April 2021
Mihoko Yoshino, Jun Yoshino, Brandon D. Kayser, Gary J. Patti, Michael P. Franczyk, Kathryn F. Mills, Miriam Sindelar, Terri Pietka, Bruce W. Patterson, Shin-Ichiro Imai, and Samuel Klein

 

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.

 

Abstract

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 (clinicaltrial.gov NCT 03151239).