High Levels of Folate From Supplements and Fortification Are Not Associated With Increased Risk of Colorectal Cancer

Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303-1002, USA.
Gastroenterology (Impact Factor: 16.72). 04/2011; 141(1):98-105, 105.e1. DOI: 10.1053/j.gastro.2011.04.004
Source: PubMed


Folate intake has been inversely associated with colorectal cancer risk in several prospective epidemiologic studies. However, no study fully assessed the influence of the high levels of folate that are frequently consumed in the United States as a result of mandatory folate fortification, which was fully implemented in 1998, and the recent increase in use of folate-containing supplements. There is evidence that consumption of high levels of folic acid, the form of folate used for fortification and in supplements, has different effects on biochemical pathways than natural folates and might promote carcinogenesis.
We investigated the association between folate intake and colorectal cancer among 43,512 men and 56,011 women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort; 1023 were diagnosed with colorectal cancer between 1999 and 2007, a period entirely after folate fortification began. Cox proportional hazards regression was used to calculate multivariate hazards ratios (RR) and 95% confidence interval (CI).
Intake of high levels of natural folate (RRQ5vsQ1=0.86; 95% CI: 0.70-1.06; P trend=.12) or folic acid (RRQ5vsQ1=0.84; 95% CI: 0.68-1.03; P trend=.06) were not significantly associated with risk of colorectal cancer. Total folate intake was significantly associated with lower risk (RRQ5vsQ1=0.81; 95% CI: 0.66-0.99; P trend=.047).
Intake of high levels of total folate reduces risk of colorectal cancer; there is no evidence that dietary fortification or supplementation with this vitamin increases colorectal cancer risk.

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Available from: Marjorie L Mccullough, May 12, 2014
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    • "However, there are many conflicting data about whether FA can inhibit or promote colorectal adenoma (CRA) from clinical or preclinical studies. Epidemiologic study shows that folic acid is significant associated with lower risk and not related to the increased risk of colorectal cancer, supporting folic acid as a protective role for colon mucosa [12,13], including several large prospective studies in 99,523 participants in the American Cancer Prevention Study II (CPS-II) Nutrition Cohort [12] and in double-blind, randomized clinical trial (RCT) conducted by 9 clinical centers incorporating 1091 participants for 3 years follow up [13]. However, the Aspirin/Folate Polyp Prevention Trial demonstrated that about 67% increased risk of advanced lesions with high malignant potential, and an increased risk of having multiple adenomas among the folic acid supplementation group by providing folic acid for 6 years at 1 mg/d [14]. "
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