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 Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1381
Author(s):  
Keiji Kuroda ◽  
Takashi Horikawa ◽  
Yoko Gekka ◽  
Azusa Moriyama ◽  
Kazuki Nakao ◽  
...  
Keyword(s):  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Homocysteine Level ◽  
Folic Acid Supplementation ◽  
Serum Folate ◽  
Folate Level ◽  
Multivitamin Supplementation ◽  
Mthfr Polymorphisms ◽  
Mthfr Genotype ◽  
Multivitamin Supplements

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.

scholarly journals Intermittent Iron Folate Supplementation: Impact on Hematinic Status and Growth of School Girls

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Aditi Sen ◽  
Shubhada Kanani
Keyword(s):  
Body Mass Index ◽  
Folic Acid ◽  
Weekly Dose ◽  
Folate Supplementation ◽  
Standard Methods ◽  
Pubertal Growth ◽  
School Girls ◽  
Iron Folic Acid ◽  
One Year ◽  
The Impact

In view of high iron needs for adolescent growth, this paper studied the impact of daily vs. intermittent (once and twice weekly) iron folic acid (IFA) supplementation on hemoglobin levels and pubertal growth among primary school girls in early adolescence (9–13 years) of Vadodara, India. Methods. Hemoglobin (Hb), height and weight of the girls were assessed using standard methods. In three experimental schools (ES) IFA tablets in a dose of 100 mg Fe+0.5 mg folic acid was given either daily, once weekly or twice weekly for one year. The fourth school (control: CS) did not receive any intervention. Results. Hb levels significantly improved (P<0.01) in all ES compared to CS. Body Mass Index (BMI) increment in ES vs CS was significant (P<0.05) in twice weekly IFA and daily IFA. Within ES groups, mean Hb and BMI increments were comparable between twice weekly IFA and daily IFA. Anemic ES girls showed higher Hb and BMI increments vs. non-anemic girls. Better the Hb response, greater was the benefit on BMI. Conclusion: Twice-weekly IFA supplementation was comparable to daily IFA as regards impact on Hb and growth; at less cost and greater feasibility. Once-weekly dose was inadequate to significantly improve growth.

scholarly journals The impact of antenatal care, iron–folic acid supplementation and tetanus toxoid vaccination during pregnancy on child mortality in Bangladesh

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0187090 ◽  
Author(s):  
Tanvir Abir ◽  
Felix Akpojene Ogbo ◽  
Garry John Stevens ◽  
Andrew Nicolas Page ◽  
Abul Hasnat Milton ◽  
...  
Keyword(s):  
Folic Acid ◽  
Antenatal Care ◽  
Child Mortality ◽  
Tetanus Toxoid ◽  
Folic Acid Supplementation ◽  
Acid Supplementation ◽  
Iron Folic Acid Supplementation ◽  
Iron Folic Acid ◽  
The Impact

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.

scholarly journals Periconceptional Folic Acid Supplementation and the Risk of Spontaneous Abortion among Women Who Prepared to Conceive: Impact of Supplementation Initiation Timing

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2264
Author(s):  
Yan-Yan Mao ◽  
Liu Yang ◽  
Min Li ◽  
Jun Liu ◽  
Qian-Xi Zhu ◽  
...  
Keyword(s):  
Folic Acid ◽  
Spontaneous Abortion ◽  
Lower Risk ◽  
Folic Acid Supplementation ◽  
Health Examination ◽  
Adjusted Risk ◽  
Adjusted Risk Ratio ◽  
Periconceptional Period ◽  
Utilization Of Healthcare ◽  
The Impact

It is unclear whether periconceptional folic acid (FA) supplementation decreases the risk of spontaneous abortion (SA). The impact of supplementation initiation timing has not been ascertained. This cohort study aimed to investigate the association between maternal periconceptional FA supplementation and risk of SA, with due consideration of the supplementation initiation timing. Through the National Free Pre-conception Health Examination Project (NFPHEP), we identified 65,643 pregnancies on FA supplementation in Chongqing, China between 2010 and 2015. After adjusting for covariates, maternal periconceptional FA supplementation was associated with a lower risk of SA (adjusted risk ratio [aRR]: 0.52; 95% confidence interval [CI]: 0.48–0.56). Pregnant women with FA supplementation initiated at least 3 months before conception had a 10% lower risk of SA (aRR: 0.46; 95% CI: 0.42–0.50) than those with FA supplementation initiated 1–2 months before conception (aRR: 0.56; 95% CI: 0.50–0.62) or after conception (aRR: 0.56; 95% CI: 0.51–0.61). These associations might not thoroughly account for FA supplementation, and to some extent our findings confirm the role of the utilization of healthcare in preventing SAs. Women who initiated healthcare, including taking FA earlier during the periconceptional period, could have a lower risk of SA.

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.

Oxidative stress and platelet activation in subjects with moderate hyperhomocysteinaemia due to MTHFR 677 C→T polymorphism

2012 ◽  
Vol 108 (09) ◽  
pp. 533-542 ◽  
Author(s):  
Alfredo Dragani ◽  
Angela Falco ◽  
Francesca Santilli ◽  
Stefania Basili ◽  
Giancarlo Rolandi ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Folic Acid ◽  
Platelet Activation ◽  
Methylenetetrahydrofolate Reductase ◽  
Folic Acid Supplementation ◽  
Control Group ◽  
Loading Test ◽  
Study Objective ◽  
Acid Supplementation

SummaryThe methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F2α and 11-dehydro-thromboxane (TX)B2 (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF2α and 11-dehydro-TXB2 were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF2α (p<0.0001) and 11-dehydro-TXB2 (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF2α excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF2α and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.

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