THE EFFECTS OF FOLIC-ACID SUPPLEMENTATION ON PLASMA TOTAL HOMOCYSTEINE ARE MODULATED BY MULTIVITAMIN USE AND METHYLENETETRAHYDROFOLATE REDUCTASE GENOTYPES

Elevated concentration of plasma total homocysteine (tHcy) is a common risk factor for arterial occlusive diseases. Folic acid (FA) suppleme ntation usually lowers tHcy levels, but initial tHcy and vitamin level s, multivitamin use, and poly morphisms in the gene for 5,10-methylene tetrahydrofolate reductase (MTHFR) may contribute to variability in re duction. We tested the effects of a 3-week daily intake of 1 or 2 mg o f FA supplements on tHcy levels in patients with and without coronary heart disease (CHD) who were analyzed for the C677T MTHFR mutation. Pr ior multivitamin intake and baseline vitamin and tHcy levels were also compared with responsiveness to folate supplementation. Both dosages of FA lowered tHcy levels similarly, regardless of sex, age, CHD statu s, body mass index, smoking, or plasma creatinine concentration. In no n-multivitamin users, FA supplements reduced tHcy by 7% in C/C homozyg otes and by 13% or 21% in subjects with one or two copies of the T677 allele, respectively; the corresponding reductions were smaller in use rs of multivitamins. Moreover, T/T homozygotes had elevated tHcy and i ncreased susceptibility to high levels of tHcy at marginally low plasm a folate levels, as well as enhanced response to the tHcy-lowering eff ects of FA. Although other factors are probably involved in the respon siveness of tHcy levels to FA supplementation, about one third of hete rogeneity in responsiveness was attributable to baseline tHcy and fola te levels and to multivitamin use.