Oral vitamin B-12 and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia

Background. Hyper-homocyst(e) inemia is an independent risk factor for athe rosclerotic vascular disease in patients with end-stage renal disease (ESRD ), although optimal treatment remains unknown. This randomized, double-blin d, placebo-controlled study was designed to measure the effect of high-dose oral vitamin B-12 and folic acid on predialysis total homocyst(e)ine level s in patients with ESRD. Methods. We studied 81 hemodialysis patients who had hyper-homocyst(e)inemi a (>16 mu mol/L) on varied doses of a multivitamin containing 1 mg of folic acid/day. After screening blood work, all patients were switched to daily multivitamin therapy, including 1 mg of folic acid for four weeks. For all patients, vitamin B-12, 1 mg/day, was added for an additional four weeks. P atients were then randomized to receive four weeks of 0, 5, or 20 mg of fol ic acid in addition to the multivitamin and vitamin Bit tall given daily). Results. Screening homocyst(e)ine levels (mean 27.7 mu mol/L) decreased by 19.2% after four weeks of treatment with a daily multivitamin containing 1 mg of folic acid (P < 0.001). Homocyst(e)ine levels were reduced further fr om 22.3 to 18.6 <mu>mol/L (mean reduction 16.7%, 95% CI 11.8 to 21.6%, P < 0.001) after four weeks of therapy with vitamin B-12 (1 mg/day). There was no significant difference in mean reduction of homocyst(e)ine levels after therapy with high-dose folic acid compared with placebo (P = 0.35). Conclusions. The optimal oral treatment of hyper-homocyst(e)inemia in hemod ialysis patients consists of 1 mg of folic acid and I mg of oral vitamin B- 12 daily. Whether this treatment will lower the risk of future atherosclero tic vascular events remains to be investigated.