Folic acid fortification and late‐onset colorectal cancer risk: A systematic assessment of the worldwide evidence

Concerns have been raised about potential hazards associated with folic acid fortification. This study aimed to explore associations between diverse folic acid fortification policies (mandatory vs. no mandatory fortification) and global late-onset colorectal cancer (LOCRC) incidence rates. The study systematically assessed (i) folic acid fortification policies in 193 member states of the World Health Organization, and (ii) age-standardized LOCRC incidence rates by country. We examined the associations between folic acid fortification types and LOCRC incidence using an ecological study design. Incidence trends before and after fortification were analyzed using a log-linear joinpoint regression model, and the annual percent change and average annual percent change with 95% confidence interval were determined for representative countries with mandatory fortification (the United States [U.S.] and Canada). By September 2024, 69 countries enacted mandatory folic acid fortification legislation, while 124 had no fortification. The overall LOCRC incidence rates per 100,000 were 70.8 and 84.0 with mandatory and no mandatory fortification, respectively. The decreasing trends after implementing folic acid fortification were more rapid than in the pre-fortification period in the U.S. and Canada. These findings suggested an association between mandatory folic acid fortification policies and reduced LOCRC incidence. These global data provide a scientific basis for transitioning fortification policies and inform strategies for cancer prevention through the fortification with folic acid.