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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

Grant number: 15/12196-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): January 01, 2016
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Nutrition - Nutritional Analysis of Population
Principal Investigator:Dirce Maria Lobo Marchioni
Grantee:Josiane Steluti
Host Institution: Faculdade de Saúde Pública (FSP). Universidade de São Paulo (USP). São Paulo , SP, Brazil

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.

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
JOSIANE STELUTI; SANDRA PATRICIA CRISPIM; MARINA CAMPOS ARAUJO; ALINE MENDES PERALTA; ROSANGELA ALVES PEREIRA; ROSELY SICHIERI; EDNA MASSAE YOKOO; DIRCE MARIA MARCHIONI. Tecnologia em Saúde: versão brasileira do software GloboDiet para avaliação do consumo alimentar em estudos epidemiológicos. Revista Brasileira de Epidemiologia, v. 23, . (16/20054-6, 15/12196-2)
STELUTI, JOSIANE; REGINALDO, CHRISTINA; SELHUB, JACOB; PAUL, LIGI; FISBERG, REGINA MARA; MARCHIONI, DIRCE MARIA. Presence of circulating folic acid in plasma and its relation with dietary intake, vitamin B complex concentrations and genetic variants. EUROPEAN JOURNAL OF NUTRITION, v. 58, n. 8, p. 3069-3077, . (15/12196-2, 12/05505-0, 11/19788-1, 10/19899-5)
STELUTI, JOSIANE; PALCHETTI, CECILIA ZANIN; MIRANDA, ANDREIA MACHADO; FISBERG, REGINA MARA; MARCHIONI, DIRCE MARIA. DNA methylation and one-carbon metabolism related nutrients and polymorphisms: analysis after mandatory flour fortification with folic acid. BRITISH JOURNAL OF NUTRITION, v. 123, n. 1, p. 23-29, . (11/19788-1, 12/05505-0, 10/19899-5, 15/12196-2)
STELUTI, JOSIANE; MIRANDA, ANDREIA MACHADO; DE CARLI, EDUARDO; PALCHETTI, CECILIA ZANIN; FISBERG, REGINA MARA; LOBO MARCHIONI, DIRCE MARIA. Unmetabolized folic acid is associated with TNF-alpha, IL-1 beta and IL-12 concentrations in a population exposed to mandatory food fortification with folic acid: a cross-sectional population-based study in Sao Paulo, Brazil. EUROPEAN JOURNAL OF NUTRITION, v. 60, n. 2, . (10/19899-5, 12/05505-0, 11/19788-1, 15/12196-2)

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