Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.

Yasir S Elhassan, Katarina Kluckova, Rachel S Fletcher, Mark S Schmidt, Antje Garten, Craig L Doig, David M Cartwright, Lucy Oakey, Claire V Burley, Ned Jenkinson, Martin Wilson, Samuel J E Lucas, Ildem Akerman, Alex Seabright, Yu-Chiang Lai, Daniel A Tennant, Peter Nightingale, Gareth A Wallis, Konstantinos N Manolopoulos, Charles Brenner, Andrew Philp, Gareth G Lavery

Journal: Cell reports 2020;28(7):1717-1728.e6

PMID: 31412242

Free Full Text on Elsevier Science View on PubMed

Plain Language Summary

As the body ages, there is a decline in muscle mass and function, which can be combatted with diet, exercise, and supplementation. Nicotinamide riboside (NR) or vitamin B3 has been shown in animal studies to promote healthy muscle, however its effects in human muscle are unknown. This randomised control trial of overweight older men aimed to determine if NR can be used by muscle and whether it has any effect on muscle function. The results showed that NR supplementation (1 g/day) for 3 weeks can be used by the muscle but had no effect on muscle function as shown by the hand grip test. Supplementation also decreased energy production in muscle and had anti-inflammatory effects. It was concluded that NR is available to muscle and that it may have anti-inflammatory properties, which may be of benefit to older individuals.

Abstract

Nicotinamide adenine dinucleotide (NAD) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.

Address: Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Centre for Human Brain Health, University of Birmingham, Birmingham, UK.; Centre for Human Brain Health, University of Birmingham, Birmingham, UK; School of Psychology, University of Birmingham, Birmingham, UK.; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.; Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK; Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia; Faculty of Medicine, St. Vincent's Clinical School, Sydney, UNSW, Australia.; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK; MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK. Electronic address: [email protected].

DOI: 10.1016/j.celrep.2019.07.043

Patient Centred Factor

Mediators: Ageing

Clinical Imbalances

Immune and inflammation Structural Integrity and Musculoskeletal

Laboratory Testing

Blood Tissue biopsy

Modifiable Lifestyle Factors

Exercise and movement

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Inflammation Metabolism Skeletal muscle Mitochondria Nicotinamide riboside

Bioactive Substances

Nicotinamide riboside

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MeSH Terms: Aged, Aged, 80 and over, Aging, Anti-Inflammatory Agents, Cross-Sectional Studies, Cytokines, Double-Blind Method, Humans, Male, Metabolome, Muscle, Skeletal, NAD, Niacinamide, Pyridinium Compounds, Transcriptome