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

Research output: Contribution to journalArticlepeer-review


  • Ben Stocks
  • Stephen P. Ashcroft
  • Sophie Joanisse
  • Linda C. Dansereau
  • Yen Chin Koay
  • Lake Ee Quek
  • John F. O'Sullivan
  • Ashleigh M. Philp

External organisations

  • Garvan Institute of Medical Research
  • UNSW Medicine
  • University of Sydney
  • Mitochondrial Metabolism and Ageing Laboratory


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, (Formula presented.) 46.5 ± 4.4 ml kg–1 min–1) received 1 week of NR or cellulose placebo (PLA) supplementation (1000 mg day–1). Muscle biopsies were collected from the medial vastus lateralis prior to supplementation and pre-, immediately post- and 3 h post-exercise (1 h 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 poly ADP-ribose polymerase 1 (PARP1), acetylation of Tumour protein 53 (p53)Lys382 and Manganese superoxide dismutase (MnSOD)Lys122 were also unaffected by NR supplementation or exercise. NR supplementation did not increase skeletal muscle NAD+ concentration, but it did increase the concentration of deaminated NAD+ precursors nicotinic acid riboside (NAR) and nicotinic acid mononucleotide (NAM) and methylated nicotinamide breakdown products (Me2PY and Me4PY), demonstrating the skeletal muscle bioavailability of NR supplementation. In summary, 1 week of NR supplementation does not alter whole-body metabolism or skeletal muscle signal transduction pathways implicated in the mitochondrial adaptation to endurance exercise.

Bibliographic note

Funding Information: This publication was supported in part through a BBSRC Midlands Integrative Biosciences Training Programme (MIBTP) studentship (BB/J014532/1) to B.S. and BBSRC New Investigator Award (BB/L023547/1) to A.P.


Original languageEnglish
Pages (from-to)1513-1531
Number of pages19
JournalJournal of Physiology
Issue number5
Early online date25 Jan 2021
Publication statusPublished - 1 Mar 2021


  • exercise, metabolism, NAD, skeletal muscle, Exercise, Pyridinium Compounds, Male, Muscle, Skeletal, Dietary Supplements, Niacinamide/analogs & derivatives

ASJC Scopus subject areas