Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation.
BACKGROUND
Hyperhomocysteinaemia, which is considered to be induced by impairment of the remethylation pathway in patients with chronic renal failure (CRF), cannot be cured solely by folic acid therapy. In the present study, we investigated the additional benefit of administration of methylcobalamin, which is a co-enzyme in the remethylation pathway, on lowering total homocysteine (tHcy) plasma concentrations in haemodialysis (HD) patients receiving high-dose folic acid supplementation.


METHODS
In order to assess the efficacy on lowering plasma tHcy levels (fasting concentration), 21 HD patients, were randomly assigned and provided folic acid supplementation: 15 mg/day orally (group I, n=7); methylcobalamin 500 mg intravenously after each HD, in addition to folic acid (group II, n=7); or vitamin B(6) (B(6)), 60 mg/day orally, in addition to folic acid and methylcobalamin (group III, n=7). All patients were treated for 3 weeks. A methionine-loading test was conducted before and after supplementation. The following measurements were also made before and after supplementation for each group: serum folic acid, B(6), and vitamin B(12) (B(12)) concentrations (including measurement of proportion of methylcobalamin fraction). Twelve HD patients receiving methylcobalamin alone served as the HD control group and seven healthy volunteers served as the normal control group for this study.


RESULTS
In our randomized HD patients the proportions of methylcobalamin fraction (48.3+/-7.5%) and plasma vitamin B(6) concentration (2.9+/-1.1 ng/ml) were significantly lower than in the normal controls (methylcobalamin 58.7+/-2.2%, P<0.01; B(6) 20.1+/-10.8 ng/ml, P<0.01), while folic acid and vitamin B(12) were not significantly different from the normal controls. Mean percentage reduction in fasting tHcy was 17.3+/-8.4% in group I, 57.4+/-13.3% in group II, 59.9+/-5.6% in group III, and 18.7+/-7.5% in HD controls. The power of the test to detect a reduction of tHcy level was 99.6% in group II and 99.9% in group III when type I error level was set at 0.05. Groups II and III had normal results for the methionine-loading test after treatment. Treatment resulted in normalization of fasting tHcy levels (<12 ng/ml) in all 14 patients treated by the combined administration of methylcobalamin and supplementation of folic acid regardless of whether there was supplementation of vitamin B(6).


CONCLUSIONS
The benefit of methylcobalamin administration on lowering plasma tHcy levels in HD patients was remarkable. Our study suggested that both supplementations of high-dose folic acid and methylcobalamin are required for the remethylation pathway to regain its normal activity. This method could be a therapeutic strategy to combat the risk associated with atherosclerosis and cardiovascular disease in patients with chronic renal failure.
Koyama
Katsushi
K
Department of Internal Medicine and Pathophysiology, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan. kk0114@med.nagoya-cu.ac.jp
Usami
Takeshi
T
Takeuchi
Oki
O
Morozumi
Kunio
K
Kimura
Genjiro
G
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009994:Osmolar Concentration; D006435:Renal Dialysis; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D025101:Vitamin B 6 / Q000097:blood / Q000627:therapeutic use
D006710:Homocysteine; D025101:Vitamin B 6; D005492:Folic Acid; D008715:Methionine; C019476:mecobalamin; D014805:Vitamin B 12