Trigonelline is a methylated form of niacin and is a recently isolated molecule that could be the secret ingredient in your stack. This form of the B vitamin is involved in the generation of NAD+, a cofactor for over 500 metabolic processes in cells. Trigonelline promotes cellular repair and energy, and as we’ll see, exerts quite a few benefits that are specifically useful for anyone training seriously.
Trigonelline is found in several plant-based foods, notably coffee beans and fenugreek seeds. Green coffee beans contain trigonelline concentrations ranging from 0.6% to 1.0% by weight. However, traditional dietary sources don’t provide sufficient amounts to elicit significant physiological effects. For instance, the average trigonelline content in a cup of coffee is approximately 53 mg, and about 50-80% of trigonelline decomposes during the roasting process, leaving virtually nothing for your body to make use of.
Recent research published on this naturally occurring alkaloid highlights its potential in enhancing muscle function and combating age-related decline. A 2024 study published in Nature Metabolism identified trigonelline as a novel precursor to nicotinamide adenine dinucleotide (NAD+), a molecule essential for energy metabolism and mitochondrial function. The study demonstrated that trigonelline supplementation improved muscle strength and reduced fatigue in aged mice, suggesting that it can head off the natural muscle decline seen in aging, even in those who are already training at capacity.
NAD+ gets discussed a lot in the longevity space because of its natural and steep decline over the years, tied to all the diseases of aging. It's a metabolic linchpin that determines how efficiently your cells convert fuel into usable energy. For athletes, that efficiency translates into faster recovery, better performance under load, and greater resilience under metabolic stress. Or, you know, complete lack of those things if you don’t have enough of it.
NAD+ is required for redox (oxidation–reduction) reactions in mitochondrial energy production and is a cofactor and substrate for longevity-promoting sirtuins and other enzymes involved in muscle repair and adaptation. During intense physical activity, NAD+ levels drop as demand for ATP surges. Replenishing intracellular NAD+ is critical not only for restoring mitochondrial output but also for initiating the cellular programs that rebuild and reinforce muscle tissue [1].
Trigonelline offers a direct path to NAD+—one that bypasses the liver and supports muscle tissue specifically. In a landmark 2024 study, researchers at EPFL and Nestlé Health Sciences (yes, that Nestlé, but there aren’t any conflicts of interest, we checked) demonstrated that trigonelline functions as a previously unidentified NAD+ precursor, rapidly taken up by skeletal muscle cells and converted into NAD+ via a salvage pathway independent of the traditional NR or NMN routes [2]. This muscle-specific uptake is particularly important for athletes, who require localized replenishment in the very tissues under stress.
Most NAD+ precursors—including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN)—undergo hepatic metabolism before entering systemic circulation. This creates a bottleneck at your liver for targeted muscle repair. Trigonelline appears to bypass that constraint by delivering precursors directly where they're needed most: the muscle fibers responsible for performance and endurance.
This shift in delivery has implications beyond simple NAD+ restoration. In the same Nature Metabolism study, aged mice supplemented with trigonelline showed significant improvements in grip strength and fatigue resistance—outcomes tightly linked to muscle NAD+ availability. Unlike systemic precursors that may elevate circulating NAD+ levels without improving localized bioenergetics, trigonelline drives changes in muscle mitochondrial density and function.
For athletes, this is the difference between feeling recovered and actually being rebuilt.
Mitochondria Make Muscles Move
Endurance Starts in the Electron Transport Chain
Every sprint, every lift, every set depends on one thing: mitochondrial output. The ability to generate ATP on demand—efficiently and cleanly—is the defining line between sustained power and early fatigue. Trigonelline’s value lies not just in elevating NAD+ levels, but in what that elevation enables at the level of mitochondrial performance.
NAD+ drives oxidative phosphorylation, the mitochondrial pathway responsible for converting nutrients into ATP. When NAD+ is depleted, electron transport slows, reactive oxygen species accumulate, and mitochondrial output tanks—resulting in performance collapse and prolonged recovery. Replenishing NAD+ restores mitochondrial throughput, enhances metabolic flexibility, and allows cells to switch between carbohydrate and fat oxidation with minimal friction [3].
Trigonelline’s role as a direct NAD+ precursor in muscle tissue makes it especially powerful in this context. By bypassing hepatic metabolism and restoring NAD+ where it's most needed, it kickstarts mitochondrial biogenesis—activating pathways like PGC-1α that drive the formation of new mitochondria and increase the efficiency of existing ones [4]. This isn’t theoretical: in the 2024 Nature Metabolism study, trigonelline supplementation significantly boosted mitochondrial content and activity in aged mice, restoring performance metrics typically lost with age and overtraining [2].
This cellular shift translates directly to the field, the track, and the gym. More mitochondria means more ATP per unit of oxygen consumed. This is the underpinning of higher VO₂ max, improved lactate clearance, and extended time-to-exhaustion. Trigonelline supports this adaptation at the source, which means athletes can train harder, go longer, and bounce back faster—without relying on stimulants or sketchy ergogenics.
More NAD+ in muscle equals better mitochondrial kinetics, which equals better athletic output. Period.
Strength and Muscle Health
Preserving Power, Not Just Mass
Strength isn’t only about size—it’s about contractile quality, neuromuscular precision, and the cellular capacity to resist breakdown under stress. Trigonelline’s impact on muscle tissue reaches beyond endurance. It supports structural integrity, performance output, and resilience across multiple pathways—especially in the context of aging or chronic training demand.
In the 2024 Nature Metabolism study, trigonelline supplementation restored muscle grip strength and improved fatigue resistance in aged mice, with outcomes exceeding those observed in control groups receiving traditional NAD+ precursors [2]. This effect was tied to increased NAD+ availability in skeletal muscle, which reactivated SIRT1- and PGC-1α-dependent pathways responsible for mitochondrial biogenesis, inflammation control, and protein maintenance—all critical for contractile performance and mass preservation [5].
NAD+ also plays a protective role against muscle wasting. It regulates the balance between anabolic and catabolic signaling, modulating FoxO transcription factors and suppressing atrophy-related genes like MuRF1 and atrogin-1 [6]. This anti-catabolic signaling becomes especially important during periods of calorie deficit, illness, or overreaching, when muscle degradation accelerates. Trigonelline, by supplying NAD+ directly to muscle cells, may help maintain lean mass even under systemic stress.
One overlooked aspect of muscle performance is neuromuscular junction (NMJ) stability, or, the connections between nerves and muscle fibers. These connections go both ways, with afferent signals carrying sensory feedback from muscle to brain, and efferent signals delivering motor commands from brain to muscle. Maintaining the integrity of this bidirectional communication is essential for coordination, strength, and rapid recovery from fatigue. NAD+ is required for the function of enzymes that protect NMJ architecture—particularly in aging or disease models where synaptic decline contributes to strength loss [7]. Trigonelline’s direct muscle delivery may therefore preserve the electrical signaling fidelity needed for explosive power and motor unit recruitment.
Muscle Fiber Type Preservation
Emerging evidence suggests that NAD+ availability influences muscle fiber type composition. High NAD+ levels favor the maintenance of fast-twitch (Type II) fibers—those responsible for strength, speed, and power—by enhancing mitochondrial support without triggering full transition to slow-twitch oxidative profiles [8]. This has implications for athletes seeking to maintain peak force output without compromising endurance. By elevating muscle NAD+ directly, trigonelline may help preserve this delicate fiber balance.
Trigonelline is formulated not to just support general energy—but to protect the architecture of athleticism at the cellular level.
For a reliable, pure form of trigonelline with zero additives, you can trust Mortalis Labs.
