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 withoral 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 micromol/L (18.8 to 21.2 micromol/L); FA, 19.5 micromol/L (18.3 to 20.7 micromol/L). Moreover, neither treatment resulted in "normalization" of tHcy levels (ie, final on-treatment values <12 micromol/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.
RCT Entities:
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 micromol/L (18.8 to 21.2 micromol/L); FA, 19.5 micromol/L (18.3 to 20.7 micromol/L). Moreover, neither treatment resulted in "normalization" of tHcy levels (ie, final on-treatment values <12 micromol/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.
Authors: June Leung; Johanna Dwyer; Patricia Hibberd; Paul Jacques; William Rand; Michael V Rocco Journal: J Ren Nutr Date: 2010-07-21 Impact factor: 3.655
Authors: Bradley L Urquhart; David J Freeman; Murray J Cutler; Rahul Mainra; J David Spence; Andrew A House Journal: Clin J Am Soc Nephrol Date: 2008-03-12 Impact factor: 8.237
Authors: Cinzia Scambi; Lucia De Franceschi; Patrizia Guarini; Fabio Poli; Angela Siciliano; Patrizia Pattini; Andrea Biondani; Valentina La Verde; Oscar Bortolami; Francesco Turrini; Franco Carta; Ciro D'Orazio; Baroukh M Assael; Giovanni Faccini; Lisa M Bambara Journal: PLoS One Date: 2009-03-11 Impact factor: 3.240