Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma.
BACKGROUND
Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma.


METHODS
The Women's Antioxidant and Folic Acid Cardiovascular Study was a randomized, double-blind, placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005. Participants were randomly assigned to receive a combination pill of folic acid (2.5mg), vitamin B(6) (50mg), and vitamin B(12) (1mg) or placebo. This study included 1470 participants who were followed up for as long as 9.2 years and underwent an endoscopy at any point during follow-up. We estimated relative risks using a generalized linear model with a natural logarithm link function and Poisson distributed errors. All statistical tests were two-sided.


RESULTS
The risk of colorectal adenoma was similar among participants receiving treatment (24.3%, 180 of 741 participants) vs placebo (24.0%, 175 of 729 participants) (multivariable adjusted relative risk = 1.00, 95% confidence interval = 0.83 to 1.20). Treatment was not associated with the risk of adenoma when data were analyzed by subsite, size, stage, and the number of adenomas. There was no statistically significant effect modification by alcohol intake, history of cancer or adenoma, or baseline plasma levels or intakes of folate, vitamin B(6), or vitamin B(12).


CONCLUSIONS
Our results indicate no statistically significant effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on colorectal adenoma among women at high risk for cardiovascular disease.
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
Yiqing
Y
Song
Joann E
JE
Manson
I-Min
IM
Lee
Nancy R
NR
Cook
Ligi
L
Paul
Jacob
J
Selhub
Edward
E
Giovannucci
Shumin M
SM
Zhang
D000236:Adenoma / Q000453:epidemiology* / Q000517:prevention & control; D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000517:prevention & control; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016012:Poisson Distribution; D018570:Risk Assessment; D012307:Risk Factors; D014805:Vitamin B 12 / Q000008:administration & dosage*; D025101:Vitamin B 6 / Q000008:administration & dosage*
D016588:Anticarcinogenic Agents; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12