Levels of trigonelline, a naturally occurring alkaloid and structurally related to nicotinic acid (vitamin B3), were found to be decreased in older people with sarcopenia. Levels of the compound also correlate positively with muscle strength, according to findings published in Nature Metabolism.
In Caenorhabditis elegans, mice and human studies, supplementation with the compound was found to boost NAD+ levels, with additional insights from the C. elegans experiments showing that trigonelline may reduce age-related muscle wasting and increase lifespan.
The current study was led by scientists from Nestlé Research in collaboration with a consortium of international academic institutions spanning four continents and eight countries.
“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,” said Assistant Professor Vincenzo Sorrentino from the National University of Singapore (NUS Medicine), one of the research institutions involved in the study, in a NUS press release.
NAD+
Nicotinamide adenine dinucleotide (NAD) is an important cellular co-factor for improvement of mitochondrial performance and energy metabolism. As organisms age, NAD+ levels drop, which leads to a decrease in mitochondrial health; this in turn leads to age-related health issues. By the age of 70, individuals may have lost as much as 80% of the NAD+ present in their 30s.
The potential long-term health benefits of boosting NAD+ levels have attracted a lot of attention over the last 10 years, led by ingredients like nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinic acid (NA) and nicotinamide (NAM).
In addition to NAD+ precursors, some companies are exploring the opportunity for plant-based products that reportedly stimulate the body's endogenous ability to produce NAD+.
Nestlé has invested in this space, with strategic investments in ChromaDex (which markets the Niagen-brand of NR) and Amazentis (which markets the Mitopure brand of Urolithin A for mitochondrial health). Nestlé Health Science also launched the Celltrient product line for cellular aging in 2020. In the US, the Celltrient range is sold under Solgar's Cellular Nutrition label, as of October 2023.
Trigonelline
The new Nestlé study indicates that trigonelline can be added to the list of dietary NAD+ boosters.
“Our work highlights that the NAD+-boosting capabilities of different precursors vary across tissues and experimental models according to the relative activity of different branches of NAD+ biosynthesis,” the researchers wrote.
“Trigonelline contributes to the NAD+ pool via a more indirect route than the ribosylated precursors NR and NMN, but our comparative studies demonstrate that trigonelline has similar cellular and physiological benefits to NA and NR in cells or nematodes, most probably because of its higher stability than ribosylated precursors.”
Taken together, the researchers stated that trigonelline exhibits the potential to act as a “nutritional geroprotector” that may help to manage sarcopenia and other age-related declines.
"We were excited to discover through collaborative research that a natural molecule from food cross-talks with cellular hallmarks of aging," said Jerome Feige, head of the physical health department at Nestlé Research and corresponding author on the new paper. "The benefits of trigonelline on cellular metabolism and muscle health during aging opens promising translational applications."
Sarcopenia
Muscle loss is a natural part of aging, and researchers have estimated that, after the age of 50, we lose 1% to 2% of our muscles each year. Strength declines as well, at a rate of 1.5% per year beginning at 50 years and accelerating to 3% after the age of 60.
According to a monograph from the U.S. Dairy Export Council, the direct health care cost attributable to sarcopenia were estimated to be $18.5 billion in 2000 in the U.S., a number that represented about 1.5% of health care expenditures for that year.
Source: Nature Metabolism
Published online ahead of print, doi: 10.1038/s42255-024-00997-x
“Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia”
Authors: M. Membrez, et al.
