Folate intake, tissue levels, and colorectal cancer deaths in a national cohort established before folic acid fortification

Objectives: The relationship between folate and the risk of colorectal cancer (CRC) remains inconclusive. To control for the interference from folic acid fortification, we assessed the relationship between folate intake, serum folate, and red blood cell (RBC) folate levels and the risk of CRC death in a cohort established before fortification. Methods: We analyzed the data of 14,528 adults aged 19 years or older who participated in the National Health and Nutrition Examination Survey (1988–1994) as the baseline examination and were followed through December 31, 2006. Hazard ratios (HR) of CRC deaths were estimated for individuals with different folate intake and biomarker levels. Covariates included age, sex, family income, race/ethnicity, cigarette smoking, alcohol drinking, serum cotinine, vitamin supplements, and dietary energy intake. Results: After 192,973 person-years (pys) of follow-up with a mean of 14 years, 78 CRC deaths were recorded. The CRC death rate was 0.75/1000 pys, 0.39/1000 pys, and 0.29/1000 pys for adults with low (lower quarter), moderate, and high (upper quarter) total dietary folate equivalent (tDFE, including both dietary and supplemental intake of folate); the adjusted HR was 0.12 (95% CI = 0.03, 0.45) for adults with high, and 0.51 (0.24, 1.11) for moderate tDFE compared to adults with low tDFE (p for trend = 0.09). Similar trends appeared with statistical significance for serum folate but not for dietary folate intake and RBC folate. Conclusion: With minimum interference from folic acid fortification, high folate intake was found to be associated with a reduced risk of CRC death.