Clinical Update on NMN: Selective Improvement in Skeletal Muscle Insulin Response in Postmenopausal Women

A randomized, double-blind, placebo-controlled study published in Science shows that nicotinamide mononucleotide (NMN) improves skeletal muscle insulin sensitivity in overweight or obese postmenopausal women with prediabetes. Participants received 250 mg of NMN or placebo daily for 10 weeks. Hyperinsulinemic-euglycemic clamp results showed that NMN significantly increased insulin-stimulated skeletal muscle glucose disposal and enhanced muscle AKT and mTOR phosphorylation, suggesting improved insulin signaling.

The effect was tissue-selective: hepatic and adipose insulin sensitivity, intrahepatic triglyceride, intra-abdominal adipose tissue, and fasting glucose showed no significant changes. Mechanistically, NMN did not change muscle NAD+ homeostasis but increased NMN metabolites, suggesting increased NAD+ turnover. RNA sequencing showed that during insulin infusion, the NMN group had significantly more differentially expressed genes. The PDGF binding pathway was most enriched; PDGFRβ and collagen-related genes were upregulated, and markers of myogenic interstitial cells and pericytes increased, suggesting enhanced muscle remodeling and regeneration. Mitochondrial oxidative capacity and physical function were unaffected.

The researchers noted that the improvement in insulin sensitivity was comparable to that after about 10% weight loss or 12 weeks of troglitazone treatment. Unlike negative results from nicotinamide riboside (NR) clinical trials, NMN’s tissue specificity and metabolic effects warrant further development. Overall, NMN shows potential for skeletal muscle insulin sensitization in women with prediabetes, but the limited sample size means its long-term safety, mechanisms, and effects in broader populations still require validation.

FOR DETAIL:https://doi.org/10.1126/science.abe9985

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