Hyperhomocysteinemia in hemodialysis patients: Effects of 12-month supplementation with hydrosoluble vitamins

Background. High-efficiency hemodialysis may induce a deficiency in hydrosoluble vitamins. Supplementation with B-complex vitamins has been shown to lower serum homocysteine concentrations in several groups, but relatively few studies have concerned hemodialysis patients. Our objectives were to determine the status in B-complex vitamins in a large cohort of unsupplemented hemodialysis patients and to assess the effects of supplementation with hydrosoluble vitamins on serum homocysteine over one year. Methods. Serum total homocysteine (tHcy), vitamin B-12, folate, pyridoxal-5'-phosphate (P-5'-P; the active moiety of vitamin B-6), as well as red blood cell folate concentrations, were measured in 168 chronic dialysis patients on three times weekly high-efficiency hemodialysis and not supplemented with hydrosoluble vitamins. Their methylenetetrahydrofolate reductase C677T (MTHFR) genotypes were also determined (homozygotes TT, heterozygotes CT, without mutation CC). All involved patients were then supplemented with hydrosoluble vitamins (once daily by mouth, DiaVite(R); R&D Laboratories, Minneapolis, MN, USA), and half of them were randomized to receive in addition 10 mg intravenously of folic acid posthemodialysis (30 mg intravenously per week). Serum tHcy was monitored after 6 and 12 months of supplementation in the 140 and 128 patients available for follow-up. Results. At baseline, serum and red blood cell folate concentrations were within normal limits in all patients except for two with borderline serum folate (mean values of 21 +/- 8 and 1195 +/- 454 nmol/L), whereas serum vitamin B-12 and P-5'-P were below normal in 11 and 65 patients, respectively (mean values of 327 +/- 215 pmol/L and 19 +/- 16 nmol/L for the 168 patients). Initial tHcy levels were increased in all patients (mean 33.3 +/- 16.6 for a normal below 11.8 +/- 1.5 mu mol/L); tHcy significantly decreased to 23.5 +/- 7.6 mu mol/L after six months (P < 0.0001 vs. baseline) and to 21.7 +/- 6.1 mu mol/L after 12 months (P < 0.0001 vs. baseline) for the entire group, but was normalized in only four patients at 12 months. After six months, the mean reduction in tHcy was slightly but significantly greater for patients receiving intravenous folic acid (12.2 +/- 18.5 mu mol/L) compared with patients not receiving it (8.3 +/- 9.8 mu mol/L, P < 0.05). However, at 12 months, no difference between both subgroups persisted. When considering the different genotypes, tHcy at baseline tended to be higher for TT than CT and CC (39.8 +/- 30.9 vs. 31.4 +/- 10.5 vs. 31.6 +/- 11.8 mu mol/L) and decreased to respective values of 21.1 +/- 6.9 versus 21.4 +/- 6.1 versus 22.2 +/- 5.9 mu mol/L at 12 months. The impact of the addition of folic acid to DiaVite(R) appeared particularly significant in TT patients at six months. Conclusions. (1) Hyperhomocysteinemia was present in 100% of our hemodialysis patients. (2) Nearly 40% of our unsupplemented hemodialysis patients were deficient in vitamin B-6. (3) Supplementation with DiaVite(R) has resulted in significant tHcy reductions for all three genotypes. (4) The impact of the proposed supplementation protocol was found after six months and was maintained, but did not increase further after 12 months of the same regimen. (5) The addition of intravenous folic acid has been associated with a more pronounced decrease in tHcy in TT patients.