Nicotinamide Riboside Supplementation and Exercise Training to Promote Healthy Longevity

The prevalence of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is mounting worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with diminished skeletal muscle mitochondrial function in humans. Nicotinamide adenosine dinucleotide (NAD) is a coenzyme that regulates mitochondrial function, therefore, plays an important role in energy metabolism. Importantly, it has been shown that high cellular NAD+ levels as well as a high NAD+/NADH ratio promote metabolic and mitochondrial health. In contrast, NAD+ bioavailability declines upon aging in humans as well as in animal models of metabolic disorders and type 2 diabetes. These findings fuel the notion of boosting the NAD+ bioavailability in order to improve metabolic disturbances and mitochondrial dysfunction in aged individuals. Supplementation with nicotinamide riboside (NR), a naturally occurring form of vitamin B3, boosts cellular NAD+ levels. However, in contrast to animal studies, NR supplementation in humans has so far been unsuccessful in improving skeletal muscle mitochondrial function, exercise capacity or insulin sensitivity. Interestingly, Recently, it has been suggested that metabolic conditions where NAD+ levels become limited, is needed for NR supplementation to exert beneficial health effects. This metabolic condition could be achieved by exercise. However, studies combining NR and exercise are lacking, and that is why we will perform the present study.