High Folate Intake May Cut Colorectal Cancer Risk

Jill Stein
Published: Tuesday, Nov 01, 2011
Victoria L. Stevens

Victoria L. Stevens, PhD

New results suggest that a high intake of both natural and synthetic folate is associated with a decreased likelihood of colorectal cancer. The findings, which are from a large prospective analysis of older adults enrolled in a cancer prevention study, also show no increased risk of colorectal cancer for the highest folate intake levels.

Victoria L. Stevens, PhD, with the American Cancer Society in Atlanta, Georgia, and her coauthors said their data suggested that “the high levels of this vitamin consumed by significant numbers of Americans should not lead to higher incidence rates of this cancer in the population.”

Their study examined the association between folate intake and colorectal cancer incidence from 1999 through 2007 in 99,523 men and women enrolled in the Cancer Prevention Study II (CPS-II) Nutrition Cohort. The Nutrition Cohort was started in 1992 as a part of CPS-II, a prospective study of cancer mortality in roughly 1.2 million Americans.

The researchers pointed out that no prior prospective epidemiologic study had explored the relationship between high folic acid intake and colorectal cancer risk exclusively in the so-called “post-fortification period.” The 8-year followup period in their study covered a time frame High Folate Intake May Cut Colorectal Cancer Risk occurring after mandatory folate fortification in the United States. Mandatory folate fortification has spawned an increase in the use of folatecontaining supplements.

They also noted that consumption of high levels of folic acid, which is the synthetic folate used in fortification and supplements, has been found to affect biochemical pathways differently than natural folates and may contribute to carcinogenesis. The study aimed to examine more closely the association between folic acid and colorectal cancer.

In the study cohort, a total of 1023 participants were diagnosed with colorectal cancer during follow-up.

The results revealed that intake of high levels of natural folate (RRQ5vsQ1 = 0.86; 95% confidence interval [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 associated with a significant 19% lower risk (RRQ5vsQ1 = 0.81; 95% CI, 0.66-0.99; P trend = .047).

Stevens and colleagues emphasized that the study’s prospective design is an important strength in that it eliminates the potential for recall bias in nutrient intake levels. Also, the availability of food composition information on natural folates and synthetic folic acid made it possible to examine the associations of each form of folate separately.

Prior research has demonstrated that it takes about 15 years for a significant inverse association with folic acid to emerge. Thus, a lengthier followup period is needed to provide a more accurate gauge about the effect of exposure to current levels of folate consumption on the incidence of colorectal cancer.

The authors also pointed out that individuals who participated in the CPS-II Nutrition Cohort are somewhat healthier than the general US population and have a lower prevalence of very low folate intake. However, despite the lower prevalence of low folate intake, their analysis still showed an inverse association with colorectal cancer risk.

The researchers acknowledged that they cannot exclude the possibility of confounding by unmeasured factors associated with both folate consumption and colorectal cancer risk.


Stevens VL, McCullough ML, Sun J, Jacobs EJ, Campbell PT, Gapstur SM. High levels of folate from supplements and fortification are not associated with increased risk of colorectal cancer [published online ahead of print April 14, 2011]. Gastroenterology. 2011;141(1):98-105.e1.



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