Of mice and men: opposing effects of nicotinamide riboside on skeletal muscle physiology at rest and during exercise

Abstract

Physical exercise is one of the most efficient and researched strategies available for improving human health span. As a way of sustaining muscle contraction during exercise, cellular mechanisms drive resources to support ATP production. The balance between the oxidized and reduced forms of NAD is important for sustaining energy-producing metabolic reactions. NAD+ is a coenzyme involved in pleiotropic cellular processes, including the regulation of various metabolic enzymes but also chromatin remodelling and DNA repair. In rodents, NAD+ levels have been shown to decrease with ageing due to a rise in the activity of the CD38 NAD glycohydrolase enzyme driving age-related phenotypes, such as the decay of mitochondrial function (Yoshino et al. 2018). Thus, because of its possible therapeutic applications, NAD+ dietary supplement precursors such as nicotinamide riboside (NR) gained a lot of attention (Yoshino et al. 2018). Although the findings are promising, they are primarily based on studies performed in invertebrates and mammalian models, while a subset of recent studies indicates that the effects of NAD supplementation in humans might be much more subtle than whatwas observed in the preclinical studies. For example, dietary NR supplementation failed to alter mitochondrial physiology in the skeletal muscle of obese individuals (Dollerup et al. 2020), conflicting with the positive findings in mice.