Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

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Science  11 Jun 2021:
Vol. 372, Issue 6547, pp. 1224-1229
DOI: 10.1126/science.abe9985

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Anti-aging supplement effects in humans

Synthesis of nicotinamide adenine dinucleotide (NAD+) decreases during aging, which is thought to limit the activity of enzymes that require it for their catalytic activity. Studies in animals indicate that replenishment of cellular NAD+ can have beneficial effects on aging and age-related diseases, but the situation in humans is less clear. Yoshino et al. report the effects of supplementation with the NAD+ precursor nicotinamide mononucleotide in overweight or obese postmenopausal women with prediabetes (see the Perspective by Hepler and Bass). The treatment improved insulin sensitivity in muscle, although a change in NAD+ content was not detected. The treatment also increased the expression of platelet-derived growth factor b. The results support potential therapeutic action of NAD+ supplementation in humans, but how various NAD+ precursors are processed in specific tissues remains to be fully explored.

Science, abe9985, this issue p. 1224; see also abj0764, p. 1147


In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction. Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling [phosphorylation of protein kinase AKT and mechanistic target of rapamycin (mTOR)] increased after NMN supplementation but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese ( NCT 03151239).

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