Comparative study of response to treatment with supraphysiologic doses of B-vitamins in hyperhomocysteinemic hemodialysis patients

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients. Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment. Methods: In a randomized prospective study, we assessed the effects of folic acid two doses of B-vitamins in 50 hemodialysis patient with hyperhomocyteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B6 daily and one monthly injection of 200 μg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 μg vitamin B12. In addition, both groups received 15mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR alleles were analyzed, as were activate protein C resistance, von Willebrand factor and lupus anticoagulant. Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects. (33.8 ± 4.3 vs 4.5 to 14.0 μmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in groups A and 18.6 ± 1.4 μmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5 was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 μmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 μmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable. Conclusions: Treatment with B-vitamins in combinations with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor the presence of diabetes was associated with higher pre- or post-treatment homocysteine level.