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1

Lucock, Mark. „Folic Acid: Beyond Metabolism“. Journal of Evidence-Based Complementary & Alternative Medicine 16, Nr. 2 (24.03.2011): 102–13. http://dx.doi.org/10.1177/1533210110392950.

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Mandatory and discretionary fortification with folic acid is eliminating deficiency of this vitamin. Blood levels of the vitamin have never been higher, with hematologic folate values commonly exceeding the upper range of calibration. The synthetic analog (pteroylmonoglutamic acid) prevents neural tube defects and lowers homocysteine, both positive attributes, yet negative correlates of pteroylmonoglutamic acid are increasingly reported. These involve increased risk for common cancers (ie, colon, breast, prostate) and antimetabolite effects on natural killer cells and at dihydrofolate reductase, a critical gatekeeper enzyme. This review, however, takes a different, human ecological perspective, examining novel folate-related phenomena distinct from the classic metabolic role of the vitamin in maintaining health and well-being. An argument is developed that at molecular, cellular, and organism levels, folate is crucial to some important events that link light to life.
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Khaitovich, M. V. „Folates: Modern Pregnant Health Support“. HEALTH OF WOMAN, Nr. 4(150) (30.05.2020): 37–42. http://dx.doi.org/10.15574/hw.2020.150.37.

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Folates (folic acid-based chemical compounds) got their name from the Latin “folio” - “leaf”, since they were first synthesized from spinach leaves, in which vitamin B9 is found in maximum quantities. As an important cofactor in carbon metabolism, folates are involved in the most important metabolic processes in the body, in particular, they play a key role in the synthesis of nucleotides and DNA replication. The article provides information on the physiological role of folates, their metabolism and its genetic aspects. The clinical significance of folate deficiency is examined, their sources and doses are described, and the interaction of folic acid and drugs is highlighted. Keywords: folate, metabolism, folic acid deficiency, pregnancy.
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3

Metz, Jack. „Folic Acid Metabolism and Malaria“. Food and Nutrition Bulletin 28, Nr. 4_suppl4 (Dezember 2007): S540—S549. http://dx.doi.org/10.1177/15648265070284s407.

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4

Pellis, Linette, Yvonne Dommels, Dini Venema, Ab van Polanen, Esther Lips, Hakan Baykus, Frans Kok, Ellen Kampman und Jaap Keijer. „High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells“. British Journal of Nutrition 99, Nr. 4 (10.09.2007): 703–8. http://dx.doi.org/10.1017/s0007114507824147.

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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 B12and 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.
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Sahar, Saniya. „Role of Folate and Folic Acid During Pregnancy“. International Journal for Research in Applied Science and Engineering Technology 9, Nr. 12 (31.12.2021): 1488–92. http://dx.doi.org/10.22214/ijraset.2021.39295.

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Abstract: Pregnancy represents a period of fast tissue growth of maternal and foetal tissues that's related to enhanced energy and nutrient needs. Maternal nutrition throughout gestation period, has being essential for best offspring development, reducing long unwellness burden and for general health throughout life. Maternal Folate throughout pregnancy might have numerous roles in offspring health, as well as neurodevelopment and psychological feature performance in childhood. Folate is crucial for C1 metabolism, a network of pathways concerned in many biological processes as well as nucleotide synthesis, deoxyribonucleic acid repair and methylation reactions. The periconceptional use of pteroylglutamic acid (Folic Acid ) containing supplements reduces the primary incidence, as well as recurrence of neural tube defects. Folic Acid (FA) are artificial form of a necessary vitamin generically considered Folates or B9. It is concerned in one-carbon metabolism, and it's been connected to lowering neural tube Defect (NTD). National programs to mandate fortification of food with Folic Acid have reduced the prevalence of NTDs worldwide . The indisputable protecting role of Folic Acid in the hindrance of NTD, in addition to the low compliance of women to Folic Acid recommendations, has aroused the choice of mandatory Folic Acid fortification, a policy currently in place in over eighty countries worldwide. Mandatory food fortification needs food makers to feature Folic Acid to certain foods (e.g. starch or grain products), whereas voluntary fortification permits Folic Acid to be added to foods at the discretion of manufacturers. Food fortification with Folic Acid because the intervention is likely to achieve increasing Folic Acid intake among populations throughout the world. The objective of this article is to discuss the Role of Folic Acid and Folate during pregnancy and to review the role of Folate and Folic Acid , metabolism , absorption and Folic Acid effects on maternal on the basis of recent findings that are important for implementation of fortified food to design future studies. Keywords: Neurodevelopment, Methylation Reactions, Pteroylglutamic Acid, Bioavailability, Monoglutamates.
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Ratajczak, Alicja Ewa, Aleksandra Szymczak-Tomczak, Anna Maria Rychter, Agnieszka Zawada, Agnieszka Dobrowolska und Iwona Krela-Kaźmierczak. „Does Folic Acid Protect Patients with Inflammatory Bowel Disease from Complications?“ Nutrients 13, Nr. 11 (12.11.2021): 4036. http://dx.doi.org/10.3390/nu13114036.

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Folic acid, referred to as vitamin B9, is a water-soluble substance, which participates in the synthesis of nucleic acids, amino acids, and proteins. Similarly to B12 and B6, vitamin B9 is involved in the metabolism of homocysteine, which is associated with the MTHFR gene. The human body is not able to synthesize folic acid; thus, it must be supplemented with diet. The most common consequence of folic acid deficiency is anemia; however, some studies have also demonstrated the correlation between low bone mineral density, hyperhomocysteinemia, and folic acid deficiency. Patients with inflammatory bowel disease (IBD) frequently suffer from malabsorption and avoid certain products, such as fresh fruits and vegetables, which constitute the main sources of vitamin B9. Additionally, the use of sulfasalazine by patients may result in folic acid deficiency. Therefore, IBD patients present a higher risk of folic acid deficiency and require particular supervision with regard to anemia and osteoporosis prevention, which are common consequences of IBD.
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Han, Xuhui, Bingqi Wang, Dongxu Jin, Kuang Liu, Hongjie Wang, Liangbiao Chen und Yao Zu. „Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish“. Biology 11, Nr. 1 (26.12.2021): 28. http://dx.doi.org/10.3390/biology11010028.

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Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. Moreover, we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid and mthfr−/− mutant all gave rise to early pericardial edema and cardiac defect at 3 days post fertilization (dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5 dpf. The expression levels of cardiac marker genes hand2, gata4, and nppa changed in the abnormality of folate metabolism embryos and mthfr−/− mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. Furthermore, our results reveal that folic acid has a dose-dependent effect on early cardiac development. Precise dosage of folic acid supplementation is crucial for the embryonic development of organisms.
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Hagberg, Bengt, und Andreas Killander. „ANTICONVULSIVE DRUGS AND DISTURBED FOLIC ACID METABOLISM“. Developmental Medicine & Child Neurology 9, Nr. 5 (12.11.2008): 647–48. http://dx.doi.org/10.1111/j.1469-8749.1967.tb02342.x.

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9

Williams, J. R. B. „Folic Acid Metabolism of Human Marrow Cells“. Scandinavian Journal of Haematology 2, Nr. 2 (24.04.2009): 155–66. http://dx.doi.org/10.1111/j.1600-0609.1965.tb01291.x.

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10

Price, John. „Folic acid metabolism in health and disease“. Trends in Food Science & Technology 2 (Januar 1991): 260. http://dx.doi.org/10.1016/0924-2244(91)90712-r.

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11

Ledowsky, Carolyn, Abela Mahimbo, Vanessa Scarf und Amie Steel. „Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review“. Nutrients 14, Nr. 13 (29.06.2022): 2715. http://dx.doi.org/10.3390/nu14132715.

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Background: In preconception and pregnancy, women are encouraged to take folic acid-based supplements over and above food intake. The upper tolerable limit of folic acid is 1000 mcg per day; however, this level was determined to avoid masking a vitamin B12 deficiency and not based on folic acid bioavailability and metabolism. This review’s aim is to assess the total all-source intake of folate in women of childbearing age and in pregnancy in high-income countries with folate food fortification programs. Methods: A systematic search was conducted in five databases to find studies published since 1998 that reported folate and folic acid intake in countries with a mandatory fortification policy. Results: Women of childbearing age do not receive sufficient folate intake from food sources alone even when consuming fortified food products; however, almost all women taking a folic acid-based supplement exceed the upper tolerable limit of folic acid intake. Conclusions: Folic acid supplement recommendations and the upper tolerable limit of 1000 mcg set by policy makers warrant careful review in light of potential adverse effects of exceeding the upper tolerable limit on folic acid absorption and metabolism, and subsequent impacts on women’s health during their childbearing years.
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Bjelakovic, Gordana, Dusica Pavlovic, Tatjana Jevtovic, Ivana Stojanovic, Dušan Sokolovic, Goran B. Bjelakovic, Jelenka Nikolic und Jelena Basic. „Vitamin Β12 and Folic Acid Effects on Polyamine Metabolism in Rat Liver“. Pteridines 17, Nr. 3 (August 2006): 90–94. http://dx.doi.org/10.1515/pteridines.2006.17.3.90.

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Abstract Polyamines, spennine, spermidine and putrescinc, small aliphatic nitrous bases, are normal constituents of microbial, plant and animal cells, where they fulfill an array of physiological roles. Metabolism of polyamines is associated with growth and differentiation of mammalian cells, spermine related to RNA and spermidine to DNA metabolism. Methyl-cobalamin, the coenzyme of methionine synthetase, catalyses the recycling of homocysteine to methionine using 5-methyltctrahydrofolate. By acceleration of methionine biosynthesis these vitamins may influence spermidine and spermine synthesis.Liver tissue is rich in polyamines and it is the place of vitamin B12 and folic acid deposition. Polyamine oxidase (PAO, EC 1.5.3) and diamino oxidase (DAO, EC 1.4.3.6) participate in the process of degradation and interconversion of spermine, spermidine and putrescinc. The idea of our work was to examine the effccts of cobalamin and folic acid on the polyamine metabolism. We have examined the amount of spermine, spermidine and putrescine in liver tissue. At the same time we have examined the activities of PAO and DAO, the catabolic enzymes of polyamine metabolism. Our result suggest that the supplementation of experimental animals with vitamin B12 alone or together with folic acid augmentais spermidine and spermine levels in rat liver, at the same time the amount of putrescine does not change. The application of vitamin cobalamin to experimental animals alone increases PAO; the supplementation of experimental animals with vitamin Β12 together with folic acid causes opposite effect - the decrease of PAO activity. DAO activity significantly decreases under the influence of cobalamin and also with cobalamin and folic acid in combination. Our experimental results indicate the importance of cobalamin and folic acid in polyamine metabolism.
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Capelli, Irene, Giuseppe Cianciolo, Lorenzo Gasperoni, Fulvia Zappulo, Francesco Tondolo, Maria Cappuccilli und Gaetano La Manna. „Folic Acid and Vitamin B12 Administration in CKD, Why Not?“ Nutrients 11, Nr. 2 (13.02.2019): 383. http://dx.doi.org/10.3390/nu11020383.

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Patients affected by chronic kidney disease (CKD) or end-stage renal disease (ESRD) experience a huge cardiovascular risk and cardiovascular events represent the leading causes of death. Since traditional risk factors cannot fully explain such increased cardiovascular risk, interest in non-traditional risk factors, such as hyperhomocysteinemia and folic acid and vitamin B12 metabolism impairment, is growing. Although elevated homocysteine blood levels are often seen in patients with CKD and ESRD, whether hyperhomocysteinemia represents a reliable cardiovascular and mortality risk marker or a therapeutic target in this population is still unclear. In addition, folic acid and vitamin B12 could not only be mere cofactors in the homocysteine metabolism; they may have a direct action in determining tissue damage and cardiovascular risk. The purpose of this review was to highlight homocysteine, folic acid and vitamin B12 metabolism impairment in CKD and ESRD and to summarize available evidences on hyperhomocysteinemia, folic acid and vitamin B12 as cardiovascular risk markers, therapeutic target and risk factors for CKD progression.
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14

James A. Greenberg, Stacey J. Bell, Yong Guan und Yan-Hong Yu. „Folic acid supplementation and pregnancy: more than just neural tube defect prevention“. REPRODUCTIVE ENDOCRINOLOGY, Nr. 34 (30.04.2017): 57–63. http://dx.doi.org/10.18370/2309-4117.2017.34.57-63.

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Folate (vitamin B9) 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.The term folate is typically used as a generic name for the group of chemically related compounds based on the folic acid structure. Folate, or vitamin B9, is thought of as one of the 13 essential vitamins. It cannot be synthesized de novo by the body, and must be obtained either from diet or supplementation. Folic acid is a synthetic dietary supplement that is present in artificially enriched foods and pharmaceutical vitamins. Neither folate nor folic acid is metabolically active. Both must be reduced to participate in cellular metabolism. L-5-Methyltetrahydrofolate (L-methylfolate) is the predominant micronutrient form of folate that circulates in plasma and that is involved in biologic processes.Periconceptional folic acid supplementation protects against fetal structural anomalies, including neural tube and congenital heart defects. Recent data suggest that it may also protect against preterm birth. Although additional studies are needed to better define the precise timing, dosing, and formulation, existing data suggest that dietary folic acid supplementation is a good idea for all reproductive-aged women.
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STAM, Frank, Yvo M. SMULDERS, Coen van GULDENER, Cornelis JAKOBS, Coen D. A. STEHOUWER und Kees de MEER. „Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects“. Clinical Science 108, Nr. 5 (22.04.2005): 449–56. http://dx.doi.org/10.1042/cs20040295.

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Folic acid treatment decreases plasma total homocysteine concentrations in healthy subjects, but the effects on homocysteine metabolism are unknown. In the present study, we investigated the effect of 3 weeks of oral treatment with 5 mg of folic acid on one-carbon flux rates in 12 healthy subjects, using in vivo stable isotope methods. In addition, we determined the effect of folic acid on blood concentrations of amino acids which may have regulatory roles in homocysteine metabolism, i.e. homocysteine, AdoMet (S-adenosylmethionine), AdoHcy (S-adenosylhomocysteine), serine and glycine. Primed, continuous infusions with [2H3-methyl-1-13C]methionine were used to determine flux rates of methionine transmethylation, homocysteine remethylation and homocysteine trans-sulphuration. Metabolic homocysteine clearance was defined as the ratio of trans-sulphuration and plasma homocysteine level. Folic acid treatment increased the homocysteine remethylation rate by 59% [95% CI (confidence interval), 13–97%; P=0.02] and methionine transmethylation rate by 20% (95% CI, 3–41%; P=0.03). Plasma total homocysteine concentration (−18%; 95% CI, −28 to −9%; P<0.01) and the serine/glycine ratio (−20%; 95% CI, −63 to −6%; P<0.01) decreased significantly, and the AdoMet/AdoHcy ratio (11%; 95% CI, 1–20%; P=0.02) increased significantly. Changes in one-carbon flux rates did not correlate significantly with changes in plasma concentration of these amino acids. In conclusion, folic acid treatment lowered plasma homocysteine concentration and increased whole-body remethylation and transmethylation flux in healthy subjects.
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Sid, Victoria, Nan Wu, Lindsei K. Sarna, Yaw L. Siow, James D. House und Karmin O. „Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism“. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, Nr. 10 (15.11.2015): R1215—R1225. http://dx.doi.org/10.1152/ajpregu.00260.2015.

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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.
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Kumar, Archana, NirmalyaRoy Moulik und Suraksha Agrawal. „Folic acid, one-carbon metabolism & childhood cancer“. Indian Journal of Medical Research 146, Nr. 2 (2017): 163. http://dx.doi.org/10.4103/ijmr.ijmr_275_15.

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18

Nielsen, Karen Brøndum, Niels Tommerup, Brigitte Fariis und Erik Hippe. „Folic acid metabolism in patient with fragile X“. Clinical Genetics 24, Nr. 3 (28.06.2008): 153–55. http://dx.doi.org/10.1111/j.1399-0004.1983.tb02231.x.

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19

Paul, Raymond T. P., Anne P. McDonnell und Christopher B. Kelly. „Folic acid: neurochemistry, metabolism and relationship to depression“. Human Psychopharmacology: Clinical and Experimental 19, Nr. 7 (27.09.2004): 477–88. http://dx.doi.org/10.1002/hup.614.

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20

Castellanos-Sinco, H. B., C. O. Ramos-Peñafiel, A. Santoyo-Sánchez, J. Collazo-Jaloma, C. Martínez-Murillo, E. Montaño-Figueroa und A. Sinco-Ángeles. „Megaloblastic anaemia: Folic acid and vitamin B12 metabolism“. Revista Médica Del Hospital General De México 78, Nr. 3 (Juli 2015): 135–43. http://dx.doi.org/10.1016/j.hgmx.2015.07.001.

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21

Köse, Süleyman, Saniye Sözlü, Hatice Bölükbaşi, Nüket Ünsal und Makbule Gezmen-Karadağ. „Obesity is associated with folate metabolism“. International Journal for Vitamin and Nutrition Research 90, Nr. 3-4 (Juni 2020): 353–64. http://dx.doi.org/10.1024/0300-9831/a000602.

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Abstract. Objective: The aim of the present study is to perform a systemic review of the previous studies executed on the association between obesity and folate. Method: In the present research, the selected keywords were scanned on the PubMed, Web of Science, Cochrane and Lilac databases between May and June, 2017 through Gazi University’s network. In total, 4236 clinical, randomized controlled, cross-sectional and prospective studies were determined and 17 of these that specifically fit the aims of the present research were reviewed. This study involved an electronic literature search of databases on folic acid and obesity published in the English language between 2000 and 2016. Results: Of the 17 studies, 5 were based on folic acid supplementation and 12 were related with participants’ folate status. As a general consequence of both intake and serum/status measurements of folic acid supplementation: It was found that obesity-associated metabolic changes might affect individual folate use and obese individuals had lower serum folate levels, although there was no change in folate intake. Conclusion: Overweight and obese individuals have lower serum folate concentrations when compared with individuals with normal weight. It is explained by increased use of folic acid, urinary excretion, dilution of blood volume, different levels in different tissues and changes in the endocrine functions of folate. Individuals with higher Body Mass Indexes have less supplement use, unhealthier diets and donot consume sufficient vegetables and fruits, all of which can affect decrease in folate levels. Furthermore, adiposity may affect folate absorption by intestinal epithelium.
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Liang, Shuang, Yuanpeng Zhou, Huijun Wang, Yanyan Qian, Duan Ma, Weidong Tian, Vishwani Persaud-Sharma et al. „The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism“. BioMed Research International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/560183.

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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.
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Lewis, Dale P., Don C. Van Dyke, Laurie A. Willhite, Phyllis J. Stumbo und Mary J. Berg. „Phenytoin-Folic Acid Interaction“. Annals of Pharmacotherapy 29, Nr. 7-8 (Juli 1995): 726–35. http://dx.doi.org/10.1177/106002809502907-816.

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Objective: To review information regarding the dual and interdependent drug-nutrient interaction between phenytoin and folic acid and other literature involving phenytoin and folic acid. Data Sources: Information was retrieved from a MEDLINE search of English-language literature conducted from 1983 (time of the last review) to March 1995. Search terms included folic acid, phenytoin, and folic acid deficiency. Additional references were obtained from Current Contents and from the bibliographies of the retrieved references. Study Selection: All human studies examining the effects of phenytoin on serum folate concentrations and folic acid supplementation on serum phenytoin concentrations were selected. These included studies of patients with epilepsy and healthy volunteers as well as case reports. Case reports were included because of the extensive length of time needed to study this drug interaction. Data Extraction: Data extracted included gender, dosing, serum folate concentrations if available, pharmacokinetics, and adverse events. Data Synthesis: Serum folate decreases when phenytoin therapy is initiated alone with no folate supplementation. Folic acid supplementation in folate-deficient patients with epilepsy changes the pharmacokinetics of phenytoin, usually leading to lower serum phenytoin concentrations and possible seizure breakthrough. Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the “pseudo-steady-state,” which is a concentration where phenytoin appears to be at steady-state, but in reality, is not. Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner. Conclusions: Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.
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Dugbaza, Jacinta, und Judy Cunningham. „Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread“. Journal of Nutrition and Metabolism 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/492353.

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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.
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Weber, Georg F., und M. G. Nair. „Inhibition of the Neutrophil Nrdph Oxidase by Folic Acid and Antagonists of the Folic Acid Metabolism“. Immunopharmacology and Immunotoxicology 14, Nr. 3 (Januar 1992): 523–38. http://dx.doi.org/10.3109/08923979209005409.

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Cao, Rui, Jun Xie und Li Zhang. „Abnormal methylation caused by folic acid deficiency in neural tube defects“. Open Life Sciences 17, Nr. 1 (01.01.2022): 1679–88. http://dx.doi.org/10.1515/biol-2022-0504.

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Abstract Neural tube closure disorders, including anencephaly, spina bifida, and encephalocele, cause neural tube defects (NTDs). This congenital disability remained not only a major contributor to the prevalence of stillbirths and neonatal deaths but also a significant cause of lifelong physical disability in surviving infants. NTDs are complex diseases caused by multiple etiologies, levels, and mechanisms. Currently, the pathogenesis of NTDs is considered to be associated with both genetic and environmental factors. Here, we aimed to review the research progress on the etiology and mechanism of NTDs induced by methylation modification caused by folic acid deficiency. Folic acid supplementation in the diet is reported to be beneficial in preventing NTDs. Methylation modification is one of the most important epigenetic modifications crucial for brain neurodevelopment. Disturbances in folic acid metabolism and decreased S-adenosylmethionine levels lead to reduced methyl donors and methylation modification disorders. In this review, we summarized the relationship between NTDs, folic acid metabolism, and related methylation of DNA, imprinted genes, cytoskeletal protein, histone, RNA, and non-coding RNA, so as to clarify the role of folic acid and methylation in NTDs and to better understand the various pathogenesis mechanisms of NTDs and the effective prevention.
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Brattström, Lars E., Björn L. Hultberg und Jan Erik Hardebo. „Folic acid responsive postmenopausal homocysteinemia“. Metabolism 34, Nr. 11 (November 1985): 1073–77. http://dx.doi.org/10.1016/0026-0495(85)90082-4.

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Devarshi, Prasad, Ryan Grant, Meredith Wilcox, Moneka Ali, Lisa Sanders, Kevin Maki und Susan Hazels Mitmesser. „Absorption of Folic Acid from Different Delivery Forms: A Randomized, Crossover Study“. Current Developments in Nutrition 4, Supplement_2 (29.05.2020): 970. http://dx.doi.org/10.1093/cdn/nzaa054_042.

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Abstract Objectives Folate, or folic acid, is a water-soluble B vitamin that plays a role in single carbon transfer reactions, which are involved in the synthesis and metabolism of nucleotides and amino acids. It has been established that adequate folic acid intake helps decrease the prevalence of neural tube defects during conception and early pregnancy. The objective of this study was to assess the bioavailability of folic acid from Prenatal Multi Gummies and Folic Acid tablets in women of childbearing age. Methods Eleven healthy, adult, premenopausal women of childbearing age (18–44 years) were recruited for a single-blind, randomized, crossover study. Each participant was randomly assigned to receive a single dose (2 gummies or 2 tablets) of Prenatal Multi Gummies or Folic Acid tablets (containing ∼800 µg folic acid) and then crossed over to receive the other study product after a wash-out period of ∼7 days. The study product was consumed along with a low folic acid breakfast meal. Blood samples were collected for the analysis of serum folate at t = −0.5, 1, 2, 4, 6 and 8 hours where t = 0 is the time of study product consumption. Results The mean serum folate total area under the curve (AUC0–8 hours) was 239.67 ± 24.50 h × ng/mL for the Prenatal Multi Gummies and 255.23 ± 30.17 h × ng/mL for the Folic Acid tablets. For both study products, the dose-adjusted net incremental AUC was significantly greater than 0 h × ng/mL (P ≤ 0.001). The maximum serum folate concentration (Cmax) was 47.69 ± 5.65 ng/mL for the Prenatal Multi Gummies and 52.45 ± 5.86 ng/mL for the Folic Acid tablets, and the median time to maximum serum concentration (Tmax) was 1.00 h for each product (interquartile limits for both included 1.00 to 1.08 hours). Conclusions In conclusion, folic acid contained in the Prenatal Multi Gummies and Folic Acid tablets was absorbed from both the Prenatal Multi Gummies and the Folic Acid tablets. Funding Sources This study was funded by Pharmavite LLC.
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Li, Shizhao, Lihui Zhi, Yanli Liu, Jing Shen, Lei Liu, Junhu Yao und Xiaojun Yang. „Effect of in ovo feeding of folic acid on the folate metabolism, immune function and epigenetic modification of immune effector molecules of broiler“. British Journal of Nutrition 115, Nr. 3 (20.11.2015): 411–21. http://dx.doi.org/10.1017/s0007114515004511.

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AbstractThis 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.
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Swart, Karin M. A., Natasja M. van Schoor und Paul Lips. „Vitamin B12, Folic Acid, and Bone“. Current Osteoporosis Reports 11, Nr. 3 (20.07.2013): 213–18. http://dx.doi.org/10.1007/s11914-013-0155-2.

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Cui, Shanshan, Wen Li, Xin Lv, Pengyan Wang, Guowei Huang und Yuxia Gao. „Folic acid attenuates homocysteine and enhances antioxidative capacity in atherosclerotic rats“. Applied Physiology, Nutrition, and Metabolism 42, Nr. 10 (Oktober 2017): 1015–22. http://dx.doi.org/10.1139/apnm-2017-0158.

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Atherosclerosis is a chronic disease that can seriously endanger human life. Folic acid supplementation modulates several disorders, including atherosclerosis, via its antiapoptotic and antioxidative properties. This study investigated whether folic acid alleviates atherogenesis by restoring homocysteine levels and antioxidative capacity in atherosclerosis Wistar rats. To this end, 28 Wistar rats were randomly divided into 4 groups (7 rats/group) as follows: (i) wild-type group, fed only the AIN-93 semi-purified rodent diet (folic acid: 2.1 mg/kg); (ii) high-fat + folic acid-deficient group (HF+DEF) (folic acid: 0.2 mg/kg); (iii) high-fat + normal folic acid group (folic acid: 2.1 mg/kg); and (iv) high-fat + folic acid-supplemented group (folic acid: 4.2 mg/kg). After 12 weeks, histopathological changes in the atherosclerotic lesions of the aortic arch were determined. In addition, serum folate levels, plasma homocysteine levels, plasma S-adenosyl-homocysteine levels, antioxidant status, oxidant status, and lipid profiles were evaluated. The results show aggravated atherosclerotic lesions in the HF+DEF group. Folic acid supplementation increased concentrations of serum folate. Further, folic acid supplementation increased high-density lipoprotein-cholesterol, decreased plasma homocysteine levels, and improved antioxidant capacity in atherogenic rats. These findings are consistent with the hypothesis that folic acid alleviates atherogenesis by reducing plasma homocysteine levels and improving antioxidant capacity in rats fed a high-fat diet.
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Boushey, Carol J., Julianne W. Edmonds und Kathleen J. Welshimer. „Estimates of the effects of folic-acid fortification and folic-acid bioavailability for women“. Nutrition 17, Nr. 10 (Oktober 2001): 873–79. http://dx.doi.org/10.1016/s0899-9007(01)00645-1.

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Villa, Paola, Concetta Perri, Rosanna Suriano, Francesco Cucinelli, Simona Panunzi, Micaela Ranieri, Cristina Mele und Antonio Lanzone. „l-Folic Acid Supplementation in Healthy Postmenopausal Women: Effect on Homocysteine and Glycolipid Metabolism“. Journal of Clinical Endocrinology & Metabolism 90, Nr. 8 (01.08.2005): 4622–29. http://dx.doi.org/10.1210/jc.2004-1954.

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Context: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. Objective: The aim of this study was to examine the effect of l-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. Design: This study was a randomized placebo, not double-blind, trial. Setting: The study was performed in an academic research center. Patients or Other Participants: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. Intervention(s): Patients underwent two hospitalizations before and after 8 wk of l-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. Main Outcome Measure(s): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. Results: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P &lt; 0.01) in l-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P &lt; 0.02). Furthermore, l-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P &lt; 0.05) and peripheral insulin sensitivity (P &lt; 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P &lt; 0.03). Conclusions: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.
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Attias, Z., H. Werner und N. Vaisman. „Folic acid and its metabolites modulate IGF-I receptor gene expression in colon cancer cells in a p53-dependent manner“. Endocrine-Related Cancer 13, Nr. 2 (Juni 2006): 571–81. http://dx.doi.org/10.1677/erc.1.01156.

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The insulin-like growth factor-I receptor (IGF-IR) has an important role in colorectal cancer development and progression. IGF-IR displays a potent anti-apoptotic activity and is overexpressed in primary tumors and colon cancer-derived cell lines. Folic acid, a member of the vitamin B family, is a chemopreventive agent whose deficiency has been linked to an enhanced colon cancer risk. The present study was aimed at testing the hypothesis that part of the modulatory effect of folic acid on malignant transformation may be attributed to its ability to regulate IGF-IR gene expression. Regulation of IGF-IR gene expression by folic acid was assessed using western blots, RT-PCR, transient transfections and chromatin immunoprecipitation assays. Activation of the IGF-IR signaling pathway was evaluated by measuring phosphorylation of ERK, and apoptosis was assayed using poly (ADP-ribose) polymerase cleavage and annexin V-FITC staining. Results obtained showed that folic acid induced a dose-dependent decrease in IGF-IR protein and mRNA levels in the HCT116 +/+ colon cancer cell line. This effect was associated with a significant reduction in IGF-IR promoter activity. Similar effects were elicited by the folic acid metabolites dihydrofolic acid and tetrahydrofolic acid. In addition, folic acid abrogated the IGF-I-stimulated phosphorylation of the downstream signaling molecule ERK1/2 and exhibited a pro-apoptotic activity. Moreover, folic acid induced a significant decrease in Sp1 binding to the IGF-IR promoter region. Finally, folic acid had no effect in wild-type p53-depleted HCT116 −/− and Caco-2 cells. In conclusion, the mechanism of action of folic acid involves regulation of IGF-IR gene expression. The ability of folic acid to downregulate the IGF-I signal transduction pathway may allow the micronutrient to function as a chemopreventive agent. Folic acid deficiency, on the other hand, may lead to increased IGF-IR gene expression, with ensuing pathological activation by endocrine and/or autocrine/paracrine IGF-I.
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GUO, YANFANG, GRAEME N. SMITH, SHI WU WEN und MARK C. WALKER. „FOLATE METABOLISM AND PREECLAMPSIA“. Fetal and Maternal Medicine Review 23, Nr. 2 (Mai 2012): 131–55. http://dx.doi.org/10.1017/s096553951200006x.

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Preeclampsia (PE) is a multisystem disorder of human pregnancy, affecting about 6% of all pregnancies worldwide, and is one of the leading causes of maternal and infant morbidity and mortality. Despite decades of research into the pathogenesis of this complex disease, the underlying mechanisms remain unclear. As a result, the options for prevention and management of PE are limited. In recent years, there has been a growing body of evidence suggesting that folate deficiency is associated with PE, and folic acid supplementation may reduce the risk of developing PE in certain populations. Folate contributes to cell division and growth, and folate metabolism is involved in a large number of physiological and pathophysiological processes in human development. Sufficient supply of folate is therefore particularly important during pregnancy. Nevertheless, the exact mechanisms of folic acid deficiency increasing the risk of developing PE are still unclear. This article reviews what is understood about the aetiology of PE and the relationship between folate metabolism and PE so as to enhance further discussions on the subject.
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R. Prinz-Langenohl, S. Brämswig und O. Tobolski. „A study of plasma folate under the influence of [6S]-5-MTHF in women with 677C→T polymorphism of mthfr with different types of inheritance“. REPRODUCTIVE ENDOCRINOLOGY, Nr. 35 (21.06.2017): 62–66. http://dx.doi.org/10.18370/2309-4117.2017.35.62-66.

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Background and purpose: 5,10-Methylenetetrahydrofolate reductase is responsible for the synthesis of 5-methyltetrahydrofolate (5-MTHF). The 677C→T mutation of 5,10-Methylenetetrahydrofolate reductase reduces the activity of this enzyme. The aim of this study was, first, to compare pharmacokinetic parameters of [6S]-5-MTHF and folic acid in women with the homozygous (TT) and wild-type (CC) 677C→T mutation, and second, to explore genotype differences. The metabolism of [6S]-5-MTHF and folic acid was evaluated by measuring plasma folate derivatives.Experimental approach: Healthy females (TT, n = 16; CC, n = 8) received a single oral dose of folic acid (400 microg) and [6S]-5-MTHF (416 microg) in a randomized crossover design.Plasma folate was measured up to 8 h after supplementation. Concentration-time-profile (area under the curve of the plasma folate concentration vs. time), maximum concentration (Cmax) and time-to-reach-maximum (tmax) were calculated.Key results: Area under the curve of the plasma folate concentration vs. time and Cmax were significantly higher, and tmax significantly shorter for [6S]-5-MTHF compared with folic acid in both genotypes. A significant difference between the genotypes was observed for tmax after folic acid only (p < 0.05). Plasma folate consisted essentially of 5-MTHF irrespective of the folate form given. Unmetabolized folic acid in plasma occurs regularly following folic acid supplementation, but rarely with [6S]-5-MTHF.Conclusions and implications: These data suggest that [6S]-5-MTHF increases plasma folate more effectively than folic acid irrespective of the 677C→T mutation of the 5,10-Methylenetetrahydrofolate reductase. This natural form of folate could be an alternative to folic acid supplementation or fortification.
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McNeil, Christopher J., Susan M. Hay, Garry J. Rucklidge, Martin Reid, Gary Duncan, Christopher A. Maloney und William D. Rees. „Disruption of lipid metabolism in the liver of the pregnant rat fed folate-deficient and methyl donor-deficient diets“. British Journal of Nutrition 99, Nr. 2 (Februar 2008): 262–71. http://dx.doi.org/10.1017/s0007114507798999.

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The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.
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Romero, Steven A., Daniel Gagnon, Amy N. Adams, Gilbert Moralez, Ken Kouda, Manall F. Jaffery, Matthew N. Cramer und Craig G. Crandall. „Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans“. American Journal of Physiology-Heart and Circulatory Physiology 313, Nr. 3 (01.09.2017): H658—H666. http://dx.doi.org/10.1152/ajpheart.00234.2017.

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Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion exercise via increased vascular conductance. Nine healthy, aged adults (two men and seven women; age: 68 ± 5 yr) performed graded handgrip and plantar flexion exercise before (control), 2 h after (acute, 5 mg), and after 6 wk (chronic, 5 mg/day) folic acid ingestion. Forearm (brachial artery) and leg (superficial femoral artery) blood velocity and diameter were measured via Duplex ultrasonography and used to calculate blood flow. Acute and chronic folic acid ingestion increased serum folate (both P < 0.05 vs. control). During handgrip exercise, acute and chronic folic acid ingestion increased forearm blood flow (both conditions P < 0.05 vs. control) and vascular conductance (both P < 0.05 vs. control). During plantar flexion exercise, acute and chronic folic acid ingestion increased leg blood flow (both P < 0.05 vs. control), but only acute folic acid ingestion increased vascular conductance ( P < 0.05 vs. control). Taken together, folic acid ingestion increases blood flow to active skeletal muscle primarily via improved local vasodilation in aged adults. NEW & NOTEWORTHY Our findings demonstrate that folic acid ingestion improves blood flow via enhanced vascular conductance in the exercising skeletal muscle of aged humans. These findings provide evidence for the therapeutic use of folic acid to improve skeletal muscle blood flow, and perhaps exercise and functional capacity, in human primary aging. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/folic-acid-and-exercise-hyperemia-in-aging/ .
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Huot, Pedro S. P., Anna Ly, Ignatius M. Y. Szeto, Sandra A. Reza-López, Daniel Cho, Young-In Kim und G. Harvey Anderson. „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“. Applied Physiology, Nutrition, and Metabolism 41, Nr. 4 (April 2016): 411–20. http://dx.doi.org/10.1139/apnm-2015-0503.

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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.
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Bjelakovic, Gordana, Ivana Stojanovic, Tatjana Jevtovic Stoimenov, Dusica Pavlovic, Gordana Kocic, Goran B. Bjelakovic, Dusan Sokolovic und Jelena Basic. „Polyamines, folic acid supplementation and cancerogenesis“. Pteridines 28, Nr. 3-4 (20.12.2017): 115–31. http://dx.doi.org/10.1515/pterid-2017-0012.

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AbstractClinical practice and experimental studies have shown the necessity of sufficient quantities of folic acid intake for normal embryogenesis and fetal development in the prevention of neural tube defects (NTDs) and neurological malformations. So, women of childbearing age must be sure to have an adequate folate intake periconceptionally, prior to and during pregnancy. Folic acid fortification of all enriched cereal grain product flour has been implemented in many countries. Thus, hundreds of thousands of people have been exposed to an increased intake of folic acid. Folate plays an essential role in the biosynthesis of methionine. Methionine is the principal aminopropyl donor required for polyamine biosynthesis, which is up-regulated in actively growing cells, including cancer cells. Folates are important in RNA and DNA synthesis, DNA stability and integrity. Clinical and epidemiological evidence links folate deficiency to DNA damage and cancer. On the other hand, long-term folate oversupplementation leads to adverse toxic effects, resulting in the appearance of malignancy. Considering the relationship of polyamines and rapidly proliferating tissues (especially cancers), there is a need for better investigation of the relationship between the ingestion of high amounts of folic acid in food supplementation and polyamine metabolism, related to malignant processes in the human body.
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Ragaller, Veronika, Liane Hüther und Peter Lebzien. „Folic acid in ruminant nutrition: a review“. British Journal of Nutrition 101, Nr. 2 (08.09.2008): 153–64. http://dx.doi.org/10.1017/s0007114508051556.

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Folic acid plays an essential role in DNA and methionine metabolism. Micro-organisms in the rumen can synthesise folates, but it has not been verified that these amounts are sufficient to achieve the best efficiency of dairy cows. However, the amount of folates synthesised in the rumen could possibly, to some extent, be affected by the forage:concentrate ratio. Degradation of orally supplemented folic acid in the rumen seems to be very high (about 97 %), as supplementation of folic acid hardly increases folate concentrations in the digesta at the duodenum. However, it must be considered that dietary supplements of folic acid higher than 0·5 mg/kg body weight increased serum folate concentrations in all available studies and milk folate concentrations in most studies. Additionally, milk production tended to be increased in some studies. Therefore, degradation of folic acid in the rumen may be overestimated as folates can be absorbed at the proximal duodenum. For future research it is necessary to consider the whole flow and the metabolic pathways of folates from the rumen to duodenum, blood, tissue, milk and transfer to calf to declare requirement values for cows. Consequently, the present review discusses current knowledge and emphasises areas for future research.
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Donnellan, Leigh, Bradley S. Simpson, Varinderpal S. Dhillon, Maurizio Costabile, Michael Fenech und Permal Deo. „Folic acid deficiency increases sensitivity to DNA damage by glucose and methylglyoxal“. Mutagenesis 37, Nr. 1 (01.01.2022): 24–33. http://dx.doi.org/10.1093/mutage/geac003.

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Abstract Type 2 diabetes (T2D) is associated with elevated frequencies of micronuclei (MNi) and other DNA damage biomarkers. Interestingly, individuals with T2D are more likely to be deficient in micronutrients (folic acid, pyridoxal-phosphate, cobalamin) that play key roles in one-carbon metabolism and maintaining genomic integrity. Furthermore, it has recently been shown that deficiencies in these nutrients, in particular folic acid leaves cells susceptible to glucose-induced DNA damage. Therefore, we sought to investigate if the B lymphoblastoid WIL2-NS cell line cultured under folic acid-deficient conditions was more sensitive to DNA damage induced by glucose, or the reactive glycolytic byproduct methylglyoxal (MGO) and subsequent advanced glycation endproduct formation. Here, we show that only WIL2-NS cultured under folic acid-deficient conditions (23 nmol/l) experience an increase in MNi frequency when exposed to high concentrations of glucose (45 mmol/l) or MGO (100 µmol/l). Furthermore, we showed aminoguanidine, a well-validated MGO and free radical scavenger was able to prevent further MNi formation in folic acid-deficient cells exposed to high glucose, which may be due to a reduction in MGO-induced oxidative stress. Interestingly, we also observed an increase in MGO and other dicarbonyl stress biomarkers in folic acid-deficient cells, irrespective of glucose concentrations. Overall, our evidence shows that folic acid-deficient WIL2-NS cells are more susceptible to glucose and/or MGO-induced MNi formation. These results suggest that individuals with T2D experiencing hyperglycemia and folic acid deficiency may be at higher risk of chromosomal instability.
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Çoban Ramazan, Dilber, Ülker Anadol, A. Destina Yalçın und A. Süha Yalçın. „Plasma homocysteine and aminothiol levels in idiopathic epilepsy patients receiving antiepileptic drugs“. Turkish Journal of Biochemistry 44, Nr. 5 (25.10.2019): 661–66. http://dx.doi.org/10.1515/tjb-2018-0218.

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Abstract Objective Homocysteine is a sulfur containing amino acid that is formed during methionine metabolism. Patients under long-term antiepileptic drug treatment often have hyperhomocysteinemia. These patients have low levels of serum folate, vitamin B12 and vitamin B6, all of which are associated with homocysteine metabolism. We have investigated the effects of valproic acid and new generation antiepileptic drugs (lamotrigine and levetiracetam) on plasma levels of homocysteine and aminothiols as well as serum vitamin B12 and folic acid. Materials and methods Forty-seven idiopathic epileptic patients on antiepileptic drugs were compared with 38 age-matched healthy controls. Commercial immunoassay methods were used for vitamin B12 and folic acid analyses. Homocysteine, cysteine, cysteinylglycine and glutathione levels were determined by high performance liquid chromatography. Results There was no significant difference in patient and control values in terms of vitamin B12, folic acid and homocysteine. Valproic acid and lamotrigine seemed to effect aminothiol redox status. Glutathione levels of epileptic patients receiving valproic acid and lamotrigine were higher than controls. Conclusion Our results suggest that redox homeostasis may be impaired and glutathione synthesis increased in response to the oxidative stress caused by antiepileptic drug use.
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Roth-Maier und Böhmer. „Fortification of Eggs with Folic Acid as a Possible Contribution to Enhance the Folic Acid Status of Populations“. International Journal for Vitamin and Nutrition Research 77, Nr. 4 (01.07.2007): 297–301. http://dx.doi.org/10.1024/0300-9831.77.4.297.

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The aim of the present study was to evaluate the enrichment of folic acid in eggs by supplementing hens’ diet. Seventy-two hens (LSL) were assigned to 5 dietary groups and supplemented with 0, 0.5, 1.0, 2.0, and 4.0 mg folic acid/ kg feed during an 8-week period. Eggs for folic acid analysis were collected in weeks 4 and 8 and analyzed by microbiological method using L. casei. The performance of the hens was not influenced by the supplementation. The content of folic acid in eggs increased significantly from 3.1 μg/g DM to 5.5 μ g/g DM (week 4) and from 2.1 μ g/g DM to 4.2 μ g/g DM (week 8), respectively. One fortified egg can provide up to 76 μ g folic acid. Additionally the intestinal availability of folic acid in eggs was determined in pigs as an animal model for human nutrition. Six pigs were fitted with ileorectal-anastomosis and received boiled eggs combined with a supplementary diet according to nutrient requirement. The metabolic trial ran for 12 days with a pre-period of 7 days and a collection period of 5 days. Feed and chyme were analyzed for folic acid as mentioned above. The availability of folate in eggs was determined as 68%, which means that one fortified egg provides up to 52 μ g folate equivalent to 13% of the recommended daily intake.
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Topless, R., R. Green, S. Morgan, P. Robinson, T. Merriman und A. Gaffo. „POS1222 FOLIC ACID AND METHOTREXATE USE AND THEIR ASSOCIATION WITH COVID-19 DIAGNOSIS AND MORTALITY: AN ANALYSIS FROM THE UK BIOBANK“. Annals of the Rheumatic Diseases 81, Suppl 1 (23.05.2022): 942.1–942. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1890.

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BackgroundFolate metabolism is implicated in SARS-CoV-2 infectivity (Ref).ObjectivesTo determine if methotrexate (an antifolate) or folic acid prescription were associated with a lowered and increased risk, respectively, for COVID-19 diagnosis or mortality in a large population-based cohort (UK Biobank).MethodsData from 380,380 UK Biobank participants with general practice prescription data were used. Criteria for COVID-19 diagnosis were 1) a positive SARS-CoV-2 test and / or 2) ICD-10 code for confirmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records, or death records. This definition identified 26,003 individuals diagnosed with COVID-19 of whom 820 were known to have died from COVID-19. Logistic regression statistical models were adjusted for age group (4 categories), sex, ethnicity, Townsend deprivation index, BMI, smoking status, presence of rheumatoid arthritis, sickle cell disease, use of anticonvulsants, statins and iron supplements.ResultsCompared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had increased risk of diagnosis of COVID-19 (OR 1.51 [1.42; 1.61]). The prescription of methotrexate with or without folic acid was not associated with COVID-19 diagnosis (P≥0.18). Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had an increased risk of death after a diagnosis of COVID-19 (OR 2.64 [2.15; 3.24]) in a fully adjusted model. The prescription of methotrexate in combination with folic acid was not associated with an increased risk for death after a diagnosis of COVID-19 (1.07 [0.57; 1.98]). (Table 1)Table 1.COVID-19 diagnosis and associated death in people prescribed methotrexate and / or folic acid in the UKBB, compared to people not prescribed methotrexate or folic acid. Model 1 adjusted for age group, sex, ethnicity, Townsend deprivation index, BMI, smoking status Model 2 is model 1 plus adjustment by the presence of rheumatoid arthritis, sickle cell disease, use of statins, anticonvulsants and iron supplementation.UnadjustedModel 1Model 2OR[95% CI]POR[95% CI]POR[95% CI]PNeither Folic acid nor Methotrexate1.0-1.0-1.0-COVID-19 diagnosisFolic acid only1.58[1.49; 1.68]<0.0011.60[1.50; 1.70]<0.0011.51[1.42; 1.61]<0.001Methotrexate and Folic acid1.09[0.96; 1.23]0.181.15[1.02; 1.30]0.0211.09[0.96; 1.23]0.18COVID-19 associated deathFolic acid only5.14 [4.23; 6.24]<0.0012.91 [2.38; 3.55]<0.0012.64[2.15; 3.24]<0.001Methotrexate and folic acid1.47 [0.81; 2.67]0.211.26 [0.70; 2.30]0.441.07 [0.57; 1.98]0.84ConclusionWe report increased risk for COVID-19 diagnosis and COVID-19-related death for people prescribed folic acid supplementation. The prescription and use of supplemental folic acid may confer risk of infection with the SARS-CoV-2 virus as well as the risk of death resulting from COVID-19. Our results also suggest that methotrexate might attenuate an increased risk for COVID-19 diagnosis and death conferred by folic acid.References[1]Zhang Y, Guo R, Kim SH, et al. SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. Nature Communications 2021;12(1):1676. doi: 10.1038/s41467-021-21903-zDisclosure of InterestsRuth Topless: None declared, Ralph Green: None declared, Sarah Morgan: None declared, Philip Robinson Consultant of: Abbvie, Atom Biosciences, Eli Lilly, Gilead, Janssen, Novartis, UCB, Roche, Pfizer, Grant/research support from: Janssen, Novartis, Pfizer and UCB Pharma, Tony Merriman: None declared, Angelo Gaffo Consultant of: SOBI, Selecta
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Mikhelson, Ar A., E. Yu Lebedenko, O. V. Gayda, Al A. Mikhelson, T. E. Feoktistova und A. M. Mikhelson. „Iron deficiencies in obstetric-gynecologic practice“. Russian Journal of Woman and Child Health 5, Nr. 2 (2022): 129–37. http://dx.doi.org/10.32364/2618-8430-2022-5-2-129-137.

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Deficiency or excess of microelements and vitamins significantly affects the vital activity at each step of human life. This is particularly significant during pregnancy because of immediate and long-term effects on the fetus and newborn. Iron is one of the essential microelements and plays an important role in the mechanisms of biological oxidation. Iron metabolism in the human body is quite complex and impossible without synergy with other metals and vitamins. Iron is most closely related to folic acid and is critical for many vital processes, including embryogenesis. Considering that iron and folic acid deficiencies (leading to anemias in extreme cases) negatively affect pregnancy course, its favorable outcome, and prognosis for a newborn, these conditions are to be addressed. Medications are diverse, they should be selected based on the specificity of iron and folic acid metabolism. Among preparations currently available in Russia, combined ones best meet the requirements (iron valence, iron compounds, association with synergid components, dosage form). KEYWORDS: iron, folic acid, iron-deficiency anemia, folate-deficiency anemia, therapy, combined preparations. FOR CITATION: Mikhelson Ar.A., Lebedenko E.Yu., Gayda O.V. et al. Iron deficiencies in obstetric-gynecologic practice. Russian Journal of Woman and Child Health. 2022;5(2):129–137 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-129-137.
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Sijko, Monika, und Lucyna Kozłowska. „Influence of Dietary Compounds on Arsenic Metabolism and Toxicity. Part I—Animal Model Studies“. Toxics 9, Nr. 10 (11.10.2021): 258. http://dx.doi.org/10.3390/toxics9100258.

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Population and laboratory studies indicate that exposure to various forms of arsenic (As) is associated with many adverse health effects; therefore, methods are being sought out to reduce them. Numerous studies focus on the effects of nutrients on inorganic As (iAs) metabolism and toxicity, mainly in animal models. Therefore, the aim of this review was to analyze the influence of methionine, betaine, choline, folic acid, vitamin B2, B6, B12 and zinc on the efficiency of iAs metabolism and the reduction of the severity of the whole spectrum of disorders related to iAs exposure. In this review, which includes 58 (in vivo and in vitro studies) original papers, we present the current knowledge in the area. In vitro and in vivo animal studies showed that methionine, choline, folic acid, vitamin B2, B12 and zinc reduced the adverse effects of exposure to iAs in the gastrointestinal, urinary, lymphatic, circulatory, nervous, and reproductive systems. On the other hand, it was observed that these compounds (methionine, choline, folic acid, vitamin B2, B12 and zinc) may increase iAs metabolism and reduce toxicity, whereas their deficiency or excess may impair iAs metabolism and increase iAs toxicity. Promising results of in vivo and in vitro on animal model studies show the possibility of using these nutrients in populations particularly exposed to As.
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Darma Putra, I. Gusti Ngurah Agung, Al Munawir und Sugiyanta Sugiyanta. „The Effect Of Folic On Different Dosage Level Against Retina Destruction Level Of Mice With Peroral Methanol 50%“. Journal of Agromedicine and Medical Sciences 3, Nr. 2 (20.07.2017): 23. http://dx.doi.org/10.19184/ams.v3i2.5066.

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In recent years, there are many methanol poisoned cases. Methanol poisoned cause of blindness, CNS problem, and metabolic acidosis. Folic acid is the one of many medicinal treatment for methanol poisoned. Folic acid has important role on methanol metabolism in our body. The aim of the study was to known the effect of addition folic acid on retina damage level of methanol poisoned. The method is experimental laboratories (true experiment design) with post test only control group design. The study included 5 separate test. The subject were mice which in 2 - 3 months age and had weight about 25 - 35 gr. There were 5 groups subject in the study. There were control group which given usual meals for mice and aquadest, negative control group which given methanol 7gr/ kgBW, treatment group 1,2, and 3 were given methanol 7gr/kgBW and folic acid 1 mg/kg BW, 3mg/kgBW, and 5 mg/kgBW. The treatment was given about 24 hours, then the eyes of the mice were taken to made blood smear. Damage of eyes were evaluated based score determined before. It can be concluded that addition folic acid can reduce retina damage level of metanol poisoned.
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Meher, Akshaya P., Asmita A. Joshi und Sadhana R. Joshi. „Maternal micronutrients, omega-3 fatty acids, and placental PPARγ expression“. Applied Physiology, Nutrition, and Metabolism 39, Nr. 7 (Juli 2014): 793–800. http://dx.doi.org/10.1139/apnm-2013-0518.

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An altered one-carbon cycle is known to influence placental and fetal development. We hypothesize that deficiency of maternal micronutrients such as folic acid and vitamin B12 will lead to increased oxidative stress, reduced long-chain polyunsaturated fatty acids, and altered expression of peroxisome proliferator activated receptor (PPARγ) in the placenta, and omega-3 fatty acid supplementation to these diets will increase the expression of PPARγ. Female rats were divided into 5 groups: control, folic acid deficient, vitamin B12 deficient, folic acid deficient + omega-3 fatty acid supplemented, and vitamin B12 deficient + omega-3 fatty acid supplemented. Dams were dissected on gestational day 20. Maternal micronutrient deficiency leads to lower (p < 0.05) levels of placental docosahexaenoic acid, arachidonic acid, PPARγ expression and higher (p < 0.05) levels of plasma malonidialdehyde, placental IL-6, and TNF-α. Omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalized the expression of PPARγ and lowered the levels of placental TNF-α. In the case of supplementation to a folic acid deficient diet it lowered the levels of malonidialdehyde and placental IL-6 and TNF-α. This study has implications for fetal growth as oxidative stress, inflammation, and PPARγ are known to play a key role in the placental development.
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Olivares, M., E. Hertrampf, S. Llaguno, P. Chadud und A. Stekel. „Folic acid nutrition in marasmic infants“. Nutrition Research 6, Nr. 12 (Dezember 1986): 1365–70. http://dx.doi.org/10.1016/s0271-5317(86)80021-5.

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