Sarcopenia is the age-related loss of skeletal muscle mass and function, which leads to impaired mobility and physical independence. A recent study published in Nature found that trigonelline, a natural alkaloid, is closely linked to sarcopenia and reduced trigonelline levels contribute to the mitochondrial dysfunction and NAD+ deficiency observed in sarcopenia. Targeting trigonelline and NAD+ metabolism may represent a promising therapeutic approach for age-related muscle loss and impairment. The study keys points are:

• Serum trigonelline levels are reduced in individuals with sarcopenia compared to healthy controls. Trigonelline levels positively correlate with muscle mass, strength, and gait speed - key clinical measures of sarcopenia.

• Pathway analysis showed that trigonelline levels are strongly associated with genes involved in mitochondrial oxidative phosphorylation and NAD+ biosynthesis in skeletal muscle. This suggests trigonelline plays an important role in muscle metabolism and function.

• Mechanistically, trigonelline was found to be a direct precursor for NAD+, a critical coenzyme for cellular metabolism. Trigonelline can increase NAD+ levels in muscle cells, including those from individuals with sarcopenia, by being metabolized through the Preiss-Handler NAD+ biosynthesis pathway.

• In animal models, supplementation with trigonelline improved mitochondrial function and exercise capacity during aging. This indicates trigonelline has the potential to counteract age-related muscle decline.

Natural sources of trigonelline

Herebelow follows a list of natural sources of trigonelline found in scientific literature:

• Sakurajima radish appears to have the highest concentration of trigonelline among the foods and beverages examined. The average trigonelline content in Sakurajima radishes was 260-360 g/kg, which is approximately 60 times higher than other radish varieties like Aokubi radish. Trigonelline is relatively stable to heat, remaining detectable even after boiling Sakurajima radish at 100°C for 1 minute, though the concentration does decrease over time.

• Trigonelline occurs naturally in high concentrations in coffee (up to 7.2 g/kg) and coffee by-products (up to 62.6 g/kg) such as coffee leaves, flowers, cherry husks or pulp, parchment, silver skin, and spent grounds. However, the trigonelline content can be reduced by certain processing methods like decaffeination and hot brewing.

• Although in smaller amounts, trigonelline is also found in both Cistus incanus (6.29–14.34 mg/kg) and Rooibos infusions (10.54–14.29 mg/kg) and in smaller amounts in in Camellia sinensis infusions (0.30–2.88 mg/kg).

• Other botanical sources like fruits and seeds may also contain trigonelline, but the search results do not provide specific quantitative comparisons.

References:

Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. (2024). https://www.nature.com/articles/s42255-024-00997-x

Risk Assessment of Trigonelline in Coffee and Coffee By-Products. (2024). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146819/

Dietary Antioxidants in Coffee Leaves: Impact of Botanical Origin and Agronomic Factors. (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023256/

Trigonelline - an overview. (n.d.). https://www.sciencedirect.com/topics/neuroscience/trigonelline

Raphanus Sativus Cv. Sakurajima Daikon as a Functional Food May Improve Vascular Function Through Trigonelline. (2019). https://www.ahajournals.org/doi/abs/10.1161/circ.140.suppl_1.10374

Characteristic Analysis of Trigonelline Contained in Raphanus sativus Cv. Sakurajima Daikon and Results from the First Trial Examining Its Vasodilator Properties in Humans. (2024). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353243/

Cistus incanus a promising herbal tea rich in bioactive compounds: LC–MS/MS determination of catechins, flavonols, phenolic acids and alkaloids—A comparison with Camellia sinensis, Rooibos and Hoan Ngoc herbal tea. (2018). https://www.sciencedirect.com/science/article/abs/pii/S0889157518308512