Effects of riboflavin and folic acid supplementation on plasma homocysteine levels in healthy subjects

Background. Observational studies have shown an inverse relationship between vitamin 132 status and total homocysteine levels, a risk factor for cardiovascular disease. We hypothesize that intervention with riboflavin will lower total homocysteine levels. The total homocysteine lowering by the three genotypes (CC, CT, TT) of methylenetetrahydrofolate reductase polymorphism (677C -> T) was also studied. Methods: The decrease in total homocysteine levels after supplementation with riboflavin (10 mg/d) or folic acid (I mg/d) for 3 weeks was compared in two groups of healthy subjects (17 per group, matched by age and gender) (Phase 1). Then, both groups received supplementation with folic acid and riboflavin for an additional 3 weeks (Phase 2). Results: During Phase 1, total homocysteine levels were lowered by 2% or 4% after supplementation with riboflavin or fatty acid, respectively, although neither decrease was statistically significant (P = 0.50 and 0.19). Compared to subjects of CC genotype, total homocysteine lowering in subjects of CT genotype was approaching significance (P = 0.059) for the folic acid group, but not for the riboflavin group. After Phase 2, total homocysteine levels were not lowered significantly in either the folic acid (1%) or the riboflavin (2%) group. However, in the folic acid-riboflavin combined group, total homocysteine lowering in subjects of TT type was larger when compared to subjects of CC and CT types (P = 0.007). Conclusions: Riboflavin supplementation did not lower total homocysteine levels in healthy subjects with CC type of C677T polymorphism. However, supplementation with folic acid or with both folic acid and riboflavin may be important for CT and TT subjects in optimizing their homocysteine metabolism. These findings are relevant in characterizing the factors controlling the high total homocysteine levels for subjects of CT and TT genotypes.