Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention.
BACKGROUND
Vitamin B-6 is necessary for the metabolism of homocysteine and is often used in combination with folic acid and vitamin B-12 in clinical trials that investigate whether the lowering of plasma total homocysteine (tHcy) can prevent vascular disease.


OBJECTIVE
We compared the effects of vitamin B-6 with the effects of folic acid and vitamin B-12, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on basal and postmethionine load (PML) tHcy and cystathionine concentrations.


METHODS
Ninety patients with suspected coronary artery disease were randomly assigned to 1 of 4 groups to receive daily oral treatment with 1) 0.8 mg folic acid, 0.4 mg vitamin B-12, and 40 mg vitamin B-6 (group A); 2) 0.8 mg folic acid and 0.4 mg vitamin B-12 (group B); 3) 40 mg vitamin B-6 (group C); or 4) placebo (group D). For the first 2 wk, groups A and B received additional folic acid (5 mg/d). A methionine-loading test was performed at baseline and after 3 mo.


RESULTS
Treatment with folic acid and vitamin B-12 caused a rapid and significant lowering of basal (31%) and PML tHcy concentrations (22%), with no effect on cystathionine. Vitamin B-6 did not change basal tHcy and had a significant but limited effect on PML tHcy concentrations. However, vitamin B-6 treatment markedly lowered basal and PML cystathionine by 31% and 42%, respectively.


CONCLUSIONS
The folic acid and vitamin B-12 combination applied in WENBIT provides rapid, substantial, and long-term tHcy-lowering effects, whereas the effect of vitamin B-6 on tHcy was relatively small and confined to PML tHcy. However, vitamin B-6 treatment caused a marked reduction in plasma cystathionine. Cystathionine could be a useful marker for assessment of the vitamin B-6 effect and should, together with tHcy, be related to clinical outcome in ongoing trials.
Institute of Medicine, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway. oyvind.bleie@haukeland.no
Øyvind
Ø
Bleie
Helga
H
Refsum
Per Magne
PM
Ueland
Stein Emil
SE
Vollset
Anne Berit
AB
Guttormsen
Ebba
E
Nexo
Jørn
J
Schneede
Jan Erik
JE
Nordrehaug
Ottar
O
Nygård
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D003540:Cystathionine / Q000097:blood*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000378:metabolism; D008875:Middle Aged; D009664:Norway; D011446:Prospective Studies; D014805:Vitamin B 12 / Q000008:administration & dosage*; D025101:Vitamin B 6 / Q000008:administration & dosage*
D006710:Homocysteine; D003540:Cystathionine; D025101:Vitamin B 6; D005492:Folic Acid; D008715:Methionine; D014805:Vitamin B 12