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

Background & Aims

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.

Methods

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).

Results

Intake of high levels of natural folate (RR_Q5vsQ1 = 0.86; 95% CI: 0.70–1.06; P trend = .12) or folic acid (RR_Q5vsQ1 = 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 (RR_Q5vsQ1 = 0.81; 95% CI: 0.66–0.99; P trend = .047).

Conclusions

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.

Keywords: Carcinogenesis, B Vitamins, Cancer Prevention, CRC, Epidemiology

Abbreviations used in this paper: CI, confidence interval, CPS-II, Cancer Prevention Study II, FFQ, food frequency questionnaire, RR, relative risk