Study summary · research use only
Trigonelline is an NAD(+) precursor that improves muscle function during ageing and is reduced in human sarcopenia
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study used human serum plus experiments in Caenorhabditis elegans, mice, and primary human myotubes to examine the alkaloid trigonelline as a NAD+ precursor related to muscle ageing and sarcopenia. Serum trigonelline was reduced in humans with sarcopenia and positively correlated with muscle strength and mitochondrial oxidative phosphorylation. Using natural and isotopically labelled trigonelline, the study showed it incorporated into the NAD+ pool and increased NAD+ in C. elegans, mice, and myotubes, acting via the Preiss-Handler pathway rather than the GPR109A receptor. In C. elegans, trigonelline was associated with improved mitochondrial respiration, reduced age-related muscle wasting, and increased lifespan and mobility; dietary supplementation in male mice was associated with enhanced muscle strength and reduced fatigue during ageing.
Abstract
Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1-3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss-Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.