Dietary Supplementation with NAD+ Precursors to Support Exercise: An Evaluation of the Clinical Evidence

Abstract

Nicotinamide Adenine Dinucleotide (NAD+) is essential for the functionality of muscle cells. Multiple studies have demonstrated that NAD+ levels decline with age but are increased with aerobic exercise and resistance training. Preclinical studies have demonstrated that supplementation with NAD+ precursors, and specifically niacin and nicotinamide riboside, have positively impacted molecular indicators of muscle biogenesis. There have been suggestions that supplementation with NAD+ precursors may be beneficial to muscle health in sarcopenia and other physiological conditions of energy and muscle decline. The objective of this analysis is to evaluate if clinical dietary supplementation with NAD+ precursors influence exercise performance and indicators of muscle health in humans. Only peer-reviewed clinical studies that orally supplemented with NAD+ precursors as individual compounds and evaluated exercise and/or muscle biomarkers were included in the analysis. Of the over 50 published clinical studies that have evaluated various NAD+ precursors, only 9 studies met our criteria of having at least one study arm measuring an NAD+ precursor alone with an outcome related to exercise performance or muscle health. Of the precursors evaluated, one study evaluated extended release niacin, one evaluated the nicotinic acid derivative acipimox, four studies evaluated nicotinamide riboside, and three studies evaluated tryptophan. Five studies evaluated the benefit of NAD+ precursor supplementation in muscle biomarkers, eight studies included evaluation of physical performance before and after supplementation, but none of the studies included an exercise protocol for the study participants. Extended release niacin may have some benefits to muscle health following chronic supplementation as indicated by various molecular markers of mitochondrial biogenesis and muscle strength, though side effects related to flushing are concerning. Nicotinamide riboside supplementation was shown to increase muscle acetylcarnitine following exercise in one study; however, extended study duration and optimal dosing protocols may be necessary to show other benefits. Tryptophan was shown to benefit exercise performance. Future research studies would benefit from including an exercise protocol with or without NAD+ precursor supplementation, whole blood and muscle NAD+ and related metabolites analyses, along with multiple time points of evaluation throughout the study. Though there is some strong evidence that NAD+ precursors may benefit physical performance, each precursor appears to have different mechanisms and benefits. Therefore, additional research is recommended.