Controlled Comparison of L-Folinic Acid Versus Folic Acid for the Treatment of Hyperhomocysteinemia in Hemodialysis Patients
Background:The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid. We evaluated whether a high dose L-folinic acid based regimen provided improved total homocysteine (tHcy) -lowering efficacy in chronic hemodialysis patients, as suggested by a recent uncontrolled report. Methods and Results: We block randomized 48 chronic, stable hemodialysis patients based on their screening pre-dialysis tHcy levels, sex, and dialysis center, into 2 groups of 24 subjects treated for 12-weeks with oral folic acid (FA) at 15 mg/day, or an equimolar amount (20 mg/day) of oral L-folinic acid(FNA)[L-5-formyltetrahydrofolate]. All 48 subjects also received 50 mg/day of oral vitamin B6, and 1.0 mg/day of oral vitamin B12. The mean percent (%) reductions (with 95% confidence intervals) in pre-dialysis tHcy were not significantly different: FNA= 22.1% (11.8-31.4%) ; FA=20.7% (11.7-30.5%) ; P= 0.950 by paired t-test. Final on-treatment values (mean with 95% confidence interval) were, FNA: 15.9 μmol/L (14.0-18.0); FA: 16.9 μmol/L (14.8-18.8). Moreover, in those subjects with baseline tHcy levels ≥14 μmol/L, neither treatment resulted in normalization of tHcy levels (i.e., final on-treatment values < 12 μmol/L) among a significantly different, or clinically meaningful number of patients: FNA= 2/22 (9.1%); FA= 2/24 (8.3%); Fisher s exact test of between groups difference, P=1.000. Conclusions: Relative to high dose folic acid, high dose oral L-folinic acid -based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (i.e., > 90%) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen.