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 ! 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 mg=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 ¼ 0.719). In contrast, folic acid supplementation (study part 2) resulted in a homocysteine lowering of 19.6% (P ¼ 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.
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