A randomized placebo-controlled clinical trial of Nicotinamide Riboside and Pterostilbene supplementation in experimental muscle injury in elderly subjects

Background Maintenance and regeneration of functional skeletal muscle are dependent on a sufficient pool of muscle stem cells (MuSCs). During ageing there is a functional decline in this cellular pool which influences the 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 In a randomized, double-blinded, placebo-controlled trial, 32 elderly men and women (55-80 yr) received 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 applied in the vastus lateralis part of the quadriceps femoris muscle by electrically induced eccentric muscle work in a dynamometer. Skeletal muscle biopsies were obtained pre, 2h, 2, 8, and 30 days post injury. The main outcome of the study was change in MuSC content 8 days post injury. Results 31 enrolled subjects completed the entire protocol. The muscle work induced a substantial skeletal muscle injury in the study participants and was associated with release of myoglobin and creatine kinase, muscle soreness, tissue edema, and a decrease in muscle strength. MuSC content increased by 107% 8 days post injury (p= 0.0002) but with no effect of NRPT supplementation (p=0.58 for supplementation effect). MuSC 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.