Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

Vitamins are essential micronutrients for humans and animals. Folic acid is a synthetic form of the naturally occurring folate (vitamin B9) that is used in fortified foods, supplements and animal feeds. Folate/folic acid is a key nutrient essential for the normal growth and development of humans and animals. The efficiency of folate/folic acid absorption and metabolism plays an important role in ensuring folate-dependent functions in humans and animals. Folate deficiency can occur when dietary intake is inadequate, intestinal absorption is decreased, liver function is impaired or when body need is increased. Although Western foods and animal feeds are fortified with folic acid, some components in energy-dense diets or mycotoxin-contaminated staple foods/feeds may interfere with folate homeostasis and compromise its cellular function. For example, the recommended total fat intake for humans is 20-35% of kcal based on a 2,000 calorie intake. However, in Western countries, dietary fat often comprises over 40% of the energy intake. In a pilot study, we observed that feeding mice a high-fat diet (60% kcal fat) for 5 and 12 weeks caused a significant decrease in blood folate levels even though they received adequate amounts of dietary folic acid. This was associated with increased oxidative stress (free radical build-up in the body) and impaired liver function. It is not clear how high-fat diets affect folate absorption and metabolism. Aside from nutrients, mycotoxins (toxins produced by fungi) are unavoidably present in the food chain as natural contaminants, which can be harmful to humans and animals. Although the maximum tolerated levels of mycotoxins in staple foods and feeds are legislated, their impact (below the legislated levels) on nutrient (i.e. folate) absorption is not known. Given the importance of folate as an essential nutrient, it is imperative to understand how dietary components regulate its intestinal absorption, cellular uptake and metabolism to ensure its optimal biological function. In the proposed research, we will investigate (1) how dietary-derived factors influence folic acid absorption in the intestine and its metabolism in the liver; (2) how oxidative stress and cellular signaling pathways are involved in nutrient balance. My long-term goal is to develop a research platform to identify how dietary components (ranging from nutrients to contaminants and additives) affect nutrient bioavailability and to investigate whether mitigating negative influences of dietary factors on folate and other nutrient absorption and metabolism can optimize their biological functions in humans and animals. Better understanding of these effects will equip the government and industry with new strategies to optimize the intake of dietary folate and other nutrients. Total of 10 students (2 PhD, 3 MSc and 5 undergraduate) will be trained as part of the proposed NSERC Discovery program.