Effect of lowering of homocysteine levels on inflammatory markers - A randomized controlled trial

Background: Elevated concentrations of homocysteine and low concentrations of folate may lead to a pro-inflammatory state that could explain their relation to vascular disease risk. We investigated the effect of lowering homocysteine concentrations by means of folic acid supplementation on markers of inflammation. Methods: In a double-blind, randomized, placebo-controlled trial among 530 men and postmenopausal women with homocysteine concentrations of 1.8 mg/L or higher (>= 13 mu mol/L) at screening, we investigated the effect of folic acid supplementation (0.8 mg/d) vs placebo for 1 year on serum concentrations of C-reactive protein, soluble intercellular adhesion molecule-1, oxidized low-density lipoprotein, and autoantibodies against oxidized low-density lipoprotein. Results: After 1 year of supplementation, concentrations of serum folate increased by 400%, (95% confidence interval [CI], 362%-436%), and those of homocysteine decreased by 28% (95% CI 24%-30%) in the folic acid group compared with the placebo group, However, no changes in plasma concentrations of the inflammatory markers were observed. Conclusions: Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by means of 1-year folic acid supplementation does not influence inflammatory responses involving C-reactive protein, soluble intercellular adhesion molecule-1, oxidized low-density lipoprotein, and autoantibodies against oxidized low-density lipoprotein.