No effect of B vitamins on ADMA levels in patients at increased cardiovascular risk.
OBJECTIVE
Asymmetric dimethylarginine (ADMA) is a recently identified potent cardiovascular risk factor. ADMA levels are increased in hyperhomocysteinaemia and the metabolism of ADMA is linked with that of homocysteine in several ways. Treatment with B vitamins effectively reduces homocysteine levels, but studies investigating the effect on ADMA levels are scarce and show conflicting results. In this study we evaluated the effect of treatment with B vitamins on ADMA levels in two high cardiovascular risk populations.


METHODS
In study I, 110 siblings of patients with clinical atherosclerotic disease and postmethionine hyperhomocysteinaemia were treated with 5 mg of folic acid and 250 mg of pyridoxine or placebo, and were analysed after 1 year. In study II, 41 patients with type 2 diabetes and mild hyperhomocysteinaemia were analysed after 6 months treatment with 5 mg of folic acid or placebo.


RESULTS
A correlation between baseline homocysteine and ADMA levels was found, which was partly due to confounding by renal function. Homocysteine levels decreased by 43% in study I and by 28% in study II. In both studies, treatment with B vitamins had no effect at all on ADMA, arginine/ADMA ratio and SDMA levels. This result was confirmed in multiple linear regression analyses with adjustment for baseline values and gender.


CONCLUSIONS
Our studies indicate that B vitamins, despite causing a substantial reduction in plasma homocysteine levels, have no beneficial effect on ADMA levels.
Spoelstra-de Man
A M E
AM
Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Teerlink
T
T
Brouwer
C B
CB
Rauwerda
J A
JA
Stehouwer
C D A
CD
Smulders
Y M
YM
D000293:Adolescent; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011736:Pyridoxine / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D014803:Vitamin B Complex / Q000627:therapeutic use*
C487735:dimethylarginine; D014803:Vitamin B Complex; C018524:N,N-dimethylarginine; D005492:Folic Acid; D001120:Arginine; D011736:Pyridoxine