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.

Autor:	Paniz C; Departments of Clinical and Toxicological Analysis and., Bertinato JF; Departments of Clinical and Toxicological Analysis and., Lucena MR; Hematology and Blood Transfusion Division, Federal University of Sao Paulo, Sao Paulo, Brazil., De Carli E; Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Amorim PMDS; Departments of Clinical and Toxicological Analysis and., Gomes GW; Departments of Clinical and Toxicological Analysis and., Palchetti CZ; Departments of Clinical and Toxicological Analysis and., Figueiredo MS; Hematology and Blood Transfusion Division, Federal University of Sao Paulo, Sao Paulo, Brazil., Pfeiffer CM; National Center for Environmental Health, CDC, Atlanta, GA; and., Fazili Z; National Center for Environmental Health, CDC, Atlanta, GA; and., Green R; Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Sacramento, CA., Guerra-Shinohara EM; Departments of Clinical and Toxicological Analysis and emguerra@usp.br.; Hematology and Blood Transfusion Division, Federal University of Sao Paulo, Sao Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	The Journal of nutrition [J Nutr] 2017 Sep; Vol. 147 (9), pp. 1677-1685. Date of Electronic Publication: 2017 Jul 19.
DOI:	10.3945/jn.117.247445
Abstrakt:	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 γ ( IFNG ), tumor necrosis factor α ( 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. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp. Competing Interests: Author disclosures: CP, JFB, MRL, EDC, PMdSA, GWG, CZP, MSF, CMP, ZF, RG, and EMG-S, no conflicts of interest. (© 2017 American Society for Nutrition.)
Databáze:	MEDLINE
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