yinghui; Yazdany, Jinoos; Gannon, Jacqueline; Boscardin, W. John; Daikh, David I.; Steinman, Michael A.

    2016-01-01

    Objectives Co-prescription of folic acid in patients receiving low dose oral methotrexate is recommended because it reduces adverse events and prolongs the use of methotrexate (MTX). However, little is known about how often new users of methotrexate are co-prescribed folic acid, and what factors are associated with its use. We aimed to determine the prevalence, predictors of, and persistence of folic acid use in a population-based cohort of MTX users with rheumatic diseases. Methods Using a national, administrative database of patients seen through the Veterans Health Administration (VHA) that included pharmacy and laboratory data, we performed an observational cohort study of veterans over 65 years old who were new users of MTX. We used log-binomial regression to identify independent predictors of folic acid use and Kaplan Meyer survival analysis to examine persistence of folic acid over time. Results We studied 2467 incident users of MTX. 27% of patients were not prescribed folic acid through the VHA pharmacy within 30 days of MTX initiation. Patients who did not see a rheumatologist were 23% less likely to receive folic acid compared to patients who did have a rheumatologist visit during the baseline period (RR (95% CI) 0.77 (0.72, 0.82). These results remained unchanged even after adjusting for demographic, clinical, and other factors (adjusted RR (95% CI) 0.78 (0.74, 0.85)). After 20 months, only 50% of patients continued to receive folic acid. Conclusions In a nationwide VHA cohort of new users of oral MTX, many patients did not receive folic acid or discontinued it over time. Rheumatologists were more likely to prescribe folic acid than other providers. These data highlight the need to improve patient safety for users of methotrexate by standardizing workflows for folic acid supplementation. PMID:27977768

  14. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention.

    PubMed

    Greenberg, James A; Bell, Stacey J; Guan, Yong; Yu, Yan-Hong

    2011-01-01

    Folate (vitamin B(9)) is an essential nutrient that is required for DNA replication and as a substrate for a range of enzymatic reactions involved in amino acid synthesis and vitamin metabolism. Demands for folate increase during pregnancy because it is also required for growth and development of the fetus. Folate deficiency has been associated with abnormalities in both mothers (anemia, peripheral neuropathy) and fetuses (congenital abnormalities). This article reviews the metabolism of folic acid, the appropriate use of folic acid supplementation in pregnancy, and the potential benefits of folic acid, as well as the possible supplementation of l-methylfolate for the prevention of pregnancy-related complications other than neural tube defects.

  15. Protective Effect of Folic Acid on Oxidative DNA Damage

    PubMed Central

    Guo, Xiaojuan; Cui, Huan; Zhang, Haiyang; Guan, Xiaoju; Zhang, Zheng; Jia, Chaonan; Wu, Jia; Yang, Hui; Qiu, Wenting; Zhang, Chuanwu; Yang, Zuopeng; Chen, Zhu; Mao, Guangyun

    2015-01-01

    Abstract Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal. In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948. Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [β (95% confidence interval) = −0.88 (−1.62, −0.14) and P = 0.020 for low-FA; and β (95% confidence interval) = −2.68 (−3.42, −1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend

  16. High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells.

    PubMed

    Pellis, Linette; Dommels, Yvonne; Venema, Dini; Polanen, Ab van; Lips, Esther; Baykus, Hakan; Kok, Frans; Kampman, Ellen; Keijer, Jaap

    2008-04-01

    Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate-methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism.

  17. [Integral bread development with soybean, chia, linseed, and folic acid as a functional food for women].

    PubMed

    Justo, Mayela Bautista; Alfaro, Alejandra Denisse Castro; Aguilar, Ernesto Camarena; Wrobel, Katarzyna; Wrobel, Kazimierz; Guzmán, Guadalupe Alanís; Sierra, Zeferino Gamiño; Zanella, Victor Da Mota

    2007-03-01

    Six bread formulations were developed, using different proportions of whole-wheat flour, chia seeds and flaxseed flour. All of our formulations were added with folic acid. Sensorial and texture evaluations were performed, showing good acceptance of the products. Proximal chemical analysis was carried out; in addition, the following parameters were determined: calcium, phosphorus, total dietary fiber, folic acid, water hydration capacity, Glucose Dialysis Retardation Index (GDRI) and fatty acids. The results obtained showed higher protein levels in the developed breads (23.23-30.24 (g/100g dry matter) as compared to a control (21.00% of proteins in bread elaborated without chia or flaxseed). Furthermore, the breads contained 10.07-12.15 of lipids (g/100g dry matter) (linoleic acid: 2.43-4.05%; linolenic acid: 1.12-4.46 %; oleic acid: 2.93-6.13 %), GDRI values were between 89.1 and 98.1 % and folic acid was in the range 699.44 - 991.3 (microg/100g dry matter). The same parameters were determined in the chia seed and in the flaxseed flour. It was concluded that; due to their high levels of protein, insaturated fatty acids (omega-3 and omega-6), dietary fiber and folic acid, these breads have a high nutritional value, so they could have special benefits for woman.

  18. Folic acid mediates activation of the pro-oncogene STAT3 via the Folate Receptor alpha.

    PubMed

    Hansen, Mariann F; Greibe, Eva; Skovbjerg, Signe; Rohde, Sarah; Kristensen, Anders C M; Jensen, Trine R; Stentoft, Charlotte; Kjær, Karina H; Kronborg, Camilla S; Martensen, Pia M

    2015-07-01

    The signal transducer and activator of transcription 3 (STAT3) is a well-described pro-oncogene found constitutively activated in several cancer types. Folates are B vitamins that, when taken up by cells through the Reduced Folate Carrier (RFC), are essential for normal cell growth and replication. Many cancer cells overexpress a glycophosphatidylinositol (GPI)-anchored Folate Receptor α (FRα). The function of FRα in cancer cells is still poorly described, and it has been suggested that transport of folate is not its primary function in these cells. We show here that folic acid and folinic acid can activate STAT3 through FRα in a Janus Kinase (JAK)-dependent manner, and we demonstrate that gp130 functions as a transducing receptor for this signalling. Moreover, folic acid can promote dose dependent cell proliferation in FRα-positive HeLa cells, but not in FRα-negative HEK293 cells. After folic acid treatment of HeLa cells, up-regulation of the STAT3 responsive genes Cyclin A2 and Vascular Endothelial Growth Factor (VEGF) were verified by qRT-PCR. The identification of this FRα-STAT3 signal transduction pathway activated by folic and folinic acid contributes to the understanding of the involvement of folic acid in preventing neural tube defects as well as in tumour growth. Previously, the role of folates in these diseases has been attributed to their roles as one-carbon unit donors following endocytosis into the cell. Our finding that folic acid can activate STAT3 via FRα adds complexity to the established roles of B9 vitamins in cancer and neural tube defects.

  19. Computational and experimental studies of the interaction between single-walled carbon nanotubes and folic acid

    NASA Astrophysics Data System (ADS)

    Castillo, John J.; Rozo, Ciro E.; Castillo-León, Jaime; Rindzevicius, Tomas; Svendsen, Winnie E.; Rozlosnik, Noemi; Boisen, Anja; Martínez, Fernando

    2013-03-01

    This Letter involved the preparation of a conjugate between single-walled carbon nanotubes and folic acid that was obtained without covalent chemical functionalization using a simple 'one pot' synthesis method. Subsequently, the conjugate was investigated by a computational hybrid method: our own N-layered Integrated Molecular Orbital and Molecular Mechanics (B3LYP(6-31G(d):UFF)). The results confirmed that the interaction occurred via hydrogen bonding between protons of the glutamic moiety from folic acid and π electrons from the carbon nanotubes. The single-walled carbon nanotube-folic acid conjugate presented herein is believed to lead the way to new potential applications as carbon nanotube-based drug delivery systems.

  20. Association of neural tube defects and folic acid food fortification in Canada.

    PubMed

    Ray, Joel G; Meier, Chris; Vermeulen, Marian J; Boss, Sheila; Wyatt, Philip R; Cole, David E C

    Many women do not receive folic acid supplements before conception. In response, most of Canada's cereal grain products were being fortified with folic acid by January, 1998, thereby providing an additional 0.1-0.2 mg per day of dietary folate to the Canadian population. We assessed the effect of supplementation on prevalence of open neural tube defects in the province of Ontario. Among 336 963 women who underwent maternal serum screening over 77 months, the prevalence of open neural tube defects declined from 1.13 per 1000 pregnancies before fortification to 0.58 per 1000 pregnancies thereafter (prevalence ratio 0.52, 95% CI 0.40-0.67, p<0.0001). At a population level, folic acid food fortification is associated with a pronounced reduction in open neural tube defects.

  1. Fortification of corn masa flour with folic acid in the United States.

    PubMed

    Fleischman, Alan R; Oinuma, Motoko

    2011-08-01

    Food fortification is an effective public health tool for addressing micronutrient deficiencies. The mandatory fortification of enriched cereal grains (e.g., wheat flour) with folic acid, which began in the United States in 1998, is an example of a successful intervention that significantly reduced the rate of neural tube defects (NTDs). However, despite the drop in NTD rates across all racial/ethnic groups after fortification, Hispanics continue to have the highest rates of this condition. One possible way to reduce this disparity is to fortify corn masa flour to increase the overall intake of folic acid in Hispanic women. We present the available evidence in favor of this approach, address possible safety issues, and outline next steps in the fortification of corn masa flour with folic acid in the United States.

  2. Intestinal absorption, liver uptake, and excretion of /sup 3/H-folic acid in folic acid-deficient, alcohol-consuming nonhuman primates

    SciTech Connect

    Blocker, D.E.; Thenen, S.W.

    1987-09-01

    Nonhuman primates fed folic acid-deficient diets +/- 30% kcal ethanol were used to determine alcohol effects on megaloblastic anemia development and folate bioavailability. Lower hemoglobin (Hb) and red blood cell (RBC) counts and higher mean corpuscular volume (MCV) occurred after 13 wk in alcohol-fed monkeys, later in controls. Plasma, RBC, and liver folate declined and urinary formiminoglutamic acid (FIGLU) was elevated in both groups with FIGLU increasing more among alcohol-fed monkeys at 38 wk. After 40 wk, the bioavailability of oral /sup 3/H-folic acid was investigated and showed increased fecal and reduced urinary tritium excretion in alcohol-fed monkeys compared with controls while plasma uptake and liver and whole body tritium retention were similar in both groups. These observations demonstrate that chronic alcohol consumption impairs folate coenzymes, accelerates appearance of hematologic indices of megaloblastic anemia, and causes possible malabsorption of enterohepatically circulated folates in folate deficiency even when other essential nutrients are provided.

  3. Preschool iron-folic acid and zinc supplementation in children exposed to iron-folic acid in utero confers no added cognitive benefit in early school-age.

    PubMed

    Christian, Parul; Morgan, Mary E; Murray-Kolb, Laura; LeClerq, Steven C; Khatry, Subarna K; Schaefer, Barbara; Cole, Pamela M; Katz, Joanne; Tielsch, James M

    2011-11-01

    In Nepal, antenatal iron-folic acid supplementation improved aspects of intellectual, executive, and fine motor function among school-age children. We examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn) and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) ± zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA) alone. Children 7-9 y old (n = 780) who participated in early childhood micronutrient supplementation trial during 2001-2004 and whose mothers participated in an antenatal micronutrient supplementation between 1999 and 2001 were followed for cognitive assessments in 2007-2009. Using multivariate analysis of variance and adjusting for confounders, M-IFA with child supplementation (either C-IFA or C-IFAZn) did not impact scores on the tests of general intelligence (Universal Nonverbal Intelligence Test), and executive function (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the C-IFAZn group had slightly lower scores on the backward digit span (-0.29, 95% CI: -0.55, -0.04) and Movement Assessment Battery for Children (1.33, 95% CI: 0.26, 2.40) relative to the referent group, whereas both C-IFA (-1.92, 95% CI: -3.12, -0.71) and C-IFAZn (-1.78, 95% CI: -2.63, -0.92) produced somewhat lower finger tapping test scores (fine motor skills). The combination of M-IFAZn and C-IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone. Preschool iron-folic acid ± zinc to children exposed to iron-folic acid in utero or addition of zinc to maternal iron-folic acid conferred no additional benefit to cognitive outcomes assessed in early school age. The late timing of supplementation during preschool may explain the lack of impact of iron and/or zinc.

  4. Impact of multiple micronutrient vs. iron - folic acid supplements on maternal anemia and micronutrient status in pregnancy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Multiple micronutrient (MMN) supplements could increase hemoglobin and improve micronutrient status of pregnant women more than iron ± folic acid supplements alone. Objective. To compare the effects of MMN vs. iron ± folic acid supplements on hemoglobin and micronutrient status of pregn...

  5. Folic Acid Education for Hispanic Women: The Promotora de Salud Model

    PubMed Central

    Flores, Alina L.; Isenburg, Jennifer; Hillard, Christina L.; deRosset, Leslie; Colen, Lisa; Bush, Troy; Mai, Cara T.

    2017-01-01

    Background Although rates of neural tube defects (NTDs) have declined in the United States since fortification, disparities still exist with Hispanic women having the highest risk of giving birth to a baby with a NTD. The Promotora de Salud model has been shown to be an effective tool for reaching Hispanics for a variety of health topics; however, literature on its effectiveness in folic acid interventions is limited. Methods An intervention using the Promotora de Salud model was implemented in four U.S. counties with large populations of Hispanic women. The study comprised: 1) a written pre-test survey to establish baseline levels of folic acid awareness, knowledge, and consumption; 2) a small group education intervention along with a 90-day supply of multivitamins; and 3) a post-intervention (post-test) assessment conducted four months following the intervention. Results Statistically significant differences in pre- and post-tests were observed for general awareness about folic acid and vitamins, and specific knowledge about the benefits of folic acid. Statistically significant changes were also seen in vitamin consumption and multivitamin consumption. Folic acid supplement consumption increased dramatically by the end of the study. Conclusions The Promotora de Salud model relies on interpersonal connections forged between promotoras and the communities they serve to help drive positive health behaviors. The findings underscore the positive impact that these interpersonal connections can have on increasing awareness, knowledge, and consumption of folic acid. Utilizing the Promotora de Salud model to reach targeted populations might help organizations successfully implement their programs in a culturally appropriate manner. PMID:28067585

  6. Prevention of neural tube defects with folic acid: The Chinese experience.

    PubMed

    Ren, Ai-Guo

    2015-08-08

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs.

  7. Functional characterization of folic acid transport in the intestine of the laying hen using the everted intestinal sac model.

    PubMed

    Tactacan, G B; Rodriguez-Lecompte, J C; Karmin, O; House, J D

    2011-01-01

    Absorption at the level of the intestine is likely a primary regulatory mechanism for the deposition of dietary supplemented folic acid into the chicken egg. Therefore, factors affecting the intestinal transport of folic acid in the laying hen may influence the level of egg folate concentrations. To this end, a series of experiments using intestinal everted sacs were conducted to characterize intestinal folic acid absorption processes in laying hens. Effects of naturally occurring folate derivatives (5-methyl and 10-formyltetrahydrofolate) as well as heme on folic acid absorption were also investigated. Folic acid absorption was measured based on the rate of uptake of (3)H-labeled folic acid in the everted sac from various segments of the small and large intestines. Folic acid concentration, incubation length, and pH condition were optimized before the performance of uptake experiments. The distribution profile of folic acid transport along the intestine was highest in the upper half of the small intestine. Maximum uptake rate (nmol·100 g tissue(-1)·min(-1)) was observed in the duodenum (20.6 ± 1.9) and jejunum (22.3 ± 2.0) and decreased significantly in the ileum (15.3 ± 1.1) and cecum (9.3 ± 0.9). Transport increased proportionately (P < 0.05) between 0.0001 and 0.1 µM folic acid. Above 0.1 µM, the slope of the regression line was not significantly different from zero (P < 0.137). Folic acid uptake in the jejunum showed a maximum rate of transport at pH 6.0, but was lowest at pH 7.5. The presence of 5-methyl and 10-formyltetrahydrofolate as well as heme impeded folic acid uptake, reducing intestinal folic acid absorption when added at concentrations ranging from 0 to 100 µM. Overall, these data indicated the presence of a folic acid transport system in the entire intestine of the laying hen. Uptake of folic acid in the cecum raises the likelihood of absorption of bacterial-derived folate.

  8. Combined iron and folic acid supplementation with or without zinc reduces time to walking unassisted among Zanzibari infants 5-11 months old

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron+folic acid (FeFA) (12.5 mg Fe + 50 'g folic acid), zinc (Zn) (10 mg), and iron+folic acid+zinc (FeFA+Z...

  9. Vitamin B12, folic acid, ferritin and haematological variables among Thai construction site workers in urban Bangkok.

    PubMed

    Tungtrongchitr, R; Pongpaew, P; Phonrat, B; Chanjanakitskul, S; Paksanont, S; Migasena, P; Schelp, F P

    1995-01-01

    Serum vitamin B12, folic acid, ferritin and haematological variables were investigated in eighty-seven male and nineteen female construction site workers in Bangkok. Haemoglobin concentration, haematocrit and MCHC were found to be higher in male than in female workers. Serum ferritin was slightly higher in males than in females. Serum B12 was found to be higher in male than in female workers and serum folic acid level were significantly higher in female than in male workers. Vitamin B12 deficiency was found in 2.3 per cent and folic acid deficiency in 6.9 per cent of the male workers. Serum vitamin B12 and folic acid levels were normal for female workers. The adequate serum levels of vitamin B12 and folic acid might be the result of the habit of the workers to consume tonic drinks which contain glucose, caffeine, and vitamins especially vitamins B6, and B12.

  10. Folic Acid Inhibits Amyloid β-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells.

    PubMed

    Li, Wen; Jiang, Mingyue; Zhao, Shijing; Liu, Huan; Zhang, Xumei; Wilson, John X; Huang, Guowei

    2015-10-20

    Alzheimer's disease (AD) is a common neurodegenerative disease resulting in progressive dementia, and is a principal cause of dementia among older adults. Folate acts through one-carbon metabolism to support the methylation of multiple substrates. We hypothesized that folic acid supplementation modulates DNA methyltransferase (DNMT) activity and may alter amyloid β-peptide (Aβ) production in AD. Mouse Neuro-2a cells expressing human APP695 were incubated with folic acid (2.8-40 μmol/L), and with or without zebularine (the DNMT inhibitor). DNMT activity, cell viability, Aβ and DNMTs expression were then examined. The results showed that folic acid stimulated DNMT gene and protein expression, and DNMT activity. Furthermore, folic acid decreased Aβ protein production, whereas inhibition of DNMT activity by zebularine increased Aβ production. The results indicate that folic acid induces methylation potential-dependent DNMT enzymes, thereby attenuating Aβ production.

  11. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

    SciTech Connect

    Dawson, Jennifer E.; Raymond, Angela M.; Winn, Louise M. . E-mail: winnl@biology.queensu.ca

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  12. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice.

    PubMed

    Dawson, Jennifer E; Raymond, Angela M; Winn, Louise M

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-kappaB, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-kappaB, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P<0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P<0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P<0.05). Folic acid also reduced VPA-induced alterations in p53, NF-kappaB, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-kappaB, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  13. Folate binding protein: therapeutic natural nanotechnology for folic acid, methotrexate, and leucovorin.

    PubMed

    Merzel, Rachel L; Boutom, Sarah M; Chen, Junjie; Frey, Carolina; Shedden, Kerby; Marsh, E Neil G; Banaszak Holl, Mark M

    2017-02-16

    Blood serum proteins play a critical role in the transport, biodistribution, and efficacy of systemically-delivered therapeutics. Here, we have investigated the concentration- and ligand-dependent aggregation of folate binding protein (FBP), focusing in particular on folic acid, an important vitamin and targeting agent; methotrexate, an antifolate drug used to treat cancer and rheumatoid arthritis; and leucovorin which is used to decrease methotrexate toxicity. We employed atomic force microscopy to characterize, on a particle-by-particle basis, the volumes of the FBP nanoparticles that form upon ligand binding. We measured the distribution of FBP nanoparticle volumes as a function of ligand concentration over physiologically- and therapeutically-relevant ranges. At physiologically-relevant concentrations, significant differences in particle volume distributions exist that we hypothesize are consistent with different trafficking mechanisms for folic acid and methotrexate. In addition, we hypothesize leucovorin is trafficked and delivered like folic acid at therapeutically-relevant concentrations. We propose that changes in dosing procedures could improve the delivery and therapeutic index for methotrexate and other folic acid-targeted drug conjugates and imaging agents. Specifically, we suggest pre-binding the drugs to FBP may provide a better formulation for drug delivery of methotrexate for both cancer and rheumatoid arthritis. This would be analogous to pre-binding paclitaxel to albumin, which is already used in the clinic.

  14. Industry experience in promoting weekly iron-folic acid supplementation in the Philippines.

    PubMed

    Garcia, Josel; Datol-Barrett, Eva; Dizon, Maynilad

    2005-12-01

    After participating in a pilot project under a government-industry partnership to promote the adoption of weekly iron-folic acid supplementation among women of reproductive age in the Philippines in 1998, United Laboratories (UNILAB), the Philippines' largest private pharmaceutical company, decided in April 2002 to launch a weekly iron-folic acid supplement for pregnant and non-pregnant women under the brand name Femina. The business objective set for the Femina brand was to build the category of preventive iron-folic acid supplements in line with the Philippine Department of Health's advocacy on weekly supplementation as an alternate to daily dosing to reduce the prevalence of anemia in the country. The brand was supported with an integrated mix of traditional advertising media with complementary direct-to-consumer educational programs that aimed to create awareness of iron-deficiency anemia, its causes and effects, and the role of weekly intake of iron-folic acid in preventing the condition. Aggressive marketing support for 1 year was successful in creating awareness among the target women. Significant lessons derived from consumers identified opportunity areas that can be further addressed in developing advocacy programs on weekly iron supplementation implemented on a nationwide scale in the future.

  15. Development and application of nanoparticles synthesized with folic acid-conjugated soy protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, soy protein isolate (SPI) was conjugated with folic acid (FA) to prepare nanoparticles for target-specific drug delivery. Successful conjugation was evidenced by UV spectrophotometry and primary amino group analysis. An increase in count rate by at least 142% was observed in FA-conjug...

  16. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

    PubMed

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.

  17. Moderately high intake of folic acid has a negative impact on mouse embryonic development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20-fold h...

  18. Public health significance of supplementation or fortification of grain products with folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The need for supplemental folate can be traced to the initial phase of the discovery of this vitamin as a micronutrient for the prevention of pregnancy related anemia. In the post discovery era, folic acid was used primarily to prevent deficiency as manifested by low blood folate levels and megalob...

  19. Pros and cons of increasing folic acid and vitamin B12 intake by fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects (NTDs). The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes brie...

  20. Folic acid fortification and cancer risk: plea for objective evaluation of the evidence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The letter from Bayston and colleagues,1 representing the Association for Spina Bifida and Hydrocephalus, dismisses concerns raised by two recent studies2, 3 of a possible increase in colorectal cancer (CRC) risk following a high intake of folic acid. In relation to the postulated link between forti...

  1. Folic Acid Promotion for Hispanic Women in Florida: A Vitamin Diary Study

    ERIC Educational Resources Information Center

    Thomas, Kamilah B.; Hauser, Kimberlea; Rodriguez, Nydia Y.; Quinn, Gwendolyn P.

    2010-01-01

    Objective: To assess the barriers and benefits of taking multivitamins among Hispanic women exposed to a folic acid social marketing campaign in Florida, USA. Design and setting: Evaluation of non-pregnant women aged 18-35 from multiple Hispanic subgroups. Method: For 6 months, participants exposed to social marketing campaign educational…

  2. Serum folic acid and RFC A80G polymorphism in Alzheimer's disease and vascular dementia.

    PubMed

    Mansoori, Nasim; Tripathi, Manjari; Alam, Rizwan; Luthra, Kalpana; Sharma, Sumit; Lakshmy, Ramakrishnan; Kalaivani, Mani; Mukhopadhyay, Asok K

    2014-02-01

    Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ≥8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism.

  3. Preconceptional and Prenatal Supplementary Folic Acid and Multivitamin Intake and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Virk, Jasveer; Liew, Zeyan; Olsen, Jørn; Nohr, Ellen A.; Catov, Janet M.; Ritz, Beate

    2016-01-01

    Objective: To evaluate whether early folic acid supplementation during pregnancy prevents diagnosis of autism spectrum disorders in offspring. Methods: Information on autism spectrum disorder diagnosis was obtained from the National Hospital Register and the Central Psychiatric Register. We estimated risk ratios for autism spectrum disorders for…

  4. Folic acid enhances early functional recovery in a piglet model of pediatric head injury.

    PubMed

    Naim, Maryam Y; Friess, Stuart; Smith, Colin; Ralston, Jill; Ryall, Karen; Helfaer, Mark A; Margulies, Susan S

    2010-01-01

    For stroke and spinal cord injury, folic acid supplementation has been shown to enhance neurodevelopment and to provide neuroprotection. We hypothesized that folic acid would reduce brain injury and improve neurological outcome in a neonatal piglet model of traumatic brain injury (TBI), using 4 experimental groups of 3- to 5-day-old female piglets. Two groups were intubated, anesthetized and had moderate brain injury induced by rapid axial head rotation without impact. One group of injured (Inj) animals received folic acid (Fol; 80 μg/kg) by intraperitoneal (IP) injection 15 min following injury, and then daily for 6 days (Inj + Fol; n = 7). The second group of injured animals received an IP injection of saline (Sal) at the same time points (Inj + Sal; n = 8). Two uninjured (Uninj) control groups (Uninj + Fol, n = 8; Uninj + Sal, n = 7) were intubated, anesthetized and received folic acid (80 μg/kg) or saline by IP injection at the same time points as the injured animals following a sham procedure. Animals underwent neurobehavioral and cognitive testing on days 1 and 4 following injury to assess behavior, memory, learning and problem solving. Serum folic acid and homocysteine levels were collected prior to injury and again before euthanasia. The piglets were euthanized 6 days following injury, and their brains were perfusion fixed for histological analysis. Folic acid levels were significantly higher in both Fol groups on day 6. Homocysteine levels were not affected by treatment. On day 1 following injury, the Inj + Fol group showed significantly more exploratory interest, and better motor function, learning and problem solving compared to the Inj + Sal group. Inj + Fol animals had a significantly lower cognitive composite dysfunction score compared to all other groups on day 1. These functional improvements were not seen on day 4 following injury. Axonal injury measured by β-amyloid precursor protein staining 6 days after injury was not affected by treatment

  5. Folic Acid Enhances Early Functional Recovery in a Piglet Model of Pediatric Head Injury

    PubMed Central

    Naim, Maryam Y.; Friess, Stuart; Smith, Colin; Ralston, Jill; Ryall, Karen; Helfaer, Mark A.; Margulies, Susan S.

    2011-01-01

    For stroke and spinal cord injury, folic acid supplementation has been shown to enhance neurodevelopment and to provide neuroprotection. We hypothesized that folic acid would reduce brain injury and improve neurological outcome in a neonatal piglet model of traumatic brain injury (TBI), using 4 experimental groups of 3- to 5-day-old female piglets. Two groups were intubated, anesthetized and had moderate brain injury induced by rapid axial head rotation without impact. One group of injured (Inj) animals received folic acid (Fol; 80 μg/kg) by intraperitoneal (IP) injection 15 min following injury, and then daily for 6 days (Inj + Fol; n = 7). The second group of injured animals received an IP injection of saline (Sal) at the same time points (Inj + Sal; n = 8). Two uninjured (Uninj) control groups (Uninj + Fol, n = 8; Uninj + Sal, n = 7) were intubated, anesthetized and received folic acid (80 μg/kg) or saline by IP injection at the same time points as the injured animals following a sham procedure. Animals underwent neurobehavioral and cognitive testing on days 1 and 4 following injury to assess behavior, memory, learning and problem solving. Serum folic acid and homocysteine levels were collected prior to injury and again before euthanasia. The piglets were euthanized 6 days following injury, and their brains were perfusion fixed for histological analysis. Folic acid levels were significantly higher in both Fol groups on day 6. Homocysteine levels were not affected by treatment. On day 1 following injury, the Inj + Fol group showed significantly more exploratory interest, and better motor function, learning and problem solving compared to the Inj + Sal group. Inj + Fol animals had a significantly lower cognitive composite dysfunction score compared to all other groups on day 1. These functional improvements were not seen on day 4 following injury. Axonal injury measured by β-amyloid precursor protein staining 6 days after injury was not affected by treatment

  6. Absorption of folic acid from a softgel capsule compared to a standard tablet.

    PubMed

    Maki, Kevin C; Ndife, Louis I; Kelley, Kathleen M; Lawless, Andrea L; Brooks, James R; Wright, Shannon B; Shields, Jocelyn M; Dicklin, Mary R

    2012-07-01

    Consumption of 400 μg folic acid per day from fortified foods and/or supplements, plus food folate from a varied diet is recommended for women of childbearing potential to reduce the risk for neural tube defects during fetal development. This randomized crossover study was designed to evaluate the bioavailability of folic acid from a multivitamin softgel capsule vs a folic acid tablet in 16 premenopausal women (18 to 45 years of age). Participants were randomly assigned to receive a single dose of ∼1,000 μg folic acid in two tablets or ∼1,000 μg folic acid in a multivitamin softgel capsule, and then crossed over to receive the other study product ∼1 week later. Products were administered with a low-folate breakfast. Blood samples were collected predose (0 hour) and 1, 2, 3, 4, 6, and 8 hours post-dose for serum folate analysis. Repeated measures analysis of variance was used to compare responses between treatments. Data from the two sequence groups (n=8 per sequence) were pooled. Mean serum folate total and net incremental areas under the curve (AUC(0-8 hours)) were not significantly different between tablets and softgel capsule (AUC(0-8 hours) 214.9±11.2 hours×ng/mL [487±25.4 hours×nmol/L] and 191.6±13.3 hours×ng/mL [434.2±30.1 hours×nmol/L]; net incremental AUC(0-8 hours) 117.3±8.5 hours×ng/mL [265.8±19.3 hours×nmol/L] and 105.8±12.5 hours×ng/mL [239.7±28.3 hours×nmol/L], respectively), nor was maximum folate concentration (45.1±2.5 ng/mL [102.2±5.7 nmol/L] and 42.5±3.8 ng/mL [96.3±8.6 nmol/L], respectively). Time to peak folate concentration was significantly (P<0.001) delayed for the softgel capsule vs tablet (3.9±0.3 vs 1.7±0.2 hours, respectively). In conclusion, apparent bioavailability of folic acid was similar for the folic acid tablets and a multivitamin softgel capsule.

  7. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    PubMed Central

    Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  8. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-09-23

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  9. Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review.

    PubMed

    Charles, Deborah H M; Ness, Andy R; Campbell, Doris; Smith, George Davey; Whitley, Elise; Hall, Marion H

    2005-03-01

    Periconceptual folic acid prevents neural tube defects. The effect of folic acid taken throughout pregnancy is unclear, however. We re-analysed data from a large randomised controlled trial performed between 1966 and 1967 and combined the results with those from trials included in a Cochrane review. A total of 2928 women were randomised: 1977 were allocated to placebo, 466 to folic acid 200 microg/day and 485 to folic acid 5 mg/day. Folic acid supplementation was not associated with any difference in mean birthweight, placental weight or gestational age. When combined with trials in the Cochrane review folic acid at high doses was associated with reduced risk of low birthweight (pooled relative risk 0.73 [95% CI 0.53, 0.99]). We found no conclusive evidence of benefit for folic acid supplementation in pregnant women given from time of booking onwards.

  10. Effect of folic acid on oxidative stress and behavioral changes in the animal model of schizophrenia induced by ketamine.

    PubMed

    Zugno, Alexandra I; Canever, Lara; Heylmann, Alexandra S; Wessler, Patrícia G; Steckert, Amanda; Mastella, Gustavo A; de Oliveira, Mariana B; Damázio, Louyse S; Pacheco, Felipe D; Calixto, Octacílio P; Pereira, Flávio P; Macan, Tamires P; Pedro, Thayara H; Schuck, Patrícia F; Quevedo, João; Budni, Josiane

    2016-10-01

    Recent studies have shown benefits for the supplementation of folic acid in schizophrenic patients. The aim of this study was to evaluate the effects of folic acid addition on adult rats, over a period of 7 or 14 days. It also sets out to verify any potential protective action using an animal model of schizophrenia induced by ketamine, in behavioral and biochemical parameters. This study used two protocols (acute and chronic) for the administration of ketamine at a dose of 25 mg/kg (i.p.). The folic acid was given by oral route in doses of 5, 10 and 50 mg/kg, once daily, for 7 and/or 14 days in order to compare the protective effects of folic acid. Thirty minutes after the last administration of ketamine, the locomotor and social interaction activities were evaluated, and immediately the brain structure were removed for biochemical analysis. In this study, ketamine was administered in a single dose or in doses over the course of 7 days increasing the animal's locomotion. This study showed that the administration of folic acid over 7 days was unable to prevent hyper locomotion. In contrast, folic acid (10 and 50 mg/kg) administrated over a period of 14 days, was able to partially prevent the hyper locomotion. Our data indicates that both acute and chronic administrations of ketamine increased the time to first contact between the animals, while the increased latency for social contact was completely prevented by folic acid (5, 10 and 50 mg/kg). Chronic and acute administrations of ketamine also increased lipid peroxidation and protein carbonylation in brain. Folic acid (10 and 50 mg/kg) supplements showed protective effects on the oxidative damage found in the different brain structures evaluated. All together, the results indicate that nutritional supplementation with folic acid provides promising results in an animal model of schizophrenia induced by ketamine.

  11. Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.

    PubMed

    Zhu, Mingming; Li, Bingfei; Ma, Xiao; Huang, Cong; Wu, Rui; Zhu, Weiwei; Li, Xiaoting; Liang, Zhaofeng; Deng, Feifei; Zhu, Jianyun; Xie, Wei; Yang, Xue; Jiang, Ye; Wang, Shijia; Wu, Jieshu; Geng, Shanshan; Xie, Chunfeng; Zhong, Caiyun; Liu, Haiyan

    2016-08-01

    Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.

  12. Effect of folic acid and metformin on insulin resistance and inflammatory factors of obese children and adolescents

    PubMed Central

    Dehkordi, Elham Hashemi; Sattari, Farnaz; Khoshdel, Abolfazl; Kasiri, Karamali

    2016-01-01

    Background: Considering the increasing trend of obesity, especially in developing countries such as Iran, and the role of inflammatory factors and insulin resistance (IR) in the occurrence of obesity-related complications as well as the safety of some agents such as folic acid and metformin, this clinical trial was designed to investigate the effect of metformin and folic acid on inflammatory factors and IR among obese children. Materials and Methods: In this randomized, double-blind, controlled clinical trial study, sixty obese children aged 6–12 years were enrolled. Selected obese children were randomly allocated in two interventional (1 mg/daily folic acid or 1000 mg metformin for 8 weeks) groups. Biochemical measurements including homeostasis model assessment of IR (HOMA-IR), homocysteine (Hcy), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured between and within the groups before and after trial. Results: In each group, thirty obese children were studied. The groups were age- and sex-matched. After folic acid and metformin administration, mean of Hcy, HOMA-IR, TNF-α, and IL-8 decreased significantly (P < 0.05). IL-6 decreased significantly after folic acid use (P < 0.05). Conclusion: The findings of this trial indicated that both metformin and folic acid could decrease IR and level of Hcy in obese children and adolescents. The effectiveness of metformin on IR was more significant than folic acid. Regarding the effectiveness of the two studied agents on inflammatory factors, it is suggested that the role of folic acid was superior to metformin. It is suggested that metformin is a proper agent for obese children with IR and folic acid is an appropriate supplement for obese children with increased inflammatory factors. PMID:27904616

  13. The effect of subchronic supplementation with folic acid on homocysteine induced seizures.

    PubMed

    Rasic-Markovic, A; Rankov-Petrovic, B; Hrncic, D; Krstic, D; Colovic, M; Macut, Dj; Djuric, D; Stanojlovic, Olivera

    2015-06-01

    Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na⁺/K⁺-ATPase and Mg²⁺-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na⁺/K⁺-ATPase and Mg²⁺-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases.

  14. Role of sodium ion in transport of folic acid in the small intestine

    SciTech Connect

    Zimmerman, J.; Selhub, J.; Rosenberg, I.H.

    1986-08-01

    The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the influx chamber and isoalted brush-border membrane vesicles. Preincubation of tissue in Na -free medium did not have a consistent effect on folic acid influx provided that Na was present in the test solution. Replacement of Na in the test solution by choline resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na -free solution were exposed to test solutions containing either Na , Li , K , Rb , Cs , Tris , or guanidinium as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na by Rb did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb . Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na than in the presence of K , but was not different from uptake in the presence of K plus valinomycin. These data suggest that 1) the saturable component of folate transport is not Na dependent, and 2) nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na in this process in vivo derives from the fact that Na is the most permeant cation available at the absorptive site in the small intestine.

  15. Correlation between maternal and childhood VitB12, folic acid and ferritin levels

    PubMed Central

    Zeeshan, Fatima; Bari, Attia; Farhan, Saima; Jabeen, Uzma; Rathore, Ahsan Waheed

    2017-01-01

    Objective: To determine the correlation between serum folic acid, vitamin B12 and ferritin of mother and child and to study various neonatal risk factors as a cause of anemia in children. Methods: One hundred eighty children two months to two years of age admitted in the department of Pediatric Medicine of The Children’s Hospital and The Institute of Child Health Lahore from January 2013 to January 2015 with common medical conditions having anemia were included. Complete blood count (CBC), serum ferritin level, folic acid and Vitamin (Vit) B12 level were sent of children and their mothers. Data was analyzed using SPSS version 20. Results: Out of 180 children with anemia, 66.7% were males. Mean age of children was 7.3months. Fifty-five percent children were malnourished according to z scoring. The mean Hemoglobin (Hb) of children was 8 g/dl. Only 4% children had low ferritin level while 60% had low folic acid and 45% had decreased VitB12. There was significant correlation between Hb of mother and child (p =0.02), Vit B12 deficiency (p=0.008) and iron deficiency (p<0.001). Premature children had lower folic acid levels (p =0.02), while prematurity, IUGR, previous admission and history of sepsis showed no association with anemia in our study. Both breast-feeding and top feeding showed significant association with anemia with p-value of 0.042 and 0.003 respectively while dilution showed no impact on anemia. Conclusion: Maternal anemia has a significant impact on child’s hemoglobin. As compared to previous concept of increased iron deficiency in children we found increased occurrence of folic acid and VitB12 deficiency in children and their mothers. PMID:28367192

  16. Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study

    PubMed Central

    Koning, Irene V.; Groenenberg, Irene A. L.; Gotink, Anniek W.; Willemsen, Sten P.; Gijtenbeek, Manon; Dudink, Jeroen; Go, Attie T. J. I.; Reiss, Irwin K. M.; Steegers, Eric A. P.; Steegers-Theunissen, Régine P. M.

    2015-01-01

    We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023–0.491, p<0.05; LCD: β = 0.171mm, 95%CI = 0.038–0.305, p<0.05; RCD: β = 0.156mm, 95%CI = 0.032–0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:β = 0.015mm/mm, 95%CI = 0.005–0.024, p<0.01; LCD/CRL:β = 0.012mm/mm, 95%CI = 0.005–0.018, p<0.01; RCD/CRL:β = 0.011mm/mm, 95%CI = 0.005–0.017, p<0.01). Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538–1813 nmol/L). These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child’s neurodevelopmental outcome are yet unknown and warrant further investigation. PMID:26491876

  17. Folic acid absorption determined by a single stool sample test--a double-isotope technique. The folic acid absorption capacity in children

    SciTech Connect

    Hjelt, K. )

    1989-10-01

    The fractional folic acid absorption (FAFol) was determined in 66 patients with various gastrointestinal diseases by a double-isotope technique, employing a single stool sample test (SSST) as well as a complete stool collection. The age of the patients ranged from 2.5 months to 16.8 years (mean 6.3 years). The test dose was administered orally and consisted of 50 micrograms of (3H)folic acid (monoglutamate) (approximately 20 muCi), carmine powder, and 2 mg 51CrCl3 (approximately 1.25 muCi) as the unabsorbable tracer. The whole-body radiation given to a 1-year-old child averaged 4.8 mrad only. The stool and napkin contents were collected and homogenized by the addition of 300 ml chromium sulfuric acid. A 300-ml sample of the homogenized stool and napkin contents, as well as 300 ml chromium sulfuric acid (75% vol/vol) containing the standards, were counted for the content of 51Cr in a broad-based well counter. The quantity of (3H)folic acid was determined by liquid scintillation, after duplicate distillation. Estimated by SSST, the FAFol, which employs the stool with the highest content of 51Cr corresponding to the most carmine-colored stool, correlated closely with the FAFol based on complete stool collection (r = 0.96, n = 39, p less than 0.0001). The reproducibility of FAFol determined by SSST was assessed from repeated tests in 18 patients. For a mean of 81%, the SD was 4.6%, which corresponded to a coefficient of variation of 5.7%.

  18. Introduction of biotin or folic acid into polypyrrole magnetite core-shell nanoparticles

    SciTech Connect

    Nan, Alexandrina; Turcu, Rodica; Liebscher, Jürgen

    2013-11-13

    In order to contribute to the trend in contemporary research to develop magnetic core shell nanoparticles with better properties (reduced toxicity, high colloidal and chemical stability, wide scope of application) in straightforward and reproducible methods new core shell magnetic nanoparticles were developed based on polypyrrole shells functionalized with biotin and folic acid. Magnetite nanoparticles stabilized by sebacic acid were used as magnetic cores. The morphology of magnetite was determined by transmission electron microscopy TEM, while the chemical structure investigated by FT-IR.

  19. Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Teow, Yiwei; Valiyaveettil, Suresh

    2010-12-01

    Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized viareduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 μg ml-1 for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.

  20. Time dependent inhibition of xanthine oxidase in irradiated solutions of folic acid, aminopterin and methotrexate

    SciTech Connect

    Robinson, K.; Pilot, T.F.; Meany, J.E. )

    1990-01-01

    The xanthine oxidase catalyzed oxidation of hypoxanthine was followed by monitoring the formation of uric acid at 290 nm. Inhibition of xanthine oxidase occurs in aqueous solutions of folic acid methotrexate and aminopterin. These compounds are known to dissociate upon exposure to ultraviolet light resulting in the formation of their respective 6-formylpteridine derivatives. The relative rates of dissociation were monitored spectrophotometrically by determining the absorbance of their 2,4-dinitrophenylhydrazine derivatives at 500 nm. When aqueous solutions of folic acid, aminopterin and methotrexate were exposed to uv light, a direct correlation was observed between the concentrations of the 6-formylpteridine derivatives existing in solution and the ability of these solutions to inhibit xanthine oxidase. The relative potency of the respective photolysis products were estimated.

  1. Modeling fortification of corn masa flour with folic acid: the potential impact on exceeding the tolerable upper intake level for folic acid, NHANES 2001–2008

    PubMed Central

    Hamner, Heather C.; Tinker, Sarah C.; Berry, R.J.; Mulinare, Joe

    2013-01-01

    Background The Institute of Medicine set a tolerable upper intake level (UL) for usual daily total folic acid intake (1,000 µg). Less than 3% of US adults currently exceed the UL. Objective The objective of this study was to determine if folic acid fortification of corn masa flour would increase the percentage of the US population who exceed the UL. Design We used dietary intake data from NHANES 2001–2008 to estimate the percentage of adults and children who would exceed the UL if corn masa flour were fortified at 140 µg of folic acid/100 g. Results In 2001–2008, 2.5% of the US adult population (aged≥19 years) exceeded the UL, which could increase to 2.6% if fortification of corn masa flour occurred. With corn masa flour fortification, percentage point increases were small and not statistically significant for US adults exceeding the UL regardless of supplement use, sex, race/ethnicity, or age. Children aged 1–8 years, specifically supplement users, were the most likely to exceed their age-specific UL. With fortification of corn masa flour, there were no statistically significant increases in the percentage of US children who were exceeding their age-specific UL, and the percentage point increases were small. Conclusions Our results suggest that fortification of corn masa flour would not significantly increase the percentage of individuals who would exceed the UL. Supplement use was the main factor related to exceeding the UL with or without fortification of corn masa flour and within all strata of sex, race/ethnicity, and age group. PMID:23316130

  2. Physico-chemical quality and homogeneity of folic acid and iron in enriched flour using principal component analysis.

    PubMed

    Soeiro, Bruno T; Boen, Thaís R; Wagner, Roger; Lima-Pallone, Juliana A

    2009-01-01

    The aim of the present work was to determine parameters of the corn and wheat flour matrix, such as protein, lipid, moisture, ash and carbohydrates, folic acid and iron contents. Three principal components explained 91% of the total variance. Wheat flours were characterized by high protein and moisture content. On the other hand, the corn flours had the greater carbohydrates, lipids and folic acid levels. The concentrations of folic acid were lower than the issued value for wheat flours. Nevertheless, corn flours presented extremely high values. The iron concentration was higher than that recommended in Brazilian legislation. Poor homogenization of folic acid and iron was observed in enriched flours. This study could be useful to help the governmental authorities in the enriched food programs evaluation.

  3. Valuation of OSA process and folic acid addition as excess sludge minimization alternatives applied in the activated sludge process.

    PubMed

    Martins, C L; Velho, V F; Ramos, S R A; Pires, A S C D; Duarte, E C N F A; Costa, R H R

    2016-01-01

    The aim of this study was to investigate the ability of the oxic-settling-anaerobic (OSA)-process and the folic acid addition applied in the activated sludge process to reduce the excess sludge production. The study was monitored during two distinct periods: activated sludge system with OSA-process, and activated sludge system with folic acid addition. The observed sludge yields (Yobs) were 0.30 and 0.08 kgTSS kg(-1) chemical oxygen demand (COD), control phase and OSA-process (period 1); 0.33 and 0.18 kgTSS kg(-1) COD, control phase and folic acid addition (period 2). The Yobs decreased by 73 and 45% in phases with the OSA-process and folic acid addition, respectively, compared with the control phases. The sludge minimization alternatives result in a decrease in excess sludge production, without negatively affecting the performance of the effluent treatment.

  4. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements.

    PubMed

    Ma, Ai G; Schouten, Evert G; Zhang, Feng Z; Kok, Frans J; Yang, Fang; Jiang, Dian C; Sun, Yong Y; Han, Xiu X

    2008-10-01

    In rural China, many pregnant women in their third trimester suffer from anemia (48%) and iron deficiency (ID; 42%), often with coexisting deficiencies of retinol and riboflavin. We investigated the effect of retinol and riboflavin supplementation in addition to iron plus folic acid on anemia and subjective well-being in pregnant women. The study was a 2-mo, double-blind, randomized trial. Subjects (n = 366) with anemia [hemoglobin (Hb) folic acid. The iron+folic acid (IF) group (n = 93) served as reference, the iron+folic acid+retinol group (IFA) (n = 91) was treated with 2000 mug retinol, the iron+folic acid+riboflavin group (IFB) (n = 91) with 1.0 mg riboflavin, and the iron+folic acid+retinol+riboflavin group (IFAB) (n = 91) with retinol and riboflavin. After the 2-mo intervention, the Hb concentration increased in all 4 groups (P < 0.001). The increase in the IFAB group was 5.4 +/- 1.1 g/L greater than in the IF group (P < 0.001). The reduced prevalence of anemia (Hb < 110g/L) and ID anemia were significantly greater in the groups supplemented with retinol and /or riboflavin than in the IF group. Moreover, gastrointestinal symptoms were less prevalent in the IFA group than in the IF group (P < 0.05) and improved well-being was more prevalent in the groups receiving additional retinol and/or riboflavin than in the IF group (P < 0.05). Thus, a combination of iron, folic acid, retinol, and riboflavin was more effective than iron plus folic acid alone. Multimicronutrient supplementation may be worthwhile for pregnant women in rural China.

  5. Differential response to an algae supplement high in DHA mediated by maternal periconceptional diet: intergenerational effects of n-6 fatty acids.

    PubMed

    Clayton, Edward H; Lamb, Tracy A; Refshauge, Gordon; Kerr, Matthew J; Bailes, Kristy L; Ponnampalam, Eric N; Friend, Michael A; Hopkins, David L

    2014-08-01

    Algae high in docosahexaenoic acid (DHA) may provide a source of long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) for inclusion in the diet of lambs to improve the LCn-3PUFA status of meat. The effect of background LCn-3PUFA status on the metabolism of high DHA algae is, however, unknown. The aim of the current study was to determine whether the response to a high in DHA algae supplement fed to lambs for six weeks prior to slaughter was mediated by a maternal periconceptional diet. Forty Poll Dorset × Border Leicester × Merino weaner lambs were allocated to receive either a ration based on oat grain, lupin grain, and chopped lucerne (control) or the control ration with DHA-Gold™ algae included at 1.92 % DM (Algae) based on whether the dams of lambs had previously been fed a diet high in n-3 or n-6 around conception. LCn-3PUFA concentration was determined in plasma and red blood cells (RBC) prior to and following feeding. The concentrations of EPA and DHA in the plasma and RBC of lambs receiving the control ration were significantly (p < 0.001) lower when lambs received the ration for 14 days compared with pre-feeding concentrations. The concentrations of EPA and DHA were also significantly (p < 0.001) higher when lambs consumed the Algae ration compared with the control ration for 42 days. The increase in EPA and DHA was, however, significantly (p < 0.05) lower if lamb dams had previously been fed a diet high in n-6 at conception. Assessing the previous nutrition and n-3 status of lambs may allow producers to more accurately predict the likely response to supplements high in LCn-3PUFA, particularly, DHA.

  6. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

    PubMed Central

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-01-01

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism. PMID:27338456

  7. Folic acid-conjugated soybean protein-based nanoparticles mediate efficient antitumor ability in vitro.

    PubMed

    Yao, Weijing; Zha, Qian; Cheng, Xu; Wang, Xin; Wang, Jun; Tang, Rupei

    2016-11-23

    In this study, soy protein isolate was hydrolyzed by compound enzymes to give aqueous soy protein with low molecular weights. Folic acid modified and free soy protein nanoparticles were successfully prepared by a desolvation method as target-specific drug delivery, respectively. Ultraviolet spectrophotometry demonstrated that folic acid was successfully grafted onto soy protein. The shape and size of folic acid modified soy protein nanoparticles were detected by transmission electron microscopy, scanning electron microscope, and dynamic light scattering. In addition, a series of characteristics including kinetic stability, pH stability, and time stability were also performed. Doxorubicin was successfully loaded into folic acid modified soy protein nanoparticles, and the encapsulation and loading efficiencies were 96.7% and 23%, respectively. Doxorubicin-loaded folic acid modified soy protein nanoparticles exhibited faster drug release rate than soy protein nanoparticles in PBS solution (pH = 5). The tumor penetration and antitumor experiments were done using three-dimensional multicellular tumor spheroids as the in vitro model. The results proved that folic acid modified soy protein nanoparticles display higher penetration and accumulation than soy protein nanoparticles, therefore possessing efficient growth inhibitory ability against multicellular tumor spheroids.

  8. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    PubMed

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  9. Vitamin B12 and Folic Acid Imbalance Modifies NK Cytotoxicity, Lymphocytes B and Lymphoprolipheration in Aged Rats

    PubMed Central

    Partearroyo, Teresa; Úbeda, Natalia; Montero, Ana; Achón, María; Varela-Moreiras, Gregorio

    2013-01-01

    Different vitamin B12 and folic acid concentrations could exacerbate the immune response. The aim was to evaluate different dietary folic acid and vitamin B12 levels on the immune response in aged rats. Male Sprague Dawley aged rats were assigned to three folic acid groups (deficient, control, supplemented) each in absence of vitamin B12 for 30 days. Several parameters of innate and acquired immune responses were measured. Serum and hepatic folate levels increased according to folic acid dietary level, while vitamin B12 levels decreased. There was a significant decrease in natural killer cell-mediated cytotoxicity in the spleen for the vitamin B12 deficient diet and folic acid control diet groups. Significant changes in CD45 lymphocyte subsets were also observed according to dietary imbalance. Lymphoproliferative response to concanavalin A and phytohemagglutinin did not differ significantly between groups. The spleen response to lipopolysaccharide increased significantly, but was unmodified for the other organs. An imbalance between dietary vitamin B12 and folic acid concentrations alters some immunological parameters in aged rats. Therefore, the ratio between folate and vitamin B12 could be as important as their absolute dietary concentrations. PMID:24288024

  10. Role of homocysteine and folic acid on the altered calcium homeostasis of platelets from rats with biliary cirrhosis.

    PubMed

    Romecín, Paola; Atucha, Noemí M; Navarro, Esther G; Clara Ortiz, M; Iyú, David; Rosado, Juan Antonio; García-Estañ, Joaquín

    2017-02-02

    Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model. The effect of chronic folic acid treatment was also analyzed. Acute treatment with HCY increased the aggregation response to ADP and calcium responses to thrombin in platelets of control and BDL rats. Capacitative calcium entry was not altered by HCY. Chronic treatment with folic acid decreased platelet aggregation in control and BDL rats, but this decrease was greater in BDL rats. In folic acid-treated rats, thrombin-induced calcium entry and release were decreased in platelet of control rats but unaltered in BDL rats; however, capacitative calcium entry was decreased in platelets of control and BDL rats treated with folic acid. Reactive oxygen species were produced at higher levels by BDL platelets after stimulation with HCY or thrombin and folic acid normalized these responses. HCY plays a role in the enhanced platelet aggregation response of BDL rats, probably through an enhanced formation of ROS. Folic acid pretreatment normalizes many of the platelet alterations shown by BDL rats.

  11. Bioinspired nanodevice based on the folic acid/titanium dioxide system.

    PubMed

    Gaweda, Sylwia; Stochel, Grazyna; Szaciłowski, Konrad

    2007-05-04

    A new bioinspired nanomaterial has been obtained by chemisorption of folic acid onto nanocrystalline titanium dioxide. The organic chromophore is linked with the semiconductor surface via the glutamate chain and anchored with the carboxylate group. The geometry and electronic structure of the chromophore was studied in detail with DFT. Photoelectrochemical studies revealed photosensitization of the new material towards visible light. The photoelectrodes composed of the folic acid/titanium dioxide hybrid material generated photocurrent over a 300-600-nm window. Moreover, the direction of the photocurrent could be changed from anodic to cathodic and vice versa by application of the appropriate photoelectrode potential. Photoelectrochemical and spectroscopic studies allowed the elucidation of the mechanism of photocurrent switching. Photoelectrodes composed of folate-modified titanium dioxide may serve as a simple model of optoelectronic switches and may constitute the basis for molecular photoelectronic devices.

  12. Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy

    PubMed Central

    Huang, Peng; Xu, Cheng; Lin, Jing; Wang, Can; Wang, Xiansong; Zhang, Chunlei; Zhou, Xuejiao; Guo, Shouwu; Cui, Daxiang

    2011-01-01

    Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer as well as non-cancer diseases, which involves the uptake of photosensitizers (PSs) by cancer cells followed by irradiation. The use of nanomaterials as carriers of PSs is a very promising approach to improve the development of PDT in clinical medicine. In this study, a novel folic acid-conjugated graphene oxide (GO) was strategically designed and prepared as targeting drug delivery system to achieve higher specificity. The second generation photosensitizer (PS) Chlorin e6 (Ce6) was effectively loaded into the system via hydrophobic interactions and π-π stacking. The nanocarriers can significantly increase the accumulation of Ce6 in tumor cells and lead to a remarkable photodynamic efficacy on MGC803 cells upon irradiation. These suggested that folic acid-conjugated GO loaded Ce6 had great potential as effective drug delivery system in targeting PDT. PMID:21562631

  13. Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida.

    PubMed

    Shaw, Gary M; Lammer, Edward J; Zhu, Huiping; Baker, Mei Wang; Neri, Eric; Finnell, Richard H

    2002-02-15

    Women who consume folic acid in early pregnancy reduced their risks for delivering offspring with neural tube defects (NTDs). The underlying process by which folic acid facilitated this risk reduction is unknown. Investigating genetic variation that influences cellular absorption, transport, and metabolism of folate will help fill this data gap. We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1). Using data from a California population-based case control interview study (1989-1991 birth cohorts), we investigated whether spina bifida risk was influenced by an interaction between a polymorphism of infant RFC1 at nucleotide 80 (A80G) and maternal periconceptional use of vitamins containing folic acid. Allelic variants of RFC1 were determined by genotyping 133 live-born spina bifida case infants and 188 control infants. The percentages of case infants with the A80/A80, G80/G80, and G80/A80 genotypes were 27.2%, 28.0%, and 44.7%, respectively. The percentages of control infants were similar: 26.1%, 29.3%, and 44.7%. Odds ratios of 1.0 (95% confidence interval 0.5-2.0) for the G80/G80 genotype and 1.1 (0.6-2.0) for the G80/A80 genotype were observed relative to the A80/A80 genotype. Among mothers who did not use vitamins, spina bifida risk was 2.4 (0.8-6.9) for infants with genotype G80/G80 compared to those with A80/A80 genotype. Among mothers who did use vitamins, the risk was 0.5 (0.1-3.1) for infants with the G80/G80 genotype. Although this study did not find an increased spina bifida risk for infants who were heterozygous or homozygous for RFC1 A80G, it did reveal modest evidence for a gene-nutrient interaction between infant homozygosity for the RFC1 G80/G80 genotype and maternal periconceptional intake of vitamins containing folic acid on the risk of spina bifida.

  14. Trends in wheat-flour fortification with folic acid and iron--worldwide, 2004 and 2007.

    PubMed

    2008-01-11

    Consumption of adequate amounts of folic acid by women before pregnancy and during early pregnancy decreases their risk for having a pregnancy affected by neural tube defects (NTDs), the most common preventable type of birth defects worldwide. Consumption of iron ameliorates iron deficiency, the most prevalent nutritional deficiency in the world, affecting approximately 2 billion persons. Although certain populations consume substantial amounts of rice and corn, worldwide, the consumption of wheat flour is greater than that of any other cereal grain. Fortification of wheat flour is an effective, simple, and inexpensive strategy for supplying folic acid, iron, and other vitamins and minerals to large segments of the world population. To assess the global change from 2004 to 2007 in 1) the percentage of wheat flour being fortified with folic acid and iron; 2) the total number of persons overall and women in particular with access to fortified wheat flour; and 3) the total number of newborns whose mothers had access to fortified wheat flour during pregnancy, CDC analyzed data from the Flour Fortification Initiative (FFI). This report summarizes the results of that assessment, which indicated that the worldwide percentage of wheat-flour fortification increased from 18% in 2004 to 27% in 2007. The estimated number of persons with access to fortified wheat flour increased by approximately 540 million, and the annual number of newborns whose mothers had access to fortified wheat flour during pregnancy increased by approximately 14 million. Nonetheless, approximately two thirds of the world population lacks access to fortified wheat flour. Programs should continue to expand coverage of wheat-flour fortification as a strategy to increase folic acid and iron consumption.

  15. Food Additives Permitted for Direct Addition to Food for Human Consumption; Folic Acid. Final rule.

    PubMed

    2016-04-15

    The Food and Drug Administration (FDA or we) is amending the food additive regulations to provide for the safe use of folic acid in corn masa flour. We are taking this action in response to a food additive petition filed jointly by Gruma Corporation, Spina Bifida Association, March of Dimes Foundation, American Academy of Pediatrics, Royal DSM N.V., and National Council of La Raza.

  16. Preclinical Evaluation to Specifically Target Ovarian Cancer with Folic Acid conjugated Nanoceria

    DTIC Science & Technology

    2013-06-01

    where we are integrating the field of nanotechnology with ovarian cancer cell’s unique property of overexpressing folic acid receptor alpha (FR-ı...to specifically target ovarian cancer . A cerium oxide nanoparticle , called Nanoceria (NCe), that has the ability to act as an anti-oxidant in... nanoparticle is Nanoceria (NCe), a cerium oxide nanoparticle . Nanotechnology -based tools and techniques are rapidly emerging in the fields of medical imaging

  17. Preclinical Evaluation to Specifically Target Ovarian Cancer with Folic Acid-Conjugated Nanoceria

    DTIC Science & Technology

    2014-08-01

    inhibiting ovarian tumor growth than NCe alone and enhanced the cytotoxicity of cisplatin in vivo. 15. SUBJECT TERMS Specific targeting of ovarian...Chemotherapy regimens for patients with ovarian cancer include cisplatin and paclitaxel for which most of the patients develop resistance and as side...modification of folic acid conjugated nanoceria to cisplatin will result in specific targeting and delivery of cisplatin resulting in exclusive

  18. Folic acid-polydopamine nanofibers show enhanced ordered-stacking via π-π interactions.

    PubMed

    Fan, Hailong; Yu, Xiang; Liu, Yang; Shi, Zujin; Liu, Huihui; Nie, Zongxiu; Wu, Decheng; Jin, Zhaoxia

    2015-06-21

    Recent research has indicated that polydopamine and synthetic eumelanins are optoelectronic biomaterials in which one-dimensional aggregates composed of ordered-stacking oligomers have been proposed as unique organic semiconductors. However, improving the ordered-stacking of oligomers in polydopamine nanostructures is a big challenge. Herein, we first demonstrate how folic acid molecules influence the morphology and nanostructure of polydopamine via tuning the π-π interactions of oligomers. MALDI-TOF mass spectrometry reveals that porphyrin-like tetramers are characteristic of folic acid-polydopamine (FA-PDA) nanofibers. X-ray diffraction combined with simulation studies indicate that these oligomers favour aggregation into graphite-like ordered nanostructures via strong π-π interactions. High-resolution TEM characterization of carbonized FA-PDA hybrids show that in FA-PDA nanofibers the size of the graphite-like domains is over 100 nm. The addition of folic acid in polydopamine enhances the ordered stacking of oligomers in its nanostructure. Our study steps forward to discover the mystery of the structure-property relationship of FA-PDA hybrids. It paves a way to optimize the properties of PDA through the design and selection of oligomer structures.

  19. Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk for Colorectal Cancer

    PubMed Central

    Zhang, Xuehong; Townsend, Mary K.; Selhub, Jacob; Paul, Ligi; Rosner, Bernard; Fuchs, Charles S.; Willett, Walter C.; Giovannucci, Edward L.

    2015-01-01

    Higher folate has been associated with a reduced colorectal cancer (CRC) risk, but excessive folate may promote tumor progression. The role of unmetabolized folic acid (UFA) from high folic acid consumption in carcinogenesis is largely unexplored. We evaluated prediagnostic plasma levels of UFA in relation to CRC risk in nested case-control studies (618 CRC case patients and 1207 matched control) with blood samples collected prior to folic acid fortification. UFA was detected in 21.4% of control UFA levels were not associated with CRC risk. Compared with undetectable levels, the multivariable relative risks (RRs) of CRC were 1.03 (95% confidence interval [CI] = 0.73 to 1.46) for less than 0.5 nmol/L and 1.12 (95% CI = 0.81 to 1.55) for 0.5 nmol/L or more (P trend = .32). A positive association between UFA levels and CRC risk was observed among men (RR = 1.57, 95% CI = 0.99 to 2.49 for ≥0.5 nmol/L vs undetectable, P interaction = .04), and a positive association was also observed among those with the methylene-tetrahydrofolate reductase (MTHFR) CT/TT genotype (RR = 2.20, 95% CI = 1.22 to 3.94 for ≥0.5 nmol/L vs undetectable, P interaction=0.02). In conclusion, prediagnostic plasma levels of UFA from the prefortification period were not associated with risk of CRC. PMID:26376686

  20. Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.

    PubMed

    Madenci, Gulizar; Bilen, Sule; Arli, Berna; Saka, Mustafa; Ak, Fikri

    2012-07-01

    We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.

  1. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men?

    PubMed

    Ebisch, I M W; Pierik, F H; DE Jong, F H; Thomas, C M G; Steegers-Theunissen, R P M

    2006-04-01

    We evaluated pre- and post-intervention endocrine and semen parameters in a double-blind, placebo-controlled intervention study to investigate the underlying mechanism of increased sperm concentration after folic acid and zinc sulphate intervention. A total of 47 fertile and 40 subfertile males participated in a 26-week intervention study consisting of a daily treatment with folic acid (5 mg/day) and zinc sulphate (66 mg/day), or placebo. Pre- and post-intervention semen parameters, serum folate, zinc, follicle-stimulating hormone (FSH), testosterone and inhibin B concentrations were measured. The results indicated that intervention treatment significantly increased sperm concentration in subfertile males. Other semen and endocrine parameters were not affected by intervention treatment. At baseline, positive correlations were found between serum zinc and sperm concentration, motility and inhibin B. Serum zinc and FSH were inversely correlated. As (already) well known from previous research, inhibin B positively correlated with sperm concentration, motility and morphology, and was inversely correlated with FSH. The latter was positively correlated with testosterone. In addition, testosterone and inhibin B were inversely correlated. After intervention, the correlations with zinc disappeared. We conclude that the increase in sperm concentration after folic acid and zinc sulphate intervention is not the result of alterations in FSH, testosterone or inhibin B concentrations. Although zinc and folate have several effects on spermatogenesis, the underlying mechanisms involved are not clear.

  2. Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials

    NASA Astrophysics Data System (ADS)

    Qin, Tingting; Du, Mulong; Du, Haina; Shu, Yongqian; Wang, Meilin; Zhu, Lingjun

    2015-07-01

    Numerous studies have investigated the effects of folic acid supplementation on colorectal cancer risk, but conflicting results were reported. We herein performed a meta-analysis based on relevant studies to reach a more definitive conclusion. The PubMed and Embase databases were searched for quality randomized controlled trials (RCTs) published before October 2014. Eight articles met the inclusion criteria and were subsequently analyzed. The results suggested that folic acid treatment was not associated with colorectal cancer risk in the total population (relative risk [RR] = 1.00, 95% confidence interval [CI] = 0.82-1.22, P = 0.974). Moreover, no statistical effect was identified in further subgroup analyses stratified by ethnicity, gender, body mass index (BMI) and potential confounding factors. No significant heterogeneity or publication bias was observed. In conclusion, our meta-analysis demonstrated that folic acid supplementation had no effect on colorectal cancer risk. However, this finding must be validated by further large studies.

  3. The role of folic acid fortification in neural tube defects: a review.

    PubMed

    Osterhues, Anja; Ali, Nyima S; Michels, Karin B

    2013-01-01

    The worldwide prevalence of neural tube defects (NTDs) has fallen noticeably during the past 30 years, but the specific etiology and causative mechanism of NTDs remain unknown. Since introduction of mandatory fortification of grains with folic acid, a further decrease in NTD prevalence has been reported in North America and other countries with large variations among ethnic subgroups. However, a significant portion of NTDs still persists. Population data suggest that women of childbearing age may not yet be adequately targeted, while the general population may be overfortified with folic acid. While an excessive folate intake may be associated with adverse effects, there remains uncertainty about the minimum effective folate intake and status required for NTD prevention, and the safe upper folate level. Besides folate, several other lifestyle and environmental factors as well as genetic variations may influence NTD development, possibly by affecting one-carbon metabolism and thus epigenetic events. In conclusion, mandatory folic acid fortification plays a significant part in the reduction of NTD prevalence, but possibly at a cost and with a portion of NTDs remaining. More effective preventive strategies require better understanding of the etiology of this group of birth defects.

  4. Unmetabolized Folic Acid in Prediagnostic Plasma and the Risk of Colorectal Cancer.

    PubMed

    Cho, Eunyoung; Zhang, Xuehong; Townsend, Mary K; Selhub, Jacob; Paul, Ligi; Rosner, Bernard; Fuchs, Charles S; Willett, Walter C; Giovannucci, Edward L

    2015-12-01

    Higher folate has been associated with a reduced colorectal cancer (CRC) risk, but excessive folate may promote tumor progression. The role of unmetabolized folic acid (UFA) from high folic acid consumption in carcinogenesis is largely unexplored. We evaluated prediagnostic plasma levels of UFA in relation to CRC risk in nested case-control studies (618 CRC case patients and 1207 matched control) with blood samples collected prior to folic acid fortification. UFA was detected in 21.4% of control UFA levels were not associated with CRC risk. Compared with undetectable levels, the multivariable relative risks (RRs) of CRC were 1.03 (95% confidence interval [CI] = 0.73 to 1.46) for less than 0.5 nmol/L and 1.12 (95% CI = 0.81 to 1.55) for 0.5 nmol/L or more (Ptrend = .32). A positive association between UFA levels and CRC risk was observed among men (RR = 1.57, 95% CI = 0.99 to 2.49 for ≥0.5 nmol/L vs undetectable, Pinteraction = .04), and a positive association was also observed among those with the methylene-tetrahydrofolate reductase (MTHFR) CT/TT genotype (RR = 2.20, 95% CI = 1.22 to 3.94 for ≥0.5 nmol/L vs undetectable, Pinteraction=0.02). In conclusion, prediagnostic plasma levels of UFA from the prefortification period were not associated with risk of CRC.

  5. Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.

    PubMed

    Ngernyuang, Nipaporn; Seubwai, Wunchana; Daduang, Sakda; Boonsiri, Patcharee; Limpaiboon, Temduang; Daduang, Jureerut

    2016-03-01

    There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction.

  6. Effects of dietary supplements of folic acid and vitamin B12 on metabolism of dairy cows in early lactation.

    PubMed

    Graulet, B; Matte, J J; Desrochers, A; Doepel, L; Palin, M-F; Girard, C L

    2007-07-01

    The present experiment was undertaken to determine the effects of dietary supplements of folic acid and vitamin B12 given from 3 wk before to 8 wk after calving on lactational performance and metabolism of 24 multiparous Holstein cows assigned to 6 blocks of 4 cows each according to their previous milk production. Supplementary folic acid at 0 or 2.6 g/d and vitamin B12 at 0 or 0.5 g/d were used in a 2 x 2 factorial arrangement. Supplementary folic acid increased milk production from 38.0 +/- 0.9 to 41.4 +/- 1.0 kg/d and milk crude protein yield from 1.17 +/- 0.02 to 1.25 +/- 0.03 kg/d. It also increased plasma Gly, Ser, Thr, and total sulfur AA, decreased Asp, and tended to increase plasma Met. Supplementary B12 decreased milk urea N, plasma Ile, and Leu and tended to decrease Val but increased homocysteine, Cys, and total sulfur AA. Liver concentration of phospholipids was higher in cows fed supplementary B12. Plasma and liver concentrations of folates and B12 were increased by their respective supplements, but the increase in plasma folates and plasma and liver B12 was smaller for cows fed the 2 vitamins together. In cows fed folic acid supplements, supplementary B12 increased plasma glucose and alanine, tended to decrease plasma biotin, and decreased Km of the methylmalonyl-coenzyme A mutase in hepatic tissues following addition of deoxyadenosylcobalamin, whereas it had no effect when cows were not fed folic acid supplements. There was no treatment effect on plasma nonesterified fatty acids as well as specific activity and gene expression of Met synthase and methylmalonyl-coenzyme A mutase in the liver. Ingestion of folic acid supplements by cows fed no supplementary B12 increased total lipid and triacylglycerols in liver, whereas these supplements had no effect in cows supplemented with B12. The increases in milk and milk protein yields due to folic acid supplements did not seem to be dependent on the vitamin B12 supply. However, when vitamin B12 was given in

  7. Environment and solute-solvent interaction effects on photo-physical behaviors of Folic acid and Folinic acid drugs

    NASA Astrophysics Data System (ADS)

    Khadem Sadigh, M.; Zakerhamidi, M. S.; Seyed Ahmadian, S. M.; Johari-Ahar, M.; Zare Haghighi, L.

    2016-12-01

    In this paper, spectral properties of Folic acid and Folinic acid as widely used drugs in the treatment of some diseases have been studied in various environments with different polarity. Our results show that the absorption, emission and stokes shifts of solute molecules depend strongly on molecular surrounding characteristics, solute-solvent interactions and, different active groups in their chemical structures. In order to investigate the contribution of specific and nonspecific interactions on various properties of drug samples, the linear solvation energy relationships concept is used. Moreover, the calculated dipole moments by means of solvatochromic method show that the high values of dipole moments in excited state are due to local intramolecular charge transfer. Furthermore, the obtained results about molecular interactions can be extended to biological systems and can indicate completely the behaviors of Folic acid and Folinic acid in polar solvents such as water in body system.

  8. Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism.

    PubMed

    Sid, Victoria; Wu, Nan; Sarna, Lindsei K; Siow, Yaw L; House, James D; O, Karmin

    2015-11-15

    AMPK is an endogenous energy sensor that regulates lipid and carbohydrate metabolism. Nonalcoholic fatty liver disease (NAFLD) is regarded as a hepatic manifestation of metabolic syndrome with impaired lipid and glucose metabolism and increased oxidative stress. Our recent study showed that folic acid supplementation attenuated hepatic oxidative stress and lipid accumulation in high-fat diet-fed mice. The aim of the present study was to investigate the effect of folic acid on hepatic AMPK during high-fat diet feeding and the mechanisms involved. Male C57BL/6J mice were fed a control diet (10% kcal fat), a high-fat diet (60% kcal fat), or a high-fat diet supplemented with folic acid (26 mg/kg diet) for 5 wk. Mice fed a high-fat diet exhibited hyperglycemia, hepatic cholesterol accumulation, and reduced hepatic AMPK phosphorylation. Folic acid supplementation restored AMPK phosphorylation (activation) and reduced blood glucose and hepatic cholesterol levels. Activation of AMPK by folic acid was mediated through an elevation of its allosteric activator AMP and activation of its upstream kinase, namely, liver kinase B1 (LKB1) in the liver. Consistent with in vivo findings, 5-methyltetrahydrofolate (bioactive form of folate) restored phosphorylation (activation) of both AMPK and LKB1 in palmitic acid-treated HepG2 cells. Activation of AMPK by folic acid might be responsible for AMPK-dependent phosphorylation of HMG-CoA reductase, leading to reduced hepatic cholesterol synthesis during high-fat diet feeding. These results suggest that folic acid supplementation may improve cholesterol and glucose metabolism by restoration of AMPK activation in the liver.

  9. Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and tributyrin in rat liver carcinogenesis

    PubMed Central

    Guariento, Aline H.; Furtado, Kelly S.; de Conti, Aline; Campos, Adriana; Purgatto, Eduardo; Carrilho, Jéssica; Shinohara, Elvira Maria Guerra; Tryndyak, Volodymyr; Han, Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.; Pogribny, Igor P.; Moreno, Fernando S.

    2014-01-01

    The steady increase in the incidence and mortality of hepatocellular carcinoma (HCC) signifies a crucial need to understand better its pathogenesis to improve clinical management and prevention of the disease. The aim of this study was to investigate molecular mechanisms for the chemopreventive effects of folic acid and tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with folic acid and tributyrin alone or in combination for 5 weeks during promotion stage. Treatment with folic acid and tributyrin alone or in combination strongly inhibited the development of glutathione-S-transferase placental form (GSTP)-positive foci. Microarray analysis showed significant changes in gene expression. A total of 501, 655, and 940 of differentially expressed genes, involved in cell cycle, p53-signaling, angiogenesis, and Wnt pathways, was identified in the livers of rats treated with folic acid, tributyrin or folic acid and tributyrin. A detailed analysis of these differentially expressed genes revealed that treatments inhibited angiogenesis in the preneoplastic livers. This was evidenced by the fact that 30 out of 77 differentially expressed genes common to all three treatments are involved in the regulation of the angiogenesis pathway. The inhibition of angiogenesis was confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing activity of folic acid and tributyrin is associated with inhibition of angiogenesis at early stages of rat liver carcinogenesis. Importantly, the combination of folic acid and tributyrin has stronger chemopreventive effect than each of the compounds alone. PMID:24302446

  10. Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways

    PubMed Central

    Salvatore, Rosaria; Porro, Chiara; Trotta, Teresa

    2016-01-01

    We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF-α and IL-1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways. PMID:27738387

  11. Folic Acid Alters Methylation Profile of JAK-STAT and Long-Term Depression Signaling Pathways in Alzheimer's Disease Models.

    PubMed

    Li, Wen; Liu, Huan; Yu, Min; Zhang, Xumei; Zhang, Yan; Liu, Hongbo; Wilson, John X; Huang, Guowei

    2016-11-01

    Dementia has emerged as a major societal issue because of the worldwide aging population and the absence of any effective treatment. DNA methylation is an epigenetic mechanism that evidently plays a role in Alzheimer's disease (AD). Folate acts through one-carbon metabolism to support the methylation of multiple substrates including DNA. We aimed to test the hypothesis that folic acid supplementation alters DNA methylation profiles in AD models. Mouse Neuro-2a cells expressing human APP695 (N2a-APP cells) were incubated with folic acid (2.8-20 μmol/L). AD transgenic mice were fed either folate-deficient or control diets and gavaged daily with water or folic acid (600 μg/kg). Gene methylation profiles were determined by methylated DNA immunoprecipitation-DNA microarray (MeDIP-chip). Differentially methylated regions (DMRs) were determined by Quantitative Differentially Methylated Regions analysis, and differentially methylated genes (DMGs) carrying at least three DMRs were selected for pathway analysis. Folic acid up-regulated DNA methylation levels in N2a-APP cells and AD transgenic mouse brains. Functional network analysis of folic acid-induced DMGs in these AD models revealed subnetworks composed of 24 focus genes in the janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and 12 focus genes in the long-term depression (LTD) signaling pathway. In conclusion, these results revealed a role for folic acid in the JAK-STAT and LTD signaling pathways which may be relevant to AD pathogenesis. This novel finding may stimulate reinvestigation of folic acid supplementation as a prophylactic or therapeutic treatment for AD.

  12. Light and ultrastructural study in the propylthiouracil-induced hypothyroid rat heart ventricles and the ameliorating role of folic acid.

    PubMed

    Massoud, Ahmed A; El-Atrash, Afaf; Tousson, Ehab; Ibrahim, Wafaa; Abou-Harga, Heba

    2012-04-01

    Thyroid hormones have marked effects on the growth, development, and metabolic function of virtually all organs and tissues. Thyroid status is an important determinant of cardiovascular function. The present work studied the histopathological and ultrastructural changes in the hypothyroid rat left ventricle at post-pubertal stage, in addition to the ameliorating role of folic acid. A total of 50 male albino rats were randomly divided into 5 groups (group I, control; group II, folic acid; group III, propylthiouracil-induced hypothyroid rats; group IV, co-treatment with folic acid; group V, post-treatment). In order to ensure the hypothyroid state, the level of serum triiodothyronine (T(3)) and thyroid stimulating hormone (TSH) through the dose period was regularly determined. The TSH levels were significantly higher while T(3) levels were significantly lower in hypothyroid rats when compared to control group. The high-performance liquid chromatography analysis showed an increase in homocysteine (Hcy) in the hypothyroid rats group when compared to the control group. The histopathological studies of the ventricle in hypothyroid rats revealed hydrophobic changes in myofibrillar structure with striations, myocardial atrophy, nuclear pyknosis, cytoplasmic vacuoles, and cytoplasmic eosinophilia. Transmission electron micrographs in the myocardium of hypothyroid rats revealed a marked reduction in muscle fibre mass, a marked degeneration of muscle fibres, swollen mitochondria, dilated sarcoplasmic reticulum and more prominent perinuclear oedema observed in the cardiac myocytes. In co-treated hypothyroid rats with folic acid, a regular arrangement of muscle fibres, mild swelling of myofibrillar structure with striations and no continuity with adjacent myofibrils were observed while the post-treated hypothyroid rat with folic acid showed normal architecture of myofibrillar structure with striations and continuity with adjacent myofibrils. In conclusion, our results indicated

  13. Decreased Vitamin B12 and Folic Acid Concentrations in Acne Patients After Isotretinoin Therapy: A Controlled Study

    PubMed Central

    Gökalp, Hilal; Bulur, I; Gürer, MA

    2014-01-01

    Background: Oral isotretinoin treatment might influence the levels of vitamin B12 and folic acid. Aims and Objectives: The aim of this study is to compare vitamin B12 and folic acid levels in patients with moderate and severe acne vulgaris with those of the healthy control group and to investigate the effect of isotretinoin treatment on these vitamins. Materials and Methods: Patients who completed 6 months of isotretinoin therapy for moderate and severe forms of acne vulgaris and a control group consisting of healthy individuals between February 2011 and March 2012 were included in the study. Before isotretinoin therapy and at 6.- months of the therapy, serum vitamin B12 and folic acid levels were measured. In the healthy control group, vitamin B12 and folic acid levels were assessed only once. Results: In total, 120 patients with moderate and severe acne vulgaris who completed 6 months isotretinoin therapy and 100 healthy individuals who constituted the control group were included in the study. Pre-treatment vitamin B12 values of the patient group were found to be statistically significantly higher (P = 0.002), but any statistically significant difference was not detected in folic acid measurements (P = 0.566). A statistically significant decrease was detected in post-treatment vitamin B12 and folic acid levels (P < 0.05). Conclusion: Vitamin B12/folic acid treatment should be given under medical surveillance before and during isotretinoin therapy. Supplementation of these vitamins should be recommended in cases of their deficiency, so as to decrease the risks of neuropsychiatric and occlusive vascular diseases. PMID:25484410

  14. Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000.

    PubMed

    2004-05-07

    Neural tube defects (NTDs) are serious birth defects of the spine (e.g., spina bifida) and the brain (e.g., anencephaly) that occur during early pregnancy, often before a woman knows she is pregnant; 50%-70% of these defects can be prevented if a woman consumes sufficient folic acid daily before conception and throughout the first trimester of her pregnancy. In 1992, to reduce the number of cases of spina bifida and other NTDs, the U.S. Public Health Service (USPHS) recommended that all women capable of becoming pregnant consume 400 microg of folic acid daily. Three approaches to increase folic acid consumption were cited: 1) improve dietary habits, 2) fortify foods with folic acid, and 3) use dietary supplements containing folic acid. Mandatory fortification of cereal grain products went into effect in January 1998; during October 1998-December 1999, the reported prevalence of spina bifida declined 31%, and the prevalence of anencephaly declined 16%. Other studies have indicated similar trends. To update the estimated numbers of NTD-affected pregnancies and births, CDC recently analyzed data from 23 population-based surveillance systems that include prenatal ascertainment of these birth defects. This report summarizes the results of that analysis, which indicate that the estimated number of NTD-affected pregnancies in the United States declined from 4,000 in 1995-1996 to 3,000 in 1999-2000. This decline in NTD-affected pregnancies highlights the partial success of the U.S. folic acid fortification program as a public health strategy. To reduce further the number of NTD-affected pregnancies, all women capable of becoming pregnant should follow the USPHS recommendation and consume 400 microg of folic acid every day.

  15. Folic acid and 5-methyltetrahydrofolate in fortified milk are bioaccessible as determined in a dynamic in vitro gastrointestinal model.

    PubMed

    Verwei, Miriam; Arkbåge, Karin; Havenaar, Robert; van den Berg, Henk; Witthöft, Cornelia; Schaafsma, Gertjan

    2003-07-01

    Dairy products are a potential matrix for folate fortification to enhance folate consumption in the Western world. Milk folate-binding proteins (FBP) are especially interesting because they seem to be involved in folate bioavailability. In this study, folate bioaccessibility was investigated using a dynamic computer-controlled gastrointestinal model [TNO gastrointestinal model (TIM)]. We used both ultrahigh temperature (UHT)-processed milk and pasteurized milk, differing in endogenous FBP concentrations and fortified with folic acid or 5-methyltetrahydrofolate (5-CH(3)-H(4)folate). To study FBP stability during gastrointestinal passage and the effect of additional FBP on folate bioaccessibility, FBP-fortified UHT and pasteurized milk products were also tested. Folate bioaccessibility and FBP stability were measured by taking samples along the compartments of the gastrointestinal model and measuring their folate and FBP concentrations. Folate bioaccessibility from folic acid-fortified milk products without additional FBP was 58-61%. This was lower (P < 0.05) than that of the 5-CH(3)-H(4)folate-fortified milk products (71%). Addition of FBP reduced (P < 0.05) folate bioaccessibility from folic acid-fortified milk (44-51%) but not from 5-CH(3)-H(4)folate-fortified milk products (72%). The residual FBP levels in the folic acid- and 5-CH(3)-H(4)folate-fortified milk products after gastrointestinal passage were 13-16% and 0-1%, respectively, of the starting amounts subjected to TIM. In conclusion, milk seems to be a suitable carrier for folate, because both folic acid and 5-CH(3)-H(4)folate are easily released from the matrix and available for absorption. However, our results suggest that folic acid remains partly bound to FBP during passage through the small intestine, which reduces the bioaccessibility of folic acid from milk in this model.

  16. Effects of dietary folic acid level and symbiotic folate production on fitness and development in the fruit fly Drosophila melanogaster.

    PubMed

    Blatch, Sydella A; Meyer, Kyle W; Harrison, Jon F

    2010-01-01

    Folic acid is a vitamin for probably all animals. When converted to folate forms, it is used in DNA synthesis and amino acid metabolism. Literature suggests insects must consume folates, folates do not affect others, is a toxin for some, and that a few insects synthesize it. It has been reported that Drosophila melanogaster does not consistently need dietary folate because it can synthesize it. This seems unlikely since animals generally lack this ability. More likely, folates thought to have been made by the fly came from microbial symbionts. We aimed to clarify how dietary folic acid affects fitness and development in fruit flies and whether flies may receive folates from microbial symbionts. We found larvae were more viable and developed faster with increasing dietary folic acid, with the surprising exception that larvae fed nearly-zero folic acid developed faster. Their body folate levels did not significantly differ from those that consumed up to 600 times more folic acid. However, these flies fed little folate only achieved normal body folate levels and development times when antibiotics were excluded from the diet. When flies consumed near-zero folates with antibiotics, their body folate levels decreased and development was prolonged. An assay for the endosymbiont Wolbachia in flies used to generate the experimental flies did not show presence of these bacteria. Our data suggest D. melanogaster can harbor unknown bacterial symbiont(s) that provide essential folates to their host when it is scarce in the diet, allowing the fruit fly to maintain growth and development.

  17. Evaluation of folic acid release from spray dried powder particles of pectin-whey protein nano-capsules.

    PubMed

    Assadpour, Elham; Jafari, Seid-Mahdi; Maghsoudlou, Yahya

    2017-02-01

    Our main goal was to evaluate release kinetics of nano-encapsulated folic acid within a double W1/O/W2 emulsion. First, W1/O nano-emulsions loaded with folic acid were prepared and re-emulsified into an aqueous phase (W2) containing single whey protein concentrate (WPC) layer or double layer complex of WPC-pectin to form W1/O/W2 emulsions. Final double emulsions were spray dried and their microstructure was analyzed in terms of scanning electron microscopy (SEM), and Fourier Transform Infrared spectroscopy (FTIR). Also the release trends of folic acid were determined and fitted with experimental models of zero and first order, Higuchi, and Hixson-Crowell. It was revealed that folic acid nano-capsules made with Span as the surfactant had the lowest release rate in acidic conditions (pH=4) and highest release in the alkaline conditions (pH=11). The best model fitting for folic acid release data was observed for single layer WPC encapsulated powders with the highest R(2). Our FTIR data showed there was no chemical interaction between WPC and pectin in double layered capsules and based on SEM results, single WPC layered capsules resulted in smooth and uniform particles which by incorporating pectin, some wrinkles and shrinkage were found in the surface of spray dried powder particles.

  18. Four-way calibration applied to the simultaneous determination of folic acid and methotrexate in urine samples.

    PubMed

    Muñoz de la Peña, A; Durán Merás, I; Jiménez Girón, A

    2006-08-01

    First-, second- and third-order calibration methods were investigated for the simultaneous determination of folic acid and methotrexate. The interest in the determination of these compounds is related to the fact that methotrexate inhibits the body's absorption of folic acid and prolonged treatment with methotrexate may lead to folic acid deficiency, and to the use of folic acid to cope with toxic side effects of methotrexate. Both analytes were converted into highly fluorescent compounds by oxidation with potassium permanganate, and the kinetics of the reaction was continuously monitored by recording the kinetics curves of fluorescence emission, the evolution with time of the emission spectra and the excitation-emission matrices (EEMs) of the samples at different reaction times. Direct determination of mixtures of both drugs in urine was accomplished on the basis of the evolution of the kinetics of EEMs by fluorescence measurements and four-way parallel-factor analysis (PARAFAC) or multiway partial least squares (N-PLS) chemometric calibration. The core consistency diagnostic (CORCONDIA) was employed to determine the correct number of factors in PARAFAC and the procedure converged to a choice of three factors, attributed to folic acid, methotrexate and to the sum of fluorescent species present in the urine.

  19. Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project.

    PubMed

    Hollis, NaTasha D; Allen, Emily G; Oliver, Tiffany Renee; Tinker, Stuart W; Druschel, Charlotte; Hobbs, Charlotte A; O'Leary, Leslie A; Romitti, Paul A; Royle, Marjorie H; Torfs, Claudine P; Freeman, Sallie B; Sherman, Stephanie L; Bean, Lora J H

    2013-03-01

    Both a lack of maternal folic acid supplementation and the presence of genetic variants that reduce enzyme activity in folate pathway genes have been linked to meiotic nondisjunction of chromosome 21; however, the findings in this area of research have been inconsistent. To better understand these inconsistencies, we asked whether maternal use of a folic acid-containing supplement before conception reduces risk for chromosome 21 nondisjunction. Using questionnaire data from the National Down Syndrome Project, a population-based case-control study, we compared the use of folic acid-containing supplements among mothers of infants with full trisomy 21 due to maternal nondisjunction (n = 702) and mothers of infants born with no major birth defects (n = 983). Using logistic regression, adjusting for maternal age, race/ethnicity, and infant age at maternal interview, we found no evidence of an association between lack of folic acid supplementation and maternal nondisjunction among all case mothers (OR = 1.16; 95% CI: 0.90-1.48). In analyses stratified by meiotic stage and maternal age (<35 or ≥35 years), we found an association among older mothers experiencing meiosis II nondisjunction errors (OR = 2.00; 95% CI: 1.08-3.71). These data suggest that lack of folic acid supplementation may be associated specifically with MII errors in the aging oocyte. If confirmed, these results could account for inconsistencies among previous studies, as each study sample may vary by maternal age structure and proportion of meiotic errors.

  20. Folic Acid potentiates the effect of memantine on spatial learning and neuronal protection in an Alzheimer's disease transgenic model.

    PubMed

    Chen, Ta-Fu; Huang, Rwei-Fen S; Lin, Sey-En; Lu, Jyh-Feng; Tang, Ming-Chi; Chiu, Ming-Jang

    2010-01-01

    Folic acid deficiency and hyperhomocysteinemia potentiate amyloid-beta (Abeta) neuron toxicity. Memantine, an NMDA antagonist used in moderate to severe AD, is considered to be neuroprotective. We propose that folic acid might have a synergistic effect for memantine in protecting neurons from Abeta accumulation. We treated 8-month-old Tg2576 transgenic mice with memantine (30 mg/kg/day) with or without folic acid (8 mg/kg/day) for 4 months. Escape latencies in the Morris water maze were significantly shorter in the folic acid-memantine treatment group Tg(+)_M+F compared to both the non-treatment transgenic controls Tg(+) and the memantine-treatment group Tg(+)_M (both p < 0.05). Analysis of Abeta40 and Abeta42 showed lower brain loads in both treatment groups but this did not reach statistical significance. Histopathology analysis showed that Tg(+)_M+F had lower ratios of neuronal damage than Tg(+) (p < 0.001) and Tg(+)_M (p< 0.005). DNA analysis revealed that in the Tg(+)M_+F group, transcription was upregulated in 72 brain genes involved in neurogenesis, neural differentiation, memory, and neurotransmission compared to the Tg(+)_M group. In conclusion, we found that folic acid may potentiate the effect of memantine on spatial learning and neuronal protection. The benefit of combination therapy may be through co-action on the methylation-controlled Abeta production, and modification of brain gene expression.

  1. Maternal folic acid supplementation modulates DNA methylation and gene expression in the rat offspring in a gestation period-dependent and organ-specific manner.

    PubMed

    Ly, Anna; Ishiguro, Lisa; Kim, Denise; Im, David; Kim, Sung-Eun; Sohn, Kyoung-Jin; Croxford, Ruth; Kim, Young-In

    2016-07-01

    Maternal folic acid supplementation can alter DNA methylation and gene expression in the developing fetus, which may confer disease susceptibility later in life. We determined which gestation period and organ were most sensitive to the modifying effect of folic acid supplementation during pregnancy on DNA methylation and gene expression in the offspring. Pregnant rats were randomized to a control diet throughout pregnancy; folic acid supplementation at 2.5× the control during the 1st, 2nd or 3rd week of gestation only; or folic acid supplementation throughout pregnancy. The brain, liver, kidney and colon from newborn pups were analyzed for folate concentrations, global DNA methylation and gene expression of the Igf2, Er-α, Gr, Ppar-α and Ppar-γ genes. Folic acid supplementation during the 2nd or 3rd week gestation or throughout pregnancy significantly increased brain folate concentrations (P<.001), while only folic acid supplementation throughout pregnancy significantly increased liver folate concentrations (P=.005), in newborn pups. Brain global DNA methylation incrementally decreased from early to late gestational folic acid supplementation and was the lowest with folic acid supplementation throughout pregnancy (P=.026). Folic acid supplementation in late gestation or throughout pregnancy significantly decreased Er-α, Gr and Ppar-α gene expression in the liver (P<.05). The kidney and colon were resistant to the effect of folic acid supplementation. Maternal folic acid supplementation affects tissue folate concentrations, DNA methylation and gene expression in the offspring in a gestation-period-dependent and organ-specific manner.

  2. Maternal and postweaning folic acid supplementation interact to influence body weight, insulin resistance, and food intake regulatory gene expression in rat offspring in a sex-specific manner.

    PubMed

    Huot, Pedro S P; Ly, Anna; Szeto, Ignatius M Y; Reza-López, Sandra A; Cho, Daniel; Kim, Young-In; Anderson, G Harvey

    2016-04-01

    Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic acid content of maternal diets would alter the offspring's metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring's diet with that of the maternal diet. Female Sprague-Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.

  3. A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate.

    PubMed

    Kalmbach, Renee D; Choumenkovitch, Silvina F; Troen, Aron P; Jacques, Paul F; D'Agostino, Ralph; Selhub, Jacob

    2008-12-01

    Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF). A 19-bp noncoding deletion allele maps to intron 1, beginning 60 bases from the splice donor site, and has been implicated in neural tube defects and cancer, presumably by influencing folate metabolism. The functional impact of this polymorphism has not yet been demonstrated. The objective of this research was to determine the effects of the DHFR mutation with respect to folate status and assess influence of folic acid intake on these relations. The relationship between DHFR genotype and plasma concentrations of circulating folic acid, total folate, total homocysteine, and concentrations of RBC folate was determined in 1215 subjects from the Framingham Offspring Study. There was a significant interaction between DHFR genotype and folic acid intake with respect to the prevalence of high circulating unmetabolized folic acid (defined as >85th percentile). Folic acid intake of >or=500 microg/d increased the prevalence of high circulating unmetabolized folic acid in subjects with the deletion (del/del genotype (47.0%) compared with the wild type (WT)/del (21.4%) and wild type (WT)/WT genotypes (24.4%) (P for interaction = 0.03). Interaction between the DHFR polymorphism and folic acid intake was also seen with respect to RBC folate (P for interaction = 0.01). When folic acid intake was <250 microg/d, the del/del genotype was associated with significantly lower RBC folate (732.3 nmol/L) compared with the WT/WT genotype (844.4 nmol/L). Our results suggest the del/del polymorphism in DHFR is a functional polymorphism, because it limits assimilation of folic acid into cellular folate stores at high and low folic acid intakes.

  4. Bioavailability of iron, vitamin A, zinc, and folic acid when added to condiments and seasonings.

    PubMed

    Degerud, Eirik M; Manger, Mari Skar; Strand, Tor A; Dierkes, Jutta

    2015-11-01

    Seasonings and condiments can be candidate vehicles for micronutrient fortification if consumed consistently and if dietary practices ensure bioavailability of the nutrient. In this review, we identify factors that may affect the bioavailability of iron, vitamin A, zinc, and folic acid when added to seasonings and condiments and evaluate their effects on micronutrient status. We take into consideration the chemical and physical properties of different forms of the micronutrients, the influence of the physical and chemical properties of foods and meals to which fortified seasonings and condiments are typically added, and interactions between micronutrients and the physiological and nutritional status of the target population. Bioavailable fortificants of iron have been developed for use in dry or fluid vehicles. For example, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and ferrous sulfate with citric acid are options for iron fortification of fish and soy sauce. Furthermore, NaFeEDTA, microencapsulated ferrous fumarate, and micronized elemental iron are potential fortificants in curry powder and salt. Dry forms of retinyl acetate or palmitate are bioavailable fortificants of vitamin A in dry candidate vehicles, but there are no published studies of these fortificants in fluid vehicles. Studies of zinc and folic acid bioavailability in seasonings and condiments are also lacking.

  5. Bioavailability of iron, vitamin A, zinc, and folic acid when added to condiments and seasonings

    PubMed Central

    Degerud, Eirik M.; Manger, Mari Skar; Strand, Tor A.

    2015-01-01

    Seasonings and condiments can be candidate vehicles for micronutrient fortification if consumed consistently and if dietary practices ensure bioavailability of the nutrient. In this review, we identify factors that may affect the bioavailability of iron, vitamin A, zinc, and folic acid when added to seasonings and condiments and evaluate their effects on micronutrient status. We take into consideration the chemical and physical properties of different forms of the micronutrients, the influence of the physical and chemical properties of foods and meals to which fortified seasonings and condiments are typically added, and interactions between micronutrients and the physiological and nutritional status of the target population. Bioavailable fortificants of iron have been developed for use in dry or fluid vehicles. For example, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and ferrous sulfate with citric acid are options for iron fortification of fish and soy sauce. Furthermore, NaFeEDTA, microencapsulated ferrous fumarate, and micronized elemental iron are potential fortificants in curry powder and salt. Dry forms of retinyl acetate or palmitate are bioavailable fortificants of vitamin A in dry candidate vehicles, but there are no published studies of these fortificants in fluid vehicles. Studies of zinc and folic acid bioavailability in seasonings and condiments are also lacking. PMID:26469774

  6. Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

    PubMed

    Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

    2015-06-01

    Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity.

  7. Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy

    PubMed Central

    Hekmati Azar Mehrabani, Zohreh; Ghorbanihaghjo, Amir; Sayyah Melli, Manizheh; Hamzeh-Mivehroud, Maryam; Fathi Maroufi, Nazila; Bargahi, Nasrin; Bannazadeh Amirkhiz, Maryam; Rashtchizadeh, Nadereh

    2015-01-01

    Introduction:There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. Methods: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. Results: Supplementation of the patients with FA for 36 week decreased the median (minimum– maximum) levels of serum Hcy from 11.40 μmol/L (4.40-28.70) to 9.70 (1.60-20.80) μmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. Conclusion:Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women. PMID:26929921

  8. Electropolymerized molecularly imprinted polymer films of a bis-terthiophene dendron: folic acid quartz crystal microbalance sensing.

    PubMed

    Apodaca, Dahlia C; Pernites, Roderick B; Ponnapati, Ramakrishna R; Del Mundo, Florian R; Advincula, Rigoberto C

    2011-02-01

    A folic acid sensor was prepared via an electropolymerized molecularly imprinted polymer (E-MIP) film of a bis-terthiophene dendron on a quartz crystal microbalance (QCM). The cyclic voltammetry (CV) electrodeposition of the imprinted polymer film was monitored by electrochemical QCM or E-QCM, enabling in situ monitoring and characterization of E-MIP film formation and the viscoelastic behavior of the film. A key component of the E-MIP process is the use of a bifunctional monomer design to precomplex with the template and function as a cross-linker. The complex was electropolymerized and cross-linked by CV to form a polythiophene matrix. Stable cavities were formed that specifically fit the size and shape of the folic acid template. The same substrate surface was used for folic acid sensing. The predicted geometry of the 1:2 folic acid/terthiophene complex was obtained through semiempirical AM1 quantum calculations. The analytical performance, expressed through the figures of merit, of the sensor in aqueous solutions of the analyte was investigated. A relatively good linearity, R(2) = 0.985, was obtained within the concentration range 0-100 μM folic acid. The detection limit was found to be equal to 15.4 μM (6.8 μg). The relative cross selectivity of the folic acid imprinted polymer against the three molecules follows this trend: pteroic acid (= 50%) > caffeine (= 41%) > theophylline (= 6%). The potential and limitations of the E-MIP method were also discussed.

  9. Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects.

    PubMed

    Tabei, Seyed Mohammad Bagher; Mazloom, Maryam; Shahriari, Mahdi; Zareifar, Soheila; Azimi, Ali; Hadaegh, Amirhossein; Karimi, Mehran

    2013-11-01

    Beta-thalassemia minor (BTM) patients usually experience fatigue, bone pain complaint, and muscle weakness. Carnitine is an essential protein for transportation of long-chain fatty acids to the matrix for beta-oxidation. BTM patients have abnormally low plasma carnitine concentrations, which results in deficient ATP production. Carnitine and folic acid together may have a role in preventing bone pain complaint and fatigue in these patients. The aim of this study is to determine the effect of carnitine and folic acid supplementation in subjects with BTM. Seventy three BTM (mean age 11.06 ± 5.46 years) and 23 healthy controls (mean age 8.48 ± 3.78 years) were enrolled in the study. Fasting blood was drawn to determine baseline free and total carnitine levels, red blood cell folate concentration, and hemoglobin level. BTM were divided into three groups and received different types of supplementation for 3 months: Group 1, 50 mg/kg/day carnitine; Group 2, 50 mg/kg/day carnitine plus 1 mg/day folic acid; and Group 3, 1 mg/day folic acid. Controls did not receive supplementation. Laboratory parameters were again evaluated after 3 months' supplementation. A detailed quality of life questionnaire was designed to investigate muscle symptoms before and after supplementation. Free and total plasma carnitine concentration and hemoglobin levels in BTM subjects increased significantly after carnitine supplementation (P < .0001). Bone pain complaint and muscle weakness decreased with carnitine. Red blood cell folate level increased after folic acid supplementation. Carnitine and folic acid supplementation resulted in a decrease in bone pain complaint and muscle weakness in cases with β-thalassemia minor.

  10. Folic acid in the prevention of neural tube defect--a programme for Malaysia?

    PubMed

    Ho, J J

    2004-03-01

    There is good evidence that folic acid is safe and efficacious for reducing neural tube defect (NTD). All women capable of becoming pregnant should take 400 microgram daily. This can be given in the form of a daily vitamin supplement, by food fortification, or by increasing natural dietary folates. Compulsory grain fortification has been shown to reduce NTD in a population but supplementation and dietary advice have not. Malaysia should work towards a programme of grain fortification and use alternative strategies to reach sections of the population that would not be covered but several research questions need to be answered before a programme could be implemented in Malaysia.

  11. Characterization of folic acid/native cyclodextrins host-guest complexes in solution

    NASA Astrophysics Data System (ADS)

    Ceborska, Magdalena; Zimnicka, Magdalena; Wszelaka-Rylik, Małgorzata; Troć, Anna

    2016-04-01

    The complexation of folic acid (FA) with native cyclodextrins was studied and this process was used for the comparison of 1H NMR, ITC and ESIMS for the evaluation of association constants. The stability increases in the series: α-cyclodextrin/FA < γ-cyclodextrin/FA < β-cyclodextrin/FA. 1H NMR and ITC gave comparable results in regard to association constant values, while results obtained for MS were considerably higher due to different interactions (electrostatic instead of hydrophobic) responsible for the stabilization of the complexes. The dimerization of FA in water was also studied, as well as its impact on the process of complexation with native cyclodextrins.

  12. Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia

    PubMed Central

    Regland, Björn; Forsmark, Sara; Halaouate, Lena; Matousek, Michael; Peilot, Birgitta; Zachrisson, Olof; Gottfries, Carl-Gerhard

    2015-01-01

    Background Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders. Objective To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years. Methods 38 patients were included in a cross-sectional survey. Based on a validated observer’s rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects. Results Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as “very much” or “much” improved, while Mild responders rated “much” or “minimally” improved. Conclusions Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. It’s important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed. PMID

  13. Microwave-assisted polyol synthesis of carbon nitride dots from folic acid for cell imaging.

    PubMed

    Guan, Weiwei; Gu, Wei; Ye, Ling; Guo, Chenyang; Su, Su; Xu, Pinxiang; Xue, Ming

    2014-01-01

    A green, one-step microwave-assisted polyol synthesis was employed to prepare blue luminescent carbon nitride dots (CNDs) using folic acid molecules as both carbon and nitrogen sources. The as-prepared CNDs had an average size of around 4.51 nm and could be well dispersed in water. Under excitation at 360 nm, the CNDs exhibited a strong blue luminescence and the quantum yield was estimated to be 18.9%, which is greater than that of other reported CNDs. Moreover, the CNDs showed low cytotoxicity and could efficiently label C6 glioma cells, demonstrating their potential in cell imaging.

  14. Fortification of corn masa flour with folic acid in the United States: an overview of the evidence.

    PubMed

    Hamner, Heather C; Tinker, Sarah C

    2014-04-01

    Corn masa flour, used to make products such as corn tortillas, is a staple food for Hispanic populations residing in the United States, particularly among Mexican Americans and Central Americans. Research has indicated that Hispanic women in the United States continue to be at a higher risk of having a neural tube defect-affected pregnancy than women of other races/ethnicities, even after the introduction of folic acid fortification of cereal grain products labeled as "enriched." Corn masa flour has, therefore, been suggested as a potential food vehicle for folic acid in the United States. This paper explores the potential impact that folic acid fortification of corn masa flour could have on the Hispanic population in the United States.

  15. Evaluation of educational materials from a social marketing campaign to promote folic acid use among Hispanic women: insight from Cuban and Puerto Rican ethnic subgroups.

    PubMed

    Quinn, Gwendolyn P; Thomas, Kamilah B; Hauser, Kimberlea; Rodríguez, Nydia Y; Rodriguez-Snapp, Nazach

    2009-10-01

    Current data indicate significant disparities in awareness and use of folic acid between Hispanic and non-Hispanic women. Hispanic women are less likely to have heard about folic acid, to know that folic acid can prevent birth defects, to take folic acid daily, and to take folic acid before pregnancy. "Three Sisters/Las Tres Hermanos" is a folic acid social marketing campaign designed for Mexican-American women. To determine the effectiveness of the materials on other Hispanic sub groups, women of childbearing age from Cuba and Puerto Rico were recruited to evaluate the materials. Participants were asked five pre-test questions about folic acid knowledge and were then provided with the folic acid educational materials that included either a photo-novella and a low literacy brochure, or a video-novella in English or Spanish. Once the participants reviewed the materials, they were asked 10 post-test questions about the materials. The results of the evaluation are discussed.

  16. [Iron, folic acid and vitamin B12 deficiencies related to anemia in adolescents from a region with a high incidence of congenital malformations in Venezuela].

    PubMed

    Suárez, Teresa; Torrealba, Mónica; Villegas, Neifred; Osorio, Crisol; García-Casal, María Nieves

    2005-06-01

    Since in recent years for certain age groups, the main cause of anemia is not iron deficiency, we intended to study the effect of iron, folic acid and vitamin B12 deficiencies on anemia prevalence in adolescents from Venezuela. One hundred adolescents aged between 12 and 19 years participated in the study. Each subject was interviewed about antecedents and habits and a physical examination and a 24-hour food recall questionnaire were performed. From a blood sample, hemoglobin and hematocrit concentrations were determined and serum was separated for quantification of ferritin, folic acid and vitamin B12 concentrations. Prevalence of anemia was 78% and for iron, folic acid and vitamin B12 deficiencies were 34.66, 90.9 and 18.18%, respectively. From anemic cases, 35.89% presented iron deficiency, while 91.02% presented folic acid deficiency. Only 19.23% of adolescents with anemia presented also vitamin B12 deficiency, but all the cases with vitamin B12 deficiency, were anemic. Simultaneous iron and folic acid deficiencies affected 30.76% of anemic cases. The high prevalence of deficiencies found in this work could be explained by insufficient intake and inadequate food habits. The prevalence of anemia was associated to folic acid deficiency rather than to iron deficiency, due to the high prevalence of folic acid deficiency. The high prevalence of nutritional deficiencies found in this work, especially regarding folic acid deficiency, require immediate interventions.

  17. Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement

    PubMed Central

    Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2–24 hours post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16–24 hpf) produced retinal defects like those seen with ethanol exposure between 2–24 hpf. Significantly, during an ethanol-sensitive time window (16–24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects. PMID:25541501

  18. Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

    PubMed

    Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A

    2015-03-01

    Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects.

  19. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI

    PubMed Central

    Ma, Fei; Wu, Tianfeng; Zhao, Jiangang; Song, Aili; Liu, Huan; Xu, Weili; Huang, Guowei

    2016-01-01

    This study aimed to evaluate whether folic acid supplementation would improve cognitive performance by reducing serum inflammatory cytokine concentrations. This RCT was performed in Tianjin, China. Participants with mild cognitive impairment (MCI) were randomly assigned to the folic acid (400 μg/day) or conventional treatment groups. Neuropsychological tests were administered, and folate, homocysteine, vitamin B12, IL-6, TNF-α, Aβ-42, and Aβ-40 were measured at baseline and at 6- and 12-month time points.152 participants (folic acid: 77, conventional: 75) completed the trial. Significant improvements in folate (ηp2 = 0.703, P = 0.011), homocysteine (ηp2 = 0.644, P = 0.009), Aβ-42 (ηp2 = 0.687, P = 0.013), peripheral IL-6 (ηp2 = 0.477, P = 0.025), TNF-α (ηp2 = 0.709, P = 0.009) levels were observed in folic acid group compared with conventional group. Folic acid supplementation improved the Full Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P = 0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months compared with conventional treatment. Based on these findings, daily oral administration of a 400-μg folic acid supplement to MCI subjects for 12 months can significantly improve cognitive performance and reduce peripheral inflammatory cytokine levels. PMID:27876835

  20. Comparison of high dose and low dose folic acid supplementation on prevalence, onset and severity of preeclampsia

    PubMed Central

    Shahraki, Azar Danesh; Dehkordi, Nastaran Zamani; Lotfizadeh, Masoud

    2016-01-01

    Background: Folic acid supplementation had previously mentioned as a protective factor against the onset of preeclampsia (PE). In this study, we aimed to compare the effect of high dose (5 mg daily) and low dose (1 mg daily) of folic acid supplementation on prevalence, onset and severity of PE. Materials and Methods: Pregnant women who were in the first trimester and referred to prenatal care university hospitals of Isfahan, Iran during October 2013–May 2015 were included in this study, then they were randomly divided into two groups of 5 mg and 1 mg (treated with daily 5 mg and 1 mg of folic acid, respectively), both groups received folic acid from the first trimester of pregnancy to 42 days after termination. Blood pressure, body mass index (BMI), and some urine and blood biochemistry parameters were measured. SPSS-22 used for statistical analysis. Results: A total of 943 pregnant women participated in the study (450 women in 1 mg group and 450 women in 5 mg group). Incidence rate of PE was 3.8% in 1 mg group and 2.4% in 5 mg group. In a comparison of preeclamptic patients in 1 mg and 5 mg group, no significant differences were seen regarding age, BMI, laboratory data, the severity of the disease, and onset (early or late) (P > 0.05). Conclusion: Although our findings support that administration of high dose folic acid may decrease the prevalence of PE, there is not enough data to support that higher amount of folic acid administration can reduce the severity of presentation's signs or ameliorate the laboratory data and the onset of PE. PMID:28217630

  1. Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

    PubMed Central

    Sarmah, Swapnalee; Marrs, James A.

    2014-01-01

    BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

  2. The Effect of Folic Acid Supplementation on Hyperhomocysteinemia and Pulmonary Function Parameters in Chronic Obstructive Pulmonary Disease: A Pilot Study

    PubMed Central

    Khan, Naushad Ahmad; Saini, Harish; Mawari, Govind; Kumar, Suman; Hira, Harmanjit Singh

    2016-01-01

    Introduction Preliminary studies have established the elevated plasma total Homocysteine (tHcy) levels as a risk factor for Chronic Obstructive Pulmonary Disease (COPD). However, studies describing plasma tHcy levels and their relationship to folic acid supplementation and Forced Expiratory Volume in 1 Second (FEV1) status in COPD patients are still lacking. Aim We investigated the role of hyperhomocysteinemia in COPD and then prospectively examined the relationship between plasma tHcy concentration and effect of folic acid supplementation on FEV1 status in COPD patients. Materials and Methods This was a prospective case-control study with 50 clinically stable patients of COPD attending the chest clinic of the hospital and 30 healthy controls. The study was done at Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi, India, from August 2011 to February 2013. Plasma levels of Hcy were measured by Enzyme Linked Immuno-Sorbent Assay (ELISA) method. All the subjects were given folic acid therapy (5mg daily) for six weeks duration and were followed up. Repeat plasma Hcy and FEV1 were measured after six weeks. Results COPD patients had higher baseline plasma tHcy concentration than controls (Mean: 27.42±23.89μmol/L, versus 15.21±15.71μmol/L, p<0.001) and COPD was associated with higher tHcy concentrations also after adjusting for smoking, and age. The mean BMI of the patients was 21.36±4.26kg/m2. The mean Hcy values decreased from 27.42±23.89μmol/L to 15.2±15.71μmol/L (p-value=0.001) after six weeks of folic acid supplementation. However, no significant change was observed in FEV1 upon folic acid supplementation (FEV1=1.14±0.60 and 1.08±0.56 respectively; p-value=0.654). A significant correlation was observed between BMI and Hcy and also between plasma Hcy levels at the baseline and after six weeks of folic acid supplementation (r=0.283, p=0.04 and r=0.340, p=0.02, respectively) and (r=0.840, p=0.001). Conclusion COPD patients seem to

  3. Folic Acid Protects Against Glutamate-Induced Excitotoxicity in Hippocampal Slices Through a Mechanism that Implicates Inhibition of GSK-3β and iNOS.

    PubMed

    Budni, Josiane; Molz, Simone; Dal-Cim, Tharine; Martín-de-Saavedra, Maria Dolores; Egea, Javier; Lopéz, Manuela G; Tasca, Carla Ines; Rodrigues, Ana Lúcia Severo

    2017-02-10

    Folic acid (folate) is a vitamin of the B-complex group crucial for neurological function. Considering that excitotoxicity and cell death induced by glutamate are involved in many disorders, the potential protective effect of folic acid on glutamate-induced cell damage in rat hippocampal slices and the possible intracellular signaling pathway involved in such effect were investigated. The treatment of hippocampal slices with folic acid (100 μM) significantly abrogated glutamate (1 mM)-induced reduction of cell viability measured by MTT reduction assay and inhibited glutamate-induced D-[(3)H]-aspartate release. To investigate the putative intracellular signaling pathways implicated in the protective effect of folic acid, we used a PI3K inhibitor, LY294002, which abolished the protective effects of folic acid against glutamate-induced cell damage and D-[(3)H] aspartate release. Moreover, hippocampal slices incubated with folic acid alone for 30 min presented increased phosphorylation of GSK-3β at Ser9, indicating an inhibition of the activity of this enzyme. Furthermore, folic acid in the presence of glutamate insult in hippocampal slices maintained for an additional period of 6 h in fresh culture medium without glutamate and/or folic acid induced phosphorylation of GSK-3β and β-catenin expression. In addition, glutamate-treated hippocampal slices showed increased iNOS expression that was reversed by folic acid. In conclusion, the results of this study show that the protective effect of folic acid against glutamate-induced excitotoxicity may involve the modulation of PI3K/GSK-3β/β-catenin pathway and iNOS inhibition.

  4. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes.

    PubMed

    Lucock, M

    2000-01-01

    This paper reviews the chemistry, metabolism, and molecular biology of folic acid, with a particular emphasis on how it is, or may be, involved in many disease processes. Folic acid prevents neural tube defects like spina bifida, while its ability to lower homocysteine suggests it might have a positive influence on cardiovascular disease. A role for this B vitamin in maintaining good health may, in fact, extend beyond these clinical conditions to encompass other birth defects, several types of cancer, dementia, affective disorders, Down's syndrome, and serious conditions affecting pregnancy outcome. The effect of folate in these conditions can be explained largely within the context of folate-dependent pathways leading to methionine and nucleotide biosynthesis, and genetic variability resulting from a number of common polymorphisms of folate-dependent enzymes involved in the homocysteine remethylation cycle. Allelic variants of folate genes that have a high frequency in the population, and that may play a role in disease formation include 677C --> T-MTHFR, 1298A --> C-MTHFR, 2756A --> G-MetSyn, and 66A --> G-MSR. Future work will probably uncover further polymorphisms of folate metabolism, and lead to a wider understanding of the interaction between this essential nutrient and the many genes which underpin its enzymatic utilization in a plethora of critical biosynthetic reactions, and which, under adverse nutritional conditions, may promote disease.

  5. Reproductive toxicity of methomyl insecticide in male rats and protective effect of folic acid.

    PubMed

    Shalaby, M A; El Zorba, H Y; Ziada, Reem M

    2010-11-01

    The acute toxicity (LD(50)) of insecticide methomyl and its effects on male reproduction in rats were carried out. Methomyl was given orally to male rats daily for 65 successive days at two doses (0.5 and 1.0 mg kg(-1) b.wt., corresponding to 1/40 and 1/20 LD(50)) alone and in combination with folic acid (1.1 mg kg(-1) b.wt., corresponding to acceptable daily intake, ADI). Fertility index, weight of sexual organs, semen picture, serum testosterone level and histopathology of testes were the parameters used to evaluate the reproductive efficiency of treated rats. The reversibility of methomyl effects was also studied after 65 days post-administration. The oral LD(50) of methomyl was 20.0 mg kg(-1) b.wt. in male rats. Methomyl significantly decreased the fertility index, weight of testes and accessory male sexual glands, serum testosterone level and sperm motility and count, but increased sperm cell abnormality. It induced testicular lesions characterized by moderate to severe degenerative changes of seminiferous tubules and incomplete arrest of spermatogenesis. These toxic effects were not persistent (reversible). Coadministration of folic acid with methomyl decreased its reproductive toxicity. A great attention should be taken during field application of methomyl to avoid its deleterious effects in farm animals and occupationally exposed humans.

  6. Perspectives on obesity and sweeteners, folic acid fortification and vitamin D requirements.

    PubMed

    Halsted, Charles H

    2008-12-01

    This review summarizes three controversial areas of clinical practice that were discussed in many articles that appeared in the American Journal of Clinical Nutrition during the author's tenure as editor in chief. Controversy 1-obesity and high-fructose corn syrup. The increased frequency of obesity in the US is paralleled by increasing annual consumption of high-fructose corn syrup, an extracted sweetener that is routinely added to soft drinks and to many processed foods in the US diet. Metabolic studies implicate increased fructose consumption in increased body fat and obesity and with increased circulating triglyceride levels and hypercholesterolaemia in children. Controversy 2-folic acid fortification and supplements. Together with widespread use of supplemental multivitamins, fortification of the US diet with folic acid has resulted in high serum folate levels in much of the population, which may be associated with increased risk of cognitive decline in ageing people with low vitamin B12 status, decreased natural killer T-cell immune function and increased risk of recurrent advanced precancerous colorectal adenomas and breast cancer. Controversy 3-recommended intakes of vitamin D. Levels of serum 25(OH)D sufficient for fracture prevention are at least 75 nmol/l (30 ng/ml) but cannot be achieved by the current recommended dietary intakes in the US. A recent fracture risk prevention trial showed that the 4-year incidence of all cancers was reduced in US women who received high supplemental doses of both calcium and vitamin D.

  7. Impact of iron and folic acid supplementation on oxidative stress during pregnancy.

    PubMed

    Lymperaki, E; Tsikopoulos, A; Makedou, K; Paliogianni, E; Kiriazi, L; Charisi, C; Vagdatli, E

    2015-01-01

    The aim of the study was to assess serum total antioxidant capacity (TAC) and the impact of supplements on oxidative stress (OS) during pregnancy. Fifty volunteer pregnant women (21-40 years old), in the 12 ± 2 weeks' and 38 ± 2 weeks' gestation of pregnancy (study group), and 25 non-pregnant healthy women (control group) were enrolled. All pregnant women were divided into two age groups (A1: < 35 years and A2: ≥ 35 years) and four groups according to supplementation (B1: iron, B2: folic acid, B3: both and B4: none). Antioxidant activity was assayed using the TAC kit (Cayman Chemical Co.). Level of statistical significance was p < 0.05. Serum TAC values in all pregnant women in the first trimester were significantly lower, as compared with those of the control group. Levels of TAC increased significantly in the third trimester of pregnancy, especially with folic acid or no supplementation. In conclusion, pregnancy is associated with OS, which is promoted by the administration of iron supplementation.

  8. If high folic acid aggravates vitamin B12 deficiency what should be done about it?

    PubMed

    Johnson, Mary Ann

    2007-10-01

    The most common cause of vitamin B12 deficiency in older people is malabsorption of food-bound vitamin B12. Thus, it is suggested that the recommended daily allowance of 2.4 microg/d be met primarily with crystalline vitamin B12, which is believed to be well absorbed in individuals who have food-bound malabsorption. There is concern that high intakes of folic acid from fortified food and dietary supplements might mask the macrocytic anemia of vitamin B12 deficiency, thereby eliminating an important diagnostic sign. One recent study indicates that high serum folate levels during vitamin B12 deficiency exacerbate (rather than mask) anemia and worsen cognitive symptoms. Another study suggests that once vitamin B12 deficiency is established in subjects with food-bound malabsorption, 40 microg/d to 80 microg/d of oral crystalline vitamin B12 for 30 d does not reverse the biochemical signs of deficiency. Together, these studies provide further evidence that public health strategies are needed to improve vitamin B12 status in order to decrease the risk of deficiency and any potentially adverse interactions with folic acid.

  9. Immunoassay for folic acid detection in vitamin-fortified milk based on electrochemical magneto sensors.

    PubMed

    Lermo, A; Fabiano, S; Hernández, S; Galve, R; Marco, M-P; Alegret, S; Pividori, M I

    2009-03-15

    An immunoassay-based strategy for folic acid in vitamin-fortified milk with electrochemical detection using magneto sensors is described for the first time. Among direct and indirect competitive formats, best performance was achieved with an indirect competitive immunoassay. The immunological reaction for folic acid (FA) detection was performed, for the first time on the magnetic bead as solid support by the covalent immobilization of a protein conjugate BSA-FA on tosyl-activated magnetic bead. Further competition for the specific antibody between FA in the food sample and FA immobilized on the magnetic bead was achieved, followed by the reaction with a secondary antibody conjugated with HRP (AntiIgG-HRP). Then, the modified magnetic beads were easily captured by a magneto sensor made of graphite-epoxy composite (m-GEC) which was also used as the transducer for the electrochemical detection. The performance of the immunoassay-based strategy with electrochemical detection using magneto sensors was successfully evaluated using spiked-milk samples and compared with a novel magneto-ELISA based on optical detection. The detection limit was found to be of the order of microgl(-1) (13.1 nmoll(-1), 5.8 microgl(-1)) for skimmed milk. Commercial vitamin-fortified milk samples were also evaluated obtaining good accuracy in the results. This novel strategy offers great promise for rapid, simple, cost-effective and on-site analysis of biological and food samples.

  10. Simultaneous Derivative Spectrophotometric Analysis of Doxylamine Succinate, Pyridoxine Hydrochloride and Folic Acid in Combined Dosage Forms

    PubMed Central

    Pathak, A.; Rajput, S. J.

    2008-01-01

    Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 μg/ml, 1-40 μg/ml and 1-30 μg/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations. PMID:20046784

  11. Simultaneous derivative spectrophotometric analysis of doxylamine succinate, pyridoxine hydrochloride and folic Acid in combined dosage forms.

    PubMed

    Pathak, A; Rajput, S J

    2008-01-01

    Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40 mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.

  12. Effect of baking process on added folic acid and endogenous folates stability in wheat and rye breads.

    PubMed

    Gujska, Elzbieta; Majewska, Katarzyna

    2005-06-01

    In Poland bread as a staple food both made from wheat and rye flour can be a potential product for future fortification with folic acid. The objective of the study was to examine the effect of fermentation and baking on added folic acid and some endogenous folates stability during breadmaking of rye and wheat breads. Breads were produced using the formulation containing enriched flour with 0.2 mg folic acid/100 g product, baker's yeast and additionally ascorbic acid for wheat bread and lactic acid for rye bread. Folates were extracted with Hepes/Ches buffer (pH = 7.85) followed by destruction of matrix by amylase and protease and deconjugation with rat serum conjugase. Affinity chromatography (FBP bovine milk) was used to purify and concentrate samples. The folates were separated by HPLC with C18 column and with a combination of fluorescence and UV detection. For both rye and wheat breads there was a decrease of folic acid from flour to bread stage. The total losses depend on baking process and ranged from 12 to 21%. Some changes in the level of different native folate forms during the stage of baking process were also observed.

  13. Physiological Characteristics and Production of Folic Acid of Lactobacillus plantarum JA71 Isolated from Jeotgal, a Traditional Korean Fermented Seafood

    PubMed Central

    Lim, Sang-Dong

    2014-01-01

    Folic acid, one of the B group of vitamins, is an essential substance for maintaining the functions of the nervous system, and is also known to decrease the level of homocysteine in plasma. Homocysteine influences the lowering of the cognitive function in humans, and especially in elderly people. In order to determine the strains with a strong capacity to produce folic acid, 190 bacteria were isolated from various kinds of jeotgal and chungkuk-jang. In our test experiment, JA71 was found to contain 9.03μg/mL of folic acid after 24 h of incubation in an MRS broth. This showed that JA71 has the highest folic acid production ability compared to the other lactic acid bacteria that were isolated. JA71 was identified as Lactobacillus plantarum by the result of API carbohydrate fermentation pattern and 16s rDNA sequence. JA71 was investigated for its physiological characteristics. The optimum growth temperature of JA71 was 37℃, and the cultures took 12 h to reach pH 4.4. JA71 proved more sensitive to bacitracin when compared with fifteen different antibiotics, and showed most resistance to neomycin and vancomycin. Moreover, it was comparatively tolerant of bile juice and acid, and displayed resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus with restraint rates of 60.4%, 96.7%, and 76.2%, respectively. These results demonstrate that JA71 could be an excellent strain for application to functional products. PMID:26760752

  14. Effects of intramuscular injections of folic acid, vitamin B12, or both, on lactational performance and energy status of multiparous dairy cows.

    PubMed

    Duplessis, M; Lapierre, H; Pellerin, D; Laforest, J-P; Girard, C L

    2017-02-22

    The purpose of this experiment was to gain understanding on changes in energy partitioning when folic acid and vitamin B12 supplements, alone or combined, were given by weekly intramuscular injections from 3 wk before the expected calving date until 7 wk postpartum. Twenty-four multiparous cows were assigned to 6 blocks of 4 cows each according to previous 305-d lactation yield to either 0 or 320 mg of folic acid and 0 or 10 mg of vitamin B12 in a 2 × 2 factorial arrangement. Plasma concentration of folates was increased by folic acid supplement, and this increase was greater with the combined supplement. Vitamin B12 supplement increased plasma concentration of vitamin B12. Even though postpartum energy balance was similar among treatments, postpartum body condition score was higher for cows receiving folic acid supplement compared with cows that did not. Milk yield of cows receiving folic acid supplement reached a plateau earlier than for cows that did not. Fat and protein, as well as total solid concentrations and yields, were unaffected by treatments. Postpartum plasma concentrations of glucose and insulin were higher and postpartum plasma concentration of nonesterified fatty acids was lower for cows that received weekly folic acid supplement compared with cows that did not. Plasma concentration of methylmalonic acid was low and unaffected by treatments, suggesting that vitamin B12 supply was not limiting, even for unsupplemented cows. Postpartum plasma concentrations of Cys, His, Phe, and Tyr were increased, whereas plasma concentration of Gly was decreased, by folic acid supplement. In the present study, supplementary folic acid altered energy partitioning in early lactation as suggested by similar milk total solid yield and postpartum energy balance, lower plasma nonesterified fatty acid concentration and body condition score losses, and higher plasma glucose and insulin concentrations for cows receiving folic acid supplement compared with cows that did not.

  15. Effect of folic acid decorated magnetic fluorescent nanoparticles on the sedimentation of starch molecules

    NASA Astrophysics Data System (ADS)

    Palanikumar, S.; Kannammal, L.; Meenarathi, B.; Anbarasan, R.

    2014-04-01

    Ferrite-folic acid (FA) nanohybrids were synthesized and characterized by various analytical tools like Fourier transform infrared spectroscopy, UV-Visible spectroscopy, fluorescence spectroscopy, field emission scanning electron microscopy, X-ray diffraction analysis and vibrating sample measurement techniques. After the nanohybrid formation, both the crystallinity and the magnetization values of ferrite were disturbed due to the surface functionalization of ferrite by FA. The role of nanohybrid on the structure-property relationship of starch, particularly the sedimentation of starch under three different pHs, was evaluated. Again the magnetization value of Fe3O4-FA/starch nanocomposite system was reduced due to the encapsulation effect. The sedimentation velocity of starch under the influence of nanohybrid was enhanced in the acidic medium.

  16. Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women.

    PubMed

    Green, Timothy J; Liu, Yazheng; Dadgar, Samira; Li, Wangyang; Böhni, Ruth; Kitts, David D

    2013-06-01

    Mandatory folic acid fortification of grains such as wheat flour has been introduced in several countries to reduce the incidence of neural tube defects. There are concerns, however, that folic acid could mask the hematologic signs of vitamin B-12 deficiency and lead to other adverse health outcomes in the population. Calcium L-5-methyltetrahydrofolic acid (L-5-MTHF), a synthetic form of reduced folate, should not mask vitamin B-12 deficiency and may be safer than folic acid. Unfortunately, L-5-MTHF is not stable in most food matrices such as bread. Microencapsulation of L-5-MTHF with sodium ascorbate and a modified starch is effective at preventing loss of the vitamin during baking and storage. Our aim was to assess the efficacy of wheat rolls fortified with microencapsulated L-5-MTHF or equimolar folic acid compared with wheat rolls containing no added folate (placebo) at increasing blood folate concentrations during 16 wk. Healthy men and women aged 18-45 y (n = 45) were randomly assigned to consume wheat rolls that contained L-5-MTHF (452 μg/d), the molar equivalent of folic acid (400 μg/d), or placebo. At 16 wk, the mean (95% CI) erythrocyte folate was 0.48 (0.27, 0.71) and 0.37 (0.17, 0.57) μmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P = 0.001) groups, respectively, than in the placebo group. Likewise, the mean plasma folate was 23 (12, 34) and 23 (12, 34) nmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P < 0.001) groups, respectively, than in the placebo group. There were no significant differences in blood folate concentrations between the L-5-MTHF and folic acid wheat roll groups. Both microencapsulated L-5-MTHF and folic acid-fortified wheat rolls increased blood folate concentrations compared with placebo.

  17. Folic acid

    MedlinePlus

    ... skin disease called vitiligo, an inflammatory disease called gout, and an inherited disease called Fragile-X syndrome. ... risk of developing some types of stomach cancer. Gout. Early research suggests that folate might reduce the ...

  18. Not all cases of neural-tube defect can be prevented by increasing the intake of folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate the beneficial effects of different levels of folic acid administration on the prevalence of neural tube defects, with a concurrent assessment of other potential benefits or adverse effects. The evaluation was based on a systematic review of the published ...

  19. Vitamin B(12) and folic acid levels as therapeutic target in preserving bone mineral density (BMD) of older men.

    PubMed

    Naharci, Ilkin; Bozoglu, Ergun; Karadurmus, Nuri; Emer, Ozdes; Kocak, Necmettin; Kilic, Selim; Doruk, Huseyin; Serdar, Muhittin

    2012-01-01

    The knowledge about vitamin B(12) and folic acid levels in preserving bone mass in older men is limited. In this retrospective study, we aimed to find out whether levels of vitamin B(12) and folic acid are related to BMD in older men. Two hundred and sixty-nine older men were included in the study. Forty-two (15.6%) of them had osteoporotic, 150 (55.8%) had osteopenic, and 77 (28.6%) had normal BMD. Vitamin B(12) and folic acid levels were categorized as indicating normal, borderline, or low vitamin statuses. Femur neck densities showed statistically significant differences in subjects having low, borderline, and normal vitamin B(12), respectively. There were no significant differences between the three tertiles of vitamin B(12) in femur total, trochanteric, and intertrochanteric densities. After adjustment for age, body mass index (BMI), alcohol, smoking, and exercise with analysis of covariance, the difference was still statistically significant between two groups for femur neck density (p=0.011). No significant difference was observed between the groups of folic acid in any femur sites. We found that the normal level of vitamin B(12) in older men may be related to a decrease of femur neck bone loss.

  20. Molar ratio iron: zinc and folic acid in Brazilian biscuits and snacks and test for classification using principal component analyses.

    PubMed

    Godoy, Adriana Teixeira; Rebelatto, Ana Paula; Borin-Nogueira, Alessandra; Lima-Pallone, Juliana Azevedo

    2014-06-01

    The aim of the present work was to evaluate molar ratio iron: zinc and the levels of folic acid in biscuit and snacks commercialized in Brazil, prepared with folic acid and iron fortified flours. These nutrients are important for human nutrition; however, iron can have a negative effect on zinc absorption. Molar ratio iron:zinc can indicate if there will be any problems for absorption of these nutrients. The folic acid content varied from 58 to 433 μg/100 g and iron and zinc levels varied from 2.9 to 9.4 mg/100 g and from 0.2 to 1.3 mg/100 g, respectively, for 75 analyzed samples. The average iron contents observed in the products and molar ratio iron:zinc (in average 8:1 for biscuits and 12.8:1 for snacks) could result in problems with the zinc absorption. Moreover, principal compo- nent analyses (PCA) indicated low uniformity in the distribution of minerals and vitamin in the majority of the samples, mainly among brands. The results indicated that for the majority of the samples tested folic acid and iron content was higher than expected for flours and could be useful to governmental authorities in their evaluation program of flour fortification.

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

    PubMed Central

    SILVA, Rafaella de Andrade; MALTA, Flávia Monteiro França; CORREIA, Maria Flora Ferreira Sampaio Carvalho; BURGOS, Maria Goretti Pessoa de Araújo

    2016-01-01

    ABSTRACT Background: Different surgical techniques to combat obesity combine malabsorption with restrictive procedures and can lead to metabolic problems, such as micronutrient deficiencies. Aim: Assess vitamin B12, iron and folic acid deficiencies associated with the lifestyle of obese individuals having been submitted to different bariatric techniques. Methods: 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). Results: 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. Conclusion: 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. PMID:27683779

  2. Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Will Increasing Folic Acid in Fortified Grain Products Further Reduce Neural Tube Defects without Causing Harm?: Consideration of the Evidence. In the January issue of this journal, Johnston (1) includes our group’s recent analysis of data from the 1999-2002 National Health and Nutrition Examination...

  3. Self-assembly of folic acid: a chiral-aligning medium for enantiodiscrimination of organic molecules in an aqueous environment.

    PubMed

    Lokesh; Suryaprakash, N

    2012-09-10

    Weak orienting medium: Self-assembly of alkaline salt of folic acid yielded a weak liquid-crystalline phase in an aqueous environment. This medium has the ability to discriminate enantiomers. The mesophase exists over a broad range and has the physical parameter dependent tunability of degree of alignment (see scheme).

  4. Folic Acid and Coenzyme Q10 Ameliorate Cognitive Dysfunction in the Rats with Intracerebroventricular Injection of Streptozotocin

    PubMed Central

    Dehghani Dolatabadi, Hamid Reza; Reisi, Parham; Alaei, Hojjatallah; Azizi Malekabadi, Hamid; Pilehvarian, Ali Asghar

    2012-01-01

    Objective(s) The present study aimed to investigate the effects of a fat soluble antioxidant, coenzyme Q10 (CoQ10) and folic acid on learning and memory in the rats with intracerebroventricular injection of streptozotocin (ICV-STZ), an animal model of sporadic type of Alzheimer's disease. Materials and Methods The lesion groups were injected bilaterally with ICV-STZ (1.5 mg/kg b.wt., in normal saline). In the treated groups, rats received folic acid (4 mg/kg; i.p.) or CoQ10 (10 mg/kg; i.p.), either alone or together, for 21 days. Passive avoidance learning test was used for evaluation of learning and memory. Results The results showed that learning and memory performance was significantly impaired in the rats with ICV-STZ (P< 0.001), however CoQ10 and folic acid, either alone or together, prevented impairments significantly (P< 0.001), as there was not any significant difference between these treated lesion groups and control group. Conclusion The present results suggest that CoQ10 and folic acid have therapeutic and preventive effects on cognitive impairments in Alzheimer’s disease. PMID:23493655

  5. Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform

    PubMed Central

    Li, Xia; Szewczuk, Myron R; Malardier-Jugroot, Cecile

    2016-01-01

    Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA). The polymeric template is pH responsive, forming amphiphilic nanostructures at pH 7, allowing the encapsulation of hydrophobic drugs on its interior. Moreover, the structure is stable only at neutral pH and collapses in the acidic tumor microenvironment, releasing drugs on-site from its core. The delivery vehicle is investigated using human pancreatic PANC-1 cancer cells and RAW-Blue™ mouse macrophage reporter cell line, both of which have overly expression of folic acid receptors. To trace the cellular uptake by both cell lines, curcumin was selected as a dye and drug mimic owing to its fluorescence nature and hydrophobic properties. Fluorescent microscopy of FA-DABA-SMA loaded with curcumin revealed a significant internalization of the dye by human pancreatic PANC-1 cancer cells compared to those with unfunctionalized polymers (SMA). Moreover, the FA-DABA-SMA polymers exhibit rodlike association specific to the cells. Both empty SMA and FA-DABA-SMA show little toxicity to PANC-1 cells as characterized by WST-1 cell proliferation assay. These results clearly indicate that FA-DABA-SMA polymers show potential as an active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics after they specifically attach to cancer cells. PMID:28008233

  6. Establishing safe and potentially efficacious fortification contents for folic acid and vitamin B12.

    PubMed

    Dary, Omar

    2008-06-01

    Determining the micronutrient contents infortified foods depends not only on the health goal (additional intake to complement the diet), but also on ensuring that fortification does not raise micronutrient intakes beyond the Tolerable Upper Intake Level (UL), i.e., the safe limit. Technological incompatibility and cost may also restrict the fortification contents. For folic acid, the limiting factor is safety, while for vitamin B12, it is cost. However, adequate fortification contents that are both safe and efficacious can be estimated for both nutrients. In order to obtain the maximum benefit from the fortification programs, three different formulas responding to three categories of consumption, as specified by the median and 95th percentile of consumption, are proposed. The model presented is based on the estimation of a Feasible Fortification Level (FFL), which then is used to determine the average, minimum, and maximum contents of the nutrients during production, taking into consideration the acceptable variation of the fortification process. Finally, the regulatory parameters, which support standards and enforcement, are calculated by reducing the proportion of the nutrient that is degraded during the usual marketing process of the fortified food. It is expected that this model will establish a common standard for food fortification, and improve the reliability and enforcement procedures of these programs. The model was applied to flours as vehicles for folic acid in the United States, Guatemala, and Chile. Analysis of the data revealed that, with the exception of Chile, where wheat flour consumption is very high and probably within a narrow range, supplementation with folic acid is still needed to cover individuals at the low end of consumption. This is especially true when the difference in flour consumption is too wide, as in the case of Guatemala, where the proportional difference between consumption at the 95th percentile of the nonpoor group is as high

  7. Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres.

    PubMed

    Shen, Zheyu; Li, Yan; Kohama, Kazuhiro; Oneill, Brian; Bi, Jingxiu

    2011-01-01

    Folic acid-conjugated albumin nanospheres (FA-AN) have been developed to provide an actively targetable drug delivery system for improved drug targeting of cancer cells with reduced side effects. The nanospheres were prepared by conjugating folic acid onto the surface of albumin nanospheres using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a catalyst. To test the efficacy of these nanospheres as a potential delivery platform, doxorubicin-loaded albumin nanospheres (DOX-AN) and doxorubicin-loaded FA-AN (FA-DOX-AN) were prepared by entrapping DOX (an anthracycline, antibiotic drug widely used in cancer chemotherapy that works by intercalating DNA) into AN and FA-AN nanoparticles. Cell uptake of the DOX was then measured. The results show that FA-AN was incorporated into HeLa cells (tumor cells) only after 2.0h incubation, whereas HeLa cells failed to incorporate albumin nanospheres without conjugated folic acid after 4.0h incubation. When HeLa cells were treated with the DOX-AN, FA-DOX-AN nanoparticles or free DOX, cell viability decreased with increasing culture time (i.e. cell death increases with time) over a 70h period. Cell viability was always the lowest for free DOX followed by FA-DOX-AN4 and then DOX-AN. In a second set of experiments, HeLa cells washed to remove excess DOX after an initial incubation for 2h were incubated for 70h. The corresponding cell viability was slightly higher when the cells were treated with FA-DOX-AN or free DOX whilst cells treated with DOX-AN nanoparticles remained viable. The above experiments were repeated for non-cancerous, aortic smooth muscle cells (AoSMC). As expected, cell viability of the HeLa cells (with FA receptor alpha, FRα) and AoSMC cells (without FRα) decreased rapidly with time in the presence of free DOX, but treatment with FA-DOX-AN resulted in selective killing of the tumor cells. These results indicated that FA-AN may be used as a promising actively targetable drug delivery system to improve drug

  8. Folic before frolic.

    PubMed

    Austin, Martine

    2012-10-01

    In 1991 studies confirmed that taking folic acid both prior to conception and during the early stages of pregnancy could help reduce the risk of neural tube defects (NTDs) like spina bifida by up to 72 per cent (Medical Research Council (MRC) 1991). Yet despite this knowledge, very little has been done to promote awareness of this in the UK since the mid 1990s, and recent studies show that awareness and intake of folic acid are low. This article introduces a new initiative which aims to boost women's awareness (and most importantly uptake) of folic acid, and highlights the important role midwives can play in creating and maintaining this awareness.

  9. The micronutrient supplements, zinc sulphate and folic acid, did not ameliorate sperm functional parameters in oligoasthenoteratozoospermic men.

    PubMed

    Raigani, M; Yaghmaei, B; Amirjannti, N; Lakpour, N; Akhondi, M M; Zeraati, H; Hajihosseinal, M; Sadeghi, M R

    2014-01-01

    We investigated the effects of folic acid and zinc sulphate supplementation on the improvement of sperm function in subfertile oligoasthenoteratozoospermic (OAT) men. Eighty-three OAT men participated in a 16-week intervention randomised, double-blind clinical trial with daily treatment of folic acid (5 mg day(-1) ) and zinc sulphate (220 mg day(-1) ), or placebo. Before and after treatment, semen and blood samples were obtained for determining sperm concentration, motility, and morphology, sperm viability, sperm mitochondrial function, sperm chromatin status using toluidine blue, aniline blue, acridine orange and chromomycin A3 staining; and semen and blood folate, zinc, B12 , total antioxidant capacity (TAC) and malondialdehyde (MDA) concentrations. Sperm concentration (×10(6)  ml(-1) ) increased in subfertile men receiving the combined treatment of folic acid and zinc sulphate and also in the group receiving only folic acid treatment; however, it was not statistically significant (P = 0.056 and P = 0.05, respectively). Sperm chromatin integrity (%) increased significantly in subfertile men receiving only zinc sulphate treatment (P = 0.048). However, this improvement in sperm quality was not significant after adjusting placebo effect. This study showed that zinc sulphate and folic acid supplementation did not ameliorate sperm quality in infertile men with severely compromised sperm parameters, OAT. Male infertility is a multifactorial disorder, and also nutritional factors play an important role in results of administration of supplementation on sperm parameters. However, these results should be confirmed by multiple studies in larger populations of OAT men.

  10. Multifunctional magnetic nanoparticles modified with polyethylenimine and folic acid for biomedical theranostics.

    PubMed

    Yoo, Hyunhee; Moon, Seung-Kwan; Hwang, Taewon; Kim, Yong Seok; Kim, Joo-Hwan; Choi, Sung-Wook; Kim, Jung Hyun

    2013-05-21

    This paper describes the preparation of magnetic nanoparticles modified with polyethylenimine (PEI)-folic acid (PF) conjugate and their potential biomedical applications. Magnetic nanoparticles modified with (3-(2-aminoethylamino)propyltrimethoxysilane) (AEAPS) were first prepared using a ligand exchange method to provide biocompatibility and hydrophilicity, and further conjugated with PF to carry gene and enhance specific uptake into cancer cells. We demonstrated the feasibility of the multifunctional magnetic nanoparticles as contrast agents in magnetic resonance imaging (MRI) and as gene carriers for gene delivery. In vitro results revealed that the cytotoxicity of the multifunctional magnetic nanoparticles was lower compared to that of pristine magnetic nanoparticles. Furthermore, we demonstrated the specific uptake of the magnetic nanoparticles modified with PF to KB cells using WI-38 cells as comparison by confocal microscopy. The PF-modified magnetic nanoparticles can potentially be employed as theranostic nanoplatforms for targeted gene delivery to cancer cells and simultaneous magnetic resonance imaging.

  11. Pharmacodynamics of folic acid-receptor targeted antiretroviral nanotherapy in HIV-1-infected humanized mice

    PubMed Central

    Puligujja, Pavan; Araínga, Mariluz; Dash, Prasanta; Palandri, Diana; Mosley, R. Lee; Gorantla, Santhi; Poluektova, Larisa; McMillan, JoEllyn; Gendelman, Howard E.

    2015-01-01

    Long acting nanoformulated antiretroviral therapy (nanoART) can sustain plasma drug levels and improve its biodistribution. Cell targeted-nanoART can achieve this and bring drug efficiently to viral reservoirs. However, if such improvements affect antiretroviral responses remains unknown. To these ends, we tested folic acid (FA)-linked poloxamer407 coated-ritonavir boosted atazanavir (FA-nanoATV/r) nanoparticles for their ability to affect chronic HIV-1 infection in humanized mice. Following three every other week 100 mg/kg FA-nanoATV/r intramuscular injection administered to infected animals viral RNA was at or below the detection limit, cell-associated HIV-1p24 reduced and CD4+ T cell counts protected. The dosing regimen improved treatment outcomes more than two fold from what was reported for untargeted nanoATV/r. We posit that these nanoformulations have potential for translation to human use. PMID:26026666

  12. Folic acid-mediated targeting of cowpea mosaic virus particles to tumor cells

    PubMed Central

    Destito, Giuseppe; Yeh, Robert; Rae, Chris S.; Finn, M. G.; Manchester, Marianne

    2007-01-01

    Summary Cowpea mosaic virus (CPMV) is a well-characterized nanoparticle that has been used for a variety of nanobiotechnology applications. CPMV interacts with several mammalian cell lines and tissues in vivo. To overcome natural CPMV targeting and re-direct CPMV particles to cells of interest, we attached a novel folic acid-PEG conjugate using the copper-catalyzed azide-alkyne cycloaddition reaction. PEGylation of CPMV completely eliminated background binding of the virus to tumor cells. The PEG-folate moiety allowed CPMV specific recognition of tumor cells bearing the folate receptor. In addition, by testing CPMV formulations with different amounts of the PEG-FA moiety displayed on the surface, we show that higher-density loading of targeting ligands on CPMV may not be necessary for efficient targeting to tumor cells. These studies help to define the requirements for efficiently targeting nanoparticles and protein cages to tumors. PMID:17961827

  13. Folic acid functionalized ZnO quantum dots for targeted cancer cell imaging

    NASA Astrophysics Data System (ADS)

    Ma, Ying-Ying; Ding, Hui; Xiong, Huan-Ming

    2015-07-01

    Aqueous stable luminescent ZnO quantum dots (QDs) were successfully synthesized with primary amine groups on the surface, which were designed to conjugate with folic acid (FA) to produce the final ZnO-FA QDs. Such ZnO-FA QDs were able to target some specific cancer cells with overexpressed FA receptors on the membranes and thus differentiate the MCF-7 cancer cells from the normal 293T cells. The nanoparticle uptaking experiments by different cells were carried out in parallel and tracked by confocal laser microscopy dynamically. The results confirmed the specificity of our ZnO-FA QDs towards the FA-receptor overexpressed cancer cells, which had potential for diagnosing cancers in vitro.

  14. Protection of folic acid through encapsulation in mesoporous silica particles included in fruit juices.

    PubMed

    Ruiz-Rico, María; Pérez-Esteve, Édgar; Lerma-García, María J; Marcos, María D; Martínez-Máñez, Ramón; Barat, José M

    2017-03-01

    Folic acid (FA) is a synthetic vitamin commonly used for food fortification. However, its vulnerability to processing and storage implies loss of efficiency, which would induce over-fortification by processors to obtain a minimum dose upon consumption. Recent studies have indicated potential adverse effects of FA overdoses, and FA protection during processing and storage could lead to more accurate fortification. In addition, sustained vitamin release after consumption would help improve its metabolism. The objective of this work was to study controlled FA delivery and stability in fruit juices to reduce potential over-fortification risks by using gated mesoporous silica particles (MSPs). The obtained results indicated that FA encapsulation in MSPs significantly improved its stability and contributed to controlled release after consumption by modifying vitamin bioaccessibility. These results confirmed the suitability of MSPs as support for controlled release and protection of bioactive molecules in food matrices in different food production and storage stages.

  15. Modified Carbon Nanotube Paste Electrode for Voltammetric Determination of Carbidopa, Folic Acid, and Tryptophan

    PubMed Central

    Esfandiari Baghbamidi, Sakineh; Beitollahi, Hadi; Karimi-Maleh, Hassan; Soltani-Nejad, Somayeh; Soltani-Nejad, Vahhab; Roodsaz, Sara

    2012-01-01

    A simple and convenient method is described for voltammetric determination of carbidopa (CD), based on its electrochemical oxidation at a modified multiwall carbon nanotube paste electrode. Under optimized conditions, the proposed method exhibited acceptable analytical performances in terms of linearity (over the concentration range from 0.1 to 700.0 μM), detection limit (65.0 nM), and reproducibility (RSD = 2.5%) for a solution containing CD. Also, square wave voltammetry (SWV) was used for simultaneous determination of CD, folic acid (FA), and tryptophan (TRP) at the modified electrode. To further validate its possible application, the method was used for the quantification of CD, FA, and TRP in urine samples. PMID:22666634

  16. Folic acid supplementation in pregnancy and implications in health and disease

    PubMed Central

    2014-01-01

    Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies. PMID:25135350

  17. The cost-effectiveness of mandatory folic acid fortification in Australia.

    PubMed

    Rabovskaja, Viktoria; Parkinson, Bonny; Goodall, Stephen

    2013-01-01

    The Australian government recently introduced mandatory folic acid fortification of bread to reduce the incidence of neural tube defects (NTDs). The economic evaluation of this policy contained a number of limitations. This study aimed to address the limitations and to reconsider the findings. Cost-effectiveness analysis was used to assess the cost and benefits of mandatory versus voluntary folic acid fortification. Outcomes measures were quality-adjusted life-years (QALYs), life-years gained (LYG), avoided NTD cases, and additional severe neuropathy cases. Costs considered included industry costs and regulatory costs to the government. It was estimated that mandatory fortification would prevent 31 NTDs, whereas an additional 14 cases of severe neuropathy would be incurred. Overall, 539 LYG and 503 QALYs would be gained per year of mandatory compared with voluntary fortification. Mandatory fortification was cost-effective at A$10,723 per LYG and at A$11,485 per QALY. Probabilistic sensitivity analysis showed that at A$60,000 and A$151,000 per QALY, the probability that mandatory fortification was the most cost-effective strategy was 79% and 85%, respectively. Threshold analysis of loss of consumer choice indicated that with a compensation value above A$1.21 [assuming a willingness to pay (WTP) threshold of A$60,000 per QALY] or A$3.19 (assuming a WTP threshold of A$151,000 per statistical life-year) per capita per year mandatory fortification would not be cost-effective. Mandatory fortification was found to be cost-effective; however, inclusion of the loss of consumer choice can change this result. Even with mandatory fortification, mean folate intake will remain below the recommended NTD preventive level.

  18. Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring.

    PubMed

    Roy, Suchitra; Kale, Anvita; Dangat, Kamini; Sable, Pratiksha; Kulkarni, Asmita; Joshi, Sadhana

    2012-01-01

    Altered maternal micronutrients (folic acid, vitamin B(12)) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B(12) and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B(12)) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B(12). Both the vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B(12) deficient diet) increases (p<0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p<0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p<0.05) the levels of brain DHA in both the vitamin B(12) deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning.

  19. Preschool Iron-Folic Acid and Zinc Supplementation in Children Exposed to Iron-Folic Acid in Utero Confers No Added Cognitive Benefit in Early School-Age123

    PubMed Central

    Christian, Parul; Morgan, Mary E.; Murray-Kolb, Laura; LeClerq, Steven C.; Khatry, Subarna K.; Schaefer, Barbara; Cole, Pamela M.; Katz, Joanne; Tielsch, James M.

    2011-01-01

    In Nepal, antenatal iron-folic acid supplementation improved aspects of intellectual, executive, and fine motor function among school-age children. We examined the impact of added zinc to the maternal antenatal supplement (M-IFAZn) and preschool supplementation from 12 to 36 mo with iron-folic acid (C-IFA) ± zinc (C-IFAZn) on cognitive outcomes compared to maternal iron-folic acid (M-IFA) alone. Children 7–9 y old (n = 780) who participated in early childhood micronutrient supplementation trial during 2001–2004 and whose mothers participated in an antenatal micronutrient supplementation between 1999 and 2001 were followed for cognitive assessments in 2007–2009. Using multivariate analysis of variance and adjusting for confounders, M-IFA with child supplementation (either C-IFA or C-IFAZn) did not impact scores on the tests of general intelligence (Universal Nonverbal Intelligence Test), and executive function (Stroop and go/no go tests) relative to the M-IFA alone. However, children in the C-IFAZn group had slightly lower scores on the backward digit span (−0.29, 95% CI: −0.55, −0.04) and Movement Assessment Battery for Children (1.33, 95% CI: 0.26, 2.40) relative to the referent group, whereas both C-IFA (−1.92, 95% CI: −3.12, −0.71) and C-IFAZn (−1.78, 95% CI: −2.63, −0.92) produced somewhat lower finger tapping test scores (fine motor skills). The combination of M-IFAZn and C-IFA or C-IFAZn did not lead to any outcome differences relative to M-IFA alone. Preschool iron-folic acid ± zinc to children exposed to iron-folic acid in utero or addition of zinc to maternal iron-folic acid conferred no additional benefit to cognitive outcomes assessed in early school age. The late timing of supplementation during preschool may explain the lack of impact of iron and/or zinc. PMID:21956955

  20. Strong electrochemiluminescent interactions between carbon nitride nanosheet-reduced graphene oxide nanohybrids and folic acid, and ultrasensitive sensing for folic acid.

    PubMed

    Zhou, Chen; Chen, Yingmei; Shang, Pengxiang; Chi, Yuwu

    2016-05-23

    Graphite-like carbon nitride nanosheets (g-C3N4 NSs) have recently emerged as electrochemiluminescent (ECL) nanomaterials and have attracted more and more attention due to their excellent ECL properties and promising applications in ECL sensing. However, the ECL study of g-C3N4 NSs is still in the early stages. Many studies are required to reveal the exact ECL mechanisms of g-C3N4 NSs and thus boost their sensing applications. In this paper, we have investigated ECL interactions between folic acid (FA) and a g-C3N4 NS/S2O8(2-) ECL system at a g-C3N4 NS-reduced graphene oxide (rGO) nanohybrid/glassy carbon electrode in aqueous solutions. Compared with bare g-C3N4 NSs, the nanohybrids of g-C3N4 NS-rGO give a much stable ECL emission due to the prevention of over electrochemical reduction of g-C3N4 by rGO. The stable ECL emission from the g-C3N4 NS-rGO/S2O8(2-) ECL system can be strongly quenched by FA, even in a very low concentration (pM levels). The ECL quenching mechanisms are investigated and discussed in detail. Based on the strong interactions between FA and g-C3N4 NSs, a novel, sensitive, stable and selective ECL sensor has been constructed for the detection of FA, with a wide linear response range from 0.1 to 90 nM, and an excellent detection limit (62 pM). This work not only further clarifies ECL mechanisms of g-C3N4 NSs, but also suggests a promising application of the newly emerging ECL nanomaterial.

  1. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease--but how and why?

    PubMed

    Das, Undurti N

    2008-01-01

    Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of EPA/DHA and thus, could augment the formation of NPD1. These results suggest that a combination of EPA, DHA, AA and folic acid could be of significant benefit in dementia, depression, and Alzheimer's disease and improve cognitive function.

  2. Bioavailability of iron, zinc, folic acid, and vitamin A from fortified maize.

    PubMed

    Moretti, Diego; Biebinger, Ralf; Bruins, Maaike J; Hoeft, Birgit; Kraemer, Klaus

    2014-04-01

    Several strategies appear suitable to improve iron and zinc bioavailability from fortified maize, and fortification per se will increase the intake of bioavailable iron and zinc. Corn masa flour or whole maize should be fortified with sodium iron ethylenediaminetetraacetate (NaFeEDTA), ferrous fumarate, or ferrous sulfate, and degermed corn flour should be fortified with ferrous sulfate or ferrous fumarate. The choice of zinc fortificant appears to have a limited impact on zinc bioavailability. Phytic acid is a major inhibitor of both iron and zinc absorption. Degermination at the mill will reduce phytic acid content, and degermed maize appears to be a suitable vehicle for iron and zinc fortification. Enzymatic phytate degradation may be a suitable home-based technique to enhance the bioavailability of iron and zinc from fortified maize. Bioavailability experiments with low phytic acid-containing maize varieties have suggested an improved zinc bioavailability compared to wild-type counterparts. The bioavailability of folic acid from maize porridge was reported to be slightly higher than from baked wheat bread. The bioavailability of vitamin A provided as encapsulated retinyl esters is generally high and is typically not strongly influenced by the food matrix, but has not been fully investigated in maize.

  3. Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention.

    PubMed

    Xu, Richard B; Kong, Xiangyi; Xu, Benjamin P; Song, Yun; Ji, Meng; Zhao, Min; Huang, Xiao; Li, Ping; Cheng, Xiaoshu; Chen, Fang; Zhang, Yan; Tang, Genfu; Qin, Xianhui; Wang, Binyan; Hou, Fan Fan; Dong, Qiang; Chen, Yundai; Yang, Tianlun; Sun, Ningling; Li, Xiaoying; Zhao, Lianyou; Ge, Junbo; Ji, Linong; Huo, Yong; Li, Jianping

    2017-03-01

    Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n = 10,160) or 10 mg enalapril alone (n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8; P < 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97; P < 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke (P = 0.01).Conclusions: In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation. This trial was registered at clinicaltrials

  4. Radiosynthesis and evaluation of a (99m)Tc-folic acid radiotracer prepared using [(99m)TcN(PNP)](2+) metal fragment.

    PubMed

    Vats, Kusum; Subramanian, Suresh; Mathur, Anupam; Sarma, Haladhar Dev; Banerjee, Sharmila

    2017-03-01

    Folate receptors (FR) are over-expressed on a wide variety of tumor cells and are a potential molecular target for radiolabeled folates. In this respect, several SPECT and PET based radiofolates have been evaluated in the past albeit with their high renal uptake posing limitation towards their clinical use. To overcome this, a new (99m)Tc labeled folic acid was synthesized via the use of [(99m)TcN(PNP)](2+) metal fragment, where the presence of the latter pharmacophore redirects in vivo clearance via the hepatobiliary pathway. In this respect, folic acid was derivatized at the γ-acid group with a cysteine BFCA (bifunctional chelating agent) and subsequently reacted with the preformed [(99m)TcN](2+) intermediate in presence of PNP2 (bisphosphine) ligand, to yield the final complex. While preliminary, in vivo distribution of the complex exhibited high association of activity with liver and intestines and provided support to the rationality of the present design as clearance of labeled folic acid could be effected via the hepatic route, the in vitro studies of the folic acid-cysteine conjugate carried out in KB-31 cells, did not show much promise with reduction in receptor affinity in comparison with the native folic acid. The route followed herein to prepare a folic-acid based radiotracer constitutes the first report of radiolabeling folic acid using the [(99m)TcN(PNP)](2+) as a radiosynthon. Modification in the structure of conjugate by linking the BFCA through a long-chain linker can be envisaged to improve the affinity of [(99m)TcN(PNP)]-folic acid complex towards FRs.

  5. Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery

    PubMed Central

    Yang, Shuang; Yang, Xuewei; Liu, Yan; Zheng, Bin; Meng, Lingjun; Lee, Robert J.; Xie, Jing; Teng, Lesheng

    2016-01-01

    Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation. PMID:26263216

  6. A combination of omega-3 fatty acids, folic acid and B-group vitamins is superior at lowering homocysteine than omega-3 alone: A meta-analysis.

    PubMed

    Dawson, Samantha Loren; Bowe, Steven John; Crowe, Timothy Charles

    2016-06-01

    The aim of the study was to assess whether omega-3 polyunsaturated fatty acid supplementation alone or in combination with folic acid and B-group vitamins is effective in lowering homocysteine. The Medline Ovid, Embase and Cochrane databases were searched for randomized-controlled trial studies that intervened with omega-3 supplementation (with or without folic acid) and measured changes in homocysteine concentration. Studies were pooled using a random effects model for meta-analysis. Three different models were analyzed: all trials combined, omega-3 polyunsaturated fatty acid trials, and omega-3 polyunsaturated fatty acids with folic acid and B-group vitamin trials. Nineteen studies were included, consisting of 3267 participants completing 21 trials. Studies were heterogeneous; varying by dose, duration and participant health conditions. Across all trials, omega-3 supplementation was effective in lowering homocysteine by an average of 1.18μmol/L (95%CI: (-1.89, -0.48), P=.001). The average homocysteine-lowering effect was greater when omega-3 supplementation was combined with folic acid and B-group vitamins (-1.37μmol/L, 95%CI: (-2.38, -0.36), P<.01) compared to omega-3 supplementation alone (-1.09μmol/L 95%CI: (-2.04, -0.13), P=.03). Omega-3 polyunsaturated fatty acid supplementation was associated with a modest reduction in homocysteine. For the purposes of reducing homocysteine, a combination of omega-3s (0.2-6g/day), folic acid (150 - 2500μg/day) and vitamins B6 and B12 may be more effective than omega-3 supplementation alone.

  7. Treatment response to iron and folic acid alone is the same as with multivitamins and/or anthelminthics in severely anemic 6- to 24-month-old children.

    PubMed

    Bhutta, Zulfiqar; Klemm, Rolf; Shahid, Farhana; Rizvi, Arjumand; Rah, Jee Hyuan; Christian, Parul

    2009-08-01

    We assessed the effectiveness of iron+folic acid for the treatment of severe anemia [hemoglobin (Hb) <70 g/L] and the efficacy of added multivitamins and/or anthelminthics among children aged 6-24 mo in periurban Karachi, Pakistan. The study design was a double blind, placebo-controlled, randomized trial of currently recommended daily iron (25 mg) and folic acid (100 microg) for 90 d with daily multivitamins [vitamin A (300 microg, as retinol palmitate), vitamin E (6 mg tocopherol equivalents), vitamin B-12 (0.9 microg), vitamin C (15 mg), riboflavin (0.5 mg)] and/or anthelminthics (100 mg mebendazole twice daily for 3 d) compared with placebos. Treatment response was defined as reaching a Hb concentration > or =100 g/L at the end of 90 d. The prevalence of severe anemia in the 9518 children screened was 5.7% and a total of 462 severely anemic children were enrolled in the study. Adherence to treatment was approximately 70% for iron+folic acid, approximately 80% for multivitamins, and almost 100% for mebendazole. Children receiving iron+folic acid alone had a response rate of 38.7% at 90 d. The additional treatment with mebendazole or multivitamins did not significantly improve cure rates or change the Hb concentration over and above iron+folic acid treatment alone. Adherence to iron+folic acid of higher than the median resulted in a better treatment response rate of 50%. High-dose daily iron+folic acid performed as well as iron+folic acid with anthelminthics and multivitamins in the treatment of severe anemia in this setting. Higher adherence may be important in enhancing treatment impact.

  8. Pre-conceptional intake of folic acid supplements is inversely associated with risk of preterm birth and small-for-gestational-age birth: a prospective cohort study.

    PubMed

    Zheng, Ju-Sheng; Guan, Yuhong; Zhao, Yimin; Zhao, Wei; Tang, Xuejuan; Chen, Hua; Xu, Meilong; Wu, Lingping; Zhu, Shanlin; Liu, Huijuan; Huang, Tao; Li, Duo

    2016-02-14

    Associations of folic acid supplementation with risk of preterm birth (PTB) and small-for-gestational-age (SGA) birth were unclear for the Chinese populations. The aim of the present study was to investigate the associations in a large Chinese prospective cohort study: the Jiaxing Birth Cohort. In the Jiaxing Birth Cohort, 240 954 pregnant women visited local clinics or hospitals within their first trimester in Southeast China during 1999-2012. Information on anthropometric parameters, folic acid supplementation and other maternal characteristics were collected by in-person interviews during their first visit. Pregnancy outcomes were recorded during the follow-up of these participants. Multinomial logistic regression was used to examine the association of folic acid supplementation with pregnancy outcomes. The prevalence of folic acid supplementation was 24·9% in the cohort. The prevalence of PTB and SGA birth was 3·48 and 9·2%, respectively. Pre-conceptional folic acid supplementation was associated with 8% lower risk of PTB (relative risk (RR) 0·92; 95% CI 0·85, 1·00; P=0·04) and 19% lower risk of SGA birth (RR 0·81; 95% CI 0·70, 0·95; P=0·008), compared with non-users. Higher frequency of pre-conceptional folic acid use was associated with lower risk of PTB (P trend=0·032) and SGA birth (P trend=0·046). No significant association between post-conceptional initiation of folic acid supplementation and either outcome was observed. In conclusion, the present study suggests an association between pre-conceptional, but not post-conceptional, folic acid supplementation and lower risk of PTB and SGA birth in the Jiaxing Birth Cohort. Further research in other cohorts of large sample size is needed to replicate these findings.

  9. Folic acid deficiency enhances abeta accumulation in APP/PS1 mice brain and decreases amyloid-associated miRNAs expression.

    PubMed

    Liu, Huan; Tian, Tian; Qin, Shanchun; Li, Wen; Zhang, Xumei; Wang, Xuan; Gao, Yuxia; Huang, Guowei

    2015-12-01

    Recent efforts have revealed the microRNA (miRNA) pathways in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have revealed an association between folic acid deficiency and AD risk. However, the effects of folic acid deficiency on miRNA expression in AD animals have not been observed. We aimed to find if folic acid deficiency may enhance amyloid-β (Aβ) peptide deposition and regulate amyloid-associated miRNAs and their target genes expression in APP/PS1 mice. APP/PS1 mice and N2a cells were treated with folic acid-deficient diet or medium. Cognitive function of mice was assessed using the Morris water maze. miRNA profile was tested by polymerase chain reaction (PCR) array. Different expressional miRNAs were validated by real-time PCR. The deposition of Aβ plaques was evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. APP and BACE1 proteins in mice brain and N2a cells were determined by Western blot. Folic acid deficiency aggravated amyloid pathology in AD mice. The AD+FD group showed shorter time spent in the target zone during the probe test. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that were differentially modulated by folic acid deficiency. In APP/PS1 mice brains and N2a cells with folic acid-deficient treatment, miR-106a-5p, miR-200b-3p and miR-339-5p were down-regulated, and their target genes APP and BACE1 were up-regulated. In conclusion, folic acid deficiency can enhance Aβ accumulation in APP/PS1 mice brain and decrease amyloid-associated miRNAs expression.

  10. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35.

    PubMed

    Yu, Huan-Ling; Li, Li; Zhang, Xiao-Hong; Xiang, Li; Zhang, Jie; Feng, Jin-Fang; Xiao, Rong

    2009-09-01

    Genistein and folic acid have been reported respectively to protect against the development of cognitive dysfunction; however, the underlying mechanism(s) for this protection remain unknown. In this report, the mechanism(s) contributing to the neuroprotective effects of genistein and folic acid were explored using rat cortical neuron cultures. We found that genistein and folic acid, both separately and collaboratively, increased cell viability and mitochondrial membrane potential in beta-amyloid (Abeta) 31-35-treated neurons. Furthermore, reduced percentage of comet cells and shortened tail length were observed in the neurons treated with genistein or folic acid. A more significant reduction in tail length of the comet neurons was observed in the co-administered neurons. RT-PCR analysis of the cultured cortical neurons showed down-regulated expression of p53, bax and caspase-3, but up-regulated expression of bcl-2 in the three neuroprotective treatment groups compared with neurons from the Abeta31-35 solo-treated group. In a nuclear dyeing experiment using Hoechst 33342, we found that both genistein and folic acid prevent neuronal apoptosis. Collectively, these findings suggest that the mechanism underlying the neuroprotection of genistein and folic acid singly or in combination observed in cultured cortical neuron studies might be related to their anti-apoptotic properties.

  11. Maternal use of folic acid supplements during pregnancy and four-year-old neurodevelopment in a population-based birth cohort.

    PubMed

    Julvez, Jordi; Fortuny, Joan; Mendez, Michelle; Torrent, Maties; Ribas-Fitó, Núria; Sunyer, Jordi

    2009-05-01

    The use of folic acid supplements during very early pregnancy is recommended in order to reduce the incidence of neural tube defects. Little is known about the possible benefits of folic acid on child neurodevelopment. A total of 420 children (87% of those eligible) from a birth cohort had complete data for final analyses at age 4 years. Information about folic acid and other over-the-counter dietary supplements was obtained prospectively using interviewer-administered questionnaires at the end of the first trimester of pregnancy. Psychological outcomes were assessed by two psychologists and teachers 4 years later. Low maternal socio-economic status, smoking, high parity and short duration of breast feeding were associated with lower prevalence of folic acid supplement use. Verbal (b = 3.98, SE = 1.69), motor (b = 4.54, SE = 1.66) and verbal-executive function (b = 3.97, SE = 1.68) scores, social competence (b = 3.97, SE = 1.61) and inattention symptom [OR = 0.46; 95% CI 0.22, 0.95] scores were associated with reported folic acid use. Reported folic acid supplement use during pregnancy was associated with improved neurodevelopment in children after adjusting for a number of sociodemographic and behavioural factors.

  12. Fabrication of folic acid sensor based on the Cu doped SnO2 nanoparticles modified glassy carbon electrode

    NASA Astrophysics Data System (ADS)

    Lavanya, N.; Radhakrishnan, S.; Sudhan, N.; Sekar, C.; Leonardi, S. G.; Cannilla, C.; Neri, G.

    2014-07-01

    A novel folic acid biosensor has been fabricated using Cu doped SnO2 nanoparticles (NPs) synthesized by a simple microwave irradiation method. Powder XRD and TEM studies confirmed that both the pure and Cu doped SnO2 (Cu: 0, 10, 20wt%) crystallized in tetragonal rutile-type structure with spherical morphology. The average crystallite size of pure SnO2 was estimated to be around 16 nm. Upon doping, the crystallite sizes decreased to 9 nm and 5 nm for 10 and 20wt% Cu doped SnO2 respectively. XPS studies confirmed the electronic state of Sn and Cu to be 4+ and 2+ respectively. Cu (20wt%) doped SnO2 NPs are proved to be a good sensing element for the determination of folic acid (FA). Cu-SnO2 NPs (20wt%) modified glassy carbon electrode (GCE) exhibited the lowest detection limit of 0.024 nM over a wide folic acid concentration range of 1.0 × 10-10 to 6.7 × 10-5 M at physiological pH of 7.0. The fabricated sensor is highly selective towards the determination of FA even in the presence of a 100 fold excess of common interferent ascorbic acid. The sensor proved to be useful for the estimation of FA content in pharmaceutical sample with satisfactory recovery.

  13. Critical micronutrients in pregnancy, lactation, and infancy: considerations on vitamin D, folic acid, and iron, and priorities for future research.

    PubMed

    Hermoso, Maria; Vollhardt, Christiane; Bergmann, Karin; Koletzko, Berthold

    2011-01-01

    The Early Nutrition Academy and the European Commission-funded EURRECA Network of Excellence jointly sponsored a scientific workshop on critical micronutrients in pregnancy, lactation, and infancy. Current knowledge and unresolved questions on the supply of vitamin D, folic acid, and iron for pregnant women, lactating women, and infants, and their health effects were discussed. The question was addressed of whether, and under which circumstances, supplementation with these micronutrients in addition to usual dietary intakes is advisable. The workshop participants concluded that public health strategies for improving supplementation with these micronutrients in pregnancy, lactation, and infancy are required. Further research priorities should focus on adequately powered human intervention trials to obtain a stronger evidence base for the amounts of vitamin D, folic acid, and iron that have optimal effects on health. The conclusions of the workshop should help to inform the scientific community as well as public health policy strategies.

  14. A validated ultra high pressure liquid chromatographic method for qualification and quantification of folic acid in pharmaceutical preparations.

    PubMed

    Deconinck, E; Crevits, S; Baten, P; Courselle, P; De Beer, J

    2011-04-05

    A fully validated UHPLC method for the identification and quantification of folic acid in pharmaceutical preparations was developed. The starting conditions for the development were calculated starting from the HPLC conditions of a validated method. These start conditions were tested on four different UHPLC columns: Grace Vision HT™ C18-P, C18, C18-HL and C18-B (2 mm × 100 mm, 1.5 μm). After selection of the stationary phase, the method was further optimised by testing two aqueous and two organic phases and by adapting to a gradient method. The obtained method was fully validated based on its measurement uncertainty (accuracy profile) and robustness tests. A UHPLC method was obtained for the identification and quantification of folic acid in pharmaceutical preparations, which will cut analysis times and solvent consumption.

  15. Electrochemical determination of hydrochlorothiazide and folic acid in real samples using a modified graphene oxide sheet paste electrode.

    PubMed

    Beitollahi, Hadi; Hamzavi, Mozhdeh; Torkzadeh-Mahani, Masoud

    2015-01-01

    A new ferrocene-derivative compound, 2-chlorobenzoyl ferrocene, was synthesized and used to construct a modified graphene oxide sheet paste electrode. The electrooxidation of hydrochlorothiazide at the surface of the modified electrode was studied. Under optimized conditions, the square wave voltammetric (SWV) peak current of hydrochlorothiazide increased linearly with hydrochlorothiazide concentration in the range of 5.0 × 10(-8) to 2.0 × 10(-4) M and a detection limit of 20.0 nM was obtained for hydrochlorothiazide. The diffusion coefficient and kinetic parameters (such as electron transfer coefficient and the heterogeneous rate constant) for hydrochlorothiazide oxidation were also determined. The prepared modified electrode exhibits a very good resolution between the voltammetric peaks of hydrochlorothiazide and folic acid which makes it suitable for the detection of hydrochlorothiazide in the presence of folic acid in real samples.

  16. Hybrid molecularly imprinted poly(methacrylic acid-TRIM)-silica chemically modified with (3-glycidyloxypropyl)trimethoxysilane for the extraction of folic acid in aqueous medium.

    PubMed

    de Oliveira, Fernanda Midori; Segatelli, Mariana Gava; Tarley, César Ricardo Teixeira

    2016-02-01

    In the present study a hybrid molecularly imprinted poly(methacrylic acid-trimethylolpropane trimethacrylate)-silica (MIP) was synthesized and modified with (3-glycidyloxypropyl)trimethoxysilane (GPTMS) with posterior opening of epoxy ring to provide hydrophilic properties of material in the extraction of folic acid from aqueous medium. The chemical and structural aggregates of hybrid material were characterized by means of Fourier Transform Infrared (FT-IR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Thermogravimetric analysis (TGA) and textural data. Selectivity data of MIP were compared to non-imprinted polymer (NIP) through competitive sorption studies in the presence of caffeine, paracetamol or 4-aminobenzamide yielding relative selectivity coefficients (k′) higher than one unit, thus confirming the selective character of MIP even in the presence of structurally smaller compounds than the folic acid. The lower hydrophobic sorption by bovine serum albumin (BSA) in the MIP as compared to unmodified MIP proves the hydrophilicity of polymer surface by using GPTMS with opening ring. Under acid medium(pH 1.5) the sorption of folic acid onto MIP from batch experiments was higher than the one achieved for NIP. Equilibrium sorption of folic acid was reached at 120 min for MIP, NIP and MIP without GPTMS and kinetic sorption data were well described by pseudo-second-order, Elovich and intraparticle diffusion models. Thus, these results indicate the existence of different binding energy sites in the polymers and a complex mechanism consisting of both surface sorption and intraparticle transport of folic acid within the pores of polymers.

  17. Folic Acid Fortification and Women’s Folate Levels in Selected Communities in Brazil – A First Look

    PubMed Central

    Chakraborty, Hrishikesh; Nyarko, Kwame A.; Goco, Norman; Moore, Janet; Moretti-Ferreira, Danilo; Murray, Jeffrey C.; Wehby, George L.

    2015-01-01

    Background Several countries have implemented a mandatory folic acid fortification of wheat flour and selected grain products to increase folate intake of reproductive-aged women. Brazil implemented a folic acid fortification program in 2004. No previous studies have examined folate differences among Brazilian women following the mandate. Objective We evaluate differences in serum and red blood cell (RBC) folate concentrations between two samples of women of childbearing age from selective communities in Brazil, one tested before (N=116) and the other after the mandate (N=240). Methods We compared baseline folate levels from women enrolled into a prevention study shortly before the fortification mandate was implemented, to baseline levels of women from the same communities enrolled in the same study shortly after fortification began. Participants were women enrolled in a folate supplementation clinical trial, at a hospital specialized in treating craniofacial anomalies in the city of Bauru from January 29, 2004 to April 27, 2005. We only compared baseline folate levels before the women received OCPP folic acid supplements. Results Women enrolled after the fortification mandate had higher means of serum folate (20.3 versus 11.2 nmol/L; p < 0.001) and RBC folate (368.3 versus 177.6 nmol/L; p < 0.001) than women enrolled before the mandate. Differences in folate levels between the two groups remained after adjusting for several co-variables. Conclusions The results suggest that serum and RBC folate levels among women of childbearing age have increased after implementing the folic acid fortification mandate in Brazil. PMID:26255550

  18. Effect of losartan with folic acid on plasma homocysteine and vascular ultrastructural changes in spontaneously hypertensive rats.

    PubMed

    Zhu, Lihe; Yu, Jiong; Jia, Baofu; Zhao, Feng; Tang, Mengmeng; Hu, Lufeng; Lin, Feiyan

    2015-01-01

    Elevated homocysteine (Hcy) is a high risk factor of hypertension due to its function in endothelial dysfunction. Its level in the blood is strongly influenced by folic acid. In order to investigate the effects of losartan with folic acid on plasma level of Hcy and vascular ultrastructural changes, thirty spontaneously hypertensive rats (SHR) involved and randomly divided into three groups (n=10): SHR-C group (control), SHR-L group (losartan 25 mg · kg(-1) · d(-1)), SHR-L+Y group (losartan 25 mg · kg(-1) · d(-1) + folic acid 0.4 mg · kg(-1) · d(-1)). Another 10 Wistar Rats involved as WKY-C group for normal control. The level of plasma Hcy was measured dynamically by LS-MS, the vascular ultrastructural changes were analyzed by light and electron microscopy. Moreover, the thickness and area of aorta was measured. The results showed the Hcy levels in four groups were WKY-C 7.49 ± 1.95 μmol/L; SHR-C 8.45 ± 1.90 μmol/L; SHR-L 8.28 ± 2.11 μmol/L; SHR-L+Y 7.53 ± 2.02 μmol/L at 80 days. There was no significant change for plasma Hcy (P>0.05). The morphological change showed the subendothelial space didn't increased significantly, the endothelial cells have a more smooth and intact cellular membrane in SHR-L+Y group. In conclusion, Losartan combined with folic acid could improve arterial endothelial structure in SHR which has no significant correlation with plasma Hcy.

  19. Folic acid mediated solid lipid nanocarriers loaded with docetaxel and oxidized single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Zhu, Xiali; Huang, Shengnan; Xie, Yingxia; Zhang, Huijuan; Hou, Lin; Zhang, Yingjie; Huang, Heqing; Shi, Jinjin; Wang, Lei; Zhang, Zhenzhong

    2014-01-01

    Single-walled carbon nanotubes (SWNT) possess high-near-infrared absorption coefficient, large surface area, and have great potential in drug delivery. In this study, we obtained ultrashort oxidized SWNT (OSWNT) using mixed acid oxidation method. Then, docetaxel (DTX) and folic acid (FA) are conjugated with OSWNT via π- π accumulation and amide linkage, respectively. A targeting and photothermal sensitive drug delivery system FA-DTX-OSWNT-SLN was prepared following a microemulsion technique. The size and zeta potential of FA-DTX-OSWNT-SLN were 182.8 ± 2.8 nm and -34.59 ± 1.50 mV, respectively. TEM images indicated that FA-DTX-OSWNT-SLN was spherical and much darker than general solid lipid nanoparticles (SLN). Furthermore, OSWNT may wind round, insert into or be encapsulated into the nanocarriers. Compared with free DTX, FA-DTX-OSWNT-SLN could efficiently cross cell membranes and afford higher antitumor efficacy in MCF-7 cells in vitro. Meanwhile, the combination of near-infrared laser (NIR) irradiation at 808 nm significantly enhanced cell inhibition. In conclusion, FA-DTX-OSWNT-SLN drug delivery system in combination with 808 nm NIR laser irradiation may be promising for targeting and photothermal cancer therapy with multiple mechanisms in future.

  20. Promoter strength of folic acid synthesis genes affects sulfa drug resistance in Saccharomyces cerevisiae.

    PubMed

    Iliades, Peter; Berglez, Janette; Meshnick, Steven; Macreadie, Ian

    2003-01-01

    The enzyme dihydropteroate synthase (DHPS) is an important target for sulfa drugs in both prokaryotic and eukaryotic microbes. However, the understanding of DHPS function and the action of antifolates in eukaryotes has been limited due to technical difficulties and the complexity of DHPS being a part of a bifunctional or trifunctional protein that comprises the upstream enzymes involved in folic acid synthesis (FAS). Here, yeast strains have been constructed to study the effects of FOL1 expression on growth and sulfa drug resistance. A DHPS knockout yeast strain was complemented by yeast vectors expressing the FOL1 gene under the control of promoters of different strengths. An inverse relationship was observed between the growth rate of the strains and FOL1 expression levels. The use of stronger promoters to drive FOL1 expression led to increased sulfamethoxazole resistance when para-aminobenzoic acid (pABA) levels were elevated. However, high FOL1 expression levels resulted in increased susceptibility to sulfamethoxazole in pABA free media. These data suggest that up-regulation of FOL1 expression can lead to sulfa drug resistance in Saccharomyces cerevisiae.

  1. LC/MS/MS identification of some folic acid degradation products after E-beam irradiation

    NASA Astrophysics Data System (ADS)

    Araújo, M. M.; Marchioni, E.; Zhao, M.; Kuntz, F.; Di Pascoli, T.; Villavicencio, A. L. C. H.; Bergaentzle, M.

    2012-08-01

    Folates belong to the B vitamin group based on the parental compound folic acid (FA). They are involved in important biochemical processes like DNA synthesis and repair. FA is composed of a pteridine ring, p-aminobenzoic acid and glutamate moieties. The human metabolism is not able to synthesize folates and therefore obtain them from diet. FA, a synthetic vitamin, is used as a food fortificant because of its low price, relative stability and increased bioavailability compared to natural folate forms. FA is known to be a sensitive compound easily degradable in aqueous solution by ultraviolet and visible light towards various by-products. Irradiation is a process for preservation of foods that uses accelerated electrons, gamma rays or X-rays. Irradiation is proposed for the treatment of various food products, eliminating or reducing pathogens and insects, increasing the storage time and replacing chemical fumigants. This study concerns the identification of degradation products of FA after E-beam irradiation. FA aqueous solutions were irradiated with a Van de Graaff electrons beam accelerator (2 MeV, 100 μA current, 20 cm scan width, dose rate about 2 kGy/s). Applied doses were between 0 (control) and 10.0 kGy. Absorbed doses were monitored with FWT 60.00 radiochromic dosimeters.

  2. Is periconceptional opioid use safe?

    PubMed Central

    Chan, Felix; Koren, Gideon

    2015-01-01

    Abstract Question A patient in my practice who takes buprenorphine for chronic pain would like to conceive. Is it safe for her to continue taking her medication? Answer The literature regarding periconceptional opioid use is conflicted as to whether opioids pose an elevated risk of birth defects. Confounding factors such as socioeconomic status, stress, and alcohol consumption might play a role. The first trimester of pregnancy is the critical period of development for many organ systems in the embryo. A chemical or environmental insult is more likely to produce major congenital malformations such as neural tube defects or mental retardation if it occurs within this window. Medical practitioners should judiciously consider a risk-benefit analysis before making their decisions. PMID:26167561

  3. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

    PubMed Central

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-01-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  4. The folic acid analogue methotrexate protects frog embryo cell membranes against damage by the potato glycoalkaloid alpha-chaconine.

    PubMed

    McWilliams, M L; Blankemeyer, J T; Friedman, M

    2000-10-01

    As part of an effort to improve the safety of plant foods, a need exists to more clearly delineate the mechanisms of toxicities of glycoalkaloids, which may be present in Solanum plant species such as potatoes, tomatoes and eggplants. Alpha-chaconine is a major glycoalkaloid present in potatoes. To assess the possible influence of structure of pteridine derivatives on toxicity of potato glycoalkaloids, a previous study that demonstrated the protective effects of folic acid against the Solanum glycoalkaloid alpha-chaconine-induced toxicity on Xenopus laevis frog embryo cell membranes was extended to two folate analogues--a synthetic compound widely used as a therapeutic agent methotrexate, and naturally occurring L-monapterin. Adverse effects on embryos were evaluated by observing changes in membrane potentials with an electrochromic dye, di-4-ANEPPS, as a fluorescent probe for the integrity of the membranes. Methotrexate decreased alpha-chaconine-induced polarization, as did folic acid. This decrease may result from an alteration of membrane conformations that prevents the binding of the glycoalkaloid to the membrane receptor sites, and/or from effects on folic acid metabolism. In contrast, L-monapterin did not significantly reduce the alpha-chaconine-induced toxicity. The possible significance of these results to food safety is discussed.

  5. DNA Methylation Profiling at Single-Base Resolution Reveals Gestational Folic Acid Supplementation Influences the Epigenome of Mouse Offspring Cerebellum

    PubMed Central

    Barua, Subit; Kuizon, Salomon; Brown, W. Ted; Junaid, Mohammed A.

    2016-01-01

    It is becoming increasingly more evident that lifestyle, environmental factors, and maternal nutrition during gestation can influence the epigenome of the developing fetus and thus modulate the physiological outcome. Variations in the intake of maternal nutrients affecting one-carbon metabolism may influence brain development and exert long-term effects on the health of the progeny. In this study, we investigated whether supplementation with high maternal folic acid during gestation alters DNA methylation and gene expression in the cerebellum of mouse offspring. We used reduced representation bisulfite sequencing to analyze the DNA methylation profile at the single-base resolution level. The genome-wide DNA methylation analysis revealed that supplementation with higher maternal folic acid resulted in distinct methylation patterns (P < 0.05) of CpG and non-CpG sites in the cerebellum of offspring. Such variations of methylation and gene expression in the cerebellum of offspring were highly sex-specific, including several genes of the neuronal pathways. These findings demonstrate that alterations in the level of maternal folic acid during gestation can influence methylation and gene expression in the cerebellum of offspring. Such changes in the offspring epigenome may alter neurodevelopment and influence the functional outcome of neurologic and psychiatric diseases. PMID:27199632

  6. Biomedical applications of SPION@APTES@PEG-folic acid@carboxylated quercetin nanodrug on various cancer cells

    NASA Astrophysics Data System (ADS)

    Akal, Z. Ü.; Alpsoy, L.; Baykal, A.

    2016-08-01

    In this study, carboxylated quercetin (CQ) was conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) which were modified by (3-aminopropyl) triethoxysilane (APTES), Folic acid (FA) and carboxylated Polyethylene glycol (PEG); (SPION@APTES@FA-PEG@CQ), nanodrug has been synthesized via polyol and accompanying by various chemical synthesis routes. The characterization of the final product was done via X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermal gravimetric analysis (TGA), Transmission electron spectroscopy (TEM) and Vibrating sample magnetometer (VSM). Its cytotoxic and apoptotic activities on over expressed folic acid receptor (FR +) (MCF-7, HeLa) and none expressed folic acid receptor (FR-) (A549) cancer cell lines were determined by using MTT assay, Real-Time Cell Analysis, TUNEL assay, Annexin assay and RT-PCR analysis for Caspase3/7 respectively. SPION@APTES@FA-PEG@CQ nanodrug showed higher cytotoxicity against HeLa and MCF-7 cell lines as compared with A549 cell line. Moreover, SPION@APTES@FA-PEG@CQ nanodrug also caused higher apoptotic and necrotic effects in 100 μg/mL HeLa and MCF-7 cells than A549 cells. The findings showed that SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 which are FR over expressed cell lines and can be potentially used for the delivery of quercetin to cervical and breast cancer cells.

  7. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

    PubMed

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-03-09

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China.

  8. Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat

    SciTech Connect

    Will, M.; Barnard, J.A.; Said, H.M.; Ghishan, F.K.

    1985-04-01

    Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed ''fetal hydantoin syndrome''. The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, the authors postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, they studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, they examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. They conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

  9. Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries.

    PubMed

    López-Camelo, Jorge S; Castilla, Eduardo E; Orioli, Iêda M

    2010-10-01

    The aim of the present investigation was to search for a reduction in birth prevalence estimates of 52 selected types of congenital anomalies, associated with folic acid fortification programs in Chile, Argentina, and Brazil. The material included 3,347,559 total births in 77 hospitals of the three countries during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341 (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared pre- and post-fortification rates within each hospital and the resulting Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant reductions in birth prevalence estimates after fortification were observed for neural tube defects (NTDs), septal heart defects, transverse limb deficiencies, and subluxation of the hip. However, only the reduction of NTDs appeared to be associated with folic acid fortification and not due to other factors, because of its consistency among the three countries, as well as with previously published reports, and its strong statistical significance. Among the NTDs, the maximum prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and cephalocele. This observation suggests etiologic and pathogenetic heterogeneity among different levels of spina bifida, as well as among different NTD subtypes. We concluded that food fortification with folic acid prevents NTDs but not other types of congenital anomalies.

  10. The evaluation of serum homocysteine, folic acid, and vitamin B12 in patients complicated with preeclampsia

    PubMed Central

    Shahbazian, Nahid; Jafari, Razieh Mohammad; Haghnia, Sahar

    2016-01-01

    Introduction Increased plasma homocysteine may be associated with adverse pregnancy outcomes, such as preeclampsia. The aim of this study was to determine the plasma homocysteine, serum folate, and vitamin B12 levels in preeclamptic pregnant women. Methods This case-control study was conducted in 2016 in Ahwaz on 51 pregnant women with preeclampsia and 51 healthy pregnant women of the same gestational age, who served as controls. The case group also was subdivided into severe and non-severe preeclampsia. Patients’ data were collected through a questionnaire and medical records. Serum homocysteine, folic acid, and vitamin B12 were analyzed using chemiluminescent assay. The results were compared between two groups. Statistical analyses were done using IBM-SPSS 20.0. A Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney test, and Chi-square test were used for data analysis. Results No different demographic characteristics were found among the groups. Pregnant women complicated with preeclampsia displayed significantly higher serum homocysteine levels (p < 0.001) and lower serum folate (p = 0.005) and vitamin B12 levels (p < 0.001) compared to controls. A statistically significant inverse correlation was evident between serum homocysteine and serum folate levels in preeclamptic patients (p = 0.005; r = −0.389). In addition, an inverse correlation was identified between homocysteine and serum vitamin B12, but it was not statistically significant (p = 0.160; r = −0.200). Significant differences occurred in serum homocysteine and folate levels between the severe and non-severe subgroups (p < 0.001, p < 0.001). Conclusion Women complicated with preeclampsia displayed higher maternal serum homocysteine and lower serum folate and vitamin B12. Further studies are needed to confirm if the prescription of folic acid and vitamin B12 in women with a deficiency of these vitamins could decrease the level of serum homocysteine and, therefore, reduce the risk of

  11. Pathway of cytotoxicity induced by folic acid modified selenium nanoparticles in MCF-7 cells.

    PubMed

    Pi, Jiang; Jin, Hua; Liu, Ruiying; Song, Bing; Wu, Qing; Liu, Li; Jiang, Jinhuan; Yang, Fen; Cai, Huaihong; Cai, Jiye

    2013-02-01

    Selenium nanoparticles (Se NPs) have been recognized as promising materials for biomedical applications. To prepare Se NPs which contained cancer targeting methods and to clarify the cellular localization and cytotoxicity mechanisms of these Se NPs against cancer cells, folic acid protected/modified selenium nanoparticles (FA-Se NPs) were first prepared by a one-step method. Some morphologic and spectroscopic methods were obtained to prove the successfully formation of FA-Se NPs while free folate competitive inhibition assay, microscope, and several biological methods were used to determine the in vitro uptake, subcellular localization, and cytotoxicity mechanism of FA-Se NPs in MCF-7 cells. The results indicated that the 70-nm FA-Se NPs were internalized by MCF-7 cells through folate receptor-mediated endocytosis and targeted to mitochondria located regions through endocytic vesicles transporting. Then, the FA-Se NPs entered into mitochondria; triggered the mitochondria-dependent apoptosis of MCF-7 cells which involved oxidative stress, Ca(2)+ stress changes, and mitochondrial dysfunction; and finally caused the damage of mitochondria. FA-Se NPs released from broken mitochondria were transported into nucleus and further into nucleolus which then induced MCF-7 cell cycle arrest. In addition, FA-Se NPs could induce cytoskeleton disorganization and induce MCF-7 cell membrane morphology alterations. These results collectively suggested that FA-Se NPs could be served as potential therapeutic agents and organelle-targeted drug carriers in cancer therapy.

  12. Structural analysis of binding functionality of folic acid-PEG dendrimers against folate receptor.

    PubMed

    Sampogna-Mireles, Diana; Araya-Durán, Ingrid D; Márquez-Miranda, Valeria; Valencia-Gallegos, Jesús A; González-Nilo, Fernando D

    2017-03-01

    Dendrimers functionalized with folic acid (FA) are drug delivery systems that can selectively target cancer cells with folate receptors (FR-α) overexpression. Incorporation of polyethylene glycol (PEG) can enhance dendrimers solubility and pharmacokinetics, but ligand-receptor binding must not be affected. In this work we characterized, at atomic level, the binding functionality of conventional site-specific dendrimers conjugated with FA with PEG 750 or PEG 3350 as a linker. After Molecular Dynamics simulation, we observed that both PEG's did not interfere over ligand-receptor binding functionality. Although binding kinetics could be notably affected, the folate fragment from both dendrimers remained exposed to the solvent before approaching selectively to FR-α. PEG 3350 provided better solubility and protection from enzymatic degradation to the dendrimer than PEG 750. Also, FA-PEG3350 dendrimer showed a slightly better interaction with FR-α than FA-PEG750 dendrimer. Therefore, theoretical evidence supports that both dendrimers are suitable as drug delivery systems for cancer therapies.

  13. Folic acid supplementation can adversely affect murine neural tube closure and embryonic survival.

    PubMed

    Marean, Amber; Graf, Amanda; Zhang, Ying; Niswander, Lee

    2011-09-15

    Neural tube defects (NTDs), a common birth defect in humans, result from the failure of the embryonic neural tube (NT) to close properly. NT closure is a complex, poorly understood morphogenetic process influenced by genes and environment. The most effective environmental influence in decreasing the risk for NTDs is folic acid (FA) fortification and supplementation, and these findings led to the recommendation of periconceptual FA intake and mandatory fortification of the US grain supply in 1998. To explore the relationship between genetics and responsiveness to FA supplementation, we used five mouse NTDs models-Zic2, Shroom3, Frem2, Grhl2 (Grainyhead-like 2) and L3P (Line3P)-and a long-term generational FA supplementation scheme. Contrary to expectations, we find that three genetic mutants respond adversely to FA supplementation with increased incidence of NTDs in homozygous mutants, occurrence of NTDs in heterozygous embryos and embryonic lethality prior to NT closure. Because of these unexpected responses, we examined NTD risk after short-term FA supplementation. Our results indicate that, for the same genetic allele, NTD risk can depend on the length of FA exposure. Our data indicate that, depending on the gene mutation, FA supplementation may adversely influence embryonic development and NT closure.

  14. Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

    PubMed Central

    Khosravian, Pegah; Shafiee Ardestani, Mehdi; Khoobi, Mehdi; Ostad, Seyed Naser; Dorkoosh, Farid Abedin; Akbari Javar, Hamid; Amanlou, Massoud

    2016-01-01

    Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer. PMID:27980423

  15. Comments on background papers related to iron, folic acid, malaria and other infections.

    PubMed

    Oppenheimer, Stephen

    2007-12-01

    This review comments on and summarizes five expert presentations and reports made at a meeting hosted by the World Health Organization (WHO) in Lyon, France, 12-14 June 2006, related to iron and folate supplementation and their interactions with infection. The meeting was called because of the mortality implications of the Pemba iron study and the possible need to change WHO policy as soon as possible. Six tabled presentations were reviewed. A majority of these expert reviews regarded the Pemba study as indicating a specific adverse interaction between iron supplementation and malaria. A majority regarded such an effect as already reviewed, demonstrated, and predicted in existing literature published prior to the Pemba study. A majority concluded that there was a risk of malarial morbidity associated with oral iron supplementation. A majority made recommendations for change, indicating either that the 1998 WHO/UNICEF recommendation for iron supplementation in malarious areas should be suspended pending further research or that it should be stopped. A majority felt that folate supplementation was a less likely cause of the Pemba result; two mentioned the interference of oral folate with antifolate antimalarials; a majority suggested suspension of folic acid supplementation to children in malarious areas. Only one presentation argued for net population benefits of folate and none for iron.

  16. Encapsulation of folic acid in different silica porous supports: A comparative study.

    PubMed

    Pérez-Esteve, Édgar; Ruiz-Rico, María; de la Torre, Cristina; Villaescusa, Luis A; Sancenón, Felix; Marcos, María D; Amorós, Pedro; Martínez-Máñez, Ramón; Barat, José Manuel

    2016-04-01

    Although folic acid is essential to numerous bodily functions, recent research indicates that a massive exposition to the vitamin could be a double-edged sword. In this study, the capacity of different caped mesoporous silica particles (i.e. Hollow Silica Shells, MCM-41, SBA-15 and UVM-7) to dose FA during its passage through the gastrointestinal tract has been evaluated. Results confirmed that the four capped materials were capable to hinder the delivery of FA at low pH (i.e. stomach) as well as able to deliver great amounts of the vitamin at neutral pH (i.e. intestine). Nevertheless, the encapsulation efficiency and the deliver kinetics differed among supports. While supports with large pore entrance exhibited an initial fast release, MCM-41, showed a sustained release along the time. This correlation between textural properties and release kinetics for each of the supports reveals the importance of a proper support selection as a strategy to control the delivery of active molecules.

  17. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study.

    PubMed

    Whitrow, Melissa J; Moore, Vivienne M; Rumbold, Alice R; Davies, Michael J

    2009-12-15

    This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n = 557) from 1998 to 2005. At 3.5 years and 5.5 years, 490 and 423 mothers and children participated in the study, respectively. Maternal folate intake from diet and supplements was assessed by food frequency questionnaire in early (<16 weeks) and late (30-34 weeks) pregnancy. The primary outcome was physician-diagnosed asthma, obtained by maternal-completed questionnaire. Asthma was reported in 11.6% of children at 3.5 years (n = 57) and in 11.8% of children at 5.5 years (n = 50). Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) = 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR = 1.32, 95% CI: 1.03, 1.69). The effect sizes did not change with adjustment for potential confounders. The association was similar at 5.5 years but did not reach statistical significance (RR = 1.17, 95% CI: 0.96, 1.42) in univariable models. These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children.

  18. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    NASA Astrophysics Data System (ADS)

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra

    2013-01-01

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  19. Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

    NASA Astrophysics Data System (ADS)

    Castillo, John J.; Rindzevicius, Tomas; Wu, Kaiyu; Schmidt, Michael S.; Janik, Katarzyna A.; Boisen, Anja; Svendsen, Winnie; Rozlosnik, Noemi; Castillo-León, Jaime

    2014-07-01

    Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experiments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors.

  20. Folic acid supplementation affects apoptosis and differentiation of embryonic neural stem cells exposed to high glucose.

    PubMed

    Jia, De-yong; Liu, Hui-juan; Wang, Fu-wu; Liu, Shang-ming; Ling, Eng-Ang; Liu, Kai; Hao, Ai-jun

    2008-07-25

    Folic acid (FA) supplementation has been shown to be extremely effective in reducing the occurrence of neural tube defects (NTDs), one of the most common birth defects associated with diabetic pregnancy. However, the antiteratogenic mechanism of FA in diabetes-induced NTDs is unclear. This study investigated the neuroprotective mechanism of FA in neural stem cells (NSCs) exposed to high glucose in vitro. The undifferentiated or differentiated NSCs were cultured in normal D-glucose concentration (NG) or high D-glucose concentration (HG) with or without FA. FA supplementation significantly decreased apoptosis induced by HG and lowered the expression of p53 in the nucleus of undifferentiated NSCs exposed to HG. Administration of FA in differentiated NSCs did not alter their precocious differentiation induced by HG. The increased mRNA expression levels of the basic helix-loop-helix factors including Neurog1, Neurog2, NeuroD2, Mash1, Id1, Id2, and Hes5 in the presence of HG were not significantly affected by FA. The present results provided a cellular mechanism by which FA supplementation may have a potential role in prevention of NTDs in diabetic pregnancies. On the other hand, FA increased the mRNA expression levels of the above transcription factors and accelerated the differentiation of NSCs in the NG medium, suggesting that it may adversely affect the normal differentiation of NSCs. Therefore, the timing and dose of FA would be critical factors in considering FA supplementation in normal maternal pregnancy.

  1. Methoxistasis: integrating the roles of homocysteine and folic acid in cardiovascular pathobiology.

    PubMed

    Joseph, Jacob; Loscalzo, Joseph

    2013-08-15

    Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or "methoxistasis", exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.

  2. Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

    PubMed

    Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

    2014-05-12

    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis.

  3. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir boosted atazanavir nanoformulations

    PubMed Central

    Puligujja, Pavan; Balkundi, Shantanu; Kendrick, Lindsey; Baldridge, Hannah; Hilaire, James; Bade, Aditya N.; Dash, Prasanta K.; Zhang, Gang; Poluektova, Larisa; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.; McMillan, JoEllyn M.; Gendelman, Howard E.

    2014-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that target monocyte-macrophage could improve the drug’s half-life and protein binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly affected several therapeutic factors: drug bioavailability increased as much as 5 times and PD activity improved as much as 100 times. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice and infected with HIV-1ADA at a tissue culture infective dose50 of 104 infectious viral particles/ml led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitate drug carriage and facilitate antiretroviral responses. PMID:25522973

  4. Pharmacodynamics of long-acting folic acid-receptor targeted ritonavir-boosted atazanavir nanoformulations.

    PubMed

    Puligujja, Pavan; Balkundi, Shantanu S; Kendrick, Lindsey M; Baldridge, Hannah M; Hilaire, James R; Bade, Aditya N; Dash, Prasanta K; Zhang, Gang; Poluektova, Larisa Y; Gorantla, Santhi; Liu, Xin-Ming; Ying, Tianlei; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S; McMillan, JoEllyn M; Gendelman, Howard E

    2015-02-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) that targets monocyte-macrophages could improve the drug's half-life and protein-binding capacities while facilitating cell and tissue depots. To this end, ART nanoparticles that target the folic acid (FA) receptor and permit cell-based drug depots were examined using pharmacokinetic and pharmacodynamic (PD) tests. FA receptor-targeted poloxamer 407 nanocrystals, containing ritonavir-boosted atazanavir (ATV/r), significantly increased drug bioavailability and PD by five and 100 times, respectively. Drug particles administered to human peripheral blood lymphocyte reconstituted NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ mice and infected with HIV-1ADA led to ATV/r drug concentrations that paralleled FA receptor beta staining in both the macrophage-rich parafollicular areas of spleen and lymph nodes. Drug levels were higher in these tissues than what could be achieved by either native drug or untargeted nanoART particles. The data also mirrored potent reductions in viral loads, tissue viral RNA and numbers of HIV-1p24+ cells in infected and treated animals. We conclude that FA-P407 coating of ART nanoparticles readily facilitates drug carriage and antiretroviral responses.

  5. Study on the adsorption of Cu(II) by folic acid functionalized magnetic graphene oxide

    NASA Astrophysics Data System (ADS)

    Wang, Cuicui; Ge, Heyi; Zhao, Yueying; Liu, Shanshan; Zou, Yu; Zhang, Wenbo

    2017-02-01

    The folic acid functionalized magnetic graphene oxide (FA-mGO) as a new adsorbent has been synthesized in this work for the elimination of Cu(II) from waste water. The as-prepared FA-mGO was tested by SEM, TEM, particle size analyzer, FTIR, XRD, Roman spectrum, TGA and magnetic properties analyzer. Some factors, such as adsorbent dose, pH, contact time, initial concentration of adsorbate and temperature were explored. The results showed that the FA-mGO had the better adsorption performance than mGO. After 40 min, the adsorption equilibrium could be reached. Furthermore, the adsorption property obeyed the pseudo-second order kinetic model and the Temkin isotherms well. The maximum adsorption capacity was 283.29 mg/g for Cu(II) from Pseudo-second-order model at pH=5 and 318 K. The chelation action between FA and Cu(II) along with electrostatic incorporation between GO and Cu(II) determined the favourable adsorption property. Besides, thermodynamic studies results ∆G0<0, ∆H0>0, ∆S0>0 suggested that the adsorption mechanism was an endothermic and spontaneous process essentially. Finally, desorption and reusability studies imply FA-mGO has an excellent reproducibility and is benefit to environmental protection and resource conservation.

  6. Hydrophilic azlactone-functionalized magnetite nanoparticle for conjugation with folic acid

    NASA Astrophysics Data System (ADS)

    Pray-in, Yingrak; Rutnakornpituk, Boonjira; Wichai, Uthai; Vilaivan, Tirayut; Rutnakornpituk, Metha

    2014-04-01

    Herein, we report the synthesis of magnetite nanoparticles (MNPs) grafted with poly(poly(ethylene glycol) methyl ether methacrylate- stat-2-vinyl-4,4-dimethylazlactone) copolymers (poly(PEGMA- stat-VDM)) prepared via a surface-initiated atom transfer radical polymerization (ATRP) and used for the immobilization of folic acid (FA). The MNPs were synthesized using a thermal decomposition method and surface functionalized to obtain ATRP-initiating sites. The particle size was in the range of 5-10 nm with the average of 8.0 ± 1.2 nm in diameter. Molar ratio of PEGMA to VDM was systematically varied (0/100, 30/70, 50/50, and 70/30, respectively) in the copolymerization to obtain water dispersible MNP with various amounts of azlactone rings, an electrophilic moiety, on its surface. Grafting density of VDM on the particle surface increased with increased VDM loading in the copolymerization reaction. These copolymer-coated MNPs were well dispersible in water with some nano-scale aggregation after FA functionalization due to hydrophobic character of FA. Since FA is a cancer cell targeting agent, it is anticipated that these novel FA-functionalized MNPs could be used as magnetically guidable vehicle for drug delivery, particularly for cancer treatment. The results of this study warrant a future investigation of this promising system.

  7. Folic acid-conjugated europium complexes as luminescent probes for selective targeting of cancer cells.

    PubMed

    Quici, Silvio; Casoni, Alessandro; Foschi, Francesca; Armelao, Lidia; Bottaro, Gregorio; Seraglia, Roberta; Bolzati, Cristina; Salvarese, Nicola; Carpanese, Debora; Rosato, Antonio

    2015-02-26

    We report the synthesis of three optical probes (Eu(3+)⊂1, Eu(3+)⊂2, and Eu(3+)⊂3) having a luminescent Eu complex (signaling unit) bonded in different positions to folic acid (FA), the folate receptor (FR) targeting unit. The structures of the two regioisomers Eu(3+)⊂1 and Eu(3+)⊂2 were assigned by mass spectrometric experiments. The optical properties and stability of these probes were assessed in phosphate-buffered saline, cell culture medium, rat serum, and cellular lysate, and results indicated that they are chemically and photophysically stable. Cytotoxicity was studied with ovarian cancer cells having high (SKOV-3), intermediate (OVCAR-3), low (IGROV-1), or null (A2780) expression of FRs. The internalized probe, evaluated in SKOV-3, IGROV-1, and A2780 cells, was in the order Eu(3+)⊂2 > Eu(3+)⊂1 > Eu(3+)⊂3. No internalization was observed for A2780 cells. Such results, together with those obtained in competition experiments of FA versus Eu(3+)⊂2 and FA or Eu(3+)⊂2 versus (3)H-FA, indicate that internalization is receptor-mediated and that Eu(3+)⊂2 shows high selectivity and specificity for FR.

  8. Tanshinone IIA Protects Against Folic Acid-Induced Acute Kidney Injury.

    PubMed

    Jiang, Chunming; Zhu, Wei; Shao, Qiuyuan; Yan, Xiang; Jin, Bo; Zhang, Miao; Xu, Biao

    2016-01-01

    Tanshinone IIA is a diterpene extracted from Salvia miltiorrhiza, a popular and safe herb medicine that has been widely used in China and other Asian countries. Previous studies have demonstrated the pleiotropic effects of Tanshinone IIA on many disease treatments via its antitoxicity, anti-inflammation, anti-oxidative stress, as well as antifibrosis activities. However, its effect on acute kidney injury (AKI) has not been fully investigated. Here, we show for the first time that systemic administration of Tanshinone IIA can lead to improved kidney function in folic acid-induced kidney injury mice. In the acute phase of AKI, Tanshinone IIA attenuated renal tubular epithelial injury, as determined by histologic changes and the detection of Neutrophil gelatinase-associated lipocalin (NGAL) in the kidney and urine. Additionally, Tanshinone IIA treatment resulted in elevated proliferating cell nuclear antigen (PCNA) expression and decreased inflammatory cells infiltration as well as chemokine expression, suggesting that Tanshinone IIA promoted renal repair following AKI and inhibited local inflammatory response in the injured kidney. This led to decreased long-term fibrosis in the injured kidney, characterized by less accumulation of fibronectin and collagen I in tubulointerstitium. Taken together, these results suggest that Tanshinone IIA may represent a potential approach for AKI treatment.

  9. Supplementation with iron and folic acid enhances growth in adolescent Indian girls.

    PubMed

    Kanani, S J; Poojara, R H

    2000-02-01

    The prevalence of anemia is high in adolescent girls in India, with over 70% anemic. Iron-folic acid (IFA) supplements have been shown to enhance adolescent growth elsewhere in the world. To confirm these results in India, a study was conducted in urban areas of Vadodora, India to investigate the effect of IFA supplements on hemoglobin, hunger and growth in adolescent girls 10-18 y of age. Results show that there was a high demand for IFA supplements and >90% of the girls consumed 85 out of 90 tablets provided. There was an increment of 17.3 g/L hemoglobin in the group of girls receiving IFA supplements, whereas hemoglobin decreased slightly in girls in the control group. Girls and parents reported that girls increased their food intake. A significant weight gain of 0.83 kg was seen in the intervention group, whereas girls in the control group showed little weight gain. The growth increment was greater in the 10- to 14-y-old age group than in the 15- to 18-y-old group, as expected, due to rapid growth during the adolescent spurt. IFA supplementation is recommended for growth promotion among adolescents who are underweight.

  10. Dual nutraceutical nanohybrids of folic acid and calcium containing layered double hydroxides

    NASA Astrophysics Data System (ADS)

    Kim, Tae-Hyun; Oh, Jae-Min

    2016-01-01

    Dual nutraceutical nanohybrids consisting of organic nutrient, folic acid (FA), and mineral nutrient, calcium, were prepared based on layered double hydroxide (LDH) structure. Among various hybridization methods such as coprecipitation, ion exchange, solid phase reaction and exfoliation-reassembly, it was found that exfoliation-reassembly was the most effective in terms of intercalation of FA moiety between Ca-containing LDH layers. X-ray diffraction patterns and infrared spectra indicated that FA molecules were well stabilized in the interlayer space of LDHs through electrostatic interaction. From the atomic force and scanning electron microscopic studies, particle thickness of LDH was determined to be varied with tens, a few and again tens of nanometers in pristine, exfoliated and reassembled state, respectively, while preserving particle diameter. The result confirmed layer-by-layer hybrid structure of FA and LDHs was obtained by exfoliation-reassembly. Solid UV-vis spectra showed 2-dimensional molecular arrangement of FA moiety in hybrid, exhibiting slight red shift in n→π* and π→π* transition. The chemical formulae of FA intercalated Ca-containing LDH were determined to Ca1.30Al(OH)4.6FA0.74·3.33H2O and Ca1.53Fe(OH)5.06FA2.24·9.94H2O by inductively coupled plasma-atomic emission spectroscopy, high performance liquid chromatography and thermogravimetry, showing high nutraceutical content of FA and Ca.

  11. Excited-State Dynamics in Folic Acid and 6-CARBOXYPTERIN upon Uva Excitation

    NASA Astrophysics Data System (ADS)

    Huang, Huijuan; Vogt, R. Aaron; Crespo-Hernandez, Carlos E.

    2013-06-01

    The excited-state dynamics of folic acid (FA) and 6-carboxypterin (6CP) are poorly understood and work is needed to uncover the relaxation pathways that ultimately lead to their oxidative damage of DNA. In our approach, broad-band transient absorption spectroscopy was used to monitor the evolution of the excited states in FA and 6CP in basic aqueous solution upon excitation at 350 nm. In addition, quantum-chemical calculations were performed to assist in the interpretation of the experimental results and in the postulation of kinetic mechanisms. The combined experimental and computational results support a kinetic model where excitation of FA results in ultrafast charge separation (τ = 0.6 ps), which decays back to the ground state primarily by charge recombination with a lifetime of 2.2 ps. A small fraction of the charge transfer state undergoes intersystem crossing to populate the lowest-energy triplet state with a lifetime of 200 ps. On the other hand, a large fraction of the initially excited singlet state in 6CP decays by fluorescence emission with a lifetime of 100 ps, while intersystem crossing to the triplet state occurs with a lifetime of 4.4 ns. The potential implications of these results to the oxidative damage of DNA by FA and 6CP will be discussed. Funding from the National Science Foundation is gratefully acknowledged (CHE-1255084).

  12. Long-term variations of folic acid concentrations in the Northern Adriatic.

    PubMed

    Plavsić, Marta

    2004-08-01

    Folic acid (FA), which belongs to B-group vitamins has recently been recognized as possible nutrient for some phytoplankton species (a diatom Phaeodactylum tricornutum). The beneficial role of FA in human health is widely documented. In some countries food fortification with FA has already become mandatory. FA is also used under commercial name of Dosfolat for the treatment of industrial and domestic wastewaters. This is an exploratory study on seasonal and depth variability of FA concentrations in the Northern Adriatic Sea (station 101-max depth 30 m, under the Po River influence). Seawater samples were analysed in the period from February 1998 to February 2003 based on monthly determinations. Those preliminary findings showed that in the upper layer (10 m) FA concentrations were in the range from 0.1 to 28 nM. In the lower layer (20-30 m) FA concentrations were in the range from 0.1 to 12 nM. It was found that phytoplankton and microorganisms which are responsible for the production of FA in the Northern Adriatic (Station 101) were situated at the depth from 5 to 10 m. The observed water column and seasonal distributions depended on a sensitive balance between the production and the consumption of FA.

  13. Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

    PubMed Central

    Vollset, Stein Emil; Clarke, Robert; Lewington, Sarah; Ebbing, Marta; Halsey, Jim; Lonn, Eva; Armitage, Jane; Manson, JoAnn E; Hankey, Graeme J; Spence, J David; Galan, Pilar; Bønaa, Kaare H; Jamison, Rex; Gaziano, J Michael; Guarino, Peter; Baron, John A; Logan, Richard FA; Giovannucci, Edward L; den Heijer, Martin; Ueland, Per M; Bennett, Derrick; Collins, Rory; Peto, Richard

    2013-01-01

    Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials. Methods Meta-analyses of data on each individual in all placebo-controlled trials of folic acid for prevention of cardiovascular disease (10 trials, n=46,969) or colorectal adenoma (3 trials, n=2652) that recorded cancer incidence and recruited >500 participants. All trials were evenly randomised. Risk ratios (RRs) compare those allocated folic acid vs those allocated placebo, giving cancer incidence rate ratios (among those still free of cancer) during, but not after the scheduled treatment period. Findings During a weighted mean follow-up duration of 5.5 years, allocation to folic acid quadrupled plasma folate, but had no statistically significant effect on overall cancer incidence (1904 vs 1809 cancers, RR=1.06 [95%CI 0.99–1.13], p=0.10; trend with duration of treatment p=0.46). There was no significant heterogeneity between the results of individual trials (p=0.23), or between the cadiovascular prevention trials and the adenoma prevention trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease site-specific cancer incidence during the first 5 years of treatment. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency. PMID:23352552

  14. Characterization of excipient and tableting factors that influence folic acid dissolution, friability, and breaking strength of oil- and water-soluble multivitamin with minerals tablets.

    PubMed

    Du, Jianping; Hoag, Stephen W

    2003-11-01

    The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a "super" disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial

  15. Effects of reducing dietary protein, methionine, choline, folic acid, and vitamin B12 during the late stages of the egg production cycle on performance and eggshell quality.

    PubMed

    Keshavarz, K

    2003-09-01

    A series of four experiments was conducted to determine whether-shell quality during the late stages of egg production can be improved by using diets that are effective in reducing egg size. The experiments involved dietary manipulation of protein, methionine, choline, folic acid, and vitamin B12. In experiment 1, reducing dietary protein in combination of reducing the dietary methionine and choline or this diet without supplemental folic acid and vitamin B12 resulted in reduced egg weight and improved shell quality. However, egg production also was drastically reduced. In experiment 2, reducing the dietary level of methionine, without adding supplemental choline, folic acid, and vitamin B12 reduced egg size and improved shell quality, but egg production was reduced as well. In this experiment reducing the dietary methionine without supplemental folic acid and vitamin B12 reduced egg size and improved shell quality with no adverse effect on egg production. In experiment 3, reducing the dietary level of methionine and choline or reducing the dietary level of choline, folic acid, and vitamin B12 reduced egg size and improved shell quality without adverse effects on egg production. On the other hand, reducing dietary methionine, folic acid, vitamin B12, and supplemental choline reduced egg weight and improved shell quality but lowered egg production. In experiment 4, reducing dietary methionine together with reducing choline and vitamin B12 reduced egg size and improved shell quality with no adverse effect on egg production. The results of this series of experiments generally indicate that certain manipulations of the combination of methionine, choline, folic acid, and vitamin B12 have the potential to reduce egg weight and improve shell quality without affecting egg production during the latter stages of the egg production cycle.

  16. Graphene decorated microelectrodes for simultaneous detection of ascorbic, dopamine, and folic acids by means of chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Namdar, N.; Hassanpour Amiri, M.; Dehghan Nayeri, F.; Gholizadeh, A.; Mohajerzadeh, S.

    2015-09-01

    In this paper, high quality and large area graphene layers were synthesized using thermal chemical vapour deposition on copper foil substrates. We use graphene incorporated electrodes to measure simultaneously ascorbic acid, dopamine and folic acid. Cyclic voltammetry and differential pulse voltammetry methods were used to evaluate electrochemical behaviour of the grown graphene layers. The graphene-modified electrode shows large electrochemical potential difference compared to bare gold electrodes with higher current responses. Also our fabricated electrodes configuration can be used easily for microfluidic analysis.

  17. Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

    PubMed

    Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

    2016-06-01

    The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

  18. Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application

    NASA Astrophysics Data System (ADS)

    Hao, Yongwei; Wang, Lei; Zhang, Bingxiang; Zhao, Hongjuan; Niu, Mengya; Hu, Yujie; Zheng, Cuixia; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong; Zhang, Yun

    2016-01-01

    It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20-60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r 1 was 2.26 mM-1 s-1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.

  19. Effect of in ovo feeding of folic acid on the folate metabolism, immune function and epigenetic modification of immune effector molecules of broiler.

    PubMed

    Li, Shizhao; Zhi, Lihui; Liu, Yanli; Shen, Jing; Liu, Lei; Yao, Junhu; Yang, Xiaojun

    2016-02-14

    This study was conducted to investigate the effect of in ovo feeding (IOF) of folic acid on the folate metabolism, immune function and the involved epigenetic modification of broilers. A total of 400 (Cobb) hatching eggs were randomly divided into four groups (0, 50, 100 and 150 µg injection of folic acid at embryonic age 11 d), and chicks hatched from each treatment were randomly divided into six replicates with 12 broilers/replicate after incubation. The results indicated that, in ovo, 100- and 150-µg folic acid injections improved the hatchability. The average daily gain and feed conversion ratio increased in the 150-µg group during the late growth stage. Simultaneously, in the 100- and 150-µg groups, an increase was observed in hepatic folate content and the expression of methylenetetrahydrofolate reductase (d1 and 42) and methionine synthase reductase (d21). IgG and IgM concentrations, as well as plasma lysozyme activity of broilers, showed a marked increase along with increasing folic acid levels. The splenic expression levels of IL-2 and IL-4 were up-regulated, whereas that of IL-6 was down-regulated, in the 100- and 150-µg folic acid treatment groups. In addition, histone methylation in IL-2 and IL-4 promoters exhibited an enrichment of H3K4m2 but a loss of H3K9me2 with the increased amount of folic acid additive. In contrast, a decrease in H3K4m2 and an increase in H3K9me2 were observed in the IL-6 promoter in folic acid treatments. Furthermore, in ovo, the 150-µg folic acid injection improved the chromatin tightness of the IL-2 and IL-4 promoter regions. Our findings suggest that IOF of 150 µg of folic acid can improve the growth performance and folate metabolism of broilers, and enhance the relationship between immune function and epigenetic regulation of immune genes, which are involved with the alterations in chromatin conformation and histone methylation in their promoters.

  20. Broadcasting behavior change: a comparison of the effectiveness of paid and unpaid media to increase folic acid awareness, knowledge, and consumption among Hispanic women of childbearing age.

    PubMed

    Flores, Alina L; Prue, Christine E; Daniel, Katherine Lyon

    2007-04-01

    Awareness about folic acid's effectiveness in reducing the risk of certain birth defects has increased among women in the United States; however, few Hispanic women are consuming enough folic acid daily. A 1998 survey conducted by the Gallup Organization for the National March of Dimes Birth Defects Foundation found that English-speaking Hispanic women had lower folic acid awareness (53% vs. 72%) and lower daily consumption (29% vs. 33%) than non-Hispanic White women. In 1999, the Centers for Disease Control and Prevention (CDC) conducted baseline surveys with Spanish-speaking Hispanic women in selected U.S. markets to measure folic acid awareness, knowledge, and consumption. A Spanish-language public service announcement (PSA) volunteer campaign and a paid Spanish-language media and community education campaign were conducted in 2000 and 2002, respectively. Comparisons of postcampaign surveys indicate that the paid media campaign was significantly more effective than the PSA campaign in increasing folic acid awareness, knowledge, and consumption among Spanish-speaking Hispanic women.

  1. Nanoparticles of deoxycholic acid, polyethylene glycol and folic acid-modified chitosan for targeted delivery of doxorubicin.

    PubMed

    Shi, Zhonggen; Guo, Rui; Li, Weichang; Zhang, Yi; Xue, Wei; Tang, Yu; Zhang, Yuanming

    2014-03-01

    Chitosan (CS) was first modified hydrophobically with deoxycholic acid (DCA) and then with polyethylene glycol (PEG) to obtain a novel amphiphilic polymer (CS-DCA-PEG). This was covalently bound to folic acid (FA) to develop nanoparticles (CS-DCA-PEG-FA) with tumor cell targeting property. The structure of the conjugates was characterised using Fourier transform infrared and (1)H nuclear magnetic resonance spectroscopy and X-ray diffraction. Based on self-aggregation, the conjugates formed nanoparticles with a low critical aggregation concentration of 0.035 mg/ml. The anti-cancer drug doxorubicin (DOX) was encapsulated into the nanoparticles with a drug-loading capacity of 30.2 wt%. The mean diameter of the DOX-loaded nanoparticles was about 200 nm, with a narrow size distribution. Transmission electron microscopy images showed that the DOX-loaded nanoparticles were spherical. The drug release was studied under different conditions. Furthermore, the cytotoxic activities of DOX in CS-DCA-PEG-FA nanoparticles against folate receptor (FR)-positive HeLa cells and FR-negative fibroblast 3T3 cells were evaluated. These results suggested that the CS-DCA-PEG-FA nanoparticles may be a promising vehicle for the targeting anticancer drug to tumor cells.

  2. BP, cardiovascular disease, and death in the Folic Acid for Vascular Outcome Reduction in Transplantation trial.

    PubMed

    Carpenter, Myra A; John, Alin; Weir, Matthew R; Smith, Stephen R; Hunsicker, Lawrence; Kasiske, Bertram L; Kusek, John W; Bostom, Andrew; Ivanova, Anastasia; Levey, Andrew S; Solomon, Scott; Pesavento, Todd; Weiner, Daniel E

    2014-07-01

    The optimal BP level in kidney transplant recipients remains uncertain. This post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial cohort assessed associations of BP with a pooled cardiovascular disease (CVD) outcome and with all-cause mortality. In 3474 prevalent kidney transplant patients, mean age was 52±9 years, 63% were men, 76% were white, 20% had a history of CVD, 40% had a history of diabetes mellitus, and the median time since transplant was 4.1 years (25th to 75th percentiles, 1.7-7.4); mean systolic BP was 136±20 mmHg and mean diastolic BP was 79±12 mmHg. There were 497 CVD events and 406 deaths. After adjustment for demographic and transplant characteristics and CVD risk factors, each 20-mmHg increase in baseline systolic BP associated with a 32% increase in subsequent CVD risk (hazard ratio [HR], 1.32; 95% confidence interval [95% CI], 1.19 to 1.46) and a 13% increase in mortality risk (HR, 1.13; 95% CI, 1.01 to 1.27). Similarly, after adjustment, at diastolic BP levels<70 mmHg, each 10-mmHg decrease in diastolic BP level associated with a 31% increase in CVD risk (HR, 1.31; 95% CI, 1.06 to 1.62) and a 31% increase in mortality risk (HR, 1.31; 95% CI, 1.03 to 1.66). However, at diastolic BP levels>70 mmHg, there was no significant relationship between diastolic BP and outcomes. Higher systolic BP strongly and independently associated with increased risk of CVD and all-cause mortality, without evidence of a J shape, whereas only lower levels of diastolic BP associated with increased risk of CVD and death in this trial.

  3. Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid-Induced AKI.

    PubMed

    Martin-Sanchez, Diego; Ruiz-Andres, Olga; Poveda, Jonay; Carrasco, Susana; Cannata-Ortiz, Pablo; Sanchez-Niño, Maria D; Ruiz Ortega, Marta; Egido, Jesus; Linkermann, Andreas; Ortiz, Alberto; Sanz, Ana B

    2017-01-01

    AKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)-induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor-interacting protein kinase 3 (RIPK3) and mixed lineage domain-like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI.

  4. Folic acid-modified methotrexate-conjugated PEGylated poly(ɛ-caprolactone) nanoparticles for targeted delivery

    NASA Astrophysics Data System (ADS)

    Issarachot, Ousanee; Suksiriworapong, Jiraphong; Takano, Mikihisa; Yumoto, Ryoko; Junyaprasert, Varaporn Buraphacheep

    2014-02-01

    Functionalized nanoparticles of polymer-drug conjugates of PEGylated poly(ɛ-caprolactone) (PEGylated P(CL)) with methotrexate (MTX) and folic acid (FOL) were developed and investigated for their targeting efficiency. FOL- and MTX-conjugated PEGylated P(CL) copolymers were employed to prepare P(MTXCLCL)2-PEG NPs and FOL-P(MTXCLCL)2-PEG NPs. By varying the amount of MTX, the different characteristics of nanoparticles were obtained. The results showed that an increase in particle size and more negative surface charge of P(MTXCLCL)2-PEG NPs were related to an increased amount of MTX along the polymer backbone. After being decorated with FOL, the particle size increased by nearly twofolds while the zeta potential decreased. All nanoparticles were spherical as observed under SEM micrographs. The release profiles showed pH-dependent and sustained release over 20 days. Higher extent of MTX was released in pH 4.5 medium as compared to the drug release in pH 7.4 medium. All nanoparticles showed greater toxicity to MCF-7 cells than A549 cells. In addition, FOL-P(MTXCLCL)2-PEG NPs exhibited the highest toxicity to MCF-7 cells as compared to all P(MTXCLCL)2-PEG NPs and free MTX. Furthermore, FOL-P(MTXCLCL)2-PEG NPs were internalized into MCF-7 cells higher than P(MTXCLCL)2-PEG NPs and FOL-P(MTXCLCL)2-PEG NPs incubated with free FOL. The results indicated that FOL-P(MTXCLCL)2-PEG NPs efficiently entered into MCF-7 cells via folate receptor-mediated endocytosis together with adsorptive endocytosis.

  5. Dual nutraceutical nanohybrids of folic acid and calcium containing layered double hydroxides

    SciTech Connect

    Kim, Tae-Hyun; Oh, Jae-Min

    2016-01-15

    Dual nutraceutical nanohybrids consisting of organic nutrient, folic acid (FA), and mineral nutrient, calcium, were prepared based on layered double hydroxide (LDH) structure. Among various hybridization methods such as coprecipitation, ion exchange, solid phase reaction and exfoliation-reassembly, it was found that exfoliation-reassembly was the most effective in terms of intercalation of FA moiety between Ca-containing LDH layers. X-ray diffraction patterns and infrared spectra indicated that FA molecules were well stabilized in the interlayer space of LDHs through electrostatic interaction. From the atomic force and scanning electron microscopic studies, particle thickness of LDH was determined to be varied with tens, a few and again tens of nanometers in pristine, exfoliated and reassembled state, respectively, while preserving particle diameter. The result confirmed layer-by-layer hybrid structure of FA and LDHs was obtained by exfoliation-reassembly. Solid UV–vis spectra showed 2-dimensional molecular arrangement of FA moiety in hybrid, exhibiting slight red shift in n→π* and π→π* transition. The chemical formulae of FA intercalated Ca-containing LDH were determined to Ca{sub 1.30}Al(OH){sub 4.6}FA{sub 0.74}·3.33H{sub 2}O and Ca{sub 1.53}Fe(OH){sub 5.06}FA{sub 2.24}·9.94H{sub 2}O by inductively coupled plasma-atomic emission spectroscopy, high performance liquid chromatography and thermogravimetry, showing high nutraceutical content of FA and Ca. - Highlights: • We successfully intercalated FA molecules into Ca-containing LDHs. • Exfoliation-reassembly was proven to be the most effective. • The interaction between LDH and FA were studied by FT-IR and UV–vis spectra. • Thermal stability of FA were enhanced by electrostatic interaction with LDH layers.

  6. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

    PubMed

    Obeid, Rima; Holzgreve, Wolfgang; Pietrzik, Klaus

    2013-09-01

    Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 μg. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.

  7. Ion-transfer voltammetric determination of folic acid at meso-liquid-liquid interface arrays.

    PubMed

    Jiang, Xuheng; Gao, Kui; Hu, Daopan; Wang, Huanhuan; Bian, Shujuan; Chen, Yong

    2015-04-21

    Voltammetric studies on the simple ion transfer (IT) behaviors of an important water-soluble B-vitamin, folic acid (FA), at the liquid-liquid (L-L) interface were firstly performed and then applied as a novel detection method for FA under physiological conditions. Meso-water-1,6-dichlorohexane (W-DCH) and meso-water-organogel interface arrays were built by using a hybrid mesoporous silica membrane (HMSM) with a unique structure of pores-in-pores and employed as the new platforms for the IT voltammetric study. In view of the unique structure of the HMSM, the impact of the ionic surfactant cetyltrimethylammonium bromide (CTAB), self-assembled within the silica nanochannels of the HMSM, was investigated. In particular, its effect on the IT voltammetric behavior and detection of FA at meso-L-L interface arrays was systematically examined by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and differential pulse stripping voltammetry (DPSV). It was found that all the voltammetric responses of CV, DPV, and DPSV and the corresponding detection limit of FA at such meso-L-L interface arrays are closely related to the CTAB in the HMSM. Significantly, the calculated detection limit of FA could be improved to 80 nM after the combination of the DPSV technique with the additional preconcentration of FA in the silica-CTAB nanochannels, achieved through an anion-exchange process between FA(-) and the bromide of CTAB in HMSM. This provides a new and attractive strategy for the detection of those biological anions.

  8. Does folic acid supplementation rescue defects in ECE-1-deficient mouse embryos?

    PubMed

    Haque, A; Šaňková, B; Kvasilová, A; Krejčí, E; Sedmera, D

    2014-01-01

    Endothelin (ET) signalling is essential for normal embryonic development. Disruption of this pathway leads to defects in the development of subsets of cranial and cephalic neural crest derivatives. Endothelin-converting enzyme 1 (ECE-1) is a ratelimiting step in the biosynthesis of ET-1. Recently, there has been considerable interest in the protective role of folic acid (FA) against congenital anomalies via increasing the expression of ET-1. We have tested whether FA supplementation can rescue craniofacial and cardiac defects observed in the ECE1-/- embryos. ECE1+/- mice were caged together to obtain litters containing embryos of all possible genotypes. The treatment group had the diet supplemented with 20 mg/kg of FA from the day of discovery of the vaginal plug. FA supplementation did not result in modified proportions of the genotypes, indicating no rescue of the embryonic mortality. There was also no effect on the litter size. Craniofacial and cardiac defects were likewise identical in the ECE1-/- embryos of both groups. There was a mild but significant reduction in the embryo size in wild-type and heterozygous FA-supplemented embryos, and there were haemorrhages in the wild-type supplemented embryos at ED14.5. Expression of ET receptor A detected by immunohistochemistry was up-regulated in the ECE1-/- embryos, but FA supplementation had no effects on the distribution of staining intensity. We conclude that FA is not able to rescue the phenotype in this model, suggesting an alternative pathway for its action. These results also caution against indiscriminate use of dietary supplements in attempts to prevent congenital anomalies.

  9. Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid.

    PubMed

    Tyagi, Neetu; Kandel, Madhavi; Munjal, Charu; Qipshidze, Natia; Vacek, Jonathan C; Pushpakumar, Sathnur B; Metreveli, Naria; Tyagi, Suresh C

    2011-10-01

    Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, Hcy accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid (FA) in genetically HHcy-associated decrease in bone blood flow and remodeling. Wild type (WT) and cystathionine-β-synthase heterozygous (CBS+/-) mice were used in this study and supplemented with or without FA (300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density (BD) was assessed by dual energy X-ray absorptiometry. The bone homogenates were analyzed for oxidative stress, NOX-4 as oxidative marker and thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/- mice. The BD was also reduced in CBS+/- mice. There was an increase in NOX-4, iNOS, MMP-9 protein as well as MMP-9 activity in CBS+/- mice and decrease in Trx-1, eNOS protein levels, in part by decreasing NO bio-availability in CBS+/- mice. Interestingly, these effects were ameliorated by FA and suggested that FA supplementation may have therapeutic potential against genetically HHcy induced bone loss.

  10. Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies.

    PubMed

    Wilson, R Douglas; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Carroll, June; Cartier, Lola; Gagnon, Alain; Johnson, Jo-Ann; Langlois, Sylvie; Murphy-Kaulbeck, Lynn; Okun, Nanette; Pastuck, Melanie; Deb-Rinker, Paromita; Dodds, Linda; Leon, Juan Andres; Lowel, Hélène L; Luo, Wei; MacFarlane, Amanda; McMillan, Rachel; Moore, Aideen; Mundle, William; O'Connor, Deborah; Ray, Joel; Van den Hof, Michiel

    2015-06-01

    Objectif : Offrir des renseignements à jour sur l’utilisation pré et postconceptionnelle d’acide folique par voie orale, avec ou sans supplément de multivitamines / micronutriments, aux fins de la prévention des anomalies du tube neural et d’autres anomalies congénitales. Ces renseignements aideront les médecins, les sages-femmes, les infirmières et les autres professionnels de la santé à contribuer aux efforts de sensibilisation des femmes quant à l’utilisation et aux posologies adéquates de la supplémentation en acide folique / multivitamines, avant et pendant la grossesse. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans PubMed, Medline, CINAHL et la Cochrane Library en janvier 2011 au moyen d’un vocabulaire contrôlé et de mots clés appropriés (p. ex. « folic acid », « prenatal multivitamins », « folate sensitive birth defects », « congenital anomaly risk reduction », « pre-conception counselling »). Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre 1985 et juin 2014. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu’en juin 2014. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques, et auprès de sociétés de spécialité médicale nationales et internationales. Coûts, risques et avantages : Les coûts financiers sont ceux de la supplémentation quotidienne en vitamines et de la consommation d’un régime alimentaire santé enrichi en folate. Les risques sont ceux qui sont li

  11. Inconsistent effects of iron-folic acid and/or zinc supplementation on the cognitive development of infants.

    PubMed

    Siegel, Emily H; Kordas, Katarzyna; Stoltzfus, Rebecca J; Katz, Joanne; Khatry, Subarna K; LeClerq, Steven C; Tielsch, James M

    2011-12-01

    Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 microg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (> or = 85% correct; A-not-B), deteriorated performance (< 75% correct and > 1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio = 0.67; 95% confidence interval 0.46-0.97; p < 0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p > 0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors.

  12. Folic acid protects against lead acetate-induced hepatotoxicity by decreasing NF-κB, IL-1β production and lipid peroxidation mediataed cell injury.

    PubMed

    Abd Allah, Eman S H; Badary, Dalia M

    2017-03-01

    Folic acid plays an important role in cellular metabolic activities. The present study was designed to investigate the protective effect of folic acid against lead acetate-induced hepatotoxicity. Twenty four male Wistar albino rats were randomly divided into four groups, six animals each. Negative control group received the vehicle, positive control group received 1mg/kg folic acid for five consecutive days/week for 4 weeks orally, lead-exposed group received 10mg/kg lead acetate intraperitoneally (IP) for five consecutive days/week for 4 weeks, and lead-treated group received 10mg/kg lead acetate IP and 1mg/kg folic acid orally for five consecutive days/week for 4 weeks concurrently. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ- glutamyltransferase (GGT) were measured. Hepatic total peroxide and interleukin-1β (IL-1β) were also investigated. Histopathological studies using hematoxylin-eosin (H&E) and periodic acid shiff's (PAS) were carried out. The expression of nuclear factor kappa B (NF-κB) was evaluated using immunohistochemistry. Serum AST, ALT and GGT and hepatic total peroxide and IL-1β were significantly increased in lead-exposed group and were positively correlated with hepatic lead level. Moreover, lead-exposed rats showed hydropic degeneration, nuclear vesiculation, high lymphocytic infiltration, depletion of glycogen content and NF-κB expression. Concomitant folic acid administration resulted in a significant alleviation of biochemical and structural alteration-induced by lead. This was associated with reduction of hepatic total peroxide and IL-1β and reduction of NF-κB expression. In conclusion, folic acid protects against lead acetate-induced hepatotoxicity by decreasing NF-κB, IL-1β production and lipid peroxidation mediataed cell injury.

  13. Effects of folic acid and vitamin B12 supplementation on culling rate, diseases, and reproduction in commercial dairy herds.

    PubMed

    Duplessis, M; Girard, C L; Santschi, D E; Laforest, J-P; Durocher, J; Pellerin, D

    2014-01-01

    This study was undertaken to determine the effect of a combined folic acid and vitamin B12 supplement given in early lactation on culling rate, metabolic disorders and other diseases, and reproduction in commercial dairy herds. A total of 805 cows (271 primiparous and 534 multiparous cows) in 15 commercial dairy herds were involved. Every 2mo from February to December 2010 and within each herd, cows were assigned according to parity, previous 305-d milk production, and calving interval to 5mL of either (1) saline 0.9% NaCl (control group) or (2) 320mg of folic acid + 10mg of vitamin B12 (vitamin group). Treatments were administered weekly by intramuscular injections starting 3wk before the expected calving date until 8wk after parturition. A total of 221 cows were culled before the next dry period. Culling rate was not affected by treatment and was 27.5%; culling rate was greater for multiparous (32.2%) than for primiparous cows (18.8%). Within the first 60d in milk (DIM), 47 cows were culled, representing 21.3% of total culling, and no treatment effect was noted. Ketosis incidence based on a threshold ≥100µmol/L of β-hydroxybutyrate in milk was 38.3±2.9% for the vitamin group and 41.8±3.0% for the control group and was not affected by treatment. The combined supplement of folic acid and vitamin B12 did not decrease incidence of retained placenta, displaced abomasum, milk fever, metritis, or mastitis. However, the incidence of dystocia decreased by 50% in multiparous cows receiving the vitamin supplement, although no effect was observed in primiparous cows. The first breeding postpartum for multiparous cows occurred 3.8d earlier with the vitamin supplement compared with controls, whereas no treatment effect was seen for primiparous cows. Days open, first- and second-breeding conception rates, number of breedings per conception, and percentage of cows pregnant at 150 DIM were not affected by treatment. The reduced percentage of dystocia combined with the

  14. Community mobilization and social marketing to promote weekly iron-folic acid supplementation: a new approach toward controlling anemia among women of reproductive age in Vietnam.

    PubMed

    Khan, Nguyen Cong; Thanh, Hoang Thi Kim; Berger, Jacques; Hoa, Pham Thuy; Quang, Nguyen Dinh; Smitasiri, Suttilak; Cavalli-Sforza, Tommaso

    2005-12-01

    Community-based social marketing and mobilization increased knowledge and participation in preventive weekly iron-folic acid supplementation among women of reproductive age in Vietnam. Rates of buying and taking the weekly supplement containing 60 mg elemental iron and 3.5 mg folic acid among non-pregnant women of reproductive age was between 55% and 92%. Free distribution to pregnant women of the weekly supplement containing 120 mg iron and 3.5 mg folic acid covered almost all pregnant women during the project. In developing countries where community women's groups and health networks are strong, preventive supplementation can be successfully promoted to encourage active participation in the prevention and control of iron-deficiency anemia.

  15. Government-industry partnership in weekly iron-folic acid supplementation for women of reproductive age in the Philippines: impact on iron status.

    PubMed

    Angeles-Agdeppa, Imelda; Paulino, Lourdes S; Ramos, Adelisa C; Etorma, Unita Marie; Cavalli-Sforza, Tommaso; Milani, Silvano

    2005-12-01

    The effectiveness of weekly iron-folic acid supplements promoted through a government-industry partnership was assessed in pregnant and non-pregnant women in the Philippines. Compliance to both weekly and daily supplementation increased during the year-long study period, but was highest with weekly supplementation. Serum ferritin and hematocrit increased significantly, whereas the hemoglobin level showed minimal change, probably because of lack of other heme-forming nutrients such as vitamin A. Serum ferritin increments were significantly higher in women taking the iron-folic acid supplements for more than 6 weeks. Weekly iron-folic acid supplementation should be recommended as a preventive strategy to control iron deficiency among reproductive-age women in the Philippines.

  16. Treatment and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial.

    PubMed

    Hadler, Maria Claret Costa Monteiro; Sigulem, Dirce Maria; Alves, Maria de Fátima Costa; Torres, Vinícius Montenegro

    2008-01-01

    The objective of this study was to assess the prevalence of anemia and the therapeutic and prophylactic response to ferrous sulfate and folic acid. A double-blind, randomized, controlled clinical trial was conducted with 196 children 6 to 24 months of age enrolled in municipal daycare centers in Goiânia, Goiás State, Brazil. The children were assigned to two treatment groups that received a daily dose (5 times a week) of either 4.2mg/kg/day of ferrous sulfate + folic acid (50microg) or 4.2mg/kg/day of ferrous sulfate + folic acid placebo. One of the prevention groups received 1.4mg/kg/day of ferrous sulfate + folic acid (50microg/day) and the other 1.4mg/kg/day of ferrous sulfate + folic acid placebo. Supplementation lasted approximately three months. Baseline anemia prevalence was 56.1% (95%CI: 48.9-63.1). After treatment, anemia prevalence in the folic acid group (14%) was lower than in the placebo group (34.9%) (p = 0.02). After prophylaxis in the non-anemic children, the incidence of anemia did not differ between the groups, but there was an increase in hemoglobin level in the folic acid group (p = 0.003). Iron plus folic acid was effective for the treatment of anemia and improvement of hemoglobin level in non-anemic children.

  17. Utilization of folic acid and iron supplementation services by pregnant women attending an antenatal clinic at a regional referral hospital in Kenya.

    PubMed

    Maina-Gathigi, L; Omolo, J; Wanzala, P; Lindan, C; Makokha, A

    2013-09-01

    To determine utilization of iron and folic acid supplementation services among pregnant women in Kenya. A cross sectional study was conducted at Nyeri Hospital, a regional referral hospital in central Kenya. Women attending the antenatal clinic were selected through systematic sampling. A semi-structured questionnaire was administered to collect information on utilization of folic acid and iron supplementation services. Women who ingested folic acid or iron supplements for >4 days in a week were considered "highly compliant". The health worker in-charge of the antenatal clinic was interviewed about the frequency of supplement stock-outs during the past year. Haemoglobin concentration was measured directly from one drop of capillary blood and measured using portable HEMOCUE B-Hb photometer. Of the 381 women interviewed, only 23.6 % obtained antenatal care in the first trimester; 69.3 and 51.2 % received folic acid and iron supplements, respectively. However, only half (45-58 %) received any information about supplementation. Most women were initiated on folic acid (80.7 %) or iron (67.7 %) after 12 and 16 weeks of gestation, respectively, well after the recommended time period. However, more than 80 % of those who received folic acid and iron were highly compliant. Stock-outs were common at the facility. Of 361 women tested for Hb level, the prevalence of anaemia (Hb levels < 11 g/dl) was 7.8 %. Health workers need to better explain the importance of supplements to pregnant women. Women who come late to antenatal clinic miss opportunities to start supplementation early in pregnancy. Problems with supply chain management exacerbate the problem.

  18. Folic Acid Attenuates Vascular Endothelial Cell Injury Caused by Hypoxia via the Inhibition of ERK1/2/NOX4/ROS Pathway.

    PubMed

    Cheng, Fei; Lan, Jun; Xia, Wenhao; Tu, Chang; Chen, Benfa; Li, Shicheng; Pan, Weibiao

    2016-06-01

    Coronary artery disease is a disease with high morbidity and mortality, in which vascular endothelial dysfunction plays an important role. Hypoxia leads to the inflammation and oxidative stress in endothelial cells, which results in the endothelial injury. The present study was designed to investigate the protective effect and mechanism of folic acid on hypoxia-induced injury in human umbilical vein endothelial cells (HUVEC). Cell counting Kit was used to detect cell survival rate, and apoptotic cells were detected by Hoechst 33258 staining. Intracellular reactive oxygen species (ROS) level was measured using dichloro-dihydro-fluorescein diacetate staining. Western blot was used to determine the protein expressions of extracellular signal protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2), NOX4 subunit of NAPDH and endothelial nitric oxide synthase (eNOS). Folic acid significantly increased the cell survival rate and decreased the apoptosis of HUVECs treated with folic acid compared with hypoxia-treated HUVEC. Folic acid also decreased ROS level, while it increased the nitrite content in HUVECs. In addition, folic acid decreased protein expressions of NOX4 and p-ERK1/2, while it increased the protein expression of eNOS in HUVECs. Furthermore, N-acetyl cysteine (NAC), the antioxidant, had similar effect on the cell survival rate and the apoptosis. In addition, DPI (NOX4 inhibitor) and U0126 (ERK1/2 inhibitor) rather than NAC decreased the protein expression of NOX4. NAC, DPI, and U0126 increased the protein expression of eNOS. Furthermore, U0126 rather than DPI and NAC decreased the protein expression of p-ERK1/2. Taken together, the results suggested that hypoxia decreased the cell survival rate and induced apoptosis via ERK1/2/NOX4/ROS pathway, which could be the target of folic acid in protecting the HUVECs from injury caused by hypoxia.

  19. Folic acid-Pluronic F127 magnetic nanoparticle clusters for combined targeting, diagnosis, and therapy applications.

    PubMed

    Lin, Jia-Jyun; Chen, Jenn-Shing; Huang, Shih-Jer; Ko, Jyun-Han; Wang, Yu-Ming; Chen, Ting-Lung; Wang, Li-Fang

    2009-10-01

    Superparamagnetic iron oxides possess specific magnetic properties in the presence of an external magnetic field, which make them an attractive platform as contrast agents for magnetic resonance imaging (MRI) and as carriers for drug delivery. In this study, we investigate the drug delivery and the MRI properties of folate-mediated water-soluble iron oxide incorporated into micelles. Pluronic F127 (PF127), which can be self-assembled into micelles upon increasing concentration or raising temperatures, is used to decorate water-soluble polyacrylic acid-bound iron oxides (PAAIO) via a chemical reaction. Next, the hydrophobic dye Nile red is encapsulated into the hydrophobic poly(propylene oxide) compartment of PF127 as a model drug and as a fluorescent agent. Upon encapsulation, PAAIO retains its superparamagnetic characteristics, and thus can be used for MR imaging. A tumor-specific targeting ligand, folic acid (FA), is conjugated onto PF127-PAAIO to produce a multifunctional superparamagnetic iron oxide, FA-PF127-PAAIO. FA-PF127-PAAIO can be simultaneously applied as a diagnostic and therapeutic agent that specifically targets cancer cells that overexpress folate receptors in their cell membranes. PF127-PAAIO is used as a reference group. Based on FTIR and UV-vis absorbance spectra, the successful synthesis of PF127-PAAIO and FA-PF127-PAAIO is realized. The magnetic nanoparticle clusters of PF127-PAAIO and FA-PF127-PAAIO are visualized by transmission electron microscope (TEM). FA-PF127-PAAIO, together with a targeting ligand, displays a higher intracellular uptake into KB cells. This result is confirmed by laser confocal scanning microscopy (CLSM), flow cytometry, and atomic absorption spectroscopy (AAS) studies. The hysteresis curves, generated by using a superconducting quantum interference device (SQUID) magnetometer analysis, demonstrate that the magnetic nanoparticles are superparamagnetic with insignificant hysteresis. The MTT assay explains the negligible

  20. Equivalent absorption and in vivo kinetics of tritiated folic acid and 5-formyl-tetrahydrofolic acid in rats

    SciTech Connect

    Bhandari, S.D.; Gregory, J.F. )

    1990-02-26

    The intestinal absorption and in vivo turnover kinetics of ({sup 3}H)folic acid (FA) and (6S)-5-formyl-({sup 3}H)tetrahydrofolate (5-CHO-THF) were examined to determine whether differences exist in the inherent bioavailability of these forms of the vitamin. Following oral administration of 2 {mu}Ci/100 g body weight (in 50 mM sodium ascorbate, pH 7), a biphasic pattern of urinary tritium excretion was observed for each labeled folate. The following kinetic results were obtained (n=9). Little tritium was found in the GI tract after 8 hours, which indicated nearly complete absorption of each folate. HPLC analysis of urine revealed similar excretory patterns over 0-8 days post-dose for each folate administered, and the patterns of hepatic ({sup 3}H)folates were equivalent when examined after 8 hours and 4 days post-dose. These findings indicate that the bioavailability FA and 5-formyl-THF is equivalent.

  1. Genome-Wide Methylation and Gene Expression Changes in Newborn Rats following Maternal Protein Restriction and Reversal by Folic Acid

    PubMed Central

    Stupka, Elia; Clark, Adrian J. L.; Langley-Evans, Simon

    2013-01-01

    A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures. PMID:24391732

  2. Folic acid supplemented goat milk has beneficial effects on hepatic physiology, haematological status and antioxidant defence during chronic Fe repletion.

    PubMed

    Alférez, María J M; Rivas, Emilio; Díaz-Castro, Javier; Hijano, Silvia; Nestares, Teresa; Moreno, Miguel; Campos, Margarita S; Serrano-Reina, Jose A; López-Aliaga, Inmaculada

    2015-02-01

    The aim of the current study was to asses the effect of goat or cow milk-based diets, either normal or Fe-overloaded and folic acid supplement on some aspects of hepatic physiology, enzymatic antioxidant defence and lipid peroxidation in liver, brain and erythrocyte of control and anaemic rats after chronic Fe repletion. 160 male Wistar rats were placed on 40 d in two groups, a control group receiving normal-Fe diet and the Fe-deficient group receiving low Fe diet. Lately, the rats were fed with goat and cow milk-based diets during 30 d, with normal-Fe content or Fe-overload and either with normal folic or folic acid supplemented. Fe-overload increased plasma alanine transaminase and aspartate transaminase levels when cow milk was supplied. Dietary folate supplementation reduced plasma transaminases levels in animals fed goat milk with chronic Fe overload. A remarkable increase in the superoxide dismutase activity was observed in the animals fed cow milk. Dietary folate supplement lead to a decrease on the activity of this enzyme in all the tissues studied with both milk-based diets. A concomitant increment in catalase was also observed. The increase in lipid peroxidation products levels in rats fed cow milk with Fe-overload, suggest an imbalance in the functioning of the enzymatic antioxidant defence. In conclusion, dietary folate-supplemented goat milk reduces both plasma transaminases levels, suggesting a hepatoprotective effect and has beneficial effects in situation of Fe-overload, improving the antioxidant enzymes activities and reducing lipid peroxidation.

  3. Influence of methionine supply on the response of lactational performance of dairy cows to supplementary folic acid and vitamin B12.

    PubMed

    Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Matte, J J; Desrochers, A; Girard, C L

    2009-04-01

    The present experiment was undertaken to determine if the effects of supplementary folic acid on lactational performance were caused by improved methylneogenesis and if the supply in vitamin B(12) could affect this metabolic pathway. In this eventuality, supplementary Met, a major source of preformed methyl groups, should reduce the requirements for these vitamins. Sixty multiparous Holstein cows were assigned to 10 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet estimated to supply Met as 1.83% metabolizable protein and 3 cows were fed the same diet supplemented with 18 g of rumen-protected methionine (RPM) to supply Met as 2.23% of metabolizable protein. Within each level of Met, cows received no vitamin supplement or weekly intramuscular injections of 160 mg of folic acid alone or combined with 10 mg of vitamin B(12) from 3 wk before to 16 wk after calving. There was no treatment effect on dry matter intake during pre- and postcalving periods: 13.4 +/- 0.4 and 21.8 +/- 0.4 kg/d, respectively. Milk production was not affected by RPM supplementation. Folic acid and vitamin B(12) given together tended to increase milk production during the 16 wk of lactation. This effect was more pronounced during the first 4 wk of lactation: 37.5, 37.7, and 40.3 +/- 0.9 kg/d for cows receiving no vitamin supplement, folic acid alone, or folic acid combined with vitamin B(12), respectively. Milk fat yield was not affected by treatments. Lactose, crude protein, and total solid yields were greater, in early lactation, in cows injected with folic acid and vitamin B(12) together but this effect diminished as lactation progressed. Intramuscular injections of folic acid alone or combined with vitamin B(12) tended to decrease plasma concentrations of homocysteine from 5.51 microM with no vitamin supplement to 4.54 and 4.77 +/- 0.37 microM, respectively. Results of the present experiment suggest that the effects of the combined

  4. Effect of cannabinoids upon the uptake of folic acid by BeWo cells.

    PubMed

    Araújo, João R; Gonçalves, Pedro; Martel, Fátima

    2009-01-01

    Folic acid (FA) is an essential micronutrient that is particularly important during pregnancy for normal placental and fetal development and growth. The placenta and the fetus become frequently exposed to drugs of abuse such as cannabinoids because of maternal use of these substances. The aim of this study was to investigate the influence of cannabinoids on the uptake of FA by BeWo cells. Acute treatment with anandamide (1-10 micromol/l) caused a 15% decrease in (3)H-FA uptake at pH 7.5. Moreover, tetrahydrocannabinol (THC) (1-10 micromol/l) caused a 30% increase, and AM630 (1 mumol/l) a 15% decrease in this parameter at pH 6.5. Neither the inhibitory effect of anandamide nor the stimulatory effect of THC were changed in the presence of cannabi- noid receptor type 1 or type 2 antagonists (AM251 and AM630, respectively). Chronic treatment (48 h) with THC (100 nmol/l) and AM251 (100 nmol/l) decreased the uptake of (3)H-FA by 20% at pH 7.5, and anandamide (1 micromol/l) and AM630 (10-500 nmol/l) increased it by 30%. Moreover, CP55,940 (10 nmol/l) increased the uptake of (3)H-FA by 30% at pH 6.5. RT-PCR analysis showed that the mRNA levels of the reduced folate transporter 1 increased by 9% after chronic treatment with AM630 (500 nmol/l). The mRNA levels of the proton-coupled folate transporter decreased by 17% and increased by 18% after chronic treatment with THC (0.1 mumol/l) and AM251 (100 nmol/l), respectively. In conclusion, (3)H-FA uptake by BeWo cells is significantly, although not very markedly, changed by several distinct CB receptor agonists and antagonists, both after acute and chronic exposure of the cells. The acute effects of cannabinoid receptor agonists do not seem to be mediated by the cannabinoid receptor, and with a few exceptions the chronic effects do not seem to be related to changes in the expression levels of FA transporters.

  5. Identification of a Chemoattractant G-Protein-Coupled Receptor for Folic Acid that Controls Both Chemotaxis and Phagocytosis.

    PubMed

    Pan, Miao; Xu, Xuehua; Chen, Yong; Jin, Tian

    2016-02-22

    Eukaryotic phagocytes search and destroy invading microorganisms via chemotaxis and phagocytosis. The social amoeba Dictyostelium discoideum is a professional phagocyte that chases bacteria through chemotaxis and engulfs them as food via phagocytosis. G-protein-coupled receptors (GPCRs) are known for detecting chemoattractants and directing cell migration, but their roles in phagocytosis are not clear. Here, we developed a quantitative phosphoproteomic technique to discover signaling components. Using this approach, we discovered the long sought after folic acid receptor, fAR1, in D. discoideum. We showed that the seven-transmembrane receptor fAR1 is required for folic acid-mediated signaling events. Significantly, we discovered that fAR1 is essential for both chemotaxis and phagocytosis of bacteria, thereby representing a chemoattractant GPCR that mediates not only chasing but also ingesting bacteria. We revealed that a phagocyte is able to internalize particles via a chemoattractant-mediated engulfment process. We propose that mammalian phagocytes may also use this mechanism to engulf and ingest bacterial pathogens.

  6. Synthesis of multifunctional Ag@Au@phenol formaldehyde resin particles loaded with folic acids for photothermal therapy.

    PubMed

    Yang, Ping; Xu, Qi-Zhi; Jin, Sheng-Yu; Lu, Yang; Zhao, Yang; Yu, Shu-Hong

    2012-07-23

    Multifunctional Ag@Au@ phenol formaldehyde resin (PFR) particles loaded with folic acids (FA) have been designed for killing tumor cells through photothermy conversion under the irradiation of near-infrared (NIR) light. Possessing the virtue of good fluorescence, low toxicity, and good targeting, the nanocomposite consists of an Ag core, an Au layer, a PFR shell, and folic acids on the PFR shell. The Ag@PFR core-shell structure can be prepared with a simple hydrothermal method after preheating. We then filled the PFR shell with a layer of Au by heating and modified the shell with polyelectrolyte to change its surface charge state. To capture tumor cells actively, FA molecules were attached onto the surface of the Ag@Au@PFR particles in the presence of 1-ethyl-3-(3-dimethly aminopropyl) carbodiimide (EDAC) and N-hydroxysuccinimide (NHS). Owing to the excellent property of Au NPs and Ag NPs as photothermal conversion agents, the Ag@Au@ PFR@FA particles can be utilized to kill tumor cells when exposed to NIR light.

  7. Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

    The folate in milk is largely bound to high-affinity folate-binding protein (FBP). With an in vivo intestinal loop technique, we examined the absorption of folic acid bound to FBP (FA-FBP) in the small intestine of the suckling rat. In contrast to unbound folic acid (FA), FA-FBP is absorbed more avidly in the ileum than in the jejunum (p less than 0.025) and its absorption is not inhibited by 1 mmol sulfasalazine/L. Folate-binding activities in the mucosa of the proximal (duodenum and jejunum combined) and distal (ileum) small intestine were also examined and found to be 0.32 and 1.31 pmol/mg protein, respectively (p less than 0.001). A 6-h fast produced a 42% decrease in folate-binding activity in the distal small intestine (p less than 0.01) but did not change activity in the proximal portion. Collectively, these observations suggest that FA-FBP is absorbed by a mechanism that is distinct from that responsible for the absorption of FA and that absorption does not require prior dissociation of the vitamin-binding protein complex.

  8. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

    PubMed Central

    Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

    2017-01-01

    Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems. PMID:28106163

  9. [Posterior-predominant leukoencephalopathy which was caused by methylenetetrahydrofolate reductase deficiency and successfully treated with folic acid].

    PubMed

    Tamura, Asako; Sasaki, Ryogen; Kagawa, Ken; Nakatani, Kaname; Osaka, Hitoshi; Tomimoto, Hidekazu

    2014-01-01

    A 35-year-old woman was admitted with subacute intellectual deterioration. Laboratory studies showed elevated total homocysteine and decreased folic acid. MRI revealed leukoencephalopathy with a posterior predominance, and hyperintensity in the pyramidal tracts on T2-weighted and FLAIR images. The enzyme assay showed a deficiency of methylenetetrahydrofolate reductase (MTHFR) activity with low residual activity of 4.2% of the mean control value in cultured fibroblasts. Sequence analysis of the MTHFR gene demonstrated two homozygous missense mutations, c.677C>T (p.Ala222Val) and c.685A>C (p.Ile225Leu). c.677C>T (p.Ala222Val) is known as a common polymorphism and c.685A>C (p.Ile225Leu) is considered to be a novel polymorphism. A diagnosis of MTHFR deficiency was made. Treatment with folic acid, vitamin B12 and B6 made significant improvement of intellectual deterioration and reduction in the total homocysteine level. They also made marked resolution of leukoencephalopathy. Posterior-predominant leukoencephalopathy was found to be an excellent marker of MTHFR deficiency, and may help to establish the diagnosis.

  10. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

    2017-01-01

    Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

  11. Attenuation of Folic Acid-Induced Renal Inflammatory Injury in Platelet-Activating Factor Receptor-Deficient Mice

    PubMed Central

    Doi, Kent; Okamoto, Koji; Negishi, Kousuke; Suzuki, Yoshifumi; Nakao, Akihide; Fujita, Toshiro; Toda, Akiko; Yokomizo, Takehiko; Kita, Yoshihiro; Kihara, Yasuyuki; Ishii, Satoshi; Shimizu, Takao; Noiri, Eisei

    2006-01-01

    Platelet-activating factor (PAF), a potent lipid mediator with various biological activities, plays an important role in inflammation by recruiting leukocytes. In this study we used platelet-activating factor receptor (PAFR)-deficient mice to elucidate the role of PAF in inflammatory renal injury induced by folic acid administration. PAFR-deficient mice showed significant amelioration of renal dysfunction and pathological findings such as acute tubular damage with neutrophil infiltration, lipid peroxidation observed with antibody to 4-hydroxy-2-hexenal (day 2), and interstitial fibrosis with macrophage infiltration associated with expression of monocyte chemoattractant protein-1 and tumor necrosis factor-α in the kidney (day 14). Acute tubular damage was attenuated by neutrophil depletion using a monoclonal antibody (RB6-8C5), demonstrating the contribution of neutrophils to acute phase injury. Macrophage infiltration was also decreased when treatment with a PAF antagonist (WEB2086) was started after acute phase. In vitro chemotaxis assay using a Boyden chamber demonstrated that PAF exhibits a strong chemotactic activity for macrophages. These results indicate that PAF is involved in pathogenesis of folic acid-induced renal injury by activating neutrophils in acute phase and macrophages in chronic interstitial fibrosis. Inhibiting the PAF pathway might be therapeutic to kidney injury from inflammatory cells. PMID:16651609

  12. Imprinted polymer-carbon consolidated composite fiber sensor for substrate-selective electrochemical sensing of folic acid.

    PubMed

    Prasad, Bhim Bali; Madhuri, Rashmi; Tiwari, Mahavir Prasad; Sharma, Piyush Sindhu

    2010-05-15

    Molecularly imprinted polymers (MIPs) are often electrically insulating materials. Due to the presence of diffusion barrier(s) in between such MIP coating and electrode surface and the absence of a direct path for the conduction of electrons from the binding sites to the electrode, the development of electrochemical sensor is significantly restricted. The direct use of MIPs those possess intrinsic electron-transport properties, is highly limited. These problems are resolved by the design of an original, substrate-selective MIP-fiber sensor that combines conventional insulating MIP and conducting carbon powder in consolidated phase. A layer of conducting carbon particles, arranged orderly as 'carbon strip', is inducted in the polymer for direct electronic conduction. MIP-carbon composite (monolithic fiber) in this work is prepared via in situ free radical polymerization of a new monomer (2,4,6-trisacrylamido-1,3,5-triazine, TAT) and subsequent cross-linkage with ethylene glycol dimethacrylate, in the presence of carbon powder and template (folic acid), at 55 degrees C in a glass capillary. The detection of folic acid with the MIP-fiber sensor was found to be specific and quantitative (detection limit 0.20 ng mL(-1), RSD=1.3%, S/N=3), in aqueous, blood serum and pharmaceutical samples, without any problem of non-specific false-positive contribution and cross-reactivity.

  13. Folic acid awareness and use among women with a history of a neural tube defect pregnancy--Texas, 2000-2001.

    PubMed

    Canfield, Mark A; Anderson, James L; Waller, D Kim; Palmer, Susan E; Kaye, Celia I

    2002-09-13

    The use of folic acid is a critical component in preventing birth defects. Health-care providers should take advantage of all health-care visits to counsel not only women at high risk (i.e., those with a history of having an infant with a neural tube defect [NTD]) but all women regarding the importance of folic acid use. A study conducted in Texas confirmed that white and Hispanic mothers were equally likely to recall receiving postpartum advice to use folic acid; however, Hispanic women were much less likely to use folic acid, compared with white women. This report covers data from May 2000 through November 2001. A study was conducted in Texas to determine whether women at high risk recall and follow recommendations to use folic acid. The study included 195 women at high risk and 223 control mothers who gave birth to infants without birth defects. These women participated in a telephone interview for a population-based case-control study of NTDs. Approximately 56.4% (110 of 195) of mothers who had infants affected by an NTD recalled receiving postpartum advice to use folic acid, compared with 25.6% (57 of 223) of control mothers (p < 0.01). Among nonpregnant case mothers, 54 (32.7%) of 165 reported regular use of supplements containing folic acid, and 53 (25.2%) of 210 nonpregnant control mothers reported this behavior (p = 0.11). Among case mothers, use of folic acid was significantly higher for whites (64.7%) versus Hispanics (16.5%) (p < 0.001); for women with some college education (57.1%) versus no college education (20.2%; p < 0.001); for women who were trying to get pregnant (66.7%) versus those using birth control (38.3%) or reporting using no contraceptive method (18.8%) (p = 0.001); and for women who reported receiving advice to use folic acid (40.9%) versus those who did not (22.2%; p = 0.01). Findings from this study support the need to implement NTD recurrence prevention activities in Texas. Data also identify a need for educational strategies in

  14. Folic acid deficiency impairs the gill health status associated with the NF-κB, MLCK and Nrf2 signaling pathways in the gills of young grass carp (Ctenopharyngodon idella).

    PubMed

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2015-11-01

    The aim of this study was to investigate the effect of dietary folic acid on fish growth, the immune and barrier functions of fish gills, and the potential mechanisms of these effects. Young grass carp (Ctenopharyngodon idella) were fed diets containing graded levels of folic acid at 0.10 (basal diet), 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results showed that acid phosphatase and lysozyme activities and the complement component 3 content in fish gills decreased with folic acid deficiency (P < 0.05). Folic acid deficiency up-regulated liver-expressed antimicrobial peptide 1, interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65, IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression. Folic acid deficiency down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in fish gills (P < 0.05). These results showed that limited folic acid decreased fish gill immune status. Furthermore, folic acid deficiency down-regulated claudin-b, claudin-c, claudin-3, occludin and zonula occludens 1 gene expression, whereas folic acid deficiency up-regulated claudin-12, claudin-15, myosin light chain kinase and p38 mitogen activated protein kinase gene expression in fish gills (P < 0.05). These results suggested that folic acid deficiency disrupted tight junction-mediated fish gill barrier function. Additionally, folic acid deficiency increased the content of reactive oxygen species, protein carbonyl and malondialdehyde (MDA); Mn superoxide dismutase activity and gene expression; and Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression (P < 0.05). Conversely, folic acid deficiency decreased Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase activities and gene expression as well as NF-E2-related factor 2 gene expression in fish gills (P < 0.05). All of these results indicated that folic acid

  15. Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats.

    PubMed

    Wadhwani, Nisha S; Manglekar, Rupali R; Dangat, Kamini D; Kulkarni, Asmita V; Joshi, Sadhana R

    2012-01-01

    A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.

  16. Disassembly of amphiphilic small molecular prodrug with fluorescence switch induced by pH and folic acid receptors for targeted delivery and controlled release.

    PubMed

    Xu, Zhigang; Shi, Xiaoxiao; Hou, Meili; Xue, Peng; Gao, Yong-E; Liu, Shiying; Kang, Yuejun

    2017-02-01

    We develop a new type of pH-responsive amphiphilic small molecular prodrug by conjugating folic acid with anti-tumour doxorubicin via a hydrazone bond. This prodrug is featured by high and precise drug loading (55.4wt%), which can self-assemble into micellar nanoparticles in neutral environment while disassemble in the presence of tumour cells expressing folic acid receptors or the acidic tumoral endosomal environment. The prodrug nanoparticles can effectively improve anticancer efficacy due to the features of pH-triggered drug release and targeted delivery. Moreover, in vitro cell study further indicated that the resulting prodrug nanoparticles had enhanced cytotoxicity for folic-acid-positive cells (HeLa) compared to folic-acid-negative cells (MCF-7). More importantly, the induced disassembly of prodrug nanoparticles can "switch on" the inherent fluorescence of the internalized doxorubicin drug in the tumour microenvironment, which can be used for the detection of tumour cells. We believe that this strategy can pave a new way for designing small molecular drug delivery systems and facilitate tumour diagnosis and treatment simultaneously.

  17. Weekly iron-folic acid supplementation to improve iron status and prevent pregnancy anemia in Filipino women of reproductive age: the Philippine experience through government and private partnership.

    PubMed

    Paulino, Lourdes S; Angeles-Agdeppa, Imelda; Etorma, Unita Mari M; Ramos, Adelisa C; Cavalli-Sforza, Tommaso

    2005-12-01

    With the participation of the government and private sectors in the Philippines, weekly iron-folic acid supplementation introduced within a social marketing framework and a social mobilization campaign successfully improved knowledge and practice of buying and regularly taking supplements by women of reproductive age, both pregnant and non-pregnant. Adolescent girls in school were also active participants.

  18. A Temporal Association between Folic Acid Fortification and a Rise in Colorectal Cancer Rates May be Illuminating Important Biological Principles: a Hypothesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nationwide fortification of enriched uncooked cereal grains with folic acid began in the U.S. and Canada in 1996 and 1997, respectively, and became mandatory in 1998. The rationale was to reduce the number of births complicated by neural tube defects. Concurrently, the U.S. and Canada experienced ab...

  19. Folic acid supplementation rescues anomalies associated with knockdown of parkin in dopaminergic and serotonergic neurons in Drosophila model of Parkinson's disease.

    PubMed

    Srivastav, Saurabh; Singh, Sandeep Kumar; Yadav, Amarish Kumar; Srikrishna, Saripella

    2015-05-08

    parkin loss associated early-onset of Parkinson's disease, involves mitochondrial dysfunction and oxidative stress as the plausible decisive molecular mechanisms in disease pathogenesis. Mitochondrial dysfunction involves several up/down regulation of gene products, one of which being p53 is found to be elevated. Elevated p53 is involved in mitochondrial mediated apoptosis of neuronal cells in Parkinson's patients who are folate deficient as well. The present study therefore attempts to examine the effect of Folic acid (FA) supplementation in alleviation of anomalies associated with parkin knockdown using RNAi approach, specific to Dopaminergic (DA) neurons in Drosophila model system. Here we show that FA supplementation provide protection against parkin RNAi associated discrepancies, thereby improves locomotor ability, reduces mortality and oxidative stress, and partially improves Zn levels. Further, metabolic active cell status and ATP levels were also found to be improved thereby indicating improved mitochondrial function. To corroborate FA supplementation in mitochondrial functioning further, status of p53 and spargel was checked by qRT-PCR. Here we show that folic acid supplementation enrich mitochondrial functioning as depicted from improved spargel level and lowered p53 level, which was originally vice versa in parkin knockdown flies cultured in standard media. Our data thus support the potential of folic acid in alleviating the behavioural defects, oxidative stress, augmentation of zinc and ATP levels in parkin knock down flies. Further, folic acid role in repressing mitochondrial dysfunction is encouraging to further explore its possible mechanistic role to be utilized as potential therapeutics for Parkinson's disease.

  20. A 19-base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF). A 19-bp noncoding deletion allele maps to intron 1, beginning 60 bases from the splice donor site, and has been implicated in neural tube defects and cancer, presumably by influencing folate metabolism. T...

  1. The Role of Zinc and Iron-Folic Acid Supplementation on Early Child Temperament and Eating Behaviors in Rural Nepal: A Randomized Controlled Trial

    PubMed Central

    Surkan, Pamela J.; Charles, Mary Katherine; Katz, Joanne; Siegel, Emily H.; Khatry, Subarna K.; LeClerq, Steven C.; Stoltzfus, Rebecca J.; Tielsch, James M.

    2015-01-01

    Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4–17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (β = −0.03, 95% CI −0.3, 0.2) or iron-folic acid and non-iron-folic acid (β = 0.08, 95% CI −0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (β = −0.14, 95% CI −0.3, 0.04) or between iron and non-iron eating behavior scores (β = −0.11, 95% CI −0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (β = −0.3, 95% CI −0.6, −0.01), Ultimately, this effect of zinc on eating behaviors was the

  2. Altered maternal micronutrients (folic acid, vitamin B(12)) and omega 3 fatty acids through oxidative stress may reduce neurotrophic factors in preterm pregnancy.

    PubMed

    Dhobale, Madhavi; Joshi, Sadhana

    2012-04-01

    Preterm pregnancies account for approximately 10% of the total pregnancies and are associated with low birth weight (LBW) babies. Recent studies have shown that LBW babies are at an increased risk of developing brain disorders such as cognitive dysfunction and psychiatric disorders. Maternal nutrition, particularly, micronutrients involved in one-carbon metabolism (folic acid, vitamin B(12), and docosahexaenoic acid (DHA)) have a major role during pregnancy for developing fetus and are important determinants of epigenesis. A series of our studies in pregnancy complications have well established the importance of omega 3 fatty acids especially DHA. DHA regulates levels of neurotrophins like brain-derived neurotrophic factor and nerve growth factor, which are required for normal neurological development. We have recently described that in one carbon metabolic pathway, membrane phospholipids are major methyl group acceptors and reduced DHA levels may result in diversion of methyl groups toward deoxyribonucleic acid (DNA) ultimately resulting in DNA methylation. In this review, we propose that altered maternal micronutrients (folic acid, vitamin B(12)), increased homocysteine, and oxidative stress levels that cause epigenetic modifications may be one of the mechanisms that contribute to preterm birth and poor fetal outcome, increasing risk for behavioural disorders in children.

  3. Effects of intramuscular administration of folic acid and vitamin B12 on granulosa cells gene expression in postpartum dairy cows.

    PubMed

    Gagnon, A; Khan, D R; Sirard, M-A; Girard, C L; Laforest, J-P; Richard, F J

    2015-11-01

    The fertility of dairy cows is challenged during early lactation, and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improve energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg of folic acid and 10 mg of vitamin B12 (treated group) beginning 24 (standard deviation=4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the precalving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the 2 groups. Plasma concentrations of folates and vitamin B12 were increased in treated animals. Daily dry matter intake was not significantly different between the 2 groups before [13.5 kg; standard error (SE)=0.5] and after (23.6 kg; SE=0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE=1.4) and 38.1 (SE=1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of β-hydroxybutyrate tended to be lower in cows injected with the vitamin supplement, 0.47 (SE=0.04) versus 0.55 (SE=0.03) for treated and control cows, respectively. The ovarian follicle ≥12 mm in diameter was collected by ovum pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the effect of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation

  4. Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation

    PubMed Central

    Morse, Nancy L.

    2012-01-01

    Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA) and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring. PMID:22852064

  5. Daily supplementation with iron plus folic acid, zinc, and their combination is not associated with younger age at first walking unassisted in malnourished preschool children from a deficient population in rural Nepal.

    PubMed

    Katz, Joanne; Khatry, Subarna K; Leclerq, Steven C; Mullany, Luke C; Yanik, Elizabeth L; Stoltzfus, Rebecca J; Siegel, Emily H; Tielsch, James M

    2010-07-01

    A community-based, cluster-randomized, placebo-controlled trial of daily zinc and/or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1-36 mo of age between 2001 and 2006. Treatment groups included placebo, zinc (10 mg), iron+folic acid (12.5 mg iron + 50 microg folic acid), and zinc+iron+folic acid (10 mg zinc + 12.5 mg iron + 50 microg folic acid). Infants received half of these doses. The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board; zinc and placebo continued until January 2006. A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo. Mean age at first walking unassisted did not differ among groups and was 444 +/- 81 d (mean +/- SD) in the placebo group, 444 +/- 81 d in the zinc group, 464 +/- 85 d in the iron+folic acid group, and 446 +/- 87 d in the iron+folic acid+zinc group. Results were similar after adjustment for age at enrollment, asset ownership, maternal literacy, and prior child deaths in the household and in children who consumed at least 60 tablets. Compared with placebo, iron+folic acid was associated with an adjusted mean delay of 28.0 d (95% CI: 11.3, 44.7) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference (MUAC) < 9.5 cm [60.6 d, (95% CI: 28.5, 92.6)]. Risks and benefits of universal iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration.

  6. Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age

    PubMed Central

    Berry, Robert J.; Hao, Ling; Li, Zhu; Maneval, David; Yang, Thomas P.; Rasmussen, Sonja A.; Yang, Quanhe; Zhu, Jiang-Hui; Hu, Dale J.; Bailey, Lynn B.

    2011-01-01

    Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (−14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation. PMID:22163281

  7. In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin

    PubMed Central

    Alvarez-Berríos, Merlis P; Vivero-Escoto, Juan L

    2016-01-01

    The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death. PMID:27920531

  8. Dual responsive dysprosium-doped hydroxyapatite particles and toxicity reduction after functionalization with folic and glucuronic acids.

    PubMed

    Sánchez Lafarga, Ana Karen; Pacheco Moisés, Fermín P; Gurinov, Andrey; Ortiz, Genaro Gabriel; Carbajal Arízaga, Gregorio Guadalupe

    2015-03-01

    The development of probes for biomedical applications demands materials with low toxicity levels besides fluorescence or magnetic properties to be detected by confocal microscopes or MRI resonators. Several drug delivery systems or other biomedical materials prepared with hydroxyapatite have been proposed, however, toxicity effects might arise when the size of particles is nanometric. In this study, hydroxyapatite functionalized with glucuronic or folic acids presented lower oxidative stress, measured from lipoperoxides and nitric oxide indicators in rats than pure hydroxyapatite. In separated experiments, hydroxyapatite was doped with dysprosium cations by coprecipitation producing a single crystal phase with fluorescent properties easily visualized by confocal microscopy when excited at 488nm. These particles also presented the ability to modify the proton relaxation time in T1 maps collected by magnetic resonance imaging. These modified hydroxyapatite nanoparticles could be candidates to design bimodal probes with low toxicity.

  9. Bioaccessibility of vitamin A, vitamin C and folic acid from dietary supplements, fortified food and infant formula.

    PubMed

    Brandon, E F A; Bakker, M I; Kramer, E; Bouwmeester, H; Zuidema, T; Alewijn, M

    2014-06-01

    In the Netherlands, vitamin intake occurs mainly via food and for some vitamins also via fortified food. In addition, some people take dietary supplements. Information on the bioavailability of vitamins is important for a good estimation of the actual exposure to vitamins. Furthermore, for a reliable intake estimation, it is important to know the accurateness of the claimed vitamin concentration on the product label. In the current study, the amount of vitamin A, vitamin C, and folic acid in different products and their maximum bioavailability (bioaccessibility) were investigated. In about half of the products, the amount of vitamins significantly deviated from the declared amounts. The vitamin bioaccessibility ranged from <1% to 100%. When assessing the dietary intake exposure of vitamins, it is important to take into account both the possible deviation from the declared level and (the variability of) the bioaccessibility of the vitamin in the products.

  10. Weekly iron and folic acid supplementation as a tool to reduce anemia among primary school children in Cambodia.

    PubMed

    Longfils, Philippe; Heang, Ung Kim; Soeng, Hay; Sinuon, Muth

    2005-12-01

    The prevalence of anemia decreased from 62% to 12% and from 57% to 26% in children 5 to 11 years of age in two rural primary schools in Kampot Province, Cambodia, after oral weekly supplementation with iron-folic acid tablets for 20 weeks and with vitamin A and mebendazole twice per year. In 12- to 15-year-old children, success was less marked. The prevalence of hookworm infestation did not change, but the number of eggs in the stool decreased drastically. The intervention had no significant influence on stunting and wasting. An integrated community approach including mass deworming, health education, and multi-micronutrient supplementation was very effective in reducing anemia in Cambodian schoolchildren and should be adopted on a larger scale.

  11. Photodynamic therapy effect of zinc monoamino phthalocyanine-folic acid conjugate adsorbed on single walled carbon nanotubes on melanoma cells

    NASA Astrophysics Data System (ADS)

    Ogbodu, Racheal O.; Ndhundhuma, Ivy; Karsten, Aletta; Nyokong, Tebello

    2015-02-01

    This work reports on the photodynamic therapy effect of zinc monoamino phthalocyanine linked to folic acid represented as ZnMAPc-FA, which was further immobilized onto single walled carbon nanotube represented as ZnMAPc-FA-SWCNT on melanoma A375 cell line, the effect of SWCNT-FA (without ZnMAPc) was also examined. All the compounds were non-toxic to the melanoma A375 cell line in the absence of light. Upon irradiation of the melanoma A375 cell line with a 676 nm diode laser at a power density of 98 mW/cm2 at 5 J/cm2 about 60% and 63% cell death was observed in the presence of ZnMAPc-FA and ZnMAPc-FA-SWCNT respectively. SWCNT-FA had no significant photodynamic therapy or photothermal effect to the cell, only 23% of cell death was observed after irradiation.

  12. In vitro evaluation of folic acid-conjugated redox-responsive mesoporous silica nanoparticles for the delivery of cisplatin.

    PubMed

    Alvarez-Berríos, Merlis P; Vivero-Escoto, Juan L

    The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction. To prove this hypothesis, internalization and localization studies in HeLa cancer cells were performed using flow cytometry and confocal microscopy. The ability of MSNs to escape from the endolysosomal compartments, the formation of DNA adducts, and the cytotoxic effects of the MSNs were also evaluated. Our results confirmed that this MSN-based delivery platform was capable of delivering cisplatin into the cytosol of HeLa cells, inducing DNA adducts and subsequent cell death.

  13. Influence of folic acid on birthweight and growth of the erythroblastotic infant. II. Growth during the first year.

    PubMed Central

    Gandy, G; Jacobson, W

    1977-01-01

    The growth of 73 erythroblastotic infants (18 mild, 19 moderate, and 36 severe) was followed. In all three grups the average centiles for weight rose during the first half of the year. There was a fall in centiles during the second half of the year in 35 of 55 infants, 17 of them dropping below their birth centiles. Throughout the first year of life there was a strong correlation between serum folate of 8 mug/1 or more and rising weight centiles, and 5 mug/1 or less and falling centiles. None of the infants had macrocytic anaemia and their haemoglobin level rose even when their weight gain fell below the expected rate. It is suggested that in some erythroblastotic infants a shortage of folic acid may be a limiting factor for a normal growth rate. PMID:556928

  14. Synthesis of Hexagonal ZnO-PQ7 Nano Disks Conjugated with Folic Acid to Image MCF - 7 Cancer Cells.

    PubMed

    Sureshkumar, S; Jothimani, B; Sridhar, T M; Santhosh, Arul; Venkatachalapathy, B

    2017-01-01

    Surface modified ZnO nanomaterial is widely used in the field of bioimaging worldwide due to its optical properties, electronic characteristics and biocompatibility. Fluorescent enhanced, Polyquaternium-7(PQ7) capped, ZnO hexagonal nano disks (ZnO-PQ7) were synthesised by simple wet chemical method. The structural and optical properties of ZnO-PQ7 hexagonal nano disks were characterized using XRD, UV-Visible, Fluorescence, HRTEM, EDAX and FTIR studies. The size of synthesised ZnO-PQ7 were around 30-45 nm as confirmed by HRTEM studies. Fluorescence emission intensity increased with increase in PQ7 concentration. ZnO-PQ7 was further conjugated with folic acid (FA) to target human breast cancer cell line (MCF-7) via EDC/NHS coupling chemistry. Conjugation of folic acid with ZnO-PQ7 was confirmed by FTIR studies. The cell viability study using Methyl thiazolyltetrazolium(MTT) assay has demonstrated that the ZnO-PQ7 conjugated FA composites (ZnO-PQ7-FA) exhibit low toxicity towards MCF-7 up to a concentration of 125 μg/mL. Confocal laser scanning microscopic images confirmed the uptake of ZnO-PQ7-FA nanoparticles by MCF-7 cells. This study reveals ZnO-PQ7-FA nano disks as a potential imaging agent for detection of cancer cells. The synthesis route reported in this article is simple and easy to follow for the synthesis of ZnO-PQ7-FA in bulk quantities with high purity.

  15. Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imaging

    PubMed Central

    2013-01-01

    Background Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. Successful development of safe and effective nanoprobes for in vivo gastric cancer targeting imaging is a big challenge. This study is aimed to develop folic acid (FA)-conjugated silica coated gold nanoclusters (AuNCs) for targeted dual-modal fluorescent and X-ray computed tomography imaging (CT) of in vivo gastric cancer cells. Method AuNCs were prepared, silica was coated on the surface of AuNCs, then folic acid was covalently anchored on the surface of AuNCs, resultant FA-conjugated AuNCs@SiO2 nanoprobes were investigated their cytotoxicity by MTT method, and their targeted ability to FR(+) MGC803 cells and FR(−) GES-1 cells. Nude mice model loaded with MGC803 cells were prepared, prepared nanoprobes were injected into nude mice via tail vein, and then were imaged by fluorescent and X-ray computed tomography (CT) imaging. Results FA-conjugated AuNCs@SiO2 nanoprobes exhibited good biocompatibility, and could target actively the FR(+) MGC-803 cells and in vivo gastric cancer tissues with 5 mm in diameter in nude mice models, exhibited excellent red emitting fluorescence imaging and CT imaging. Conclusion The high-performance FA-conjugated AuNCs@SiO2 nanoprobes can target in vivo gastric cancer cells, can be used for fluorescent and CT dual-mode imaging, and may own great potential in applications such as targeted dual-mode imaging of in vivo early gastric cancer and other tumors with FR positive expression in near future. PMID:23718865

  16. Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid.

    PubMed

    Sriraman, Shravan Kumar; Salzano, Giusseppina; Sarisozen, Can; Torchilin, Vladimir

    2016-08-01

    Cancer-specific drug delivery represents an attractive approach to prevent undesirable side-effects and increase the accumulation of the drug in the tumor. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the up-regulated receptors on the surface of tumor cells thus represents an effective strategy. Furthermore, since this receptor expression can be heterogeneous, using a dual-combination of targeting moieties may prove advantageous. With this in mind, the anti-cancer activity of PEGylated doxorubicin-loaded liposomes targeted with folic acid (F), transferrin (Tf) or both (F+Tf) was evaluated. The dual-targeted liposomes showed a 7-fold increase in cell association compared to either of the single-ligand targeted ones in human cervical carcinoma (HeLa) cell monolayers. The increased penetration and cell association of the dual-targeted liposomes were also demonstrated using HeLa cell spheroids. The in vitro cytotoxicity of the doxorubicin liposomes (LD) was then evaluated using HeLa and A2780-ADR ovarian carcinoma cell monolayers. In both these cell lines, the (F+Tf) LD showed significantly higher cytotoxic effects than the untargeted, or single-ligand targeted liposomes. In a HeLa xenograft model in nude mice, compared to the untreated group, though the untargeted LD showed 42% tumor growth inhibition, both the (F) LD and (F+Tf) LD showed 75% and 79% tumor growth inhibition respectively. These results thus highlight that though the dual-targeted liposomes represent an effective cytotoxic formulation in the in vitro setting, they were equally effective as the folic acid-targeted liposomes in reducing tumor burden in the more complex in vivo setting in this particular model.

  17. Neural Tube Defects in Costa Rica, 1987–2012: Origins and Development of Birth Defect Surveillance and Folic Acid Fortification

    PubMed Central

    de la Paz Barboza-Argüello, María; Umaña-Solís, Lila M.; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L.; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-01-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica—through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas—CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987–2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992–1995 data excluded); 628 were identified during the baseline pre-fortification period (1987–1991; 1996–1998); 191 during the fortification period (1999–2002); and 351 during the post-fortification time period (2003–2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1–10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3–5.3) for the post–fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica’s experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs. PMID:24952876

  18. Comparative Studies of Three Pairs of α- and γ-Conjugated Folic Acid Derivatives Labeled with Fluorine-18.

    PubMed

    Boss, Silvan D; Betzel, Thomas; Müller, Cristina; Fischer, Cindy R; Haller, Stephanie; Reber, Josefine; Groehn, Viola; Schibli, Roger; Ametamey, Simon M

    2016-01-20

    The folate receptor (FR) is upregulated in various epithelial cancer types (FR α-isoform), while healthy tissues show only restricted expression. FR-targeted imaging using folate radiopharmaceuticals is therefore a promising approach for the detection of FR-positive cancer tissue. Almost all folate-based radiopharmaceuticals have been prepared by conjugation at the γ-carboxylic functionality of the glutamate moiety of folic acid. In this work, three pairs of fluorinated α- and γ-conjugated folate derivatives were synthesized and their in vitro and in vivo properties compared. The syntheses of all six regioisomers were obtained in good chemical yields using a multistep synthetic approach including the highly selective Cu(I)-catalyzed 1,3-dipolar cycloaddition. The radiosyntheses of the α- and γ-conjugated (18)F-labeled folate derivatives were accomplished in moderate to good radiochemical yields, high radiochemical purities (>95%), and specific activities ranging from 25 to 196 GBq/μmol. In vitro, all folate derivatives showed high binding affinity to the FR-α (IC50 = 1.4-2.2 nM). In vivo PET imaging and biodistribution studies in FR-positive KB tumor-bearing mice demonstrated similar FR-specific tumor uptake for both regioisomers of each pair of compounds. However, FR-unspecific liver uptake was significantly lower for the α-regioisomers compared to the corresponding γ-regioisomers. In contrast, kidney uptake was up to 50% lower for the γ-regioisomers than for the α-regioisomers. These results show that the site of conjugation in the glutamyl moiety of folic acid has a significant impact on the in vivo behavior of (18)F-based radiofolates, but not on their in vitro FR-binding affinity. These findings may potentially stimulate new directions for the design of novel (18)F-labeled folate-based radiotracers.

  19. Neural tube defects in Costa Rica, 1987-2012: origins and development of birth defect surveillance and folic acid fortification.

    PubMed

    Barboza-Argüello, María de la Paz; Umaña-Solís, Lila M; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-03-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica-through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas-CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987-2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992-1995 data excluded); 628 were identified during the baseline pre-fortification period (1987-1991; 1996-1998); 191 during the fortification period (1999-2002); and 351 during the post-fortification time period (2003-2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1-10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3-5.3) for the post-fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica's experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs.

  20. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    PubMed

    Kumar, Dev; Singla, Surinder K; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI.

  1. Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands

    PubMed Central

    2014-01-01

    Background In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear. Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open. The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae. Methods/Design This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information. We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis. Discussion The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of

  2. Folic acid and protein content in maternal diet and postnatal high-fat feeding affect the tissue levels of iron, zinc, and copper in the rat.

    PubMed

    Król, Ewelina; Krejpcio, Zbigniew; Chmurzynska, Agata

    2011-12-01

    Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n = 48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10 weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6 weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p < 0.001), and with decreased liver Zn and Cu contents (p < 0.01 and p < 0.05, respectively), as well as with decreased renal Cu contents (p < 0.001). Moreover, the offspring's tissue mineral levels were also affected by protein and folic acid content in the maternal diet. Both prenatal protein restriction and folic acid supplementation increased the liver Zn content (p < 0.05) and the kidney Zn content (p < 0.001; p < 0.05, respectively), while folic acid supplementation resulted in a reduction in renal Cu level (p < 0.05). Summarizing, the results of this study show that maternal dietary folic acid and protein intake during pregnancy, as well as the type of postweaning diet, affect Fe, Zn, and Cu levels in the offspring of the rat. However, the mechanisms responsible for this phenomenon are unclear, and warrant further investigation.

  3. Effect of Folic Acid therapy on Homocysteine Level in patients with Atherosclerosis or Buerger’s Disease and in Healthy individuals: A clinical trial

    PubMed Central

    Modaghegh, Mohammad Hadi Saeed; Ravari, Hassan; Haghighi, Mohammad Zare; Rajabnejad, Ata’ollah

    2016-01-01

    Background Hyperhomocysteinemia is considered a risk factor for atherosclerosis and some other vascular diseases such as Buerger’s disease. Objective The aim of this study was to measure the Homocysteine levels in 3 different groups of participants (Buerger’s disease, atherosclerosis patients, and healthy cases) and determine the therapeutic effect of folic acid therapy on homocysteine levels for these three groups Methods This nonrandomized clinical trial study was conducted in the vascular and endovascular surgery research center of Mashhad University of Medical Sciences in Mashhad, Iran. This interventional study consisted of 44 participants of which 22 patients had Buerger’s disease and a control group of 22 healthy individuals, all of which were enrolled in this study. All of the study’s participants had their serum homocysteine levels measured both before and after 12 weeks of folic acid (5mg/day) therapy. The data analysis used fo data analysis was a Chi square and t-test or their non-parametrical equivalents for data analysis by means of Statistical Package for the Social Sciences (SPSS) version 16 Results The homocysteine levels were found to be significantly higher in patients with Buerger’s disease as compared to other groups before treatment with folic acid (Buerger = 21.8 ± 8.5 Mm/L, atherosclerosis = 17.3 ± 6.9, healthy = 13.8 ± 3.1; p < 0.001). After treatment with folic acid at 5 mg/daily for 12 weeks, the new plasma homocysteine levels did not show any significant difference (p = 0.38) between the Buerger’s disease group (14.6 ± 4.5 Mm/L) and atherosclerosis group (13.9 ± 4.7), but it was found to besignificantly higher in both groups when compared to the healthy group (10.7 ± 3.9, p<0.05). The plasma homocysteine level was reduced significantly when compared to its initial level in all 3 groups. The comparison of differences among three groups was found not to be significant (p=0.41) Conclusions It seems that supplementary

  4. Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells

    PubMed Central

    Kumar, Manoj; Singh, Gurpal; Arora, Vikas; Mewar, Sujeet; Sharma, Uma; Jagannathan, NR; Sapra, Sameer; Dinda, Amit K; Kharbanda, Surender; Singh, Harpal

    2012-01-01

    The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8–10 nm), and relatively high T2 relaxivity (R2 = 222L · mmol−1 · sec−l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer. PMID:22848174

  5. Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

    PubMed

    Taha, M O; Aiedeh, K M; Al-Hiari, Y; Al-Khatib, H

    2005-10-01

    The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.

  6. [Prevention of congenital malformations by means of folic acid - insurmountable problems due to the German penal code and German drug legislation when preparing a preconceptional model in Saxony-Anhalt].

    PubMed

    Rösch, C; Steinbicker, V; Robra, B P; Kolbe, M; Heinrich, C

    2001-07-01

    For the last 20 years the prophylactic effect of the vitamin folic acid against the occurrence of neural tube defects has been known but in Germany this fact has not been realized by the public. The recommendations by medical institutions fail, among other reasons, because a folic acid prescription by gynaecologists comes too late in the course of events, i.e., women go to the gynaecologist when pregnancy has already set in and it is too late for preventive measures. An effective folic acid prophylaxis must take place before the onset of pregnancy. Data from the regional surveillance of congenital anomalies of the German Federal State of Saxony-Anhalt and interviews with women in maternity, as well as gynaecologists, indicate that there is a substantial knowledge deficit concerning folic acid prophylaxis. In 1998, therefore, a working group was set up in Saxony-Anhalt. It comprises representatives from interested institutions and has the goal of rectifying the knowledge deficit of women of childbearing age by way of a broad-based campaign while making use of the results of regional congenital anomalies monitoring. A pharmaceutical company was enlisted for cost-free distribution of its folic acid product. Legal problems with the prescription drug laws, the law against unfair competitive practices, the advertising of medicaments law and the SGB V (social code) made it impossible to procure multivitamins containing folic acid free of charge for women wanting a child. A highly differentiated legislation has hitherto prevented an elementary improvement in prevention.

  7. Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy

    PubMed Central

    Bwatanglang, Ibrahim Birma; Mohammad, Faruq; Yusof, Nor Azah; Abdullah, Jaafar; Hussein, Mohd Zobir; Alitheen, Noorjahan Banu; Abu, Nadiah

    2016-01-01

    In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange–red fluorescence around 600 nm and investigated to the highest intensity at Mn2+ doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB-231) up to a 500 µg/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor-overexpressed cells. Therefore, we

  8. MoS2/reduced graphene oxide as active hybrid material for the electrochemical detection of folic acid in human serum.

    PubMed

    Chekin, Fereshteh; Teodorescu, Florina; Coffinier, Yannick; Pan, Guo-Hui; Barras, Alexandre; Boukherroub, Rabah; Szunerits, Sabine

    2016-11-15

    In this study, a new matrix based on a molybdenum disulfide-reduced graphene oxide hybrid (MoS2-rGO) was prepared and characterized. Modification of a glassy carbon electrode (GCE) with MoS2-rGO (MG) using drop casting allowed for the selective analysis of folic acid in the presence of a variety of interference species with a limit of detection of 10nM, a linear range between 0.01μM and 100μM with a sensitivity of 14µAµM(-1). In addition, the analytical performance of the proposed sensor was successfully conducted for the determination of folic acid in human serum samples, making MG-GC electrodes promising interfaces for bio-electrochemical applications.

  9. Application of a nanostructured sensor based on NiO nanoparticles modified carbon paste electrode for determination of methyldopa in the presence of folic acid

    NASA Astrophysics Data System (ADS)

    Fouladgar, Masoud; Ahmadzadeh, Saeid

    2016-08-01

    A new method for determination of methyldopa in the presence of folic acid has been described in this work. This method is based on modification of carbon paste electrode with NiO nanoparticles and an ionic liquid (1-Butyl-3-methylimidazolium hexafluorophosphate). Electrochemical studies showed that on the surface of modified electrode, oxidation current of methyldopa has been enhanced and shifted to negative potentials. The fabricated electrode exhibited a linear response to concentration of methyldopa from 0.1 to 700.0 μmol L-1. The sensitivity of the modified electrode to methyldopa not changed in the presence of folic acid and simultaneous or independent measurements of them are possible. The performance of proposed method was investigated by determination of methyldopa in real samples.

  10. Synthesis, Spectroscopic and Thermal Characterization of Copper(II) and Iron(III) Complexes of Folic Acid and Their Absorption Efficiency in the Blood

    PubMed Central

    Hamed, E.; Attia, M. S.; Bassiouny, K.

    2009-01-01

    The absorption efficiency of any drug in blood is of prime importance. Compounds having the general formula: Kn[M(FO)2(H2O)2] · xH2O, where (M = Cu(II) or Fe(III), n = 2 or 1, FO = folate anion, x = 2 or 3 with respect), were prepared, and their absorption efficiency in rodent's blood was determined. The obtained compounds were characterized by elemental analysis, infrared as well as thermogravimetric analysis and polarization of light. The results suggest that the two folate complexes were formed in 1 : 2 molar ratio (metal : folic acid) which acted as a bidentate ligand through both carboxylic groups. Polarization of light proved that the folate complexes have symmetric geometry. Biological application proved that Cu(II) and Fe(III) complexes were absorbed more efficiently in rodent blood than folic acid itself. PMID:19746175

  11. [Effects of both folic acid, p16 protein expression and their interaction on progression of cervical cancerization].

    PubMed

    Jia, W L; Ding, L; Ren, Z Y; Wu, T T; Zhao, W M; Fan, S L; Wang, J T

    2016-12-10

    Objective: To explore the effects of both folic acid, p16 protein expression and their interaction on progression of cervical cancerization. Methods: Participants were pathologically diagnosed new cases, including 80 women with normal cervical (NC), 55 patients with low-grade cervical intraepithelial neoplasia (CINⅠ), 55 patients with high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ) and 64 patients with cervical squamous cell carcinoma (SCC). Serum folate levels were detected by microbiological assay method while p16 protein expression levels were measured by Western-blot. In vitro, cervical cancer cell lines C33A (HPV negative) and Caski (HPV16 positive) were treated with different concentrations of folate. Proliferation and apoptosis of cells and the levels of p16 protein expression were measured in groups with different folic acid concentrations. Results: Results showed that the levels of serum folate were (5.96±3.93) ng/ml, (5.08±3.43) ng/ml, (3.92±2.59) ng/ml and (3.18±2.71) ng/ml, and the levels of p16 protein were 0.80±0.32, 1.33±0.52, 1.91±0.77, and 2.09±0.72 in the group of NC, CINⅠ, CINⅡ/Ⅲ and SCC, respectively. However, the levels of serum folate decreased (trend χ(2)=32.71, P<0.001) and p16 protein expression increased (trend χ(2)=56.06, P<0.001) gradually along with the severity of cervix lesions. An additive interaction was seen between serum folate deficiency and high expression of p16 protein in the CINⅠ, CINⅡ/Ⅲ and SCC group. Results in vitro showed that, with the increase of folate concentration, the inhibition rate of cell proliferation (C33A: r=0.928, P=0.003; Caski: r=0.962, P=0.001) and the rate on cell apoptosis (C33A: r=0.984, P<0.001; Caski: r=0.986, P<0.001) all increased but the levels of p16 protein expression (C33A: r=-0.817, P=0.025; Caski: r=-0.871, P=0.011) reduced. The proliferation inhibition rate (C33A: r=-0.935, P=0.002; Caski: r=-0.963, P=0.001) and apoptosis rate of cells (C33A: r=-0.844, P=0

  12. Vitamin B12 and folic acid supplementation and plasma total homocysteine concentrations in pregnant Indian women with low B12 and high folate status.

    PubMed

    Katre, Prachi; Bhat, Dattatray; Lubree, Himangi; Otiv, Suhas; Joshi, Suyog; Joglekar, Charudatta; Rush, Elaine; Yajnik, Chittaranjan

    2010-01-01

    Maternal vitamin B12 deficiency and hyperhomocysteinemia predict poor pregnancy outcome, foetal adiposity and insulin resistance. In India amongst practicing clinicians and policy makers there is little appreciation of widespread vitamin B12 deficiency. We investigated 163 (86 rural, 77 urban) pregnant women attending antenatal clinics in a rural health centre and a referral hospital in the city of Pune, at 17, 28, and 34 weeks gestation for vitamin supplements, and circulating concentrations of vitamin B12, folate, and total homocysteine. At enrolment 80% rural and 65% urban women had low vitamin B12 but only two rural women had low folate concentrations. During pregnancy 85% rural and 95% of urban women received folic acid; 12% rural and 84% urban women also received vitamin B12. In women receiving no supplementation (n=17) plasma vitamin B12 and folate did not change from 17 to 34 weeks gestation, but homocysteine increased (p<0.05). Homocysteine concentrations at 34 weeks gestation in women receiving only folic acid (n=71, mean 8.4 (95% CI 7.8, 9.1) micromol/L) were comparable to the unsupplemented group (9.7 (7.3, 12.7), p=0.15), but women who received a total dose of >1000 microg of vitamin B12 up to 34 weeks (n=42, all with folic acid) had lower concentrations (6.7 (6.0, 7.4), p<0.001). Increasing dose of vitamin B12 (rs=-0.31, p=0.006) but not folic acid (rs=-0.19, p=0.11) was associated with lower plasma total homocysteine concentration. In vitamin B12 insufficient, folate replete pregnant women, vitamin B12 supplementation is associated with a reduction of plasma total homocysteine concentration in late pregnancy.

  13. Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil-DNA glycosylase impair learning in a mouse model of vascular cognitive impairment.

    PubMed

    Jadavji, Nafisa M; Farr, Tracy D; Lips, Janet; Khalil, Ahmed A; Boehm-Sturm, Philipp; Foddis, Marco; Harms, Christoph; Füchtemeier, Martina; Dirnagl, Ulrich

    2015-04-15

    Dietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil-DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfursion in an animal model. Ung(+/+) and Ung(-/-) mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung(-/-) FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung(+/+) FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung(-/-) hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don't lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion or UNG deficiency is required.

  14. The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial

    PubMed Central

    Sayyah-Melli, Manizheh; Ghorbanihaghjo, Amir; Alizadeh, Mahasti; Kazemi-Shishvan, Maryamalsadat; Ghojazadeh, Morteza; Bidadi, Sanam

    2016-01-01

    Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. Trial Registration: Iranian Registry of Clinical Trials IRCT201402175283N9 PMID:27166794

  15. The use of imidazolium ionic liquid/copper complex as novel and green catalyst for chemiluminescent detection of folic acid by Mn-doped ZnS nanocrystals

    NASA Astrophysics Data System (ADS)

    Azizi, Seyed Naser; Shakeri, Parmis; Chaichi, Mohammad Javad; Bekhradnia, Ahmadreza; Taghavi, Mehdi; Ghaemy, Mousa

    2014-03-01

    A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as CL emitter is proposed for the chemiluminometric determination of folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using L-cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation and its ionic liquid-sensitized effect in aqueous solution were then investigated. It was found that oxidants, especially hydrogen peroxide, could directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission enhancement is observed, related to a strong interaction between Cu2+ and the imidazolium ring. Therefore, a new CL analysis system was developed for the determination of folic acid. Under the optimum conditions, there is a good linear relationship between the relative CL intensity and the concentration of folic acid in the range of 1 × 10-9-1 × 10-6 M of folic acid with a correlation coefficient (R2) of 0.9991. The limit of detection of this system was found to be 1 × 10-10 M. This method is not only simple, sensitive and low cost, but also reliable for practical applications.

  16. The use of imidazolium ionic liquid/copper complex as novel and green catalyst for chemiluminescent detection of folic acid by Mn-doped ZnS nanocrystals.

    PubMed

    Azizi, Seyed Naser; Shakeri, Parmis; Chaichi, Mohammad Javad; Bekhradnia, Ahmadreza; Taghavi, Mehdi; Ghaemy, Mousa

    2014-03-25

    A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as CL emitter is proposed for the chemiluminometric determination of folic acid in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using L-cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. The CL of ZnS QDs induced by directly chemical oxidation and its ionic liquid-sensitized effect in aqueous solution were then investigated. It was found that oxidants, especially hydrogen peroxide, could directly oxidize ZnS QDs to produce weak CL emission in basic conditions. In the presence of 1,3-dipropylimidazolium bromide/copper a drastic light emission enhancement is observed, related to a strong interaction between Cu(2+) and the imidazolium ring. Therefore, a new CL analysis system was developed for the determination of folic acid. Under the optimum conditions, there is a good linear relationship between the relative CL intensity and the concentration of folic acid in the range of 1×10(-9)-1×10(-)(6) M of folic acid with a correlation coefficient (R(2)) of 0.9991. The limit of detection of this system was found to be 1×10(-)(10) M. This method is not only simple, sensitive and low cost, but also reliable for practical applications.

  17. A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles

    PubMed Central

    Zu, Yuangang; Wang, Dan; Zhao, Xiuhua; Jiang, Ru; Zhang, Qi; Zhao, Dongmei; Li, Yong; Zu, Baishi; Sun, Zhiqiang

    2011-01-01

    In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy. PMID:21845075

  18. Maternal multiple micronutrient supplementation has limited impact on micronutrient status of Bangladeshi infants compared with standard iron and folic acid supplementation.

    PubMed

    Eneroth, Hanna; El Arifeen, Shams; Persson, Lars-Ake; Lönnerdal, Bo; Hossain, Mohammad Bakhtiar; Stephensen, Charles B; Ekström, Eva-Charlotte

    2010-03-01

    Knowledge about the impact of maternal food and micronutrient supplementation on infant micronutrient status is limited. We examined the effect of maternal food and micronutrient supplementation on infant micronutrient status in the Maternal and Infant Nutrition Interventions in Matlab Trial. Pregnant women (n = 4436) were randomized to Early or Usual promotion of enrollment in a food supplementation program. In addition, they were randomly allocated to 1 of the following 3 types of daily micronutrient supplements provided from wk 14 of gestation to 3 mo postpartum: 1) folic acid and 30 mg iron (Fe30Fol); 2) folic acid and 60 mg iron; or 3) a multiple micronutrient including folic acid and 30 mg iron (MMS). At 6 mo, infant blood samples (n = 1066) were collected and analyzed for hemoglobin and plasma ferritin, zinc, retinol, vitamin B-12, and folate. The vitamin B-12 concentration differed between the micronutrient supplementation groups (P = 0.049). The prevalence of vitamin B-12 deficiency was lower in the MMS group (26.1%) than in the Fe30Fol group (36.5%) (P = 0.003). The prevalence of zinc deficiency was lower in the Usual food supplementation group (54.1%) than in the Early group (60.2%) (P = 0.046). There were no other differential effects according to food or micronutrient supplementation groups. We conclude that maternal multiple micronutrient supplementation may have a beneficial effect on vitamin B-12 status in infancy.

  19. Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children.

    PubMed

    Bhandari, Nita; Taneja, Sunita; Mazumder, Sarmila; Bahl, Rajiv; Fontaine, Olivier; Bhan, Maharaj K

    2007-01-01

    Studies have found a substantial reduction in diarrhea and respiratory morbidity in young children receiving zinc supplementation. The impact of daily zinc supplementation administered with iron plus folic acid (IFA) in young children on all-cause hospitalizations and mortality in comparison with IFA alone was evaluated. In a double blind cluster-randomized controlled trial, 94,359 subjects aged 1-23 mo were administered a daily dose of zinc plus IFA or IFA alone for a duration of 12 mo after enrollment. The intervention group tablet contained 10 mg of elemental zinc, 12.5 mg of iron, and 50 microg of folic acid. The control group tablets were similar except that they contained a placebo for zinc. Infants aged <6 mo were administered half a tablet, and those older received 1 tablet dissolved in breast milk or water. Hospitalizations were captured by trained study physicians through the surveillance of 8 hospitals. Deaths and hospitalizations were ascertained through visits to households by study supervisors once every 2 mo. The overall death rates did not differ significantly between the 2 groups when adjusted for cluster randomization (hazard ratio = 1.02, 95% CI 0.87, 1.19). Zinc and IFA supplementation compared with IFA alone did not affect adjusted hospitalization rates (overall rate ratio = 1.08, 95% CI 0.98, 1.19; diarrhea-specific rate ratio = 1.15, 95% CI 0.99, 1.34; or pneumonia-specific rate ratio = 1.09, 95% CI 0.94, 1.25). The lack of impact of zinc on mortality and hospitalization rates in this study may have been due to the use of lower daily zinc dosing than used in some of the morbidity prevention trials or from an interaction between zinc and iron, where the addition of iron may have adversely affected potential effects of zinc on immune function and morbidity. Future research should address iron and zinc interaction effects on important functional outcomes.

  20. Folate-mediated targeted and intracellular delivery of paclitaxel using a novel deoxycholic acid-O-carboxymethylated chitosan–folic acid micelles

    PubMed Central

    Wang, Feihu; Chen, Yuxuan; Zhang, Dianrui; Zhang, Qiang; Zheng, Dandan; Hao, Leilei; Liu, Yue; Duan, Cunxian; Jia, Lejiao; Liu, Guangpu

    2012-01-01

    Background A critical disadvantage for successful chemotherapy with paclitaxel (PTX) is its nontargeting nature to cancer cells. Folic acid has been employed as a targeting ligand of various anticancer agents to increase their cellular uptake within target cells since the folate receptor is overexpressed on the surface of such tumor cells. In this study, a novel biodegradable deoxycholic acid-O-carboxymethylated chitosan–folic acid conjugate (DOMC-FA) was used to form micelles for encapsulating the anticancer drug PTX. Methods and results The drug-loading efficiency, encapsulation efficiency, in vitro drug release and physicochemical properties of PTX-loaded micelles were investigated in detail. In vitro cell culture studies were carried out in MCF-7 cells, a human breast carcinoma cell line, with folate receptor overexpressed on its surface. An increased level of uptake of folate-conjugated micelles compared to plain micelles in MCF-7 cells was observed, and the enhanced uptake of folate-micelles mainly on account of the effective process of folate receptor-mediated endocytosis. The MTT assay, morphological changes, and apoptosis test implied that the folate-conjugated micelles enhanced the cell death by folate-mediated active internalization, and the cytotoxicity of the FA-micellar PTX (DOMC-FA/PTX) to cancer cells was much higher than micelles without folate (DOMC/PTX) or the commercially available injectable preparation of PTX (Taxol). Conclusion Results indicate that the PTX-loaded DOMC-FA micelle is a successful anticancertargeted drug-delivery system for effective cancer chemotherapy. PMID:22287842

  1. Population prevalence, attributable risk, and attributable risk percentage for high methylmalonic acid concentrations in the post-folic acid fortification period in the US

    PubMed Central

    2012-01-01

    Background Serum methylmalonic acid (MMA) is regarded as a sensitive marker of vitamin B-12 status. Elevated circulating MMA is linked to neurological abnormalities. Contribution of age, supplement use, kidney dysfunction, and vitamin B-12 deficiency to high serum MMA in post-folic acid fortification period is unknown. Methods We investigated prevalence, population attributable risk (PAR), and PAR% for high MMA concentrations in the US. Data from 3 cross-sectional National Health and Nutrition Examination Surveys conducted in post-folic acid fortification period were used (n = 18569). Results Likelihood of having high serum MMA for white relative to black was 2.5 (P < 0.0001), ≥ 60 y old persons relative to < 60 y old persons was 4.0 (P < 0.0001), non-supplement users relative to supplement users was 1.8 (P < 0.0001), persons with serum creatinine ≥ 130 μmol/L relative to those with < 130 μmol/L was 12.6 (P < 0.0001), and persons with serum vitamin B-12 < 148 pmol/L relative to those with ≥ 148 pmol/L was 13.5 (P < 0.0001). PAR% for high MMA for old age, vitamin B-12 deficiency, kidney dysfunction, and non-supplement use were 40.5, 16.2, 13.3, and 11.8, respectively. By improving serum vitamin B-12 (≥ 148 pmol/L), prevalence of high MMA would be reduced by 16-18% regardless of kidney dysfunction. Conclusions Old age is the strongest determinant of PAR for high MMA. About 5 cases of high serum MMA/1000 people would be reduced if vitamin B-12 deficiency (< 148 pmol/L) is eliminated. Large portion of high MMA cases are not attributable to serum vitamin B-12. Thus, caution should be used in attributing high serum MMA to vitamin B-12 deficiency. PMID:22233538

  2. Folic Acid and Vitamins D and B12 Correlate With Homocysteine in Chinese Patients With Type-2 Diabetes Mellitus, Hypertension, or Cardiovascular Disease.

    PubMed

    Mao, Xudong; Xing, Xubin; Xu, Rong; Gong, Qing; He, Yue; Li, Shuijun; Wang, Hongfu; Liu, Cong; Ding, Xin; Na, Rishu; Liu, Zhiwen; Qu, Yi

    2016-02-01

    Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM).We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50 ± 13.26 years) with T2DM (N = 839), hypertension (N = 490), or CVD (N = 7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged < 50, 50 to 64, 65 to 80, and ≥80 years. A subgroup analysis was also performed to identify correlations between the serum biochemical markers. Stratified chi-squared analyses were performed b