Singapore - With age, our muscles naturally tend to atrophy. This process, known as sarcopenia, can lead to frailty, falls, and loss of independence in the golden years.
But what if there is a natural compound that can help slow this process and maintain muscle health and strength over time?
A new study conducted by scientists from the National University of Singapore, published in the journal Nature Metabolism, points to a promising candidate: trigonelline.
What is trigonelline?
Trigonelline is a compound found in many plant-based foods, such as coffee, fenugreek seeds, and garden peas. Previous studies have shown that low levels of trigonelline in the blood are associated with weaker muscles and slower walking speeds in older adults.
The effect of trigonelline on muscle health
The researchers, curious about this connection, decided to investigate in depth whether trigonelline directly affects muscle health. Through experiments on human muscle cells, mice, and even tiny worms (C. elegans), they discovered that trigonelline serves as a precursor to NAD+, a critical coenzyme whose levels decline with age.
NAD+ and cellular metabolism
NAD+, or nicotinamide adenine dinucleotide, is essentially the currency of cellular metabolism. It enables the basic chemical reactions that produce energy and sustain our lives. Mitochondria, the powerhouses of the cell, rely on NAD+ for proper function. Muscle cells are packed with mitochondria to power movement. Consequently, the age-related decline in NAD+ is considered a key factor in mitochondrial dysfunction and muscle deterioration over time.
Study findings
"Our findings expand the current understanding of NAD+ metabolism with the discovery of trigonelline as a new NAD+ precursor and increase the potential for developing vitamin-based interventions that produce NAD+ for healthy longevity as well as age-related diseases," says Vincenzo Sorrentino from the Translational Longevity Research Program at NUS Medicine, in a press release.
Experiments and results
- Treatment with trigonelline increased NAD+ levels and improved markers of mitochondrial function in aged human and mouse muscle cells.
- Feeding trigonelline to elderly mice for 12 weeks increased their grip strength and protected them from muscle fatigue.
- Trigonelline extended the lifespan of C. elegans worms, improved the structural integrity of their muscle cells, and helped maintain their ability to twist with age.
- Worms with a genetic modification that abolished their ability to process trigonelline into NAD+ did not benefit from these anti-aging effects, confirming the link to NAD+.
Trigonelline vs. niacin
Chemically, trigonelline is very similar to niacin (vitamin B3). However, unlike niacin supplements, which are directly incorporated into NAD+, trigonelline must first undergo several metabolic steps. Enzymes remove the additional methyl group of trigonelline (the "M" in its chemical name: "N-methylnicotinic acid") to produce nicotinic acid.
Then, nicotinic acid is transported to the cell's NAD+ factory via a pathway called the Preiss-Handler pathway.
Interestingly, certain tissues, such as the liver, are very efficient at converting trigonelline to NAD+, while others, like skeletal muscles, receive a smaller NAD+ boost from trigonelline. The researchers believe this is why the elderly mice did not accumulate more muscle mass with trigonelline, even though their muscle strength and endurance improved.
Further research needed
Is trigonelline a new miracle muscle supplement? Not yet. The researchers caution that sarcopenia is a complex disease, and diet alone is unlikely to cure it completely. Trigonelline could be an important part of the puzzle, but older adults will still need adequate protein intake, vitamin D, omega-3, and physical activity to fully combat muscle loss.
Also, it is not yet clear how much of the trigonelline found in foods like coffee translates into the benefits seen in the lab. The mice and worms in this study received relatively high doses, and human data is still correlational. Randomized controlled trials are needed to prove that trigonelline supplements can slow or reverse muscle aging.
In conclusion
This study breaks new and exciting ground by discovering that this humble plant compound, as a dietary NAD+ precursor, could be an ally in the fight against sarcopenia. If the preclinical promise of trigonelline holds up in human trials, it may one day be a key ingredient in the recipe for stronger muscles and healthier aging.
Trigonelline is particularly abundant in plant-based food products, such as coffee beans, oats, peas, and fenugreek seeds.
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References:
https://www.nature.com/articles/s42255-024-00997-x
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