A daily dose of 5 mg of folic acid for 90 days is associated with increased serum unmetabolized folic acid and reduced natural killer cell cytotoxicity in healthy Brazilian adults

Autor: Zia Fazili, Maylla Rodrigues Lucena, Ralph Green, Clóvis Paniz, Eduardo De Carli, Juliano Felix Bertinato, Maria Stella Figueiredo, Cecília Zanin Palchetti, Guilherme Wataru Gomes, Patrícia Mendonça da Silva Amorim, Christine M. Pfeiffer, Elvira Maria Guerra-Shinohara
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Adult
Male
medicine.medical_specialty
medicine.medical_treatment
Medicine (miscellaneous)
Nutritional Status
Real-Time Polymerase Chain Reaction
Article
03 medical and health sciences
Immune system
Folic Acid
Reference Values
Internal medicine
Dihydrofolate reductase
medicine
Humans
Interleukin 8
Prospective Studies
RNA
Messenger

Cytotoxicity
Methylenetetrahydrofolate Reductase (NADPH2)
030109 nutrition & dietetics
Nutrition and Dietetics
biology
business.industry
Tumor Necrosis Factor-alpha
Interleukin-8
Immunity
Killer Cells
Natural

Tetrahydrofolate Dehydrogenase
030104 developmental biology
Real-time polymerase chain reaction
Endocrinology
Cytokine
Methylenetetrahydrofolate reductase
Immunology
Dietary Supplements
Vitamin B Complex
biology.protein
Tumor necrosis factor alpha
Female
Inflammation Mediators
business
Brazil
Popis: 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/m2) 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 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.
Databáze: OpenAIRE