Positive Benefits of NR Supplementation on Muscle Mitochondrial Biogenesis


This is the first clinical study to demonstrate an increase in muscle mitochondrial biogenesis following NR supplementation in humans and is one of the longest NR supplementation studies to date, at five months.


Lapatto et al., Science Advances, January 2023. “Nicotinamide Riboside Improves Muscle Mitochondrial Biogenesis, Satellite Cell Differentiation and Gut Microbiota Composition in a Twin Study.” 


The authors of the study set out to investigate the effects of long-term NR supplementation on mitochondrial biogenesis and metabolic health in BMI-discordant identical twin pairs (one leaner, one heavier). Mitochondrial biogenesis is the process by which mitochondria increase their number and size by generating new mitochondria from pre-existing ones. It is a process cells use to improve their function and adapt to an increase in exercise to help produce more energy.


NR (1000 mg/day for five months) was well-tolerated and increased whole-blood NAD+ levels by 2.3-fold in all BMI-discordant twins and increased muscle and fat NAD+ biosynthesis.

NR improved muscle mitochondrial biogenesis, increasing the number of mitochondria in muscle. NR also increased muscle mitochondrial DNA (mtDNA) by about 30%, and increased the expression of genes responsible for stimulating mitochondrial biogenesis.

NR improved muscle myoblast differentiation—the process by which muscle stem cells mature into myoblasts (or young, immature muscle cells).

NR improved gut microbiota composition as seen through an increase in the abundance of Faecalibacterium prausnitzii—one of the most beneficial bacteria found in the microbiome of healthy humans.

NR increased body weight and whole-body fat percentage, and decreased insulin sensitivity; there are several factors to note surrounding these outcomes:​​​​​​​

The small placebo group of BMI-concordant twins included in the study that experienced increases in body weight and fat mass had similar outcomes to the BMI-discordant twins that were supplemented with NR. This suggests the weight gain observed in the study may be due to increases in fat over time and not due to NR. However, some of these results warrant further investigation, as they have not been observed in other studies.

A study limitation to note is the BMI-discordant twin study protocol did not include a parallel placebo arm to adequately monitor changes. Therefore additional research is needed to validate these findings.
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