Folate in colorectal cancer: beneficial or detrimental?

Folate is a water-soluble B-group vitamin found in various foods including green leafy vegetables, hens’ eggs, and legumes. Folate has an essential role in DNA repair, methylation, and synthesis. Folate deficiency causes neural tube defects, megaloblastic anemia, cardiovascular diseases, and cancer. Foods are enriched with folic acid, a synthetic monoglutamate form of folate, and folic acid supplementation is provided in many countries because the increased need for folate during pregnancy cannot be met only with food. Due to the important roles of folate in DNA synthesis, there are concerns that exposure to high doses of folic acid may cause colorectal cancer. Studies support that folic acid taken before polyp development has protective effects from colorectal cancer. On the other hand, folic acid supplementation induces colorectal cancer after polyp formation. It is also thought that epigenetic modifications affecting folate metabolism play a role in this process. In conclusion, folate intake at optimal levels and appropriate timing may exert protective effects against colorectal cancer, whereas folic acid consumed in supraphysiological doses and at later stages may promote tumor progression and increase the likelihood of carcinogenic progression of premalignant lesions.