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 atherosclerotic vascular disease in patients with end-stage renal disease (ESRD), although optimal treatment remains unknown. This randomized, double-blind, 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 levels in patients with ESRD.


METHODS
We studied 81 hemodialysis patients who had hyper-homocyst(e)inemia (>16 micromol/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. Patients were then randomized to receive four weeks of 0, 5, or 20 mg of folic acid in addition to the multivitamin and vitamin B(12) (all given daily).


RESULTS
Screening homocyst(e)ine levels (mean 27.7 micromol/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 from 22.3 to 18.6 micromol/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 hemodialysis patients consists of 1 mg of folic acid and 1 mg of oral vitamin B(12) daily. Whether this treatment will lower the risk of future atherosclerotic vascular events remains to be investigated.
Division of Nephrology, Department of Internal Medicine, Department of Pediatrics and Medical Genetics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada.
B
B
Manns
E
E
Hyndman
E
E
Burgess
H
H
Parsons
J
J
Schaefer
F
F
Snyder
N
N
Scott-Douglas
D000284:Administration, Oral; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014805:Vitamin B 12 / Q000627:therapeutic use*
D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12