Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial.
OBJECTIVE
Homocysteinemia may play an etiologic role in the pathogenesis of type 2 diabetes by promoting oxidative stress, systemic inflammation, and endothelial dysfunction. We investigated whether homocysteine-lowering treatment by B vitamin supplementation prevents the risk of type 2 diabetes.


METHODS
The Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a randomized, double-blind, placebo-controlled trial of 5,442 female health professionals aged > or = 40 years with a history of cardiovascular disease (CVD) or three or more CVD risk factors, included 4,252 women free of diabetes at baseline. Participants were randomly assigned to either an active treatment group (daily intake of a combination pill of 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12) or to the placebo group.


RESULTS
During a median follow-up of 7.3 years, 504 women had an incident diagnosis of type 2 diabetes. Overall, there was no significant difference between the active treatment group and the placebo group in diabetes risk (relative risk 0.94 [95% CI 0.79-1.11]; P = 0.46), despite significant lowering of homocysteine levels. Also, there was no evidence for effect modifications by baseline intakes of dietary folate, vitamin B6, and vitamin B12. In a sensitivity analysis, the null result remained for women compliant with their study pills (0.92 [0.76-1.10]; P = 0.36).


CONCLUSIONS
Lowering homocysteine levels by daily supplementation with folic acid and vitamins B6 and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for CVD.
Song
Yiqing
Y
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. ysong3@rics.bwh.harvard.edu.
Cook
Nancy R
NR
Albert
Christine M
CM
Van Denburgh
Martin
M
Manson
JoAnn E
JE
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006710:Homocysteine / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D012307:Risk Factors; D014805:Vitamin B 12 / Q000627:therapeutic use; D025101:Vitamin B 6 / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D019207:beta Carotene / Q000627:therapeutic use
D010919:Placebos; D019207:beta Carotene; D006710:Homocysteine; D014810:Vitamin E; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12; D001205:Ascorbic Acid