Parenteral vitamin B-12 reduces hyperhomocysteinemia in end-stage renal disease

Objective: The authors found considerably lower plasma total homocysteine ( tHcy) concentrations in patients with end-stage renal disease (ESRD) on mai ntenance hemodialysis, who routinely received high-dose parenteral vitamin B-12, than in comparable patients receiving much higher doses of folic acid but only replacement-dose oral vitamin B-12. They therefore sought prospec tive evidence that high-dose parenterally administered vitamin B-12 may par tially ameliorate renal failure-associated hyperhomocysteinemia. Design: Open phase 2 clinical trial. Setting: Outpatient hemodialysis unit. Patients: Fourteen clinically stable patients on maintenance hemodialysis w ith normal baseline serum vitamin B-12 concentrations. Intervention: Three parenteral injections of 1 mg vitamin B-12 given at 4-w eek intervals. Outcome measures: Plasma tHcy and serum vitamin B-12 concentrations were me asured before, during and 7 months after the termination of vitamin B-12 th erapy. Results: The mean land standard error) baseline plasma tHcy was 26.5 (1.8) mu mol/L. The plasma tHcy value fell successively after each vitamin inject ion to reach a value of 23.6 (1.6) mu mol/L 1 month after the final injecti on (p < 0.05), while the serum vitamin B-12 concentration increased from 47 1 (42) pmol/L to 890 (74) pmol/L (p < 0.05). Seven months after the final i njection, the serum B-12 concentration had fallen and tHcy had risen to nea r their original values. Conclusions: Three monthly vitamin B-12 injections modestly but distinctly reduced tHcy concentrations in hemodialysis patients whose prior vitamin B- 12 status was normal. Randomized placebo-controlled clinical trials of long er duration and using larger or more frequent parenteral doses are indicate d to determine whether administration of this safe and inexpensive vitamin can improve hyperhomocysteinemia in ESRD.