Folic acid fortification and colorectal cancer risk

The U.S. has been reported as the only country experiencing a decline in incidence rates of colorectal cancer (CRC), despite increasing prevalence of CRC major risk factors, including the Western dietary pattern and obesity. This paper presents a hypothesis that improved folate status in the U.S. is the factor that could most likely explain the seemingly contradictory phenomenon, although a momentary increase in CRC incidence rates was observed in the later 1990s with the initiation of nationwide folic acid fortification. To corroborate this hypothesis, time trends in CRC incidence rates and death rates in the U.S. were plotted by age, race, and gender based on data from the Surveillance, Epidemiology, and End Results (SEER); data were analyzed by simultaneously addressing the following four critical factors: (1) a long induction period between improved folate status and potential protection of CRC; (2) a change in the U.S. Food and Drug Administration regulation in 1973 on the dose of folic acid allowed in supplements; (3) differential impacts of 1973 regulatory change and 1990s mandatory fortification by race; and (4) changes in CRC screening over time in the U.S. Although this type of analysis precludes a definitive conclusion, available evidence suggests that the increase in CRC incidence rates in the later 1990s is unlikely due to folic acid fortification and, assuming a time lag of a decade or longer to see a benefit on CRC, folate appears to be one of the most promising factors that could explain the downward trend of CRC incidence rates in the U.S.