Location: Jean Mayer Human Nutrition Research Center On Aging
2019 Annual Report
Objectives
LAB NAME: Vitamin Metabolism & Aging
1. Develop new and efficient methods for assessing nutritional status in individuals for B vitamins and their functional markers with internal standards obtained from plants grown on D2O or yeast grown on C-13 glucose.
2. Determine the biochemical, pathological and functional impact of nutritional status and genetic variations in B complex vitamin metabolism with special emphasis on the effect of age, in human, animal and cell culture models. Consider the nutritional status of other B vitamins while studying the effect of each B vitamin.
3. Determine the impact of mandatory folic acid fortification of cereals including effects of improved nutritional status as well as excess intake of folic acid on outcomes including disease risk, cognitive function, inflammation and immune response, with emphasis on understanding the mechanism behind the side-effects.
Approach
LAB NAME: Vitamin Metabolism & Aging
We will use biochemical, molecular biological and epidemiological approaches to study the role of B vitamins and the genes involved in their metabolism, in modulating processes associated with aging, disease development and increased risk for diseases. We will explore the association between pyridoxal 5’-phosphate, the active form of vitamin B6 and inflammation by measuring the immunomodulatory compounds in plasma that are produced from pyridoxal 5’-phosphate-dependent reactions in a cohort of elders. Decrease in vitamin B12 status can potentially result in decrease in muscle strength. We will explore the association between vitamin B12 and muscle strength and power, to determine the feasibility of an intervention trial to improve muscle strength. Fortification of cereals with folic acid was adopted by the US and many other countries to reduce neural tube defects. While natural folate from plants and meat can enter the metabolic pathway directly, folic acid, the synthetic form of the vitamin in supplements and fortified foods, has to be reduced by dihydrofolate reductase prior to entering the metabolic pathway. A 19bp deletion polymorphism in intron 1 of dihydrofolate reductase has been associated with increased risk for cancer in supplement users. We will determine the effect of this 19bp deletion on gene expression and enzyme activity of dihydrofolate reductase and the reactions of folate pathway. Intake of folic acid in excess of the ability of the body to metabolize it has been associated with negative health outcomes. Using a mouse model we will determine the effect of excess intake of folic acid on immune function and response to infections. We will explore the association between the polymorphism in dihydrofolate reductase gene and folic acid intake in modulating the risk for breast cancer using the samples and data from the PLCO cohort.
Progress Report
This is the final report for the project 8050-51000-093-00D. Researchers in the Vitamin Metabolism Laboratory discovered that high folate intake is linked with nerve-damage risk in older adults with a common gene variant. Among study subjects who consumed more than twice the Recommended Dietary Allowance (RDA) of 800 micrograms per day of folate, individuals with the GG gene variant had seven-fold higher odds for peripheral neuropathy compared to those without the variation. The data generated by researchers in the Vitamin Metabolism Lab suggest that increased risk of peripheral neuropathy in older adults with the TCN2 variation may be avoided by limiting folate intake to the Recommended Dietary Allowance and exercising caution with regard to the consumption of folic acid supplements. The lab also discovered that folate from bacteria regulates cell growth of host nematode, a high folic acid diet results in lower natural killer cell activity in aged mice, exposure to supplemental folic acid at recommended levels during pregnancy does not lead to increased unmetabolized folic acid concentrations in maternal or cord blood, and genetic variations in maternal folate pathway genes interact with arsenic in drinking water to influence risk of neural tube defects.
Accomplishments
Review Publications
Selhub, J., Rosenberg, I.H. 2016. Excessive folic acid intake and relation to adverse health outcome. Biochimie. 126:71-78. http://doi.org/10.1016/j.biochi.2016.04.010.
