Folic acid in endothelial function in familial hypercholesterolemia.

Familial Hypercholesterolemia To the Editor: Verhaar and colleagues, in their recent article,1 report on improvement in forearm endothelial function after 4 weeks’ oral treatment with folic acid at a dose of 5 mg daily in 20 subjects. They used a randomized crossover design without an intervening washout period. Our research group conducted a similar randomized crossover study of folate supplementation in healthy subjects with hyperhomocysteinemia2 in which 18 subjects received oral folic acid 5 mg daily for a slightly longer period of 6 weeks. We included a washout period of 6 weeks between treatments, but despite this, there was a considerable carryover effect in those subjects who received folic acid before placebo. This was not surprising considering the high dose of folic acid used and the fact that folic acid is stored in red blood cells, which have a life span of '120 days. Such carryover effects in trials involving the use of folic acid have important implications in the interpretation of results and in the design of such studies. The authors do not mention any carryover effect in their article. Was any such effect observed in those subjects randomized to receive folic acid first? Examination of the red cell, folate levels of the baseline and placebo groups given in their article would suggest there was.