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Access Type

WSU Access

Date of Award

January 2020

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Ahmad R. Heydari

Abstract

Since its synthesis in 1945, Folic acid (FA) is widely used as a supplement/additive to our food due to its stability and high bioavailability. FA is proposed to alleviate anemia and reduce neural tube defects (NTD). As a provitamin, FA is activated through a two-step reaction catalyzed by dihydrofolate reductase (DHFR) in the folate metabolism pathway. FA activation rate is found to be slow in humans. After the implementation of mandatory food fortification program of grain and grain products with folic acid in the USA in 1998, many concerns have been raised about the unintended deleterious consequence of exposing the whole population to vast amounts of folic acid. These concerns have been further escalated after several studies reported that upon fortification, certain human populations are exceeding the UL intake of FA, resulting in an increase in cancer rate (e.g., colon, stomach, and breast cancer) associated with an increment in mortality rate. Furthermore, recent studies have proposed the U-shape effect of folic acid on the onset and progression of cancer. In this study, we analyzed the correlation between the high intake of folic acid and the level of genome damage in lymphocytes by utilizing

the CBMN cytome assay in human and cell culture models, and their relation to folate systemic markers. We hypothesized that the chronic and excessive exposure of folic acid via fortified food consumption induces functional folate deficiency.

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