Folate and its preventive potential in colorectal carcinogenesis. How strong is the biological and epidemiological evidence?

Based on a 15-year old hypothesis, it is believed that an adequate ingestion of folate vitamins decreases, whereas a nutritional depletion of folate increases the risk of colorectal cancer. The present article reviews the efforts to provide biochemical and epidemiological evidence for folate as a chemopreventive agent against colorectal carcinogenesis. Biological evidence: Tetrahydrofolates govern the intracellular one-carbon metabolism and account for proper DNA biosynthesis and macro-molecular modification. Numerous experimental studies traced different molecular pathways and tried to link folate depletion with DNA instability and/or mutagenesis. However, none of the proposed underlying molecular mechanisms appear clearly defined. Epidemiological evidence: Numerous case-control and prospective studies have been conducted on folate and colorectal cancer, which all together miss a clinical bottom line. The recommendation of folate intake to prevent colorectal cancer is therefore not evidence-based. (c) 2005 Elsevier Ireland Ltd. All rights reserved.