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 ; J Nutr

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 of 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 intervention. Serum folate concentrations were measured by microbiologic 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 concentration 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 reduction 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 ...