Coffee Compound Trigonelline Could Keep Muscles ‘Young’ In Old Age

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This is a reprint of the original article.

The information provided in the following paragraphs discusses recent research conducted by scientists from the National University of Singapore regarding the potential benefits of trigonelline, a compound found in various plant-based foods, including coffee, in maintaining muscle health as individuals age.

While the findings present promising insights into potential interventions for age-related muscle decline, it's important to note that further research and clinical studies may be necessary to fully understand the efficacy and safety of trigonelline supplementation or its impact on muscle health in humans.

As with any nutritional or health-related information, individuals should consult with qualified healthcare professionals before making any changes to their diet or lifestyle based on this research.

The project was funded by Nestlé Research, Nestlé Health Sciences and direct funding to the senior authors of the article (not me).

First Sip


MARCH 22, 2024 by StudyFinds

Senior couple

SINGAPORE — As we get older, our muscles naturally start to decline. This process, known as sarcopenia, can lead to frailty, falls, and a loss of independence in our golden years. But what if there was a natural compound that could help slow down this process and keep our muscles healthy and strong as we age?

New research by scientists from the National University of Singapore, published in Nature Metabolism, identifies a promising candidate: trigonelline.

Trigonelline is a compound found in many plant-based foods like coffee, fenugreek seeds, and garden peas. Research shows that levels of trigonelline in the blood were lower in older adults with weaker muscles and slower walking speeds.

Intrigued by this correlation, the researchers decided to dig deeper into whether trigonelline could actually directly impact muscle health. Through a series of experiments in human muscle cells, mice, and even tiny worms called C. elegans, they discovered that trigonelline acts as a precursor for NAD+, a critical coenzyme that declines with age.

Roughly 1 in 4 adults over 65 years-old suffers a fall, according to the CDC. Over 3 million older adults receive emergency treatment for falls each year. More than 300,000 of these injuries are hip fractures needing hospitalization.

NAD+, or nicotinamide adenine dinucleotide, is essentially the currency of metabolism in our cells, enabling the fundamental chemical reactions that generate energy and keep us alive. Mitochondria, the powerhouses of the cell, rely on NAD+ to function properly. Muscle cells are packed with mitochondria to power movement. So, the age-related decline in NAD+ is thought to be a key driver of mitochondrial dysfunction and muscle deterioration over time.

“Our findings expand the current understanding of NAD+ metabolism with the discovery of trigonelline as a novel NAD+ precursor and increase the potential of establishing interventions with NAD+ producing vitamins for both healthy longevity and age-associated diseases applications,” says Vincenzo Sorrentino from the Healthy Longevity Translational Research Program at NUS Medicine, in a media release.

It’s All About NAD+

The scientists found that trigonelline treatment boosted NAD+ levels and improved markers of mitochondrial function in aged muscle cells from both humans and mice. Remarkably, feeding trigonelline to elderly mice for 12 weeks increased their grip strength and protected them against muscle fatigue.

Even the little C. elegans worms got a boost from trigonelline – it extended their lifespan, improved the structural integrity of their muscle cells, and helped maintain their ability to wriggle around with age. The worms with a genetic tweak that eliminated their ability to process trigonelline into NAD+ didn’t get these anti-aging perks, confirming that the NAD+ connection is key.

From a chemical perspective, trigonelline looks a lot like niacin (vitamin B3). But unlike niacin supplements, which are incorporated directly into NAD+, the researchers determined that trigonelline has to go through a few more metabolic steps first. Enzymes strip off trigonelline’s extra methyl group (that’s the “M” in its chemical name: “N-methylnicotinic acid”) to produce nicotinic acid. Nicotinic acid then gets ushered into the cell’s NAD+ factory through a pathway called the Preiss–Handler pathway.

Interestingly, some tissues, like the liver, are really efficient at this trigonelline-to-NAD+ conversion, while others, like skeletal muscle, get a smaller NAD+ boost from trigonelline.

The researchers think this might be why the aged mice didn’t pack on more muscle mass with trigonelline, even though their muscle strength and endurance improved.

Final Sip

More Trigonelline Research Needed. Recent research from the National University of Singapore, published in Nature Metabolism, reveals trigonelline, a compound found in plant-based foods like coffee, as a potential solution to sarcopenia, the age-related decline in muscle mass and strength. Lower levels of trigonelline correlate with weaker muscles in older adults, prompting investigation into its impact on muscle health.

Experiments show trigonelline acts as a precursor for NAD+, crucial for cellular metabolism. Supplementation enhances NAD+ levels, improving mitochondrial function and muscle strength in aged subjects. Trigonelline may serve as a dietary supplement to mitigate muscle deterioration, suggesting promising avenues for combating sarcopenia with novel dietary interventions, though further research is needed to fully understand its benefits and translation to human applications.

The project was funded by Nestlé Research, Nestlé Health Sciences and direct funding to the senior authors (not me).

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