NAD
+ and NADP
+ are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating thereby cellular metabolism and homeostasis. This fueled the interest of many researchers to investigate whether increasing the levels of NAD
+ and NADP
+ can enhance exercise performance. Many NAD
+ and NADP
+ precursors have developed; yet, all were accompanied by side effects such as severe flushing [
7]. A recently identified NAD
+ precursor, namely nicotinamide riboside, has been demonstrated to increase the levels of NAD
+ in the absence of any adverse effects [
7]. With regard to exercise performance, only one study has been published utilizing nicotinamide riboside and reported marginally non-significant ergogenic effects in low-fat diet mice (approximately 10 % increase in distance run,
P = 0.08), while this effect became significant in their high-fat diet counterparts (approximately 36 % increase in distance run,
P < 0.05) [
5]. Contrary to this evidence, our findings indicate that administration with nicotinamide riboside decreased (though marginally non-statistically significant) exercise performance in rats. The exact sources of this disagreement are unclear, however, methodological differences such as the animal model (i.e., rats vs. mice), type of exercise (i.e., swimming vs. treadmill running) and route of nicotinamide riboside administration (i.e., gavage vs. food mixture) may have potentially accounted for the conflicting results. On the other hand, our results are in line with some of the studies investigating the effect of another NAD
+ precursor, namely nicotinic acid, on exercise performance [
8,
9]. In particular, the authors of those studies demonstrated that nicotinic acid impaired the ability for prolonged exercise. Despite the fact that nicotinamide riboside is currently preferred compared to nicotinic acid (due to the absence of side effects), both precursors almost similarly increase NAD
+ levels in most cell types and tissues [
5], while they likely share common pathways for NAD
+ synthesis [
7].
Based on the similar effects of nicotinic acid and nicotinamide riboside on NAD
+ metabolism, the impairments in exercise performance observed in our study may stem from the same sources as in the studies used nicotinic acid [
8,
9]. These studies found that nicotinic acid reduced exercise-induced increases in plasma free fatty acids. Therefore, it is likely that nicotinamide riboside decreased fatty acid oxidation during exercise leading to an earlier fatigue. In addition, the redox properties of NAD
+ and NADP
+ could also provide a plausible explanation for the impaired performance observed, namely by disrupting redox homeostasis [
10]. In particular, nicotinamide riboside administration may have altered redox homeostasis leading cells to a more reductive (non-optimal) state, according to the hormetic theory of reactive oxygen and nitrogen species activity [
11]. This is in line with other recent studies stressing the potential detrimental effects of redox-related supplements on exercise capacity [
12]. Evidently, these hypotheses are speculative and are currently being investigated in order to reveal the potential metabolic and redox mechanisms involved in our finding. Further studies are warranted to acquire mechanistic insights on the effect of nicotinamide riboside on exercise performance.