Published Online
on December 22, 2005

A more recent version of this article appeared on February 1, 2006

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Submitted on October 7, 2005
Revised on November 13, 2005
Accepted on November 16, 2005

Efficacy of B Vitamins in Lowering Homocysteine in Older Men. Maximal Effects for Those With B₁₂ Deficiency and Hyperhomocysteinemia

Leon Flicker PhD, FRACP^*; Samuel D. Vasikaran MD, FRCPA; Jenny Thomas RN; John M. Acres Psych; Paul Norman DS, FRACS; Konrad Jamrozik DPhil, FAFPHM; Graeme J. Hankey MD, FRACP; and Osvaldo P. Almeida PhD, FRANZCP

From the Department of Core Clinical Pathology and Biochemistry (S.D.V.) and Stroke Unit (G.H.), Royal Perth Hospital, Perth; Schools of Medicine and Pharmacology (L.F., J.T., J.M.A., G.H.), Psychiatry and Clinical Neurosciences (J.M.A., O.P.A.), and Surgery and Pathology (P.N.), University of Western Australia, Perth; School of Population Health (K.J.), University of Queensland, Brisbane, Queensland, Australia.

^* To whom correspondence should be addressed. E-mail: leonflic{at}cyllene.uwa.edu.au.

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.

Key words: aged • clinical trial • homocysteine • vitamins • vitamin B₁₂ deficiency

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