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

β-Nicotinamide mononucleotide (NMN) inhibits acute inflammation in injured animal tissues.

We examined whether NMN supplementation attenuates inflammation induced by blood flow restriction-resistance exercise (BFR-exercise) in human skeletal muscle.

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.

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.

NMN supplementation, while inhibiting inflammatory signaling in exercised human skeletal muscle, may also suppress mitochondrial replenishment from phagocytes to repairing myofibers.