Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial.

BACKGROUND Young children in low- and middle-income countries frequently have inadequate vitamin B-12 (cobalamin) status. Poor folate status is also common and is associated with increased diarrheal and respiratory morbidity. OBJECTIVE The objective was to measure the effect of folic acid and/or vitamin B-12 administration on the incidence of diarrhea and acute lower respiratory tract infections. DESIGN One thousand North Indian children (6-30 mo of age) were enrolled in a randomized, double-blind, placebo-controlled trial to receive 2 times the Recommended Dietary Allowance of folic acid and/or vitamin B-12 or placebo daily for 6 mo. Children were individually randomly assigned in a 1:1:1:1 ratio in blocks of 16. Primary outcomes were the number of episodes of acute lower respiratory infections, diarrhea, and prolonged diarrhea. RESULTS Folic acid and vitamin B-12 supplementation significantly improved vitamin B-12 and folate status, respectively. Neither folic acid nor vitamin B-12 administration reduced the incidence of diarrhea or lower respiratory infections. In comparison with placebo, children treated with folic acid alone or in combination with vitamin B-12 had a significantly higher risk of persistent diarrhea (OR: 2.1; 95% CI: 1.1, 3.8). CONCLUSIONS Folic acid or vitamin B-12 supplementation did not reduce the burden of common childhood infections. In view of the increased risk of diarrhea, the safety of folic acid supplements in young children should be further assessed. This trial was registered at www.clinicaltrials.gov as NCT00717730 and at www.ctri.nic.in as CTRI/2010/091/001090.