L-folinic acid versus folic acid for the treatment of hyperhomocysteinemiain hemodialysis patients Rapid Communication

Background. The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysi ological doses of folic acid (FA). We evaluated whether a high-dose L-folin ic acid-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients, as suggested by a recent uncontr olled report. Methods. We block-randomized 48 chronic, stable hemodialysis patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 24 subjects treated for 12 weeks with oral FA at 15 mg/day or an equimolar amount (20 mg/day) of oral L-folinic acid (FNA) [L-5-formylte trahydrofolate]. All 48 subjects also received 50 mg/day of oral vitamin B- 6 and 1.0 mg/day of oral vitamin B-12 Results. The mean percentage (%) reductions (with 95% CIs) in predialysis t Hcy were not significantly different [FNA = 22.1% (11.8 to 31.4%), FA = 20. 7% (11.7 to 30.5%), P = 0.950 by paired t test]. Final on-treatment values (mean with 95% CI) were as follows: FNA, 15.9 mu mol/L (14.0 to 18.0); FA, 16.9 mu mol/L (14.8 to 18.8). Moreover, in those subjects with baseline tHc y levels greater than or equal to 14 mu mol/L, neither treatment resulted i n "normalization" of tHcy levels (that is, final on-treatment values <12 <m u>mol/L) among a significantly different or clinically meaningful number of patients [FNA = 2 out of 22 (9.1%); FA = 2 out of 24 (8.3%); Fisher's exac t test of between groups difference, P=1.000]. Conclusions. Relative to high-dose FA, high-dose oral L-folinic acid-based supplementation does not afford improved tHcy-lowering efficacy in hemodial ysis patients. The preponderance of hemodialysis patients (that is, >90%) e xhibits mild hyperhomocysteinemia refractory to treatment with either regim en.