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

Stocks, Ben, Ashcroft, Stephen P, Joanisse, Sophie ORCID: https://orcid.org/0000-0001-9983-9401, Dansereau, Linda C, Koay, Yen Chin, Elhassan, Yasir S, Lavery, Gareth G, Quek, Lake‐Ee, O'Sullivan, John F, Philp, Ashleigh M, Wallis, Gareth A and Philp, Andrew (2021) Nicotinamide riboside supplementation does not alter whole‐body or skeletal muscle metabolic responses to a single bout of endurance exercise. The Journal of Physiology, 599 (5). pp. 1513-1531. ISSN 0022-3751

Preview

Accepted Version Available under License In Copyright. Download (3MB) | Preview

Abstract

Oral supplementation of the NAD+ precursor Nicotinamide Riboside (NR) has been reported to alter metabolism alongside increasing sirtuin (SIRT) signalling and mitochondrial biogenesis in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study assessed the effect of 7‐day NR supplementation on whole‐body metabolism and exercise‐induced mitochondrial biogenic signalling in skeletal muscle. 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). Muscle biopsies were collected from the medial vastus lateralis prior to supplementation and pre‐, immediately post‐ and three‐hours post‐exercise (one‐hour of 60% Wmax cycling) performed following the supplementation period. There was no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Global acetylation, auto‐PARylation of PARP1, acetylation of p53Lys382 and MnSODLys122 were also unaffected by NR supplementation or exercise. NR supplementation did not increase skeletal muscle NAD+ concentration, however did increase the concentration of deaminated NAD+ precursors (NAR and NAMN) and methylated NAM breakdown products (Me2PY and Me4PY), demonstrating the skeletal muscle bioavailability of NR supplementation. In summary, one week of NR supplementation does not alter whole‐body metabolism or skeletal muscle signal transduction pathways implicated in the mitochondrial adaptation to endurance exercise.