Vitamin B3 nicotinamide riboside improves muscle mitochondria and gut microbiota composition

The newest vitamin B3 family member, nicotinamide riboside has been found to have beneficial effects on mitochondria in the human muscle. Findings from the University of Helsinki encourages further investigation of whether this vitamin B3 form could serve as a potential therapeutic option on mitochondrial dysfunction.

In a recent twin study at the University of Helsinki, it was found that nicotinamide riboside (NR) increased the number of mitochondria, i.e.  the powerhouses of the cells, in the muscle after long-term administration. In addition, NR improved the gut bacterial composition and increased the blood NAD+ concentrations.

Different forms of vitamin B3, such as niacin, nicotinamide and NR, boost cellular energy metabolism, as they serve as precursors for the important molecule for mitochondria, NAD+.

“NAD+ precursors are currently the focus of active research world-wide, as NR has been found to improve mitochondrial function as well as to alleviate metabolic syndrome and obesity in rodents,” Associate Professor Eija Pirinen says.

However, it has been unclear whether NR has beneficial effects on mitochondria and metabolic health in humans.

“Our study demonstrated the beneficial effects of long-term supplementation of NR on NAD+ metabolism, and particularly on muscle mitochondria and gut microbiota in humans for the first time,” Pirinen says.

Blood, lipid, muscle and stool samples were collected before and after NR supplementation from the identical twins who participated in the study. The samples were analysed, among other methods, by measuring NAD+ metabolites in the blood, investigating the amount of mitochondria in tissues and determining the microbiota composition of the stool samples.

The beneficial effects of NR were observed in both leaner and heavier cotwins. In other words, NR supplementation is likely to benefit all individuals regardless of their weight.

A future drug for treating mitochondrial and gut microbiota imbalance?

NR was also found to affect several muscle tissue functions. It increased the differentiation of muscle stem cells and modified gene expression by modulating DNA methylation, i.e. an incorporation of methyl groups to DNA.

Based on the findings, NR supplementation appears to be a promising therapeutic option to be studied in diseases characterised by gut microbiota imbalance and/or muscle mitochondrial dysfunction, such as sarcopenia i.e. age-related muscle loss. According to the authors of this study, long-term administration of NR should be investigated further in clinical trials, although in carefully selected patients, as NR was found to impair insulin sensitivity.

“This is a significant step forward in the development of vitamin B3 forms for the therapeutic use. Since NR supplementation has been used in the short term only in prior studies, this study has increased our understanding of the long-term effects of NR,” Professor Kirsi Pietiläinen from the University of Helsinki notes.

The study was published in the Science Advances journal.

Original article: Lapatto H, Kuusela M, Heikkinen A, Muniandy M, van der Kolk BW Gopalakrishnan S, Pöllänen N, Sandvik M, Schmidt MS, Heinonen S, Saari S, Kuula J, Hakkarainen A, Tampio J, Saarinen T, Taskinen M-R, Lundbom N, Groop P-H, Tiirola M, Katajisto P, Lehtonen M, Brenner C, Kaprio J, Pekkala S, Ollikainen M, Pietiläinen KH and Pirinen E. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota in a twin study. Sci. Adv. doi/10.1126/sciadv.add5163 

Further information

Eija Pirinen, Associate Professor, University of Oulu and University of Helsinki



Kirsi Pietiläinen, Gyllenberg Professor of Clinical Metabolism, University of Helsinki