Effect of riboflavin supplementation on plasma homocysteine in elderly people with low riboflavin status

Eur J Clin Nutr. 2002 Sep;56(9):850-6. doi: 10.1038/sj.ejcn.1601402.


Objective: To investigate the effect of riboflavin supplementation on plasma homocysteine (tHcy) concentrations in healthy elderly people with sub-optimal riboflavin status.

Design: A double-blind, randomized, placebo-controlled riboflavin supplementation trial.

Setting: Community based study in Northern Ireland.

Subjects: From a screening sample of 101 healthy elderly people, 52 had sub-optimal riboflavin status (erythrocyte glutathione reductase activation coefficient, EGRAC>or=1.20) and were invited to participate in the study.

Intervention: The intervention had two parts. Part 1 was a 12 week randomized double blind, placebo-controlled intervention with riboflavin (1.6 mg/day). Following completion of part 1, the placebo group went on to part 2 of the study which involved supplementation with folic acid (400 micro g/day) for 6 weeks followed by folic acid and riboflavin (1.6 mg/day) for a further 12 weeks, with a 16 week washout period post-supplementation. The purpose of part 2 was: (a) to address the possibility that homocysteine-lowering in response to riboflavin may be obscured by a much greater effect of folate, and that, once folate status was optimized, a dependence of homocysteine on riboflavin might emerge; and (b) to demonstrate that these subjects had homocysteine concentrations which could be lowered by nutritional intervention.

Results: Although riboflavin supplementation significantly improved riboflavin status in both parts 1 and 2 of the study (P<0.001 for each), tHcy concentrations were unaffected (P=0.719). In contrast, folic acid supplementation (study part 2) resulted in a homocysteine lowering of 19.6% (P=0.001).

Conclusion: Despite the metabolic dependency of tHcy on riboflavin, it did not prove to be an effective homocysteine-lowering agent, even in the face of sub-optimal riboflavin status.

Publication types

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

MeSH terms

  • Aged
  • Analysis of Variance
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Folic Acid / blood
  • Homocysteine / blood*
  • Humans
  • Male
  • Northern Ireland
  • Photosensitizing Agents / therapeutic use*
  • Riboflavin / therapeutic use*
  • Riboflavin Deficiency / diet therapy*
  • Vitamin B 12 / blood


  • Photosensitizing Agents
  • Homocysteine
  • Folic Acid
  • Vitamin B 12
  • Riboflavin