Folate supplementation's effect on epidemiology of Colorectal Cancer

Introduction: It has been reported that there is approximately 40% reduction in the risk of colorectal cancer (CRC) and adenomas in individuals with the highest dietary intake of folate and vitamin B12 as compared with those with the lowest intake of these nutrients. Given that folic acid (FA) has a crucial role in gene expression that may be blocked by DNA methylation which potentially increase the rate of carcinogenesis.Description: The existence of 5-methyltetrahydrofolate (an active form of FA) is necessary for the function of the ubiquitous enzyme methionine synthesis (MS) as a methyl donor and vitamin B12 as a cofactor. When methionine amount is low, more folate is applied as methyl-tetrahydrofolate to form methionine. The possibility of low amount of methylene-tetrahydrofolate is required for DNA synthesis. Before being changed to tetrahydrofolate where it can enter to the folate pool, FA have to be altered to dihydrofolate by dihydrofolate reductase (DHFR) in the liver with one absorbance. It has been reported that 400 mcg surplus FA might saturate the DHFR enzyme, as a result it doesn't alter to folate and enter the folate pool, therefore the amount of unexpected FA that has been hypothesized as a possible pathway for carcinogenesis is considerable. Obviously, high folate consumption may be associated with diminishing CRC risk.Discussion and conclusion: Various studies have indicated that lower folate level is related to higher risk of colorectal adenomas and cancer, while some epidemiological researches have reported evidence recommending that FA supplementation and high amounts of folate in blood potentially be associated with an increased CRC incidence. More studies should be done due to clarifying whether this discrepancy.