Efficacy of B vitamins in lowering homocysteine in older men: Maximal effects for those with B12 deficiency and hyperhomocysteinemia

Abstract

Background and Purpose— A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. Methods— We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged 75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B6, and 400 µg of B12 or placebo. The study groups were balanced regarding age (mean±SD, 78.9±2.8 years), B vitamins, and tHcy at baseline. Results— Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 µmol/L (95% CI, 3.94 to 9.55 µmol/L) compared with 2.88 µmol/L (95% CI, 0.07 to 5.69 µmol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 µmol/L (95% CI, 0.6 to 4.9 µmol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r=0.252, r=0.522, and r=–0.903, respectively; P=0.003, <0.001, and <0.001, respectively) in the vitamin group. Conclusions— The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.