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Effects of unmetabolized folic acid on global DNA methylation, mRNA expression and NK cells cytotoxicity in individuals exposed to mandatory fortification with folic acid and / or therapeutic use of this vitamin

Grant number: 12/12912-1
Support Opportunities:Regular Research Grants
Duration: January 01, 2013 - June 30, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Elvira Maria Guerra Shinohara
Grantee:Elvira Maria Guerra Shinohara
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Ana Paula de Melo Loureiro ; Claudia Regina Bonini Domingos ; Dirce Maria Lobo Marchioni ; Maria Stella Figueiredo ; Maysa Seabra Cendoroglo ; Regina Alexandre Silva ; Rodolfo Delfini Cançado

Abstract

Folic acid is a vitamin of B complex which plays an important role in several reactions in the body. Its deficiency produces several clinical complications, such as anemia, increase in cancer risk and cardiovascular disease, defects in neural tube formation, among others. However, with the onset of wheat and corn flour fortification with folic acid in Brazil, since 2004, the population began to be exposed to amounts of this vitamin, beyond that normally present in foods. Its known folic acid in synthetic form cannot be completely metabolized leading to the appearance of a unmetabolized fraction in the body. This is more worrying in individuals who beyond fortification food take therapeutic use of this vitamin, such as those with beta-thalassaemic trait and hereditary spherocytosis. The aim of this study will be assess whether serum concentration of unmetabolized folic acid affect the global methylation, mRNA expression of beta-globin, interferon-gamma, TNF-alpha, interleukin-8, MTHFR and DHFR in mononuclear leukocytes and cytotoxicity of NK cells in 30 patients with hereditary spherocytosis and 100 patients with beta-thalassaemic trait exposed to mandatory fortification and use of 5 mg/day of folic acid, from the Hematology Clinical by Universidade Federal de São Paulo - UNIFESP, Santa Casa de Misericórdia de São Paulo Clinical and 260 healthy individuals exposed to mandatory fortification from the Universidade de São Paulo and UNIFESP. (AU)

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Scientific publications (5)
(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)
PANIZ, CLOVIS; LUCENA, MAYLLA RODRIGUES; BERTINATO, JULIANO FELIX; LOURENCO, FELIPE REBELLO; BARROS, BRUNA CIPRIANO A.; GOMES, GUILHERME WATARU; FIGUEIREDO, MARIA STELLA; CANCADO, RODOLFO DELFINI; NASCIMENTO BLAIA-D AVILA, VERA LUCIA; PFEIFFER, CHRISTINE M.; et al. Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis. JOURNAL OF INVESTIGATIVE MEDICINE, v. 67, n. 8, p. 1110-1117, . (12/12912-1)
PANIZ, CLOVIS; LUCENA, MAYLLA RODRIGUES; BERTINATO, JULIANO FELIX; DOS SANTOS, MAGNUN NUELDO NUNES; GOMES, GUILHERME WATARU; FIGUEIREDO, MARIA STELLA; SONATI, MARIA DE FATIMA; BLAIA-D AVILA, VERA LUCIA NASCIMENTO; GREEN, RALPH; GUERRA-SHINOHARA, ELVIRA MARIA. Serum folate and cytokines in heterozygous beta-thalassemia. INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, v. 42, n. 6, p. 718-726, . (12/12912-1)
PALCHETTI, CECILIA ZANIN; PANIZ, CLOVIS; DE CARLI, EDUARDO; MARCHIONI, DIRCE M.; COLLI, CELIA; STELUTI, JOSIANE; PFEIFFER, CHRISTINE M.; FAZILI, ZIA; GUERRA-SHINOHARA, ELVIRA MARIA. Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods. JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION, v. 36, n. 7, p. 572-578, . (14/23195-4, 12/12912-1)
BERTINATO, JULIANO FELIX; GREEN, RALPH; LONNERDAL, BO; DU, TINA; PANIZ, CLOVIS; LUCENA, MAYLLA RODRIGUES; GOMES, GUILHERME WATARU; GUERRA-SHINOHARA, ELVIRA MARIA. High Concentrations of Folic Acid Are Associated with Decreased Hemin Absorption in Caco-2 Cells. Blood, v. 130, p. 1-pg., . (12/12912-1)
PANIZ, CLOVIS; BERTINATO, JULIANO FELIX; LUCENA, MAYLLA RODRIGUES; DE CARLI, EDUARDO; DA SILVA AMORIM, PATRICIA MENDONCA; GOMES, GUILHERME WATARU; PALCHETTI, CECILIA ZANIN; FIGUEIREDO, MARIA STELLA; PFEIFFER, CHRISTINE M.; FAZILI, ZIA; et al. A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults. Journal of Nutrition, v. 147, n. 9, p. 1684-1692, . (12/12912-1)

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