Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women

Background: Increased plasma total homocysteine (tHcy) is a risk factor for vascular disease and adverse pregnancy outcomes. Health authorities recommend periconceptional supplementation with 400 microgram folic acid to prevent neural tube defects. Several countries have implemented food fortification with folic acid. However, excessive intake of folic acid could mask an undiagnosed vitamin B-12 deficiency. The biologically active [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF) may be an alternative to folic acid because it is unlikely to mask vitamin B-12 deficiency symptoms. Objective: We compared the tHcy-lowering potential of 2 dosages of [6S]-5-MTHF with that of 400 microgram folic acid during 24 wk of supplementation. Design: In this double-blind, randomized, controlled intervention trial, 144 female participants were supplemented daily with 400 microgram folic acid, 416 microgram [6S]-5-MTHF, 208 microgram [6S]-5-MTHF, or placebo. Concentrations of tHcy and plasma folate were measured at baseline and at 4-wk intervals. Results: After supplementation, there was a significant interaction between time and treatment with respect to changes in tHcy and plasma folate (both P < 0.001 by two-factor repeated-measures analysis of variance). The decrease in tHcy did not differ significantly between the 3 supplemented groups (P > 0.05; Tukey's post hoc test). The increase in plasma folate in the group receiving 208 microgram [6S]-5-MTHF was significantly lower than that in the groups receiving 400 microgram folic acid (P < 0.001) or 416 microgram [6S]-5-MTHF (P < 0.05). Conclusions: [6S]-5-MTHF was shown to be an adequate alternative to folic acid in reducing tHcy concentrations. Supplementation with 416 microgram [6S]-5-MTHF was no more effective than that with 208 microgram [6S]-5-MTHF.