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7108009 
Journal Article 
Controlled comparison of l-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients 
Bostom, AG; Selhub, J; Shemin, D; Bagley, P; Massy, ZA; Zanabli, A; Christopher, K; Spiegel, P; Jacques, PF; Dworkin, L; , 
2000 
Yes 
Circulation
ISSN: 0009-7322
EISSN: 1524-4539 
LIPPINCOTT WILLIAMS & WILKINS 
PHILADELPHIA 
2829-2832 
10859289 
WOS:000087731100010 
Background-The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid. We evaluated whether a high-dose L-5-methyltetrahydrofolate-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients.Methods and Results-We block-randomized 50 chronic, stable hemodialysis patients on the basis of their screening predialysis tHcy levels, sex, and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d (FA group) or an equimolar amount (17 mg/d) of oral L-5-methyltetrahydrofolate (MTHF group). All 50 subjects also received 50 mg/d of oral vitamin B-6 and 1.0 mg/d of oral vitamin B-12. The mean percent reductions (+/-95% Cls) in predialysis tHcy were not significantly different: MTHF, 17.0% (12.0% to 22.0%); FA, 14.8% (9.6% to 20.1%); P=0.444 by matched ANCOVA adjusted for pretreatment tHcy. Final on-treatment values (mean with 95% CI) were MTHF, 20.0 mu mol/L (18.8 to 21.2 mu mol/L); FA, 19.5 mu mol/L (18.3 to 20.7 mu mol/L). Moreover, neither treatment resulted in "normalization" of tHcy levels (ie, final on-treatment values <12 mu mol/L) among a significantly different or clinically meaningful number of patients: MTHF, 2 of 25 (8%); FA, 0 of 25 (0%); Fisher's exact test of between-groups difference, P=0.490.Conclusions-Relative to high-dose folic acid, high-dose oral L-5-methyltetrahydrofolate-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (ie, >90%) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution.