Trigonelline is an NAD + precursor that improves muscle function during ageing and is reduced in human sarcopenia.
Level 4 - case-series / case-control
Preclinical animal and cellular experiments combined with cross-sectional human observational correlation
PubMed 38504132 · doi:10.1038/s42255-024-00997-x
What was done
The authors investigated circulating levels of the natural alkaloid trigonelline in humans, evaluating its relationship with sarcopenia, muscle strength, and mitochondrial oxidative phosphorylation in skeletal muscle. They traced the incorporation of naturally occurring and isotopically labelled trigonelline into NAD+ pools across Caenorhabditis elegans, mice, and primary human myotubes from healthy and sarcopenic donors. They investigated its metabolic route regarding GPR109A receptor activation and the nicotinate phosphoribosyltransferase/Preiss-Handler pathway. Finally, they assessed the effects of dietary trigonelline supplementation on mitochondrial biogenesis, respiration, muscle wasting, lifespan, and mobility in C. elegans, as well as muscle strength and fatigue resistance in aged male mice.
What was found
The abstract reports qualitative directions of effect without numerical values or effect sizes. Circulating trigonelline levels were lower in humans with sarcopenia and showed a positive correlation with muscle strength and skeletal muscle mitochondrial oxidative phosphorylation. Trigonelline increased NAD+ levels in human myotubes, mice, and worms, and was metabolized via the Preiss-Handler pathway without activating GPR109A. In C. elegans, supplementation enhanced mitochondrial respiration, reduced muscle wasting, and increased mobility and lifespan via a sirtuin-dependent mechanism. In ageing male mice, dietary supplementation enhanced muscle strength and prevented fatigue.
Why it matters
This study identifies trigonelline as a dietary NAD+ precursor that utilizes the Preiss-Handler pathway rather than GPR109A, presenting a potential nutritional candidate for counteracting age-associated muscle decline.
Limits
The abstract provides no numerical data, confidence intervals, or sample sizes for any of the human, mouse, or nematode cohorts. Human evidence is strictly observational and in vitro, meaning therapeutic efficacy in humans remains unproven. In vivo interventional experiments were restricted to nematodes and male mice, leaving potential sex-specific effects unaddressed.
Cited by
- supports Studies demonstrate a correlation between lower NAD levels in muscle and reduced metabolic activity or metabolic syndrome.