Nicotinamide Riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise

Oral supplementation of the NAD+ precursor Nicotinamide Riboside (NR) has been reported to increase Sirtuin (SIRT) signalling, mitochondrial biogenesis and endurance capacity in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study aimed to assess the effect of 7-day NR supplementation on exercise-induced transduction and transcriptional responses in skeletal muscle of young, healthy, recreationally active human volunteers. In a double-blinded, randomised, counter-balanced, crossover design, eight male participants (age: 23 ± 4 years, VO2peak: 46.5 ± 4.4 mL.kg-1.min-1) received one week of NR or cellulose placebo (PLA) supplementation (1000 mg.d-1) before performing one hour of cycling at 60% Wmax. Muscle biopsies were collected prior to supplementation and pre-, immediately and three-hours post-exercise from the medial vastus lateralis, whilst venous blood samples were collected throughout the trial. Global acetylation, auto-PARylation of PARP1, acetylation of p53Lys382 and MnSODLys122 were unaffected by NR supplementation or exercise. Exercise led to an increase in AMPKThr172 (1.6-fold), and ACCSer79 (4-fold) phosphorylation, in addition to an increase in PGC-1α (~5-fold) and PDK4 (~10-fold) mRNA expression, however NR had no additional effect on this response. There was also no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Finally, NR supplementation blunted the exercise induced activation of skeletal muscle NNMT mRNA expression, but had no effect on mRNA expression of NMRK1, NAMPT or NMNAT1, which were not significantly affected by NR supplementation or exercise. In summary, one week of NR supplementation does not augment skeletal muscle signal transduction pathways implicated in mitochondrial adaptation to endurance exercise.