In this study, an international team of researchers looked specifically at the role of oxidized nicotinamide adenine dinucleotide (NAD+) levels, on sarcopenia.

NAD+ is a coenzyme involved in metabolism in all cells in eukaryotic organisms. It is involved in redox reactions in the Krebs cycle and glycolysis, for example. It is present in the mitochondria where it plays an important role in energy homeostasis.

Previous researchTrusted Source by these scientists had shown that low levels of it, along with lower mitochondrial energy production, were associated with greater skeletal muscle aging and sarcopenia.

Many members of the team are based at food-manufacturer Nestle-owned Nestle Research in Lausanne, Switzerland.

The researchers analyzed serum levels of 20 male Chinese individuals ages 65-79 with sarcopenia and age-matched healthy controls and found patients with sarcopenia had lower circulating concentrations of trigonelline, a chemical found in plants and animals.

Upon further analysis, the researchers found that trigonelline levels were positively associated with muscle mass, grip strength, and gait speed, and higher levels of NAD+ in skeletal muscle. They saw similar results in another cohort.

Tissue samples were exposed to trigonelline in vitro, and researchers found myotubes, a type of tissue found in the muscles, had raised NAD+ levels when treated with trigonelline, but other muscle cells, liver cells, and kidney cells did not. Treating muscle tissue samples from participants and aged-matched healthy controls with trigonelline raised NAD+ levels in both.

Worms were then treated with trigonelline on day one of adulthood and experienced an extended lifespan compared to controls. They also showed increased mitochondrial respiration.

The researchers gave male older (20 months old) mice a dietary supplement of trigonelline, and a 5-day course improved mitochondrial activity in the mice. A 12-week course of supplementation increased plasma, liver and muscle levels of trigonelline, compared to controls. Further experiments showed that grip strength increased in mice given trigonelline supplementation, compared to controls.

The authors suggest that the findings show that rather than changing the structure of muscle fibers, trigonelline improves mitochondrial activity in these cells.

The authors make the point that trigonelline is present in coffee and fenugreek. They cited research that shows that higher levels of caffeine are associated with lower levels of sarcopenia in Korea but said their own analysis showed this association is not found in the Middle East. They suggest this could be due to low coffee consumption there.

Nestle owns the Nescafe coffee brand.

A spokesperson from Nestle Research, Katharina Fischer, R&D Scientific Communications Manager told Medical News Today:

“Trigonelline is an endogenous metabolite both in women and men and NAD and mitochondrial metabolism are conserved between sexes. In this study, our work has mainly focused on male subjects for technical and clinical feasibility reasons, although some female subjects were also included in a small subset of the experiments. The conclusions of the study are therefore most likely applicable to both men and women.”

The researchers also found that dietary fiber and folate were associated with higher trigonelline levels in the body, and explained that the compound could also be made in the gut due to the actions of the microbiome.

“As reported in the paper, our clinical dietary modeling analysis identified links between dietary fiber and folate intake and trigonelline levels in the human body. While these signals open new opportunities to modulate endogenous trigonelline production, we focused the work on providing trigonelline orally given its high abundance in certain foods like fenugreek or coffee,” Fischer explained.

“The work opens new translational opportunities to test the clinical efficacy of increasing trigonelline consumption and to develop food products enriched in trigonelline for muscle health. The importance of maintaining NAD levels in other organs during aging also opens applications to other health benefits for healthy longevity,” she added.

Source - Medical News Today