Measuring Folate Status can Trump Genetics
As a proponent of nutrition status assessments, a common reaction is that personalized insights into our genetics will be the most meaningful information. True but genetic assessments have to be interpreted to be meaningful. For micronutrients, deficiency states are already known. The cutoffs have been established. See the CDC Second Nutrition Report: A Comprehensive Biochemical Assessment of Nutrition Status.
A lack of B vitamins, especially folic acid, vitamin B6 and vitamin B12, contributes to high plasma homocysteine concentrations. About 10% of western populations have a mutation in the homocysteine-metabolizing enzyme, methelenetetrahydrafolate reductase (MTHFR); mutations associated with higher serum homocysteine concentrations, a 25% higher risk of cardiovascular disease (CVD), and elevated blood pressure.
Li and colleagues measured serum folate status and MTHFR genotypes in 480 subjects (28-75y) living in China. Folate deficiency was significantly affected by MTHFR genotype. Using serum folate concentrations (< 10 nmol/L) as cutoffs, two polymorphisms (MTHFR C677T and MTR A2756G) were independently associated with reduced serum folate concentrations.
Herein lies the beauty of measuring nutrient status. Yes, genetics affect nutrient requirements. Yes, some genotypes may require an individual to consume more folate to maintain adequate serum folate concentrations. This information can drive two public health approaches. Genotypes can be measured and health professionals can adjust dietary intake recommendations (assuming enough data exists to develop polymorphism-specific dietary recommendations). Alternatively, the simpler strategy is to measure nutrient status and advise everyone with low serum folate to eat more folate-rich foods and/or use a dietary supplement. Then measure status again to see if serum folate concentrations have been normalized. Both approaches work.
Remember, the goal is to maintain normal serum folate status and healthy homocysteine concentrations.
Genetics may influence the dietary intake required to maintain normal homocysteine concentrations which are the risk factor. Although folic acid supplementation of individuals with increased risk of CVD reduces plasma homocysteine concentrations by 25%, the best dietary guide would be knowing one’s B vitamin status.
Li W-X, Dai S-X, Zheng J-J, Liu J-Q, Huang J-F. Homocysteine metabolism gene polymorphisms (MTHFRM C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) jointly elevate the risk of folate deficiency. 2015 Nutrients doi: 10.3390/nu7085303
Wilson CP, McNulty H, Scott JM, Strain JJ, Ward M. Postgraduate Symposium: The MTHFR C677T polymorphism, B-vitamins and blood pressure. 2010 Proc Nutr Soc doi: 10.1017/S0029665109991728
Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE, Bonaa KH, Spence JD, Nygard O, Jamison R, Gaziano JM, Guarino P, Bennett D, Peto R, Collins R, and B Vitamin Treatment Trialists’ Collaboration. 2010 Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37,485 individuals. JAMA Intern Med doi: 10.1001/archinternmed.2010.348