Effect of physiological doses of oral vitamin [B.sub.12] on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India

Background/Objectives: Vitamin [B.sub.12] ([B.sub.12]) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of [B.sub.12] and folic acid on plasma total homocysteine (tHcy) concentration. Subjects/Methods: A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. [B.sub.12] was given as 2 or 10 µg capsules, with or without 200 µg folic acid, forming six groups ([B.sub.0][F.sub.0],[B.sub.2][F.sub.0], [B.sub.10][F.sub.o],[B.sub.0][F.sub.200],[B.sub.2][F.sub.200] and [B.sub.10]F200). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation. Results: From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between [B.sub.12] and folic acid (P = 0.14) in relation to tHcy concentration change and their effects were analyzed separately: [B.sub.0] vs. [B.sub.2] vs. [B.sub.10]; and [F.sub.0] vs. [F.sub.200]. At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) µmol/l in [B.sub.2], and by 7.1 (95% CI: -8.9, -5.4) µmol/l in [B.sub.10], compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) µmol/l in [B.sub.0].[B.sub.2] and [B.sub.10] did not differ significantly. In [F.sub.200], tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) µmol/l compared to 2.8 (95% CI: -4.3, -1.2) µmol/l in [F.sub.0]. Conclusion: Daily oral supplementation with physiological doses of [B.sub.12] is an effective community intervention to reduce tHcy. Folic acid (200 mg per day) showed no additional benefit, neither had any unfavorable effects. doi: 10.1038/ejcn.2010.15; published online 10 March 2010 Keywords: cyanocobalamin; folic acid; homocysteine; randomized controlled trial; South Asian Indians; vitamin [B.sub.12]