TY - JOUR
T1 - A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals
AU - Jensen, Jonas Brorson
AU - Dollerup, Ole Lindgård
AU - Møller, Andreas Buch
AU - Billeskov, Tine B
AU - Dalbram, Emilie
AU - Chubanava, Sabina
AU - Damgaard, Mads V
AU - Dellinger, Ryan W
AU - Trošt, Kajetan
AU - Moritz, Thomas
AU - Ringgaard, Steffen
AU - Møller, Niels
AU - Treebak, Jonas T
AU - Farup, Jean
AU - Jessen, Niels
PY - 2022/10
Y1 - 2022/10
N2 - BACKGROUND: During ageing there is a functional decline in the pool of muscle stem cells (MuSCs) which influences the functional and regenerative capacity of skeletal muscle. Preclinical evidence have suggested that Nicotinamide Riboside (NR) and Pterostilbene (PT) can improve muscle regeneration e.g. by increasing MuSC function. The objective of the present study was to investigate if NRPT-supplementation promotes skeletal muscle regeneration after muscle injury in elderly humans by improved recruitment of MuSCs.METHODS: 32 elderly men and women (55-80 yr) were randomized to daily supplementation with either NRPT (1000 mg NR + 200 mg PT) or matched placebo. Two weeks after initiation of supplementation, a skeletal muscle injury was induced by electrically-induced eccentric muscle work. Skeletal muscle biopsies were obtained pre, 2h, 2, 8, and 30 days post 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 post injury but was not affected by NRPT. Furthermore, histological analyses of muscle fiber area, internal nuclei and embryonic Myosin Heavy Chain showed no effect of NRPT supplementation.CONCLUSION: Daily supplementation with 1000 mg NR+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 subjects.TRIAL REGISTRATION: NCT03754842.FUNDING: Novo Nordisk Foundation (Ref. NNF17OC0027242) given to JTT and NJ. JTT, ED, SC, MVD, KT, and TM are supported by the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR). CBMR is an independent Research Center at the University of Copenhagen that is partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900).
AB - BACKGROUND: During ageing there is a functional decline in the pool of muscle stem cells (MuSCs) which influences the functional and regenerative capacity of skeletal muscle. Preclinical evidence have suggested that Nicotinamide Riboside (NR) and Pterostilbene (PT) can improve muscle regeneration e.g. by increasing MuSC function. The objective of the present study was to investigate if NRPT-supplementation promotes skeletal muscle regeneration after muscle injury in elderly humans by improved recruitment of MuSCs.METHODS: 32 elderly men and women (55-80 yr) were randomized to daily supplementation with either NRPT (1000 mg NR + 200 mg PT) or matched placebo. Two weeks after initiation of supplementation, a skeletal muscle injury was induced by electrically-induced eccentric muscle work. Skeletal muscle biopsies were obtained pre, 2h, 2, 8, and 30 days post 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 post injury but was not affected by NRPT. Furthermore, histological analyses of muscle fiber area, internal nuclei and embryonic Myosin Heavy Chain showed no effect of NRPT supplementation.CONCLUSION: Daily supplementation with 1000 mg NR+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 subjects.TRIAL REGISTRATION: NCT03754842.FUNDING: Novo Nordisk Foundation (Ref. NNF17OC0027242) given to JTT and NJ. JTT, ED, SC, MVD, KT, and TM are supported by the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR). CBMR is an independent Research Center at the University of Copenhagen that is partially funded by an unrestricted donation from the Novo Nordisk Foundation (NNF18CC0034900).
KW - Aged
KW - Creatine Kinase, MM Form
KW - Dietary Supplements
KW - Humans
KW - Muscle, Skeletal
KW - Muscular Diseases
KW - Myoglobin/pharmacology
KW - Myosin Heavy Chains
KW - Niacinamide/analogs & derivatives
KW - Pyridinium Compounds
KW - Stilbenes
UR - http://www.scopus.com/inward/record.url?scp=85139570662&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.158314
DO - 10.1172/jci.insight.158314
M3 - Journal article
C2 - 35998039
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 19
M1 - e158314
ER -