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Cochrane, Kelsey M.

University of British Columbia

Folic acid supplementation is recommended to support fetal development. However, folic acid is an oxidized form that must undergo reduction for use in the body, and unmetabolized folic acid (UMFA) is widely detected in circulation. (6S)-5-methyltetrahydrofolic acid (5-MTHF) is an alternative to folic acid which is reduced; however, the effect of (6S)-5-MTHF on maternal folate status during pregnancy is unknown. Thus, we conducted a pilot study to estimate the impact of supplementation with (6S)-5-MTHF versus folic acid on maternal folate status. Pregnant individuals (n=60) were randomized to 0.6 mg/day folic acid or (6S)-5-MTHF x 16-weeks, with the option to continue until 1-week postpartum. Fasting (3-hr) blood specimens were collected at baseline (8-21-weeks’ gestation) and after 16-weeks (endline); at 1-week postpartum, non-fasting blood and human milk specimens were collected. Red blood cell (RBC) and serum folate were quantified via microbiological assay and UMFA (plasma and human milk) via LC-MS/MS. Differences in blood folate markers were evaluated using multivariable linear/quantile regression, adjusting for dietary folate, baseline concentrations (endline concentrations for postpartum estimates), and weeks of gestation (total weeks’ supplementing for postpartum estimates). At endline, mean ± SD (or median, IQR) RBC folate, serum folate, and plasma UMFA (nmol/L) in the (6S)-5-MTHF and folic acid groups, respectively, were: 1826 ± 471 and 1998 ± 421 (adjusted difference: 161, 95% CI: -79, 400); 70 ± 13 and 78 ± 17 (adjusted difference: 7.4, 95% CI: -1.4, 16); 0.5 (0.4, 0.8) and 1.3 (0.9, 2.1) (adjusted difference: 0.6, 95% CI: 0.2, 1.1). Postpartum median (IQR) RBC folate concentrations (nmol/L) were 1724 (1474, 1877) and 1962 (1576, 2284) (adjusted difference: 11, 95% CI: -272, 294). The mean ± SD proportion of human milk UMFA as part of total milk folate was 2% (±2%) and 28% (±14%) in the (6S)-5-MTHF and folic acid groups, respectively. In conclusion, concentrations of RBC and serum folate were comparable between groups, although confidence intervals were not sufficiently precise to conclusively rule out a potential difference. The clinical significance of higher UMFA following folic acid supplementation has yet to be elucidated, including whether it has adverse consequences for the mother or baby.

Text

2024-06-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/85189

Human Nutrition

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/