A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals
Jonas Brorson Jensen, Ole L. Dollerup, Andreas B. Møller, Tine B. Billeskov, Emilie Dalbram, Sabina Chubanava, Mads V. Damgaard, Ryan W. Dellinger, Kajetan Trošt, Thomas Moritz, Steffen Ringgaard, Niels Møller, Jonas T. Treebak, Jean Farup, Niels Jessen
Jonas Brorson Jensen, Ole L. Dollerup, Andreas B. Møller, Tine B. Billeskov, Emilie Dalbram, Sabina Chubanava, Mads V. Damgaard, Ryan W. Dellinger, Kajetan Trošt, Thomas Moritz, Steffen Ringgaard, Niels Møller, Jonas T. Treebak, Jean Farup, Niels Jessen
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Clinical Research and Public Health Aging Muscle biology

A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals

Abstract

BACKGROUND During aging, there is a functional decline in the pool of muscle stem cells (MuSCs) that influences the functional and regenerative capacity of skeletal muscle. Preclinical evidence has suggested that nicotinamide riboside (NR) and pterostilbene (PT) can improve muscle regeneration, e.g., by increasing MuSC function. The objective of this study was to investigate if supplementation with NR and PT (NRPT) promotes skeletal muscle regeneration after muscle injury in elderly individuals by improved recruitment of MuSCs.METHODS Thirty-two elderly individuals (55–80 years of age) were randomized to daily supplementation with either NRPT (1,000 mg NR and 200 mg PT) or matched placebo. Two weeks after initiation of supplementation, skeletal muscle injury was induced by electrically induced eccentric muscle work. Skeletal muscle biopsies were obtained before, 2 hours after, and 2, 8, and 30 days after injury.RESULTS A substantial skeletal muscle injury was induced by the protocol and associated with release of myoglobin and creatine kinase, muscle soreness, tissue edema, and a decrease in muscle strength. MuSC content, proliferation, and cell size revealed a large demand for recruitment after injury, but this was not affected by NRPT. Furthermore, histological analyses of muscle fiber area, central nuclei, and embryonic myosin heavy chain showed no NRPT supplementation effect.CONCLUSION Daily supplementation with 1,000 mg NR and 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly individuals.TRIAL REGISTRATION ClinicalTrials.gov NCT03754842.FUNDING Novo Nordisk Foundation (NNF17OC0027242) and Novo Nordisk Foundation CBMR.

Authors

Jonas Brorson Jensen, Ole L. Dollerup, Andreas B. Møller, Tine B. Billeskov, Emilie Dalbram, Sabina Chubanava, Mads V. Damgaard, Ryan W. Dellinger, Kajetan Trošt, Thomas Moritz, Steffen Ringgaard, Niels Møller, Jonas T. Treebak, Jean Farup, Niels Jessen

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Figure 5

Muscle stem cell response to skeletal muscle injury.

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Muscle stem cell response to skeletal muscle injury. (A) CD56 (neural ce...
(A) CD56 (neural cell adhesion molecule 1) versus CD82 (KAI1) contour flow plots of single CD45–CD31–CD34–PI– cells from skeletal muscle biopsies before, 2, 8, and 30 days after injury. (B) MuSCs content was quantified per milligram of skeletal muscle tissue, and (C) size was measured from forward scatter (FSC) of flow cytometry. (D and E) As a measure of MuSC proliferation, MuSCs were sorted and ex vivo EdU incorporation was measured after 48 hours of incubation and expressed relatively to DAPI. Scale bar: 75 μm. (F) Total content of hematopoietic cells (CD45+). Data are expressed as geometric mean ± SD, with the exception of MuSC proliferation data, which is expressed as mean ± SD, and compared using repeated-measurement mixed-model analysis. NRPT, n = 16; PLA, n = 15. *P < 0.05 vs. Pre. DPI, days after injury; MuSC, muscle stem cell; TPI, time after injury.