Maternal folic acid supplementation with vitamin B 12 deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet

2018 ◽  
Vol 32 (9) ◽  
pp. 5039-5050 ◽  
Author(s):  
Amanda M. Henderson ◽  
Daven C. Tai ◽  
Rika E. Aleliunas ◽  
Abeer M. Aljaadi ◽  
Melissa B. Glier ◽  
...  
Keyword(s):  
Folic Acid ◽  
Adult Female ◽  
Female Offspring ◽  
Folic Acid Supplementation ◽  
Metabolic Health ◽  
Vitamin B ◽  
Acid Supplementation ◽  
Pregnancy And Lactation ◽  
Vitamin B 12

scholarly journals Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation

2019 ◽  
Vol 109 (5) ◽  
pp. 1452-1461 ◽  
Author(s):  
Meng-Yu Chen ◽  
Charles E Rose ◽  
Yan Ping Qi ◽  
Jennifer L Williams ◽  
Lorraine F Yeung ◽  
...  
Keyword(s):  
Folic Acid ◽  
Intervention Group ◽  
Population Based ◽  
Folic Acid Supplementation ◽  
Reproductive Age ◽  
Vitamin B ◽  
Acid Supplementation ◽  
Folate Concentration ◽  
Plasma Folate ◽  
Vitamin B 12

ABSTRACT Background For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. Objective The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. Methods We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. Results Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3–4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). Conclusions The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

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 Low-dose folic acid supplementation does not influence plasma methionine concentrations in young non-pregnant women

1999 ◽  
Vol 82 (2) ◽  
pp. 85-89 ◽  
Author(s):  
Ingeborg A. Brouwerv ◽  
Marijke van Dusseldorp ◽  
Marinus Duran ◽  
Chris M. G. Thomas ◽  
Joseph G. A. J. Hautvast ◽  
...  
Keyword(s):  
Folic Acid ◽  
Low Dose ◽  
Inverse Correlation ◽  
Folic Acid Supplementation ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Acid Supplementation ◽  
Erythrocyte Folate ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

An elevated plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease and for having offspring with a neural-tube defect. Folate is a methyl donor in the remethylation of homocysteine into methionine. Although folic acid supplementation decreases tHcy concentrations, effects of folic acid supplementation on plasma methionine concentrations are unclear. There is also concern that folic acid supplementation negatively affects vitamin B12 status. We studied effects of low-dose folic acid supplementation on methionine and vitamin B12 concentrations in plasma. We also investigated whether baseline plasma methionine and tHcy concentrations correlated with the baseline folate and vitamin B12 status. For a period of 4 weeks, 144 young women received either 500 μg folic acid each day, or 500 μg folic acid and placebo tablets on alternate days, or a placebo tablet each day. Plasma methionine, tHcy and plasma vitamin B12 concentrations were measured at start and end of the intervention period. Folic acid supplementation had no effect on plasma methionine or plasma vitamin B12 concentrations although it significantly decreased tHcy concentrations. Plasma methionine concentrations showed no correlation with either tHcy concentrations (Spearman rs - 0·01, P = 0·89), or any of the blood vitamin variables at baseline. Baseline tHcy concentrations showed a slight inverse correlation with baseline concentrations of plasma vitamin B12 (rs - 0·25, P < 0·001), plasma folate (rs - 0·24, P < 0·01) and erythrocyte folate (rs - 0·19, P < 0·05). In conclusion, low-dose folic acid supplementation did not influence plasma methionine or plasma vitamin B12 concentrations. Furthermore, no correlation between plasma methionine concentrations and the blood folate and vitamin B12 status was shown.

Meta-analysis of folic acid efficacy trials in stroke prevention

Neurology ◽  
2017 ◽  
Vol 88 (19) ◽  
pp. 1830-1838 ◽  
Author(s):  
Min Zhao ◽  
Guangliang Wu ◽  
Youbao Li ◽  
Xiaobin Wang ◽  
Fan Fan Hou ◽  
...  
Keyword(s):  
Folic Acid ◽  
Fixed Effects ◽  
Stroke Risk ◽  
Meta Analysis ◽  
Folic Acid Supplementation ◽  
Vitamin B ◽  
Fixed Effects Model ◽  
Folic Acid Fortification ◽  
Acid Supplementation ◽  
Low Dosage

Objective:To examine the efficacy and effect modifiers of folic acid supplementation in the prevention of stroke in regions without folic acid fortification based on relevant, up-to-date published randomized trials.Methods:Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of stroke using a fixed effects model.Findings:Overall, folic acid supplementation significantly reduced the stroke risk by 11% (22 trials, n = 82,723; RR 0.89, 95% confidence interval [CI] 0.84–0.96). The effect was greater in low folate regions (2 trials, n = 24,020; Asia, 0.78, 0.67–0.90) compared to high folate regions (7 trials, n = 14,655; America, 1.05, 0.90–1.23), and among patients without folic acid fortification (11 trials, n = 49,957; 0.85; 0.77–0.94) compared with those with folic acid fortification (7 trials, n = 14,655; 1.05, 0.90–1.23). In further stratified analyses among trials without folic acid fortification, a larger beneficial effect was found in those trials that used a low dosage of folic acid (≤0.8 mg: 0.78, 0.69–0.88) or low baseline vitamin B12 levels (<384 pg/mL: 0.78, 0.68–0.89). In the corresponding comparison groups, the effect sizes were attenuated and insignificant (p for interaction <0.05 for both). Although the interaction tests were not significant, there might be a higher benefit in trials with a low dosage of vitamin B12, a low prevalence of statin use, but a high prevalence of hypertension.Conclusions:Folic acid supplementation could reduce the stroke risk in regions without folic acid fortification, particularly in trials using a relatively low dosage of folic acid and with low vitamin B12 levels.

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