Acute supplementation with a curcuminoid-based formulation fails to enhance resting or exercise-induced NRF2 activity in males and females†

Purpose: Exercise and (poly)phenols may activate nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that coordinates antioxidant synthesis. The purpose of this study was to determine whether curcuminoid supplementation augments resting and exercise-induced NRF2 activity. Methods: In a double-blinded, randomised, between-subjects design, 14 males and 12 females performed plyometric exercise (100 drop jumps, 50 squat jumps) following 4 d supplementation with a curcuminoid-based formulation (CUR + EX; n = 13; ∼200 mg d⁻¹ curcuminoids) or a placebo (PLA + EX; n = 13). NRF2/DNA binding in peripheral blood mononuclear cells, plasma glutathione peroxidase (GPX), and plasma cytokines (interleukin-6 [IL-6], tumour necrosis factor-alpha [TNF-α]) were measured pre-, post-, 1, 2 h post-exercise. Curcuminoid metabolites were measured 0, 1, 2 h post-administration of a single bolus. Results: Total area under the curve for total curcuminoid metabolites was greater in CUR + EX (p < 0.01), with bioavailability peaking at 2 h post administration (CUR + EX: [0 h] 80.9 ± 117 nM [1 h] 76.6 ± 178.5 nM [2 h] 301.1 ± 584.7 nM; PLA + EX: [0 h] 10.4 ± 1.6 [1 h] 8.5 ± 2.6 [2 h] 10.6 ± 2.1). NRF2 activity did not increase in PLA + EX (p = 0.78) or CUR + EX (p = 0.76); however, curcuminoid metabolite concentrations did positively predict NRF2/DNA binding (R² = 0.39; p = 0.02). Exercise increased IL-6 (p = 0.03) but TNF-α was unresponsive (p = 0.97) and lower across PLA + EX (p = 0.03). GPX activity was higher in CUR + EX (p < 0.01) but not in PLA + EX (p = 0.94). Conclusion: Supplementation with a curcuminoid-based formulation failed to augment resting or exercise-induced NRF2/DNA binding; however, higher concentrations of curcuminoid metabolites predicted NRF2/DNA binding response, suggesting effects may be dependent on bioavailability.