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

Author(s):Show less -

Paniz, Clovis ^[1] ; Bertinato, Juliano Felix ^[1] ; Lucena, Maylla Rodrigues ^[2] ; De Carli, Eduardo ^[3] ; da Silva Amorim, Patricia Mendonca ^[1] ; Gomes, Guilherme Wataru ^[1] ; Palchetti, Cecilia Zanin ^[1] ; Figueiredo, Maria Stella ^[2] ; Pfeiffer, Christine M. ^[4] ; Fazili, Zia ^[4] ; Green, Ralph ^[5] ; Guerra-Shinohara, Elvira Maria ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Hematol & Blood Transfus Div, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Food & Expt Nutr, Fac Pharmaceut Sci, Sao Paulo - Brazil

^[4] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 - USA

^[5] UC Davis Sch Med, Dept Pathol & Lab Med, Sacramento, CA - USA

• Document type: Journal article
• Source: Journal of Nutrition; v. 147, n. 9, p. 1684-1692, SEP 2017.
• Web of Science Citations: 10

Abstract

Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown. Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon gamma (IFNG), tumor necrosis factor a (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers. Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m 2) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry {[} folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells. Results: Serum folate concentrations increased by; 5-fold after the intervention (P < 0.001), and UMFA concentrations increased by 11.9-and 5.9-fold at 45 and 90 d, respectively, when compared with baseline (P < 0.001). UMFA concentrations increased (> 1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number (P < 0.001) and cytotoxicity (P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d (P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d (P = 0.001 for both). Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. (AU)

• FAPESP's process: 12/12912-1 - 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
• Grantee: Elvira Maria Guerra Shinohara
• Support Opportunities: Regular Research Grants