High Folate Supplementation Not Associated with Colorectal Cancer

Deficiency in folate intake is known to cause cancer. However, a very high level of synthetic folate consumption in the form of folic acid in food supplements and fortified food products is believed to promote cancer as well. Fortification of food products was made mandatory in the United States in 1998. Epidemiologic studies have shown that folate intake reduces the risk of colorectal cancer. However, the influence of higher levels of folate has not been investigated. The results of the present study show a statistically significant reduction in the risk of colorectal cancer because of higher consumption of folates.

Folates are essential nutrients available naturally in food and are critical for cell growth and differentiation. Low folate intake is one of the predisposing factors for the development of cancer, especially colorectal cancer.  Folic acid needs to be metabolized by enzymes in the human body before it can undergo the normal physiologic metabolism. High intake of folic acid results in unmetabolized folic acid, which can contribute to carcinogenesis. Since the fortification of certain food products has been made mandatory in the United States, there has been a steady rise in the amount of folate consumed by Americans. This has led to concerns on the safety of such a measure. This study aimed to investigate the risk of colorectal cancer due to high folate intake, since detailed studies on this aspect are unavailable. The effects of different forms of folate, namely naturally available folates and synthetic folates were also evaluated.

* In this study, conducted during 1999 to 2007, 99,523 participants (43,512 men and 56,011 women) from the Cancer Prevention Study II Cohort, aged 50 to 75 years were included.
* The participants answered self-administered questionnaires with respect to their lifestyle, medical conditions, and diagnosis of cancer, every two years from the inception of the study.
* Dietary assessment included frequency of servings of various foods, and their nutrient content was obtained from a nutrient database.
* Questions regarding the frequency of intake of fortified food and food supplements were included in the dietary questionnaire.

Key findings
* High total folate intake (natural and synthetic) was associated with significant reduction in the risk of cancer for both men and women from 2002 to 2007. However, there was no change in the risk profile in the first two years of the study (1999 to 2001).
* The benefits were stronger in women for natural folate, and in men with synthetic folic acid consumption.
* Men showed a significantly reduced risk of colon cancer compared to rectal cancer. Women showed significantly reduced risk of rectal cancer compared to colon cancer due to high folate consumption.
* The overall reduction in both types of cancers was more significant in men than in women.

Next steps/Shortcomings
The reported literature indicates that 15 years of study are required to show significant benefits of folic acid consumption in the reduction of cancer risk. Therefore, longer follow-up studies are needed to confirm the findings of this investigation. Errors in the measurement of folate intake cannot be ruled out. Although most of the risk factors associated with colorectal cancer were accounted for, there could still be a bias due to unmeasured factors.

High folate intake as natural folate or its synthetic variant (folic acid) shows a significant reduction of the risk of colorectal cancer. There was no risk of colorectal cancer due to intake of high levels of folate. This study provides evidence that there is no increase in the incidence of cancer due to consumption of high levels of this vitamin by Americans, and that the risk is fairly reduced because of folate consumption. The reduction in risk of the type of cancer was different in men and women. No scientific explanation could be given for these gender-based differences, and they could have been due to chance.

For More Information:
High Levels of Folate from Supplements and Fortification Are Not Associated with Increased Risk of Colorectal Cancer
Publication Journal: Gastroenterology, July 2011
By Victoria L. Stevens, PhD; Marjorie L. McCullough; American Cancer Society, Atlanta, Georgia

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