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 4

Clinical parameters associated with skeletal muscle injury.

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Clinical parameters associated with skeletal muscle injury. (A) T2-weigh...
(A) T2-weighted axial image of the thigh shows increased signal intensity in the vastus lateralis part of the quadriceps femoris muscle 8 days after injury, with no difference between groups (NRPT, n = 14; PLA, n = 12). (B) P-creatinine kinase, (C) p-myoglobin, (D) maximal voluntary contraction and rate of force development at 50- and 70-angle degrees (MVC, 50°/70° and RFD, 50°/70°), and (E) muscle soreness did response to injury but not to NRPT supplementation (NRPT, n = 16; PLA, n = 15). Data are expressed as geometric mean ± SD, with the exception of MVC and RFD data in D, which are expressed as mean ± SD. Data were compared using repeated-measurement mixed-model analysis, with the exception of MRI and muscle soreness data, which were compared using a Student’s t test. *P < 0.05 vs. Pre. TPI, time after injury; MVC, maximal voluntary contraction; RFD, rate of force development; AUC, area under the curve.