Controlled Comparison of l -5-Methyltetrahydrofolate Versus Folic Acid for the Treatment of Hyperhomocysteinemia in Hemodialysis Patients Article (Web of Science)


  • 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% CIs) 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 μmol/L (18.8 to 21.2 μmol/L); FA, 19.5 μmol/L (18.3 to 20.7 μmol/L). Moreover, neither treatment resulted in “normalization” of tHcy levels (ie, final on-treatment values <12 μmol/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.


  • Bostom, Andrew G.
  • Shemin, Douglas
  • Bagley, Pamela
  • Massy, Ziad A.
  • Zanabli, Abdul
  • Christopher, Kenneth
  • Spiegel, Paul
  • Jacques, Paul F.
  • Dworkin, Lance D
  • Selhub, Jacob

publication date

  • 2000

published in

number of pages

  • 3

start page

  • 2829

end page

  • 2832


  • 101


  • 24