Submitted to: Journal of the National Cancer Institute
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/25/2012
Publication Date: 7/26/2012
Citation: Song, Y., Manson, J.E., Lee, I., Cook, N.R., Paul, L., Selhub, J., Giovannucci, E., Zhang, S. 2012. Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma. Journal of the National Cancer Institute. 104(20):1562-1575. Interpretive Summary: There have been some reports which suggest that the combination of a higher supplement of the B vitamins folic acid, b12 and B6 would enhance the risk of colorectal adenoma (cancer). In this study which included over 5000 women who were divided into placebo and supplemental vitamin arms and were followed over several years, found no effect of vitamin supplementation in causing a greater amount of cancer incidents when compared to women who did not receive these vitamins.
Technical Abstract: 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. 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. 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 sub site, 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). 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.