Vitamin B12, Folate, and Cognition in 6- to 9-Year-Olds: A Randomized Controlled Trial

Pediatrics. 2020 Mar;145(3):e20192316. doi: 10.1542/peds.2019-2316. Epub 2020 Feb 4.


Background and objectives: Vitamin B12 and folate are important for normal brain development. Our objective for this study was to measure the effects of 6-month supplementation of vitamin B12 and/or folic acid in early childhood on cognition when the children were 6 to 9 years old.

Methods: The study is a follow-up of a factorial randomized, double-blind, placebo-controlled trial in 1000 North Indian children. Children 6 to 30 months of age were randomly assigned to receive a placebo or 1.8 µg of vitamin B12, 150 mg of folic acid, or both daily for 6 months. After 6 years, we re-enrolled 791 of these children for cognitive assessments. We compared the scores of the main outcomes (the Wechsler Intelligence Scale for Children, Fourth Edition [India], the Crichton Verbal Scale, and subtests of the NEPSY-II) between the study groups. We also measured the associations between markers of the B vitamins (plasma cobalamin, folate, and total homocysteine concentrations) in early childhood and the cognitive outcomes.

Results: There were no differences between the intervention groups and the placebo group on the cognitive outcomes. Plasma cobalamin, folate, and total homocysteine concentrations in early childhood were associated with the cognitive outcomes at follow-up in the unadjusted models. These associations disappeared in models adjusted for relevant confounders.

Conclusions: Our findings, from both an observational and a randomized design suggest that vitamin B12 and folate in children 6 to 36 months have limited public health relevance for long-term cognition.

Trial registration: NCT00717730.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child Development*
  • Cognition*
  • Double-Blind Method
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • India
  • Intelligence Tests
  • Language Development
  • Male
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / blood
  • Vitamin B Complex / administration & dosage*


  • Homocysteine
  • Vitamin B Complex
  • Folic Acid
  • Vitamin B 12

Associated data

  • CTRI/CTRI/2010/091/001090
  • CTRI/CTRI/2016/11/007494