Folate, Methyl-Related Nutrients, Alcohol, and the MTHFR 677C→T Polymorphism Affect Cancer Risk: Intake Recommendations

Abstract

Colorectal cancer and adenoma risk are inversely associated with higher total folate intake. Significant modifiers of cancer risk also include other methyl-related nutrients and alcohol. Adequate folate intake is particularly important for women at higher risk for breast cancer because of moderate alcohol consumption. The methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism is associated with a reduced risk of some forms of cancer. The protective effect of this folate-related polymorphism is dependent on adequate folate status. Cancer risk may be increased in individuals with the homozygous genotype for the MTHFR 677C→T polymorphism who have low status of methyl-related nutrients including folate. Intake recommendations to potentially reduce cancer risk include substitution of low folate foods with folate-dense fruits and vegetables and in countries where there is no mandatory folic acid fortification, increased consumption of folic acid from available fortified foods or supplements. Adequate dietary intake of vitamin B-6 and methionine can be achieved by consumption of low fat, concentrated food sources of these nutrients. The recommended intake for vitamin B-12 for individuals ≥51 y should be provided predominately in crystalline form (e.g., fortified ready-to-eat cereal, supplements). If alcohol is consumed, consumption should be restricted to <15 g/d or <1 drink/d. The negative effects of low intakes of the methyl-related nutrients with high intakes of alcohol are additive, therefore changes in overall dietary patterns to ensure the consumption of a protective high methyl diet are recommended.