In 1996, the FDA published that the consumption of folic acid-rich grains such as wheat, rice, and oats could prevent neural tube abnormalities in postpartum infants. Folic acid supplementation came of age. However, in the following years, studies have found that folic acid supplementation promotes the development of colorectal cancer. Does folic acid promote or inhibit the development of colorectal cancer? First of all, let’s review the biochemistry of folic acid. After being absorbed by the stomach and intestines, food-derived folic acid is transformed into various intermediates through a series of biometabolic reactions in the body. These intermediates are involved in nucleic acid synthesis (e.g. purine and thymine synthesis) and protein synthesis (e.g. glycine – serine, histidine – glutamate conversion). The role of nucleic acid and protein synthesis in living organisms needs no further explanation. Evidence for folic acid in cancer prevention: The first three studies investigating the relationship between folic acid and colorectal cancer found that folic acid supplementation may prevent colorectal cancer. Importantly, all three studies were conducted in countries that do not have a folic acid supplementation program. When the U.S. Folic Acid Supplementation Program was expanded, scientists also found that folic acid reduced the risk of colorectal cancer in the general population. Evidence that folic acid promotes cancer: One study looked at patients with colorectal adenomas and found that supplementation with high levels of folic acid (1 mg/day) did not delay tumor progression, but rather promoted colorectal cancer development. Another Meta-analysis (covering 6 large clinical trials of folic acid supplementation) also found that supplementation was associated with an increased risk of cancer development. Rodents, the sentinels of new drug development, were also involved in folic acid trials. It was found that reducing folic acid intake slowed tumor development in rodents after tumor formation. Folic acid’s ‘dual role’: Folic acid is a candidate for cancer prevention because it is at the center of a one-carbon metabolic network. This metabolic network not only provides precursors for nucleotide synthesis, but also provides one-carbon carriers for DNA methylation, two biological processes that are often attacked as lethal targets during cancer development.