Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B-6, B-12 and folate

Hyperhomocyst(e)inemia is commonly accepted as an independent. atherosclero tic risk factor. In most hemodialysis patients, serum homocyst(e)ine is mar kedly elevated and may contribute to premature atherosclerosis in these pat ients. Whereas the beneficial effect of folate supplementation on serum hom ocyst(e)ine has been extensively studied, there are less detailed studies o n the effects of cobalamin and pyridoxal phosphate alone, or in combination with folate. We examined the effect of a four-week course of intravenous t reatment with folate (1.1 mg), cobalamin (1.0 mg), and pyridoxal phosphate (5.0 mg), administered once (group 1), twice (group 2) or thrice (group 3) weekly in 33 hemodialysis patients divided in three groups of 11 patients. All patients were followed for a further four weeks after treatment was sto pped. Serum homocyst(e)ine, cobalamin, folate and pyridoxal phosphate, as w ell as the metabolites of homocyst(e)ine, methylmalonate, 2-methylcitrate a nd cystathionine, were determined before, during and after treatment. Basel ine serum homocyst(e)ine correlated significantly with serum folate (P = 0. 0149), cobalamin (P = 0.0047) and pyridoxal phosphate (P = 0.0408). Correla tions independent from the other metabolites or vitamins were found for met hylmalonate (P = 0.003) and folate (P = 0.029). All regimens increased seru m cobalamin significantly (in group 1 from 444 +/- 215 to 17,303 +/- 11,989 pg/ml, P < 0.01; in group 2 from 542 <plus/minus> 633 to 44,896 +/- 15,772 pg/ml, P < 0.001; in group 3 from 548 <plus/minus> 394 to 77,961 +/- 31,54 6 pg/ml, P < 0.001), but did not increase any of the other vitamin levels. Serum homocyst(e)ine was lowered significantly by 39.8% <plus/minus> 31.9% (P < 0.05) with two and by 30.1% <plus/minus> 26.9% (P < 0.05) with three v itamin dosages weekly, but not with one dosage weekly. Since methylmalonate is known to be a sensitive marker of cobalamin deficiency, the data suppor t an important influence of cobalamin levels on baseline homocyst(e)ine lev els. Increasing cobalamin levels and additional treatment with folate and p yridoxal phosphate may decrease serum homocyst(e)ine in the same way as hig h doses of folate alone.