Effect of Combined Folic Acid, Vitamin B-6, and Vitamin B-12 on Colorectal Adenoma

Harvard University, Cambridge, Massachusetts, United States
Journal of the National Cancer Institute (Impact Factor: 12.58). 10/2012; 104(20):1562-75. DOI: 10.1093/jnci/djs370
Source: PubMed


Background Folic acid, vitamin B6, and vitamin B12 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 B6 (50mg), and vitamin B12 (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 B6, or vitamin B 12. Conclusion Our results indicate no statistically significant effect of combined folic acid, vitamin B6, and vitamin B12 treatment on colorectal adenoma among women at high risk for cardiovascular disease.

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    • "Biomarkers or dietary histories indicative of nutritional deficiencies associated with defects in one-carbon metabolism (for example, folate deficiency) have frequently been associated with an increased risk of cancer in epidemiological studies. Disappointingly, however, intervention trials have failed to demonstrate a reduction of cancer risk in individuals randomized to receive folic acid supplements compared to controls (Andreeva et al., 2012; Cole et al., 2007; Song et al., 2012; Zhang et al., 2008). This might suggest that folate deficiency correlates with, but does not cause, cancer or that folate is important during an early time window, perhaps occurring at an early age and prior to or during tumor initiation, but not thereafter . "
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