Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients

Abstract

The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, ≥6 months posttransplantation) renal transplant recipients (RTRs) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid. There are no controlled data evaluating the comparative efficacy of supraphysiological versus standard multivitamin dose folic acid supplementation in reducing fasting total homocysteine (tHcy) levels among RTRs. We block-randomized 60 chronic, stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid at either 2.4 (group 1), 0.4 (ie, standard multivitamin dose) (group 2), or 0.0 (group 3) mg/d. All 60 study participants also received 50 mg/d vitamin B6 and 0.4 mg/d vitamin B12. The mean percent reductions (±SEM) in fasting tHcy were as follows: group 1, 32.3±2.4%; group 2, 23.4±2.3%; and group 3, 19.1±2.3%. ANCOVA accounting for the pretreatment matching and adjusted for pretreatment levels of fasting tHcy, folate, and albumin; change in creatinine during the study; and cyclosporine A use revealed significant overall group differences (P=0.005) and significant differences between groups 1 and 2 (P=0.038) and groups 1 and 3 (P=0.001), but not between groups 2 and 3 (P=0.153). Moreover, a χ2 analysis of participants with pretreatment tHcy levels ≥ 15 μmol/L (n=29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels <12 μmol/L: group 1, 5 of 10 (59%); group 2, 1 of 11 (9%); and group 3, 0 of 8 (0%) (P=0.016; test of trend P=0.007). We conclude that a supraphysiological dose of folic acid is superior to standard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs.