Comparative effects of hydroxocobalamin and cyanocobalamin on plasma homocysteine concentrations in end-stage renal disease.

End-stage renal disease (ESRD) is associated with marked hyperhomocysteinemia which is only partially corrected by folic acid and pyridoxine supplementation. We and others have reported that various forms of parenteral cobalamin reduce plasma total homocysteine (tHcy) concentrations of patients with ESRD substantially below the lowest levels attainable with folic acid. We here report a 16-week randomized controlled crossover trial which directly compared the Hcy-lowering effect of intravenous hydroxocobalamin (HC) with that of cyanocobalamin (CC). Folic acid- and vitamin B12-replete maintenance hemodialysis patients were randomly assigned to receive either 1 mg intravenous HC weekly for 8 weeks followed by CC for a further 8 weeks, or CC for 8 weeks followed by HC for 8 weeks. Hydroxocobalamin increased serum cobalamin concentrations 40-fold, whereas CC increased them only 10-fold, but both treatments reduced plasma tHcy concentrations similarly by 33% (P < .001). Crossover to the alternate form of the vitamin greatly affected the serum cobalamin concentration but was without further effect on the plasma tHcy concentration. These results confirm that weekly cobalamin injections lower plasma tHcy concentrations of hemodialysis patients well below the level attainable with folic acid. Hydroxocobalamin and CC are equipotent despite producing very different serum cobalamin concentrations.

Cobalamin dose regimen for maximum homocysteine reduction in end-stage renal disease.

Plasma total homocysteine (tHcy) concentrations are markedly increased in end-stage renal disease and only partially corrected by folic acid supplementation. We and others have reported that cobalamin, administered parenterally, reduces plasma tHcy substantially below the lowest concentrations attainable with folic acid. We have now carried out a randomized controlled clinical trial to compare the plasma Hcy-lowering effect of 3 intravenous cyanocobalamin dose regimens in maintenance hemodialysis patients: 1 mg postdialysis every 28, 14, and 7 days in addition to routine oral vitamin B supplementation. All patients in the hemodialysis unit where the study was carried out routinely received 1 mg intravenous cyanocobalamin every month, so participants who were randomized to receive the vitamin every 28 days simply continued with their existing treatment program. Serum cobalamin and plasma tHcy concentrations in the control group did not change over the course of the study. As measured after 8 weeks of therapy, intravenous cyanocobalamin every 14 days increased serum cobalamin approximately 2.5-fold and reduced plasma tHcy by 11.5% ( P = .035) below the concentration previously attained with monthly administration, whereas treatment every 7 days increased serum cobalamin concentrations approximately 5-fold and reduced plasma tHcy by 11.0% ( P = .013). These results show that intravenous cyanocobalamin at 7- or 14-day intervals reduces plasma tHcy concentrations of hemodialysis patients below the levels brought about by prior long-term administration every 4 weeks and confirms that plasma tHcy lowering with parenteral cobalamin is a true pharmacological effect and not merely correction of a latent deficiency state.

N-acetyl-L-tyrosine as a tyrosine source in adult parenteral nutrition.

BACKGROUND: N-acetyl-L-tyrosine (NAT) is commonly used in place of tyrosine in parenteral nutrition, but human studies carried out to date indicate considerable amounts of it are excreted unchanged in the urine. NAT retention has not been well studied in parenterally fed adults. METHODS: NAT retention was measured in 13 adults receiving continuous parenteral nutrition with Aminosyn II 15% (Abbott Laboratories, Abbott Park, IL). RESULTS: Approximately 35% of administered NAT was excreted unchanged in the urine, with no important effect of infusion rate, N balance, or level of renal function on this value. Sufficient NAT was retained that the prescription of 1 g total amino acids/kg x day(-1) using this product exceeded the combined recommended dietary allowance for aromatic amino acids CONCLUSION: As used in the clinical setting, the phenylalanine and NAT composition of Aminosyn II is sufficient to meet the combined aromatic amino acid needs of adults with normal phenylalanine hydroxylase activity.