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

Abstract

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 NRPTsupplementation 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, central 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. 4

ATP and NAD+ Deficiency in Parkinson’s Disease

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NAD+ precursor nutritional supplements sensitize the brain to future ischemic events

“…Clinically, a wide range of doses have been tested, and doses as high as 1-5 g/day have been safe upon long-term use in humans. [40][41][42][43] Therefore, we believe the doses tested here are clinically relevant. It should also be noted that we have not comprehensively examined other therapeutic paradigms (e.g., pre-ischemic treatment onset with continued treatment after MCAO, treatment onset during MCAO, prolonged post-ischemic treatment) that may yield different outcomes.…”

NAD metabolism: Role in senescence regulation and aging

“…Also, these precursors differ in their mechanisms of absorption in the gut and how they enter the cell. Importantly, several studies with the NAD precursor nicotinamide riboside (NR) failed to demonstrate clinical or functional effects in the obese and the elderly (Dollerup et al, 2018(Dollerup et al, , 2020Jensen et al, 2022;Martens et al, 2018), highlighting the importance of large, double-blind, randomized studies.…”