High dose B-vitamin treatment of hyperhomocysteinemia in dialysis patients

Andrew G. Bostom, Jean Mayer USDA Human Nutrition Research Center on Aging
Douglas Shemin
Kate L. Lapane
Anne L. Hume
David Yoburn
Marie R. Nadeau
Adrianne Bendich
Jacob Selhub
Irwin H. Rosenberg


Hyperhomocysteinemia, an arteriosclerotic risk factor, persists in 75% of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism, and normal or supernormal plasma status of these vitamins (Atherosclerosis 114:93, 1995). We conducted a placebo-controlled eight-week trial of the effect on plasma homocysteine of adding supraphysiologic dose folic acid (15 mg/day), B-6 (100 mg/day), and B-12 (1 mg/day) to the usual daily dosing of 1 mg folic acid, 10 mg B-6, and 12 μg B-12, in 27 hyperhomocysteinemic dialysis patients. Total plasma homocysteine was measured at baseline, and after four and eight weeks. Blinded analyses revealed no evidence of toxicity in the group randomized to supraphysiologic dose B-vitamin supplementation. Plasma homocysteine was significantly reduced after both four weeks (-29.8% vs. -2.0%; P = 0.0024) and eight weeks (-25.8% vs. +0.6%; P = 0.0009) of active versus placebo treatment. Also, 5 of 15 treated versus 0 of 12 placebo group patients had their plasma Hey reduced to within the normative range (< 15 μmol/liter). Supraphysiologic doses of B-vitamins may be required to correct hyperhomocysteinemia in dialysis patients.