UNMETABOLIZED FOLIC ACID AND ITS ASSOCIATIONS WITH GLOBAL DNA METHYLATION, OXIDATIVE STRESS, INFLAMMATORY MARKERS AND METABOLIC SIGNATURE: ANALYSIS AFTER MANDATORY FORTIFICATION OF FLOUR WITH FOLIC

Abstract

For decades folate has been studied in health promotion and disease prevention. Almost 50 countries worldwide, included Brazil, adopted the food fortification with folic acid for controlling micronutrient malnutrition. Recently, the researchers discuss the need for exposure to high doses of the vitamin for all population, and have hypothesized that the overexposure to the vitamin could be associated with the risk of adverse health effects. Researches showed when the folic acid intakes exceed a specific physiologic threshold, oral doses greater than 260 to 280 µg, resulting in appearance of unmetabolized form of the vitamin in the plasma, also known as unmetabolized folic acid (UMFA). Although the biological effects of UMFA are not well known, it is recognized that it arises after intake of synthetic form of the vitamin, occurring in fortified foods. Thus, the UMFA could be a biomarker of high intakes of folic acid. Some studies were suggested that high folic acid intake might promote the growth of preexisting cancers or malignant lesions. These results are relevant in public health if we consider the high intake of folic acid from mandatory fortification of flour in Brazil and the high presence of UMFA (80%) in the population from Sao Paulo, according recent study. Therefore, the present study aims to assess new associations with folic acid, UMFA and health outcomes, considering oxidative stress (MDA and 8-oxo-dG), inflammatory markers (cytokines, CRP and adhesion molecules) and Global DNA methylation; and to compare the metabolic signature between the group with and without UMFA at the circulation who are exposed to high intake of folic acid.