RCT supports nicotinamide riboside boost for muscle mitochondrial biogenesis

By Stephen Daniells

- Last updated on GMT

Mitochondria – the powerhouses of our cells.   Image © CIPhotos / Getty Images
Mitochondria – the powerhouses of our cells. Image © CIPhotos / Getty Images

Related tags Nicotinamide riboside Nad Niagen Nicotinamide adenine dinucleotide healthy aging mitochondrial function

Supplementation with nicotinamide riboside may improve muscle mitochondrial biogenesis, according to data from a first-of-its kind five-month-long clinical study with twins.

Data published in Science Advances​ indicated that nicotinamide riboside (NR) supplementation improved NAD+ metabolism, the number of mitochondria in muscle, and the composition of the gut microbiota in BMI-discordant (one leaner, one heavier) identical twins.

“We here provide the first evidence that long-term NR supplementation increases muscle and WAT [white adipose tissue] NAD+ biosynthesis in humans regardless of BMI,” ​wrote scientists led by Dr Eija Pirinen from the Universities of Helsinki and Oulu in Finland and Dr Kirsi Pietiläinen, from the University of Helsinki.

“This NAD+ biosynthesis–boosting effect occurred even in the heavier cotwins from the BMI-discordant pairs, which showed lower expression of NAD+ biosynthetic genes, NMNAT3 and NRK1, especially in WAT, compared with the leaner cotwins, at baseline.”


In 2004, Dr Charles Brenner discovered that nicotinamide riboside (NR) is a potent precursor to nicotinamide adenine dinucleotide (NAD). NAD is an important cellular co-factor for improvement of mitochondrial performance and energy metabolism.

As organisms age, NAD levels drop, which leads to a decrease in mitochondrial health; this in turn leads to age-related health issues.  By boosting NAD, NR may increase mitochondrial health and induce the creation of new mitochondria.

The new study used Niagen, ChromaDex’s branded nicotinamide riboside, which has been shown to increase NAD+ levels safely and efficaciously in multiple published human trials. The trial was part of the ChromaDex External Research Program (CERPTM) that has executed over 250 material transfer agreements (MTAs) featuring Niagen and other proprietary ingredients.

“An important milestone”

The study’s findings were welcomed by Dr Andrew Shao, ChromaDex Senior Vice President of Global Scientific & Regulatory Affairs. “While previous preclinical research has demonstrated that increasing NAD+ through precursor supplementation improves the quality and quantity of muscle stem cells, promotes muscle function, increases mitochondrial health and respiration, and has therapeutic effects in mitochondrial and muscle disorders, many of these benefits have yet to be translated in human clinical studies,”​ said Dr Shao.

“This study marks an important milestone in research between NR supplementation and mitochondrial biogenesis.”

Study details

Drs Pirinen and Pietiläinen and their co-workers recruited 20 BMI-discordant identical twin pairs to participate in their open-label, parallel-assignment study. The study also included four pairs of BMI-concordant (same amount of body fat and muscle) identical twins. All BMI-discordant twins were supplemented with NR, while the BMI-concordant twins only had one twin randomized to NR supplementation and the other received placebo.

The data indicated that NR was well tolerated and increased mitochondrial biogenesis, increasing the number and density of muscle mitochondria.

NR was also associated with 30% increases in muscle mitochondrial DNA (mtDNA) as well as increases in the expression of genes responsible for stimulating mitochondrial biogenesis.

The supplement was also found to improve muscle myoblast differentiation, a process by which muscle stem cells mature into myotubes and is a developmental stage of a muscle fiber.

Looking at the composition of the gut microbiota, the researchers observed an increase in the abundance of beneficial Faecalibacterium prausnitzii​.

“Our findings are a great advance in the field of muscle mitochondrial research, and they encourage us and others to continue to test the impact NR may have on muscle mitochondrial dysfunction,”​ said Dr Pirinen in a press release.

Source: Science Advances
2023, Vol 9, Issue 2, doi: 10.1126/sciadv.add5163
“Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study”
Authors: H.A.K. Lapatto et al.

Related topics Research

Related news

Follow us


View more