Trigonelline: the coffee compound that combats muscle ageing?

Why do muscles lose strength as we age?

As we age, muscle mass, strength and quality can gradually decline. Several factors are involved: reduced physical activity, a less effective response of muscle protein synthesis to anabolic stimuli, alterations in mitochondrial function, and disruptions to cellular metabolism (1)...

When this muscular decline becomes pronounced, it may indicate sarcopenia. This age-related condition is characterised primarily by a reduction in muscle strength associated with a decrease in muscle mass or quality. A decline in physical performance is indicative of a severe form (2).

However, not all muscle wasting is attributable to this condition, the diagnosis of which is based on specific medical and functional criteria.

What is trigonelline, the molecule found in coffee?

Trigonelline is a natural alkaloid found in various plants, notably coffee beans and fenugreek seeds. Chemically, it is a methylated derivative of nicotinic acid, or niacin, a form of vitamin B3 (3).

It differs from caffeine in both its structure and its metabolism. An important point to note: the study in question here does not assess the effects of coffee consumption. Drinking more coffee cannot therefore, under any circumstances, be presented as a strategy to combat muscle ageing.

One of the main reasons trigonelline is of such interest to researchers is its potential link to NAD+ (nicotinamide adenine dinucleotide). This coenzyme plays a role in energy metabolism and the functioning of mitochondria, the powerhouses of our cells.

A study conducted in humans found lower muscle levels of NAD+ in older adults than in younger adults. This decrease was more pronounced in subjects with physical limitations than in fit older adults (4).

These findings explain the growing interest in NAD+ metabolism and the search for its precursors in the context of ageing. Trigonelline is currently one of the avenues being explored in this field. It is worth noting that it is available as a dietary supplement.

Discover Trigonelline, which provides 300mg of trigonelline hydrochloride per daily dose.

Trigonelline, muscle strength and NAD+: what does the study show?

A study published in 2024 in *Nature Metabolism* specifically examined the link between trigonelline, NAD+ and muscle ageing. It combined data collected from humans with experiments on muscle cells and animal models. However, it does not constitute a clinical trial evaluating the effects of trigonelline supplementation in humans (5).

Levels associated with muscle function

The researchers first compared 20 people with sarcopenia to 20 control subjects. They noted that blood concentrations of trigonelline were significantly lower in those with sarcopenia.

More interestingly, higher concentrations were associated with several favourable indicators: greater appendicular muscle mass (skeletal muscles of the arms and legs), better grip strength and a faster walking speed.

This same link was confirmed in a second cohort comprising 186 men aged over 60: higher trigonelline levels were associated with greater grip strength.

It should be noted, however, that these associations do not prove that trigonelline improves strength or prevents sarcopenia.

Preclinical findings on NAD+

The study also seeks to shed light on the mechanisms that may explain these observations.

In human muscle cells cultured in the laboratory, trigonelline was used as a precursor to NAD+, leading to an increase in its concentrations. The researchers identified its utilisation via the so-called Preiss-Handler pathway, a pathway involved in NAD+ biosynthesis.

Experiments were then carried out on worms (Caenorhabditis elegans). It was reported that trigonelline had increased NAD+ levels and improved several parameters related to mitochondrial function, mobility and muscle preservation during ageing.

Finally, in aged male mice, trigonelline supplementation improved muscle strength and reduced fatigue.

Whilst these preclinical results point to a promising avenue, they cannot, however, be directly extrapolated to humans.

These results must be interpreted with caution. The initial human analysis involved only 40 people, whilst the second cohort consisted exclusively of elderly men. The benefits of trigonelline for muscle ageing therefore remain to be confirmed in humans: the study does not allow us to determine either an effective dose or the effects of supplementation on sarcopenia, falls, independence or longevity.

How can you maintain your muscle mass and cellular vitality as you age?

Trigonelline: an emerging avenue to explore

Trigonelline lies precisely at the intersection of three areas of intensive research: muscle ageing, energy metabolism and NAD+.

The results published in *Nature Metabolism* are encouraging: they link trigonelline to muscle function in humans and highlight a mechanism for NAD+ production as well as functional effects in several animal models. Clinical trials are, however, still needed to determine its benefits in humans.

The Trigonelline supplement boasts an exceptional purity of 98% (compared with a concentration of 5% in fenugreek extracts).

Physical activity and protein: the fundamentals of muscle maintenance

Maintaining muscle mass and function relies first and foremost on regular physical activity, including appropriate strength training, as well as sufficient energy and protein intake.

Protein helps to maintain and increase muscle mass. When dietary intake is insufficient, a high-quality whey supplement makes it easier to meet these requirements.

In older adults, studies evaluating whey in combination with resistance training also show promising results for certain muscle parameters, although the extent of the benefits varies across studies and populations (6).

Native Whey Protein Isolate is a native whey isolate providing 27.5g of protein per serving, including 6g of BCAAs.

However, maintaining muscle mass is not enough to guarantee strength. Strength also depends on the quality of the muscle, its activation by the nervous system and its ability to exert force. These are therefore two complementary aspects of muscle health (7).

Vitamin D: for maintaining good muscle function

Vitamin D is another nutrient directly linked to muscle physiology. It helps maintain normal muscle function. Clinical trials have specifically analysed its influence on muscle strength: a meta-analysis of 30 randomised trials reports a modest positive effect of supplementation, which is more pronounced in people with low vitamin D levels and in those aged over 65 (8).

Vitamin D3 5000 IU, a supplement providing 5,000 IU of vitamin D3 per dose.

New muscle-supporting nutrients under investigation

Other compounds are now attracting the interest of researchers. PeptiStrong® broad bean peptides, ursolic acid and spermidine are, in particular, being studied from various angles for their potential effects on muscle mass or quality, as well as on certain mechanisms associated with ageing (9–11).

Muscle Mass Booster Formula combines them in a comprehensive, synergistic formula enriched with vitamin D3.

NAD+: from muscle to cellular ageing

The significance of NAD+ extends far beyond the issue of muscle alone. This cofactor plays a central role in cellular energy metabolism, particularly in mitochondrial function and ATP production. However, its levels tend to decline with age, making it a closely scrutinised target in the field of cellular ageing and longevity (12).

Several nutritional strategies therefore aim to support its availability. One of these relies on precursors, such as nicotinamide riboside (NR). Human trials report an increase in NAD+ and some of its metabolites following NR supplementation (13).

Another avenue of research concerns CD38, an enzyme that ‘consumes’ NAD+. Preclinical studies suggest that its activity increases with ageing and may contribute to the decline in NAD+ levels as well as to certain mitochondrial dysfunctions (14).

Certain flavonoids act via this pathway, such as apigenin. Cell and animal experiments have notably highlighted its potential ability to inhibit CD38 whilst boosting NAD+ concentrations (15).

A relevant approach is therefore to tackle the issue from both angles: stimulating NAD+ production and slowing its breakdown.

NAD+ Booster Formula combines nicotinamide riboside (NR), apigenin and BluNAD Booster™, three complementary active ingredients designed to maintain NAD+ levels.