Anti-inflammatory effects of nicotinamide mononucleotide (NMN) in human skeletal muscle after BFR-exercise.

BACKGROUND: β-Nicotinamide mononucleotide (NMN) inhibits acute inflammation in injured animal tissues. AIM: We examined whether NMN supplementation attenuates inflammation induced by blood flow restriction-resistance exercise (BFR-exercise) in human skeletal muscle. METHODS: Eleven untrained men (22.8 ± 1.5 y) completed a randomized, placebo-controlled, counterbalanced crossover trial, receiving either Placebo or NMN (1200 mg/d) for 7 d, with a 3-week washout between conditions. Multiple muscle biopsies were obtained before and after BFR-exercise. RESULTS: BFR-exercise-induced significant muscle necrosis at 0 h, which resolved within 24 h in both conditions. NMN supplementation suppressed exercise-induced increases in TNF-α and IL-10 mRNA but delayed the rise in p21 mRNA, suggesting attenuated inflammatory signaling and delayed myogenic differentiation. The resolution of infiltrating cells from necrotic regions was moderately delayed by NMN. BFR-exercise increased the mitochondrial content in exercised muscle by 171% after 24 h of recovery. However, this adaptation was abolished with NMN. Immunofluorescence staining with TOM20 and myeloperoxidase (MPO) revealed that infiltrating phagocytes carried substantially more mitochondria than myofiber cytoplasm, forming a diffusion gradient toward damaged regions of myofibers. This concentration difference between phagocytes and myofibers was further confirmed using COX4 immunostaining in biopsied muscle from an additional participant. CONCLUSIONS: NMN supplementation, while inhibiting inflammatory signaling in exercised human skeletal muscle, may also suppress mitochondrial replenishment from phagocytes to repairing myofibers.