TIME TO FLY | THE TEACRINE® ADVANTAGE

How PreRace 3.0’s newest nootropic boosts every performance metric.

By Dr. Luke Bucci

INTRODUCTION

PreRace 2.0 was based on extensive records of clinical research showing benefits to body-wide performance markers, including boosting circulation, sustaining cell hydration, reducing muscle damage, speeding recovery, and maintaining optimal performance – athletes’ engines burned longer and stronger, and their minds were clearer and faster.

The new PreRace 3.0 formula pushes even further, adding theacrine – an alkaloid similar to caffeine’s paraxanthine – as an additional performance multiplier. If we had to summarize, we’d say that theacrine has several things going for it:

1. Provides stimulatory benefits in time of need or in absence of caffeine, which happens to be very helpful during exhaustive exercise or when fuel is running low;
2. Sharpens mental toughness and cognition;
3. Activates dopamine receptors to improve mood and motivation;
4. Increases sirtuin activity to help muscles rebuild and recover;
5. Smooths and extends the duration of caffeine’s ergogenic effects;
6. Reduces anxiety and perceived fatigue;
7. Is a natural derivative of tea, is not addictive or habit-forming, and doesn’t impact sleep.

But we don’t have to summarize, because we’ve got Dr. Luke Bucci to explain the what, why, and how of TeaCrine ®. (You knew we weren’t going to leave you with just a summary.) We’ll let Dr. B take it from here.

NEVER ACCEPT “EASY”

Pre-race nutrition used to be easy. Hydration, carbs, maybe a dribble (or a deluge) of caffeine – you’re all set. Easy.

Well to us, “easy” is a giant blinking red neon sign suggesting that whatever it’s pointing at could be improved. So a couple of years ago, we engineered a PreRace 2.0 formula that included nootropics like caffeine, of course, but also taurine and theobromine to boost mental toughness and keep your motivation and decision-making faculties as sharp as your fitness. We also added Nitrosigine®, a patented vasodilator that increases circulation to turbocharge the delivery of oxygen and everything else your muscles burn up during exercise.

And we still weren’t satisfied, so we engineered PreRace 3.0 to add another layer of similar ergogenic effect that also magnifies the impact of caffeine, which is the granddaddy of all these nootropics and a good place to begin our exploration of theacrine.

CAFFEINE: WHERE WE STARTED

Using caffeine as a performance supplement is low-hanging fruit for endurance training, because it’s entrenched as a daily ritual for athletes and non-athletes alike in the form of those low-hanging beans and leaves that bring us coffee, cocoa, and tea. Its prevalence means it’s also a readily accepted ergogenic aid, so it’s been incorporated into all manner of pre-performance supplements and gels (like Konda Mocha Liquid Shot).

But as with all low-hanging solutions, there is room for improvement, because caffeine has shortcomings. Some people have different genetics that make caffeine less effective or even counterproductive. Keeping the right amount of caffeine in your body throughout a long, torturous performance has its ups and downs. Too much caffeine can be a bummer, messing with performance by tweaking things like body heat.

Dr. Matt Hanson explains more about caffeine’s potential pitfalls in a separate blog post, but for our purposes here, we’re moving on to focus on theacrine, an alternative that provides similar ergogenic effects without the downsides and with results that can be felt throughout an entire day of activity.

THEACRINE: WHERE WE’RE GOING

Theacrine (included in PreRace as TeaCrine®) is another naturally occurring purine alkaloid in the human diet, but it has not received the attention of fellow bitter alkaloids caffeine, paraxanthine (caffeine's major metabolite and effector), and theobromine (in cacao extracts, chocolate, and also PreRace).

Theacrine is found in Kucha tea (Camellia kucha) leaves and buds, a rare but closely related species to green tea (Camellia sinensis) (Qin 2021; Sheng 2020). Kucha tea is isolated to a small area of cloudy, foggy mountains in China, where it's valued for improving mood while maintaining energy levels and a long, healthy life. Theacrine makes up ~2% by weight, along with similar amounts of caffeine. 

THEACRINE HUMAN STUDIES

Theacrine was not studied systematically until about 2010, and the number of human studies on theacrine is dwarfed by the multitude of caffeine human studies, but what studies do exist show demonstrable benefits from the understudied prodigy. Right away it was found that theacrine was different from caffeine – not least of all because it works the same for everyone – but there were also a lot of differences.

Like caffeine, theacrine activates adenosine receptors, and shares most of the same effects we all know, love, and crave. One theacrine study approximated real-life endurance racing and training (Bello 2019). 24 Male and female soccer players were tested four times after taking placebo, 275mg theacrine, 275mg caffeine, or 125/150mg theacrine/caffeine 30 minutes before exercise. All subjects then proceeded to simulate a 90-minute soccer match load, with cognitive testing performed at halftime and after the match. That was followed by a run time to exhaustion (TTE) at 85% VO2max on a treadmill.

Caffeine and caffeine+theacrine periods showed significant improvements vs. placebo for cognitive tests, with the biggest differences at match end. TTE showed 27-38% improvements (P=0.052) for theacrine and caffeine+theacrine periods, lasting from 194 seconds during placebo to 246, 255, and 267 seconds for theacrine, caffeine, and caffeine+theacrine periods, respectively. Ratings of Perceived Exertion showed small-to-moderate effects for caffeine and caffeine+theacrine periods.

Though the Bello study did not last as long as most endurance races, it did show improved cognitive measures and improved physical performance at extended efforts – that translates to sharper thinking, more mental toughness, and more of a finishing kick at the end of a race. Also, this study used trained athletes vs. relatively untrained athletes (who have notoriously high inter-subject variabilities), so the results are more relevant to dedicated endurance athletes.

Those mental toughness effects may connect in part to theanine’s activation of dopamine receptors, the feel-good neurotransmitter (Feduccia 2012; Duan 2020). The dopamine difference for theacrine was illustrated by a human study of 200mg theacrine that increased feelings of energy, motivation to train, willingness to exercise, and concentration vs. placebo (Ziegenfuss 2017). No changes in heart rate or blood pressure were noted – something very unlike caffeine. Theacrine has shown enhanced mental functions – especially cognition and mood – to the point of being called an antidepressant.

Notice the overlap with caffeine? Energy, focus, and reduced fatigue. Notice the difference between caffeine and theacrine? Less anxiety – the opposite of caffeine. Theacrine counteracts caffeine's "upper" effects, imbuing a sense of cool, calm confidence when both are taken together.

IMPROVED RECOVERY

One of the more recently discovered functions of theacrine is an increase in sirtuin (SIRT) enzyme activities. If you’re versed in certain alt-med and supplement discourse, then you might recognize sirtuins as being pushed for longevity. Whether you knew that before or you just learned it now, you’re probably wondering: What does that have to do with maximal endurance performance?

Actually, quite a lot. Sirtuins are a key regulatory step for making big changes in cell structures, controlling which genes get turned on/off or lower/higher using the same cell machinery and controls that fix exercise-induced muscle damage.

Studies of mouse muscle cells (Lopez 2018; Mumford 2020, 2022) and real living humans (Hellenbrand 2024; Roberts 2022, 2023) have shown that theacrine activates mitochondrial biogenesis, fights muscular inflammation, regulates autophagy (which is needed to recover and repair from muscular stress from exertion), and releases stem cells into circulation. The human data on theacrine specifically found unprecedented increases in the ratio of NAD+/NADH levels in humans (peripheral blood white blood cells) (Roberts 2022, 2023).

That equals pure, unadulterated mitochondrial energy in cells, triggered by increasing sirtuins at the right time and place. For endurance athletes, the right time and place is during stressful, muscle-damaging exercise, making PreRace the ideal delivery vehicle to ensure your cells have an effective supply when it’s needed.

Does that mean PreRace is a longevity supplement, too? Is endurance exercise healthy? The research says: Yes squared.

BETTER TOGETHER: EFFECT + DURATION

Theacrine not only helps us achieve our best, it also pushes caffeine to the next level by softening the edges. Human studies to date have shown that compared to caffeine alone, theacrine-caffeine combinations with methylliberine (another tea alkaloid) improved high-stress coordination by decreasing unwanted caffeine side effects (Evans 2023), reduced fatigue more than caffeine alone three hours after coadministration (Raub 2020), and showed better hemodynamics and similar efficacy on vigilance tasks to twice the dose of caffeine with lower blood pressure in tactical personnel (Cintineo 2022).

The two are also mutually supportive in another way: Coadministration of caffeine and theacrine increases the duration of both in the bloodstream. This means that the combination of theacrine and caffeine in PreRace will keep on giving for 6-8 hours or longer, with less of a drop-off over time for effects – ideal for a pre-race supplement. (Theacrine itself has a half-life of 20-24 hours, but don't worry; unlike caffeine in many people, it will not keep you awake at night [Harris 2021].)

Everything caffeine does well, it does better when theacrine is there to support it.

SUMMARY

PreRace includes TeaCrine® theacrine to bolster caffeine effects and minimize unwanted side effects, adding to the clinically studied improvements in endurance exercise performance from each of the other ingredients.

Theacrine offers a new dimension for maintaining and extending mental and physical performance in endurance events via an additive effect with caffeine, while introducing two new mechanisms of action – a dopamine neurotransmitter boost (for better mental drive, concentration, focus, and decision-making) and the promise of a new factor in recovery and preventing muscle damage via sirtuin activation.

REFERENCES

Bello ML, Walker AJ, McFadden BA, Sanders DJ, Arent SM. The effects of TeaCrine® and caffeine on endurance and cognitive performance during a simulated match in high-level soccer players. J Int Soc Sports Nutr. 2019 Dec;16:1-0.

Cintineo HP, Bello ML, Chandler AJ, Cardaci TD, McFadden BA, Arent SM. Effects of caffeine, methylliberine, and theacrine on vigilance, marksmanship, and hemodynamic responses in tactical personnel: a double-blind, randomized, placebo-controlled trial. J Int Soc Sports Nutr. 2022 Dec31;19(1):543-64.

Duan WJ, Liang L, Pan MH, Lu DH, Wang TM, Li SB, Zhong HB, Yang XJ, Cheng Y, Liu B, Li WX. Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation. Phytomedicine. 2020 Oct1;77:153281.

Evans C, Antonio J, Khan A, Vanderkley A, Berrocales M, Rojas J, Sakaria S, Petruzzelli J, Santana JC, Curtis J, Ricci T. A combination of caffeine, teacrine, and dynamine improves the neurophysiological and performance measures of electronic (E)-gamers. Cureus. 2023 Aug;15(8).

Feduccia AA, Wang Y, Simms JA, Henry YY, Li R, Bjeldanes L, Ye C, Bartlett SE. Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors. Pharmacol Biochem Behav. 2012 Aug1;102(2):241-8.

Harris D, Machek S. Theacrine as a potential caffeine alternative for enhanced ergogenic and cognitive performance in athletes: a call to action and brief review. J Exer Nutr. 2021 Jul9;4(3).1-9.

Hellenbrand J, Bloomer RJ, Van der Merwe M. The Effect of Short-Term NAD3® Supplementation on Circulating Adult Stem Cells in Healthy Individuals Aged 40-70 Years. Cureus. 2024 Mar;16(3).

Lopez HL, Wells S, Ziegenfuss TN, inventors; ORTHO-NUTRA LLC, assignee. Theacrine-based supplement and method of use thereof in a synergistic combination with caffeine. United States patent US 10,398,701. 2019 Sep3.

Mumford PW, Osburn SC, Fox CD, Godwin JS, Roberts MD. A theacrine-based supplement increases cellular NAD+ levels and affects biomarkers related to sirtuin activity in C2C12 muscle cells in vitro. Nutrients. 2020 Dec 3;12(12):3727.

Mumford P, Osburn S, Roberts MD. The Effects of a Theacrine-based Supplement on mRNAs Related to Various Metabolic Processes and Sirtuin Activity in vitro. Res Square. 2020 Aug4;PPR196221. https://doi.org/10.21203/rs.3.rs-51095/v1 

Qin DD, Wang QS, Li HJ, Fang KX, Jiang XH, Pan CD, Wang Q, Li B, Wu HL. Progress in research on Camellia kucha (Chang et Wang) Chang and its special constituent theacrine. Food Sci. 2021;42(13):353-9.

Raub B, Cesaro K, Carney M, Kersick C, Sandrock J. Methylliberine (DynamineTM) and theacrine (TeaCrine®) magnify indices of cognitive affect when combined with coffee. J Int Soc Sports Nutr. 2020;17(Suppl 2):59, A1.

Roberts MD, La Monica MB, Raub B, Sandrock JE, Ziegenfuss TN, Smith R, Dwaraka VB, Lopez HL. The Effects of a Multi-Ingredient Supplement Containing Wasabia Japonica Extract, Theacrine, and Copper (I) Niacin Chelate on Peripheral Blood Mononuclear Cell DNA Methylation, Transcriptomics, and Sirtuin Activity. Physiologia. 2023 Apr18;3(2):233-46.

Roberts MD, Osburn SC, Godwin JS, Ruple BA, La Monica MB, Raub B, Sandrock JE, Ziegenfuss TN, Lopez HL. Enhance trial: effects of NAD3® on hallmarks of aging and clinical endpoints of health in middle aged adults: a subset analysis focused on blood cell NAD+ concentrations and lipid metabolism. Physiologia. 2022 Mar21;2(1):20-31.

Sheng YY, Xiang J, Wang ZS, Jin J, Wang YQ, Li QS, Li D, Fang ZT, Lu JL, Ye JH, Liang YR. Theacrine from Camellia kucha and its health beneficial effects. Front Nutr. 2020 Dec17;7:596823.

Ziegenfuss TN, Habowski SM, Sandrock JE, Kedia AW, Kerksick CM, Lopez HL. A two-part approach to examine the effects of theacrine (TeaCrine®) supplementation on oxygen consumption, hemodynamic responses, and subjective measures of cognitive and psychometric parameters. J Diet Suppl. 2017 Jan2;14(1):9-24.