Project Number: 1950-51520-008-00
Project Type: Appropriated

Start Date: May 01, 2004
End Date: Apr 30, 2009

Objective:
1. To determine the impact of mandatory food folic acid fortification in the United States (U.S.). 2 Determine the interrelationships between B vitamin status, methionine intake, genetic polymorphism and plasma homocysteine (tHcy). 3. Determine the hereditary association of plasma homocysteine and vitamin status. 4. Determine the impact of aging on one-carbon metabolism in rats by measuring folate form distribution. 5. Determine the biochemical, pathological and functional impact of nutritional and genetic disruptions of one-carbon metabolism, in animal models of age-related vascular and neurological dysfunction, with emphasis on the roles of B vitamins, homocysteine and methionine in tissue-specific susceptibility to disease. 6. Determine the role of folate receptors in brain function and brain inflammation.

Approach:
Determine amount of folic acid in fortified foods using the affinity/HPLC method to modify the food folate tables and to estimate dietary folate equivalents. Use these values to determine folate intake and assess relationships to folate and homocysteine status in the Framingham Study. Relate folate, homocysteine, other B vitamins status, methionine intake and genetic polymorphism in the Framingham Study to the prevalence of age-related impairments such as cardiovascular disease, cognitive dysfunction and dementia. Measure homocysteine and B vitamins in Gen-3 in the Framingham Study and compare data with those in the Offspring Cohort of the Framingham Study to determine heritability of homocysteine and B12 status. Use animal models (mice and rats) which were made vitamin deficient or fed with excess methionine, to raise plasma homocysteine levels to determine effects on vascular system and brain function and assess mechanisms that underlie the association between homocysteine and age related dysfunctions.