Increased folic acid intake may reduce colorectal cancer risk

March 1, 2014

New data analysis suggests that the improved folate status in the US due to folic acid fortification could most likely explain the decline in incidence rates of colorectal cancer.

The study analyzed available information on chronological changes in colorectal cancer (CRC) incidence rates and death rates in the US and linked them with points in time when the US Food and Drug Administ- ration had allowed the increase of doses of folic acid in supplements, as well as the introduction of manda- tory fortification. It also took into account more efficient CRC screening over time and the long period between improved folate status and potential preventive effects on CRC development (1). The analysis showed that although protective agents such as calcium, aspirin and hormone replacement therapy, as well as screening endoscopy and a nationwide reduction in smoking, could have contributed to the downward trend of CRC incidence rates in the US, the high prevalence of supplement users and mandatory folic acid fortification of flour and grains more likely explain the fact that the US is the only country in the world where CRC incidence rates are decreasing.

The researchers concluded that these findings support the hypothesis that an adequate folate status during the ages of 45 to 64 years may reduce the CRC risk in later life. At the same time, they alleviate the en- during concern that the momentary, abrupt increase in CRC incidence rates in the mid-1990s might have resulted from excessive folate intake caused by folic acid fortification. At present, long-term cohort studies and their pooled analysis provide compelling evidence for the benefit of adequate folate intake on CRC (2, 3). However, results from randomized controlled trials are conflicting and meta-analyses of trials found no significant effect of folic acid supplementation on CRC (4, 5), in some cases even suggesting that excessive folate intake might promote CRC (6, 7). Assuming a long induction period for folate to exert its full positive effect on CRC risk, most of the existing trials are limited by their short duration of follow-up as to provide a definite conclusion.


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  2. Lee J. E. et al. Folate intake and risk of colorectal cancer and adenoma: modification by time. Am J Clin Nutr. 2011; 93(4):817–825.
  3. Kim D. H. et al. Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer. Cancer Causes Control. 2010; 21(11):1919–1930.
  4. Qin X. et al. Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials. Int J Cancer. 2013; 133(5):1033–1041.
  5. Vollset S. E. et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet. 2013; 381(9871):1029–1036.
  6. Mason J. B. et al. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007; 16(7):1325–1329.
  7. Osterhues A. et al. Shall we put the world on folate? Lancet. 2009; 374(9694):959–961.