Randomized trial of methylcobalamin and folate effects on homocysteine in hemodialysis patients

There are no data available on the effects of intravenous (i.v.) methylcobalamin (Me-Cbl), the coenzymatically active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of total homocysteine (tHcy) to methionine, with or without oral folic acid (FA) supplementation, on fasting tHcy levels in hemodialysis (HD) patients.

We performed a prospective randomized trial in which 62 chronic HD patients without previous vitamin supplementation were divided into four groups. Group A received Me-Cbl 500 microg twice/week plus FA 10 mg/day; group B received FA 10 mg/day alone; group C received no vitamin supplementation, and group D was on Me-Cbl 500 microg twice/week alone. Fasting tHcy, vitamin B12, serum (s) FA and erythrocytic (e) FA were measured predialysis before and after 4 months of therapy.

Final tHcy levels were significantly lower in group A (10.2 +/- 3.1 micromol/l) compared to groups C (27.3 +/- 9.7 micromol/l, p < 0.001) and group D (24.3 +/- 11.8 micromol/l, p < 0.001) and similar to group B (11.2 +/- 1.9 micromol/l, p = n.s.). Mean tHcy levels showed a significant decrease in group A from 22.5 +/- 15.6 to 10.2 +/- 3.1 micromol/l (p = 0.003) and in group B from 19.9 +/- 4.0 to 11.2 +/- 1.9 micromol/l (p = 0.012), while no significant changes were observed in groups C (25.9 +/- 9.3 vs. 27.3 +/- 9.7 micromol/l, p = n.s.) and D (26.6 +/- 14.3 vs. 24.3 +/- 11.8 micromol/l, p = n.s.).

Oral FA (10 mg/day) supplementation appears to be an effective approach to normalize plasma tHcy in chronic HD patients; the addition of i.v. Me-Cbl (500 microg twice/week) to this regimen showed no benefit. Separately, FA corrected hyperhomocysteinemia (HtHcy), while Me-Cbl showed no change.