Trigonelline for Peak Performance: The Molecule for Powering Strength, Endurance, and Recovery

Beyond the Buzz – Why Trigonelline Is the Molecule Athletes Should Be Watching

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.

The Real NAD+ Level Up for Athletes

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.

Breathing and VO₂ Max

Cellular Efficiency Becomes Cardiovascular Edge

Most performance metrics—VO₂ max, lactate threshold, oxygen pulse—are measured at the level of the lungs, blood, and heart. But the real bottleneck for oxygen utilization doesn’t start in the chest. It starts in the mitochondria. Trigonelline supports athletic breathing capacity not by altering the respiratory system directly, but by optimizing the cellular machinery that determines how efficiently oxygen is used once it arrives.

Mitochondrial efficiency is the central variable in VO₂ max—the maximum rate at which the body can use oxygen during exercise. NAD+ has direct role in this equation by enabling electron transfer through Complex I of the electron transport chain, which drives ATP synthesis from aerobic metabolism [9]. When NAD+ is depleted, this throughput breaks down. That leads to a reliance on anaerobic pathways, quicker lactate buildup, and faster fatigue.

Trigonelline restores NAD+ levels specifically in muscle tissue, where the oxygen is being delivered and consumed. This translates to improved mitochondrial respiration and delayed onset of anaerobic metabolism. In aged mice, trigonelline supplementation preserved muscle oxygenation capacity and enhanced mitochondrial density—factors tightly linked with increased VO₂ max and muscular endurance [2].

Indirectly, this affects respiratory performance. When skeletal muscles become more efficient at oxygen uptake and ATP production, the entire cardiorespiratory system adapts:

• Heart rate at submaximal workloads drops

• Pulmonary ventilation is reduced for the same output

• Lactate threshold rises, allowing sustained efforts at higher intensities

Although no direct studies have yet measured trigonelline's effect on VO₂ max in humans, the mechanistic link is strong. Increased muscle NAD+ availability and mitochondrial optimization have already been shown to shift oxygen kinetics and improve aerobic performance in studies using other NAD+ precursors [10].

Trigonelline focuses on cellular oxygen utilization—where true endurance begins.

Recovery, Inflammation, and Resilience

Rebuild the System—Don’t Just Rest It

Recovery is not passive. It’s a high-demand physiological process that rebuilds tissue, regulates inflammation, restores neurotransmitter balance, and recharges the nervous system. Trigonelline addresses this phase of performance with precision—by supporting NAD+ regeneration in both muscle and brain tissue, where fatigue and dysfunction accumulate fastest.

Emerging data point to trigonelline’s ability to elevate NAD+ in the brain—not just the periphery. In the 2024 Nature Metabolism study, oral trigonelline was detected in the cerebrospinal fluid of treated mice, suggesting central nervous system penetration [11]. This is important because brain NAD+ availability influences neuroinflammation, cognitive performance, and mental fatigue—all of which degrade physical output and recovery when compromised.

NAD+ is essential for the activity of sirtuins and PARPs that modulate neuroinflammation and neuronal repair. Low brain NAD+ levels are associated with microglial activation and elevated pro-inflammatory cytokines like TNF-α and IL-6 [11]. By supplying a precursor that crosses the blood–brain barrier, trigonelline may support CNS recovery in a way other NAD+ precursors cannot. This means lower perceived fatigue, better focus, and faster return to training intensity after neurologically demanding sessions. It isn’t a masking effect or a stimulant – trigonelline is supplying cells with the necessary fuel to recover faster and perform better under greater demand.

Athletic inflammation isn't pathological—it’s functional. But poor resolution of inflammation post-training leads to longer recovery windows, greater risk of overtraining, and diminished adaptations. Trigonelline, by enhancing intracellular NAD+ pools, may support the regulation of key inflammatory mediators including NF-κB, IL-1β, and IL-6 through sirtuin activation and mitochondrial repair pathways [12]. These effects contribute to resilience—both in terms of immune readiness and tissue regeneration.

Trigonelline builds biological capacity to recover harder and faster than you ever thought possible.

Who Should Use Trigonelline (and Why They’ll Never Go Back)

From Peak Performers to Tactical Operators—Trigonelline Redefines the Edge

Trigonelline is not a casual supplement. It's engineered for those operating at the threshold—where performance, precision, and recovery can’t be compromised. Whether you’re chasing podiums, pushing PRs, or preparing for missions, the need is the same: sustained mitochondrial output, fast-twitch preservation, and nervous system resilience under pressure.

Endurance Athletes – Runners, Cyclists, Triathletes

These athletes operate in the oxidative zone. VO₂ max, lactate threshold, and mitochondrial density determine race-day results and mission-critical outcomes. Trigonelline enhances muscle oxygen use by restoring NAD+ where it matters: inside the muscle cell [2]. That means fewer crashes, faster splits, and greater metabolic flexibility when switching between fat and carb fuel systems. It's a molecular upgrade to the aerobic engine.

Strength-Focused Lifters – Clean Gains, Maximum Output

Muscle isn’t just about mass—it’s about fiber quality, contractility, and neuromuscular firing. Trigonelline supports Type II fiber preservation, anabolic signaling, and ATP availability under load [2]. Unlike pre-workouts that spike and crash, this is foundational fuel replenishment—restoring the internal chemistry that allows progressive overload to translate into real strength gains.

Older Athletes – Keeping Output High Without Compromise

Aging athletes face the double burden of recovery slowdowns and mitochondrial decline. Trigonelline addresses both. It ramps up mitochondrial biogenesis, supports neuromuscular junction integrity, and suppresses muscle wasting signals—helping maintain strength, speed, and stamina long past the age most competitors tap out [2].

Tactical Professionals – Military, First Responders, Elite Operators

Physical fitness is mission-critical in high-stress, high-stakes environments. Trigonelline doesn’t just support output—it buffers the system against inflammatory cascades, central fatigue, and energy collapse. When your recovery window is short and your next task is already loading, you don’t need hype. You need molecular readiness.

Trigonelline isn’t for weekend warriors. It’s for athletes serious about capacity, adaptation, and longevity in high-performance domains. Once your cells experience what targeted NAD+ replenishment actually feels like, there’s no going back.

The Future of Natural Performance Enhancement Is Molecular

Performance isn't fueled by macros alone. It’s driven by the molecules that dictate how cells generate energy, repair damage, and resist fatigue under stress. Trigonelline is a signal molecule—one that tells your body to build more mitochondria, recover faster, and keep power output high even under pressure. It’s not hype. It’s molecular physiology, applied with precision.

Mortalis Labs isolates what nature only hints at and delivers it in a form your biology can immediately use. Trigonelline isn’t about stacking stimulants or chasing short-term pumps. It’s about equipping your cells with the precursors they need to function like you’re still in your prime—and then some.

If your protocol is still built around protein percentages and caffeine timing, it’s time to rethink what performance support actually means. Upgrade to molecular interventions that don’t just fill gaps—they redefine baselines.

You’ve optimized your training. Now optimize your metabolism. Mortalis Labs makes that possible.

References:

1. Yaku, K., Okabe, K., & Nakagawa, T. (2018). NAD metabolism: Implications in aging and longevity. Ageing Research Reviews, 47, 1–17. https://doi.org/10.1016/j.arr.2018.05.006

2. Zhu, X., et al. (2024). Trigonelline is a novel NAD+ precursor enhancing muscle function during aging. Nature Metabolism, 6, 442–458. https://www.nature.com/articles/s42255-024-00997-x

3. Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x

4. Liang, H., Ward, W. F. (2006). PGC-1α: a key regulator of energy metabolism. Advances in Physiology Education, 30(4), 145–151. https://doi.org/10.1152/advan.00052.2006

5. Cantó, C., & Auwerx, J. (2009). PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current Opinion in Lipidology, 20(2), 98–105. https://doi.org/10.1097/MOL.0b013e328328d0a4

6. Sandri, M., et al. (2004). Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 117(3), 399–412. https://doi.org/10.1016/S0092-8674(04)00400-3

7. Liu, J., et al. (2013). NAD+ supplementation delays muscle degeneration in aged mice by preserving neuromuscular junctions. Cell Reports, 2(5), 1400–1410. https://doi.org/10.1016/j.celrep.2012.11.006

8. Gong, Y., et al. (2022). NAD+ precursors modulate muscle fiber-type composition and function. Journal of Cachexia, Sarcopenia and Muscle, 13(4), 2092–2105. https://doi.org/10.1002/jcsm.12984

9. Yin, X., et al. (2021). NAD⁺ metabolism in skeletal muscle and mitochondria: insights into exercise and aging. Frontiers in Physiology, 12, 724989. https://doi.org/10.3389/fphys.2021.724989

10. Martens, C. R., et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9(1), 1286. https://doi.org/10.1038/s41467-018-03421-7

11. Xie, N., et al. (2020). NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy, 5, 227. https://doi.org/10.1038/s41392-020-00333-8

12. Lautrup, S., et al. (2019). NAD+ in brain aging and neurodegenerative disorders. Cell Metabolism, 30(4), 630–655. https://doi.org/10.1016/j.cmet.2019.09.001