scholarly journals Developmental Impairments in a Rat Model of Methyl Donor Deficiency: Effects of a Late Maternal Supplementation with Folic Acid

2019 ◽  
Vol 20 (4) ◽  
pp. 973 ◽  
Author(s):  
Andréa Geoffroy ◽  
Lynda Saber-Cherif ◽  
Grégory Pourié ◽  
Déborah Helle ◽  
Rémy Umoret ◽  
...  
Keyword(s):  
Folic Acid ◽  
Folic Acid Supplementation ◽  
Vitamin Deficiency ◽  
Folate Supplementation ◽  
Control Of Gene Expression ◽  
Methyl Donors ◽  
Maternal Supplementation ◽  
One Carbon Metabolism ◽  
The One ◽  
B Vitamin

Vitamins B9 (folate) and B12 act as methyl donors in the one-carbon metabolism which influences epigenetic mechanisms. We previously showed that an embryofetal deficiency of vitamins B9 and B12 in the rat increased brain expression of let-7a and miR-34a microRNAs involved in the developmental control of gene expression. This was reversed by the maternal supply with folic acid (3 mg/kg/day) during the last third of gestation, resulting in a significant reduction of associated birth defects. Since the postnatal brain is subject to intensive developmental processes, we tested whether further folate supplementation during lactation could bring additional benefits. Vitamin deficiency resulted in weaned pups (21 days) in growth retardation, delayed ossification, brain atrophy and cognitive deficits, along with unchanged brain level of let-7a and decreased expression of miR-34a and miR-23a. Whereas maternal folic acid supplementation helped restore the levels of affected microRNAs, it led to a reduction of structural and functional defects taking place during the perinatal/postnatal periods, such as learning/memory capacities. Our data suggest that a gestational B-vitamin deficiency could affect the temporal control of the microRNA regulation required for normal development. Moreover, they also point out that the continuation of folate supplementation after birth may help to ameliorate neurological symptoms commonly associated with developmental deficiencies in folate and B12.

Folic Acid Supplementation and Twin Pregnancy in Patients with Sickle Cell Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3744-3744
Author(s):  
Samir K. Ballas ◽  
Jason Baxter ◽  
Gaye Riddick
Keyword(s):  
Folic Acid ◽  
Sickle Cell Disease ◽  
Pregnant Women ◽  
Sickle Cell ◽  
Folic Acid Supplementation ◽  
Multiple Births ◽  
Cell Disease ◽  
Folate Supplementation ◽  
Acid Supplementation ◽  
Twin Pregnancies

Abstract Patients with sickle cell disease (SCD) usually take 1mg of folic acid daily. The rationale for this approach is to maintain effective erythropoiesis with a stable hemoglobin level. Other potential advantages of folate therapy in patients with SCD include the prevention of hyperhomocysteinemia that may predispose to thrombotic events, which, in turn, may lead to painful episodes. Moreover, folate supplementation during pregnancy is known to prevent neural tube defects in infants. The major disadvantage of folate supplementation in patients with SCD is that it may mask vitamin B12 deficiency. Another controversial effect of folic acid supplementation pertains to its potential effect on the number of twins coming to term. We reviewed our database on patients with SCD to determine the effect, if any, of folic acid supplementation on twin pregnancies. The data were collected prospectively since 1981. All patients routinely took 1.0 mg of folic acid orally on a daily basis. Random testing of the level of folic acid in the steady state in women with SCD including those who became pregnant showed increased levels to > 20ng/ml (Normal range: 3.0–18.0 ng/ml) in most patients. Pregnant patients also took additional perinatal vitamins that also contained folic acid. We selected those pregnant patients in whom the outcome of pregnancy was either a liveborn or stillborn at or after 20 weeks’ gestation. We found that 46 patients with SCD became pregnant 60 times between 1981 and 2002 and who met the defined criteria mentioned above. The average maternal age at delivery was 26 years. Fifty-six pregnancies (93%) ended in liveborn and the remaining four (7%) in intrauterine fetal death. Five pregnancies (8.3%) resulted in the delivery of twins. This is a significantly higher rate of multiple births compared to other pregnant women. The reported rate of multiple births is between 0.34 and 1.1% both in Black and Caucasian women respectively. All twin births were dizygotic in nature. Patients with SCD take higher amounts of folic acid on a regular basis for a longer period of time before and after pregnancy than other pregnant women. This may explain why twin pregnancies are higher in these patients. The reason why folate therapy is associated with twinning is unknown at the present. Further studies may clarify the pathogenetic pathway of this phenomenon.

Inhibition of MTOR signaling impairs rat embryo organogenesis by affecting folate availability

Reproduction ◽  
2021 ◽  
Vol 161 (4) ◽  
pp. 365-373
Author(s):  
Romina Higa ◽  
Fredrick J Rosario ◽  
Theresa L Powell ◽  
Thomas Jansson ◽  
Alicia Jawerbaum
Keyword(s):  
Folic Acid ◽  
Embryo Development ◽  
Neural Tube ◽  
Folic Acid Supplementation ◽  
Mtor Signaling ◽  
Neural Tube Closure ◽  
Folate Supplementation ◽  
Mtor Inhibition ◽  
Resorption Rate ◽  
Tube Closure

Mechanistic target of rapamycin (MTOR) is essential for embryo development by acting as a nutrient sensor to regulate cell growth, proliferation and metabolism. Folate is required for normal embryonic development and it was recently reported that MTOR functions as a folate sensor. In this work, we tested the hypothesis that MTOR functions as a folate sensor in the embryo and its inhibition result in embryonic developmental delay affecting neural tube closure and that these effects can be rescued by folate supplementation. Administration of rapamycin (0.5 mg/kg) to rats during early organogenesis inhibited embryonic ribosomal protein S6, a downstream target of MTOR Complex1, markedly reduced embryonic folate incorporation (−84%, P < 0.01) and induced embryo developmental impairments, as shown by an increased resorption rate, reduced embryo somite number and delayed neural tube closure. These alterations were prevented by folic acid administered to the dams. Differently, although an increased rate of embryonic rotation defects was observed in the rapamycin-treated dams, this alteration was not prevented by maternal folic acid supplementation. In conclusion, MTOR inhibition during organogenesis in the rat resulted in decreased folate levels in the embryo, increased embryo resorption rate and impaired embryo development. These data suggest that MTOR signaling influences embryo folate availability, possibly by regulating the transfer of folate across the maternal–embryonic interface.

scholarly journals B vitamins for stroke prevention

2018 ◽  
Vol 3 (2) ◽  
pp. 51-58 ◽  
Author(s):  
Graeme J Hankey
Keyword(s):  
Clinical Trials ◽  
Folic Acid ◽  
Stroke Prevention ◽  
Stroke Risk ◽  
Folic Acid Supplementation ◽  
Adverse Outcomes ◽  
B Vitamins ◽  
Vitamin B ◽  
Folate Supplementation ◽  
Acid Supplementation

Supplementation with B vitamins (vitamin B9(folic acid), vitamin B12 and vitamin B6) lowers blood total homocysteine (tHcy) concentrations by about 25% and reduces the relative risk of stroke overall by about 10% (risk ratio (RR) 0.90, 95% CI 0.82 to 0.99) compared with placebo. Homocysteine-lowering interventions have no significant effect on myocardial infarction, death from any cause or adverse outcomes. Factors that appear to modify the effect of B vitamins on stroke risk include low folic acid status, high tHcy, high cyanocobalamin dose in patients with impaired renal function and concurrent antiplatelet therapy. In regions with increasing levels or established policies of population folate supplementation, evidence from observational genetic epidemiological studies and randomised controlled clinical trials is concordant in suggesting an absence of benefit from lowering of homocysteine with folic acid for prevention of stroke. Clinical trials indicate that in countries which mandate folic acid fortification of food, folic acid supplementation has no significant effect on reducing stroke risk (RR 1.05, 95% CI 0.90 to 1.23). However, in countries without mandatory folic acid food fortification, folic acid supplementation reduces the risk of stroke by about 15% (RR 0.85, 95% CI 0.77 to 0.94). Folic acid alone or in combination with minimal cyanocobalamin (≤0.05 mg/day) is associated with an even greater reduction in risk of future stroke by 25% (RR 0.75, 95% CI 0.66 to 0.86), whereas the combination of folic acid and a higher dose of cyanocobalamin (≥0.4 mg/day) is not associated with a reduced risk of future stroke (RR 0.95, 95% CI 0.86 to 1.05). The lack of benefit of folic acid plus higher doses of cyanocobalamin (≥0.4 mg/day) was observed in trials which all included participants with chronic kidney disease. Because metabolic B12 deficiency is very common and usually not diagnosed, future randomised trials of homocysteine-lowering interventions for stroke prevention should probably test a combination of folic acid and methylcobalamin or hydroxocobalamin instead of cyanocobalamin, and perhaps vitamin B6.

scholarly journals Moderate Folic Acid Supplementation in Pregnant Mice Results in Behavioral Alterations in Offspring with Sex-Specific Changes in Methyl Metabolism

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1716
Author(s):  
Marta Cosín-Tomás ◽  
Yan Luan ◽  
Daniel Leclerc ◽  
Olga V. Malysheva ◽  
Nidia Lauzon ◽  
...  
Keyword(s):  
Folic Acid ◽  
Motor Development ◽  
Methylenetetrahydrofolate Reductase ◽  
Negative Impact ◽  
Folic Acid Supplementation ◽  
Behavioral Alterations ◽  
Folate Supplementation ◽  
Pregnancy And Lactation ◽  
Behavioural Tests ◽  
The Impact

Fifteen to 20% of pregnant women may exceed the recommended intake of folic acid (FA) by more than four-fold. This excess could compromise neurocognitive and motor development in offspring. Here, we explored the impact of an FA-supplemented diet (5× FASD, containing five-fold higher FA than recommended) during pregnancy on brain function in murine offspring, and elucidated mechanistic changes. We placed female C57BL/6 mice for one month on control diets or 5× FASD before mating. Diets were maintained throughout pregnancy and lactation. Behavioural tests were conducted on 3-week-old pups. Pups and mothers were sacrificed at weaning. Brains and livers were collected to examine choline/methyl metabolites and immunoreactive methylenetetrahydrofolate reductase (MTHFR). 5× FASD led to hyperactivity-like behavior and memory impairment in 3-week-old pups of both sexes. Reduced MTHFR protein in the livers of FASD mothers and male pups resulted in choline/methyl metabolite disruptions in offspring liver (decreased betaine) and brain (decreased glycerophosphocholine and sphingomyelin in male pups, and decreased phosphatidylcholine in both sexes). These results indicate that moderate folate supplementation downregulates MTHFR and alters choline/methyl metabolism, contributing to neurobehavioral alterations. Our findings support the negative impact of high FA on brain development, and may lead to improved guidelines on optimal folate levels during pregnancy.

scholarly journals AWARENESS OF FOLIC ACID USE AND ITS EFFECTS AMONG MEDICAL STUDENTS IN UKRAINE

2021 ◽  
Vol 74 (9) ◽  
pp. 2033-2038
Author(s):  
Kateryna Hlushko ◽  
Oksana Boyarchuk ◽  
Maria Kinash ◽  
Emillia Burbela ◽  
Yana Rohalska ◽  
...  
Keyword(s):  
Folic Acid ◽  
Medical Students ◽  
Folic Acid Supplementation ◽  
Folic Acid Deficiency ◽  
General Knowledge ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Acid Deficiency ◽  
The One ◽  
High Level

The aim: To evaluate the awareness of folic acid, its use and effects, general knowledge about neural tube defects among medical students in Ukraine. Materials and methods: This cross-sectional survey was conducted by questioning 114 fourth and fifth years’ students of the Faculty of Medicine. The questionnaire contained questions about folic acid, its dietary sources, effects and periconceptional uses; spina bifida and its main symptoms. Results: Overall, 96.5% of students knew that folic acid was a vitamin and 95.6% were aware of the one natural product which had a high folate level. However, awareness of its amount in different products was insufficient. Overall, 86.8% of surveyed knew that folic acid deficiency during pregnancy caused the congenital malformations. The knowledge of the synthetic folic acid supplementation before and during pregnancy was low (67.5% and 53.5% respectively). Only 10 % of women among medical students consumed folic acid regularly. Conclusions: Despite the high level of general knowledge about folic acid and its effects among medical students in Ukraine, there is a poor awareness of the pre-conception administration of folic acid, and the number of people who regularly take folic acid among the respondents was very low.

scholarly journals One‐carbon metabolism in the aged colon after folic acid supplementation

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Ella M Zimmerly ◽  
Kyong‐Chol Kim ◽  
Hyeran Jang ◽  
Sang‐Woon Choi
Keyword(s):  
Folic Acid ◽  
Carbon Metabolism ◽  
Folic Acid Supplementation ◽  
Acid Supplementation ◽  
One Carbon Metabolism

scholarly journals Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age

2008 ◽  
Vol 11 (8) ◽  
pp. 822-830 ◽  
Author(s):  
J Rosenthal ◽  
G Milla ◽  
A Flores ◽  
M Yon ◽  
C Pfeiffer ◽  
...  
Keyword(s):  
Folic Acid ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Folic Acid Supplementation ◽  
Conclusive Evidence ◽  
Reproductive Age ◽  
Serum Folate ◽  
Folate Supplementation ◽  
Double Blind ◽  
Supplementation Period

AbstractBackgroundObservational studies and clinical trials have shown conclusive evidence that periconceptional folic acid supplementation prevents up to 70 % of neural tube defects (NTD). The Honduran government wanted to implement a supplementation programme of folic acid but needed to assess the relative effects of two dosages of folic acid.ObjectiveTo determine the effect of two dosages of folic acid on blood folate levels in Honduran female factory workers aged 18 to 49 years.DesignThis was a randomized, double-blind control supplementation trial conducted in Choloma, Honduras. A total of 140 eligible women were randomly assigned to two dosage groups and followed up for 12 weeks. One group received a daily dosage of 1 mg folic acid and the other a once weekly dosage of 5 mg. Serum folate and red blood cell folate levels were determined by radioassay at baseline, 6 weeks and 12 weeks.ResultsSerum folate levels increased from 6·3 (se 0·2) to 14·9 (se 0·6) ng/ml (P < 0·0001) in women assigned to the 1 mg/d group and from 6·9 (se 0·3) to 10·1 (se 0·4) ng/ml (P < 0·0001) in those assigned to the 5 mg/week group. Red blood cell folate concentrations also increased significantly in both groups, albeit more slowly. Educational level, age and BMI were not associated with the changes in serum and red blood cell folate levels during the supplementation period. However, a differential effect on serum folate levels by dosage group and time was observed.ConclusionsAlthough both folate supplementation regimens increased serum and red blood cell folate levels significantly among the women studied, blood folate levels that are considered to be protective of NTD were reached faster with the daily dosage of 1 mg folic acid.

Folic Acid Supplementation in the Gestational Phase of Female Rats Improves Age-Related Memory Impairment and Neuroinflammation in Their Adult and Aged Offspring

2020 ◽  
Author(s):  
Michelle Lima Garcez ◽  
Francielle Mina ◽  
Tatiani Bellettini-Santos ◽  
Fernanda Melo Ribeiro ◽  
Alessandra Zanette Ghisi Frassetto ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Folic Acid ◽  
Memory Impairment ◽  
Natural Aging ◽  
Female Offspring ◽  
Folic Acid Supplementation ◽  
Female Rats ◽  
Deficient Diet ◽  
Age Related ◽  
Maternal Supplementation

Abstract Folic acid (FA) supplementation is important during pregnancy to avoid malformations in the offspring. However, it is unknown if it can affect the offspring throughout their lives. To evaluate the offspring, female mother rats (dams) were separated into 5 groups: Four groups received the AIN-93 diet, divided into control and FA (5, 10, and 50 mg/kg), and an additional group received a FA-deficient diet, and the diet was performed during pregnancy and lactation. We evaluated the female offspring of these dams (at 2 and 18 months old). The aged offspring fed with FA-deficient diet presented habituation, spatial and aversive memory impairment and the FA maternal supplementation prevented this. The natural aging caused an increase in the TNF-α and IL-1β levels in the hippocampus from 18-month-old offspring. FA maternal supplementation was able to prevent the increase of these cytokines. IL-4 levels decreased in the prefrontal cortex from aged control rats and FA prevented it. FA deficiency decreased the levels of IL-4 in the hippocampus of the young offspring. In addition, natural aging and FA deficiency decreased brain-derived neurotrophic factor levels in the hippocampus and nerve growth factor levels in the prefrontal cortex and FA supplementation prevented it. Thus, the present study shows for the first time the effect of FA maternal supplementation on memory, cytokines, and neurotrophins in the aged offspring.

Effects of dietary supplements of folic acid on reproductive performance in ewes

2008 ◽  
Vol 88 (3) ◽  
pp. 489-497 ◽  
Author(s):  
H. Méthot ◽  
C. L. Girard ◽  
J. J. Matte ◽  
F. W. Castonguay
Keyword(s):  
Folic Acid ◽  
Key Words ◽  
Breeding Season ◽  
Reproductive Performance ◽  
Folic Acid Supplementation ◽  
Red Cell ◽  
Folic Acid Supplement ◽  
Acid Supplementation ◽  
The One ◽  
The Impact

The objective of this project was to assess the impact of periconceptional folic acid supplementation on the reproductive performance of prolific and non-prolific ewes, in the estrous and anestrous seasons. Two initial trials took place during the estrous season at two experimental sites where 38 Dorset and 39 half-Finn half-Dorset ewes (site A) as well as 80 Dorset ewes (site C) were divided into two groups receiving either 0 or 210 mg ewe-1 d-1 of folic acid over a period which extended from 21 d premating to 30 d postmating. Three other trials were conducted in the anestrous season where 80 Dorset ewes (site A), 56 half-Romanov ewes (site B) and 78 Dorset ewes (site C) were subjected to the same protocol as the one used in the breeding season. In all the trials, the folic acid supplement increased plasma and red cell folates, but had no effect on fertility, embryonic mortality, or the size or weight of the litter at birth. Folic acid supplementation did not improve the reproductive performance of prolific and non-prolific ewes, either in the estrous season or in the anestrous period. Key words: Ewes, reproduction, vitamins, folic acid, fertility, prolificacy

scholarly journals Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods

2018 ◽  
Vol 7 ◽  
Author(s):  
Mohammed E. Hefni ◽  
Cornelia M. Witthöft ◽  
Ali A. Moazzami
Keyword(s):  
Folic Acid ◽  
Folic Acid Supplementation ◽  
Folate Intake ◽  
Plasma Metabolites ◽  
Folic Acid Supplement ◽  
Significance Level ◽  
Healthy Women ◽  
Acid Supplement ◽  
Public Health Authorities ◽  
One Carbon Metabolism

AbstractPublic health authorities recommend all fertile women to increase their folate intake to 400 µg/d by eating folate-rich foods or by taking a folic acid supplement to protect against neural tube defects. In a previous study it was shown that folate-rich foods improved folate blood status as effectively as folic acid supplementation. The aim of the present study was to investigate, using NMR metabolomics, the effects of an intervention with a synthetic folic acid supplement v. native food folate on the profile of plasma metabolites. Healthy women with normal folate status received, in parallel, 500 µg/d synthetic folic acid from a supplement (n 18), 250 µg/d folate from intervention foods (n 19), or no additional folate (0 µg/d) through a portion of apple juice (n 20). The metabolic profile of plasma was measured using 1H-NMR in fasted blood drawn at baseline and after 12 weeks of intervention. Metabolic differences between the groups at baseline and after intervention were assessed using a univariate statistical approach (P ≤ 0·001, Bonferroni-adjusted significance level). At baseline, the groups showed no significant differences in measured metabolite concentrations. After intervention, eight metabolites, of which six (glycine, choline, betaine, formate, histidine and threonine) are related to one-carbon metabolism, were identified as discriminative metabolites. The present study suggests that different folate forms (synthetic v. natural) may affect related one-carbon metabolites differently.

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