Effects of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes

Background: Treatment with folic acid and vitamin B-12 appears to be effective in lowering total plasma homocysteine (tHcy) concentrations, but whether vitamin B-12 alone lowers tHcy in patients with normal vitamin B-12 status is unknown. The aims of the present study were to explore the effect of individual supplementation with folic acid or vitamin B-12 on tHcy concentrations in hemodialysis (HD) patients and to compare changes in tHcy concentrations with MTHFR genotype. Methods: We recruited 200 HD patients (119 men) from the '' Umberto I '' Hospital (Frosinone, Italy) and the Dialysis Unit of University Hospital '' Tor Vergata ''. These patients were randomized blindly into 2 groups of 100 each. Unfortunately, during the study, 36 patients in the first group and 16 in the second group died. The first group was treated initially with vitamin B-12 for 2 months and with folic acid for a following 2 months. The second group was treated initially with folic acid and then with vitamin B-12. Samples were drawn before administration of either, after the first and second periods, and again 2 months after treatment. Results: The concentrations of tHcy decreased in both groups after the consecutive vitamin therapies, and the decrease was genotype-dependent. The decrease was greater for the T/T genotype (P < 0.05) and was more significant when the treatment was started with folic acid (P < 0.01). Conclusion: The alternating vitamin treatment demonstrated for the first time the importance of folate therapy and the secondary contribution of vitamin B-12 in lowering tHcy in HD patients. (c) 2006 American Association for Clinical Chemistry.