Vitamin B6 should be added to the combination of folic acid and vitamin B12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients.

We conclude that renal function is the overriding independent determinant of fasting tHcy levels among stable renal transplant recipients. In comparison to renal function, vitamin status has a relatively marginal influence on tHcy levels and cyclosporine use has essentially none at all.

Abstract-The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, Ն6 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 B 6 and 0.4 mg/d vitamin B 12 . The mean percent reductions (ϮSEM) in fasting tHcy were as follows: group 1, 32.3Ϯ2.4%; group 2, 23.4Ϯ2.3%; and group 3, 19.1Ϯ2.3%. 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 (Pϭ0.005) and significant differences between groups 1 and 2 (Pϭ0.038) and groups 1 and 3 (Pϭ0.001), but not between groups 2 and 3 (Pϭ0.153). Moreover, a 2 analysis of participants with pretreatment tHcy levels Ն15 mol/L (nϭ29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels Ͻ12 mol/L: group 1, 5 of 10 (50%); group 2, 1 of 11 (9%); and group 3, 0 of 8 (0%) (Pϭ0.016; test of trend Pϭ0.007). 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. Key Words: hyperhomocysteinemia Ⅲ renal insufficiency Ⅲ treatment Ⅲ controlled trial M ild to moderate hyperhomocysteinemia, either fasting or after methionine loading, appears to be an independent risk factor for arteriosclerotic outcomes in general populations of men and women. 1,2 Stable renal transplant recipients (RTRs) experience an extremely high incidence of arteriosclerotic events relative to general populations free of renal disease. 3 We recently provided controlled evidence that stable RTRs have an excess prevalence of both fasting and post-methionine loading hyperhomocysteinemia, 4 which may contribute to their increased risk for arteriosclerotic cardiovascular disease. Open-label studies using high-dose (5 to 10 mg/d) folic acid supplementation have demonstrated significant reductions in fasting non-protein bound or total homocysteine (tHcy) among RTRs. 5,6 More recently, we provided confirmation of these findings in a randomized, placebo-controlled 6-week study using 5 mg/d of folic acid in combination with 0.4 mg/d of vitamin B 12 . 7 No controlled studies have evaluated the effect of lower, physiological doses of folic acid (eg, 0.4 mg/d, as contained in standard US multivitamins), alone or in combination with vitamins B 12 and B 6 , on fast...

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