Search

Background Achieving optimal folate status during early gestation reduces the risk of neural tube defects (NTDs). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit. Objective Here, we sought to investigate the determinants, including FA supplement dose and use, of plasma total and individual folate vitamer concentrations in the first and third trimesters of pregnancy. Methods Using data from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study, a cohort exposed to mandatory FA fortification, we measured plasma total folate and individual folate vitamer [5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), and non-methyl folates (sum of THF, 5-formylTHF, 5,10-methenyl-THF)] concentrations in the first and third trimesters (n  = 1,893). Using linear mixed models, we estimated associations between plasma folate concentrations, total daily supplemental FA intake, plasma vitamin B-12 concentrations, and multiple demographic, maternal, and reproductive factors. Results Almost 95% of MIREC study participants met or exceeded the recommended daily supplemental FA intake from supplements (≥400 μg/d), with approximately 25% consuming more than the Tolerable Upper Intake Level (>1000 μg/d). Over 99% of MIREC participants had a plasma total folate status indicative of maximal NTD risk reduction (25.5 nmol/L) regardless of FA supplement dose. UMFA was detected in almost all participants, with higher concentrations associated with higher FA doses. Determinants of adequate FA supplement intake and folate status associated with reduced NTD risk included indicators of higher socioeconomic position, higher maternal age, nulliparity, and lower prepregnancy BMI. Conclusions In the context of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses. [ABSTRACT FROM AUTHOR]

Background Periconceptional folic acid (FA) supplementation is recommended to prevent the occurrence of neural tube defects. Currently, most over-the-counter FA supplements in Canada and the United States contain 1 mg FA and some women are prescribed 5 mg FA/d. High-dose FA is hypothesized to impair 1-carbon metabolism. We aimed to determine folate and 1-carbon metabolism biomarkers in pregnant women exposed to 1 mg or 5 mg FA. Objectives This was an ancillary study within the Folic Acid Clinical Trial (FACT), a randomized, double-blinded, placebo-controlled, phase III trial designed to assess the efficacy of high-dose FA to prevent preeclampsia. Methods For FACT, women were randomized at 8–16 gestational weeks to receive daily 4.0 mg FA (high dose) or placebo (low dose) plus their usual supplementation (≤1.1 mg). Women were recruited from 3 Canadian FACT centers and provided nonfasting blood samples at 24–26 gestational weeks for measurement of RBC and serum total folate, serum unmetabolized FA (UMFA), tetrahydrofolate (THF), 5-methylTHF, 5-formylTHF, 5,10-methenylTHF, and MeFox (pyrazino-s-triazine derivative of 4α-hydroxy-5-methylTHF, a 5-methylTHF oxidation product); total vitamins B-12 and B-6; and plasma total homocysteine. Group differences were determined using χ2, Fisher exact, and Wilcoxon rank-sum tests. Results Nineteen (38%) women received high-dose FA and 31 (62%) received low-dose FA. The median RBC folate concentration was 2701 (IQR: 2243–3032) nmol/L and did not differ between groups. The high-dose group had higher serum total folate (median: 148.4 nmol/L, IQR: 110.4–181.2; P  = 0.007), UMFA (median: 4.6 nmol/L, IQR: 2.5–33.8; P  = 0.008), and 5-methylTHF (median: 126.6 nmol/L, IQR: 98.8–158.6; P  = 0.03) compared with the low-dose group (median: 122.8 nmol/L, IQR: 99.5–136.0; median: 1.9 nmol/L, IQR: 0.9–4.1; median: 108.6 nmol/L, IQR: 96.4–123.2, respectively). Other biomarkers of 1-carbon metabolism did not differ. Conclusions High-dose FA supplementation in early pregnancy increases maternal serum folate but not RBC folate concentrations, suggesting tissue saturation. Higher UMFA concentrations in women receiving high-dose FA supplements suggest that these doses are supraphysiologic but with no evidence of altered 1-carbon metabolism. [ABSTRACT FROM AUTHOR]

Background: We were interested in identifying possible nutritional reasons for growth faltering among breastfed infants in the rural farming community of San Mateo, Capulhuac, Mexico (2800 m above sea level). Objective: We examined the prevalence of inadequate iron and folate status among lactating Otomi women and determined to what extent their iron and folate nutriture influenced the milk concentrations of these nutrients. Design: Lactating women (n = 71) provided blood and milk samples and dietary information at a mean (± SD) of 22 ± 13 d postpartum. Blood indexes included hemoglobin, hematocrit, serum iron, total-iron-binding capacity, ferritin, transferrin receptor, mean cell volume, plasma folate, and erythrocyte folate. Results: Approximately 62% and 58% of the women had nutritional anemia defined as a hemoglobin concentration = 133 g/L and a hematocrit value of 41.0%, respectively. With the use of a 3- index iron assessment model, 2 of the 66 women whose iron status was assessed (3%) had iron-deficient erythropoiesis, and 24 (36%) had iron deficiency anemia. Among the 67 women whose folate status was assessed, 29 (43%) had a low plasma folate concentration, and 13 (19%) had a low blood folate concentration in conjunction with a low hemoglobin concentration. Milk iron content was unrelated to maternal iron status, and the milk provided more than adequate amounts of iron to the infants. In contrast, the infants' predicted folate intake was ≈45 μg/d, or 70% of the current recommended intake. Conclusion: Milk folate concentrations in Otomi women are low and may not support optimal folate status in all breastfed infants. [ABSTRACT FROM AUTHOR]

Background: The major route of folate turnover is by catabolic cleavage of the C9-N10 bond producing p-aminobenzoylglutamate (pABG) and its primary excretory form, p-acetamidobenzoylglutamate (ApABG). We hypothesize that total pABG (ApABG + pABG) excretion parallels both the mass of body folate pools from which these catabolites originate and the folate-status indicators. Objective: The objective was to determine whether urinary folate catabolite excretion reflects body pool size and parallels the static and functional measures of folate status. Design: Urinary folate catabolite excretion was measured in women (aged 60-85 y) consuming controlled amounts of folate for 14 wk. A low-folate diet (120 μg/d) was consumed (n = 33) for 7 wk, and then subjects were randomly assigned to consume either 200 (n = 14) or 400 (n = 16) μg folate/d. Urinary pABG and ApABG concentrations were measured by HPLC at 0, 7, and 14 wk. Results: Urinary excretion of total pABG was significantly lower (P = 0.001) after depletion (73.9 ± 4.7 nmol/d) than at baseline (115 ± 12.7 nmol/d). This rate of decline (≈0.7% per day) is consistent with the kinetically measured rate of turnover of total body folate at moderate folate intakes. The average percentage increase in total pABG in response to folate repletion with 400 μg/d (75%) was significant (P = 0.02). Folate catabolite excretion was significantly (P = 0.0001) associated with serum and red blood cell folate, plasma homocysteine, and DNA hypomethylation after depletion and with serum folate (P = 0.001) and plasma homocysteine (P = 0.0002) after repletion with 400 μg folate/d. Conclusions: Total urinary pABG excretion reflects total body folate pool size and is a long-term indicator that parallels functional measures of folate status. [ABSTRACT FROM AUTHOR]