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

BFR-exercise induced significant muscle necrosis at 0 h that resolved within 24 h in both placebo and NMN conditions.

• Eleven untrained men (22.8 ± 1.5 y) completed the study.
• Randomized, placebo-controlled, counterbalanced crossover trial design was used.
• Multiple muscle biopsies were obtained before and after BFR-exercise.
• Necrosis resolution occurred within 24 h regardless of supplementation condition.

NMN supplementation suppressed exercise-induced increases in TNF-α and IL-10 mRNA in skeletal muscle.

• NMN dose was 1200 mg/d administered for 7 days.
• A 3-week washout period separated the two conditions.
• Suppression of both TNF-α and IL-10 mRNA suggests attenuated inflammatory signaling.
• These findings are consistent with NMN inhibiting acute inflammation as previously observed in injured animal tissues.

NMN supplementation delayed the rise in p21 mRNA, suggesting delayed myogenic differentiation.

• p21 mRNA rise was delayed compared to placebo condition.
• p21 is implicated in myogenic differentiation signaling.
• This delay occurred in the context of suppressed inflammatory signaling with NMN.
• The resolution of infiltrating cells from necrotic regions was also moderately delayed by NMN.

BFR-exercise increased mitochondrial content in exercised muscle by 171% after 24 h of recovery, but this adaptation was abolished with NMN supplementation.

• Mitochondrial content was assessed using immunofluorescence staining with TOM20.
• The 171% increase in mitochondrial content was observed in the placebo condition.
• NMN supplementation completely abolished this post-exercise mitochondrial increase.
• This finding suggests NMN may suppress mitochondrial replenishment during muscle recovery.

Infiltrating phagocytes carried substantially more mitochondria than myofiber cytoplasm, forming a diffusion gradient toward damaged regions of myofibers.

• Immunofluorescence staining with TOM20 and myeloperoxidase (MPO) was used to identify phagocytes and mitochondria.
• The concentration difference between phagocytes and myofibers was confirmed using COX4 immunostaining.
• COX4 staining was performed in biopsied muscle from an additional participant.
• The gradient pattern suggests a mechanism by which phagocytes may transfer mitochondria to repairing myofibers.

NMN supplementation may suppress mitochondrial replenishment from phagocytes to repairing myofibers by inhibiting inflammatory signaling.

• NMN inhibited inflammatory signaling while simultaneously abolishing post-exercise mitochondrial content increases.
• The proposed mechanism involves phagocyte-to-myofiber mitochondrial transfer being disrupted by NMN.
• This finding raises concerns about NMN supplementation interfering with exercise-induced muscle adaptations.
• The study design used a crossover trial with 3-week washout, providing within-subject comparisons.

NMN supplementation (1200 mg/d for 7 days) was administered in a randomized, placebo-controlled, counterbalanced crossover design in untrained men.

• Sample consisted of 11 untrained men aged 22.8 ± 1.5 years.
• Counterbalanced crossover design with 3-week washout between conditions was used.
• BFR-exercise was used as the exercise stimulus to induce muscle damage and inflammation.
• Multiple muscle biopsies were obtained at multiple time points before and after exercise.