Theacrine: what it is and how it works

Theacrine is a purine alkaloid, a close relative of caffeine, that over the past decade has been actively appearing in pre-workout complexes and “energy” supplements. It is advertised as a stimulant without tolerance and without an energy “crash.” The editorial team examined where this substance comes from, how it works in the body and how it actually differs from caffeine.

What theacrine is

Theacrine, or 1,3,7,9-tetramethyluric acid, is a natural purine alkaloid. In significant amounts it is found in the leaves of the Chinese kucha tea (Camellia assamicavar.kucha), which is traditionally grown in Yunnan province. Theacrine has also been found in some species of cupuaçu and in insignificant amounts in other plants.

A study by Zheng et al. (2002) showed that in kucha tea leaves theacrine is synthesized from caffeine in several enzymatic steps. Interestingly, in the young leaves of this plant the theacrine content can exceed the caffeine content — unlike ordinary tea, where caffeine dominates.

In traditional Chinese practice, kucha tea was consumed as a tonic drink. Modern interest in theacrine began in the 2010s, when a standardized form of the substance for food supplements appeared, the best known under the trademark TeaCrine®.

Today theacrine is positioned as a substance for supporting energy, concentration and mood, and also as a complement to caffeine in pre-workout formulas. The regulatory status differs between countries: in the USA the substance is sold as a dietary supplement ingredient, while in the EU and other jurisdictions its admission to the food market may fall under separate rules.

Chemistry: the family of methylxanthines and methyluric acids

Caffeine (1,3,7-trimethylxanthine), theobromine and theophylline belong to the methylxanthines — derivatives of xanthine with methyl groups. Theacrine is structurally very similar to caffeine but has two differences: an additional methyl group at position 9 and an oxygen at position 8, which makes it a derivative of uric acid rather than xanthine.

These small changes in structure affect how the molecule binds to receptors, how it is metabolized and how long it stays in the body. That is why, despite their similarity, theacrine and caffeine are not interchangeable.

In the same chemical “family” there are other substances that appear in sports nutrition, for example methylliberine (trademark Dynamine™) — another methyluric acid. Manufacturers often combine these compounds with caffeine in order to change the duration and profile of the stimulating action.

Below is a comparison of the main representatives of the group by structure and typical sources.

Mechanism of action

The main mechanism of caffeine is the blockade of adenosine A1 and A2A receptors. Adenosine accumulates in the brain over the course of the day and signals fatigue; caffeine “blocks” this signal. Theacrine, as studies in animals have shown, also interacts with the adenosine system, although its affinity for the receptors and the strength of its action differ from caffeine.

Work by Feduccia et al. (2012) in mice showed that theacrine increases locomotor activity, and this effect depends on both adenosine receptors and dopamine D1 and D2 receptors. The dopamine system is linked to motivation, reward and a feeling of alertness, so it is with it that the subjective improvement in mood described by users is associated.

It is worth noting that early animal studies gave a contradictory picture. Xu et al. (2007) described sedative and hypnotic properties of theacrine in mice, whereas other work described stimulating ones. Perhaps the effect depends on the dose, model and experimental conditions; for humans this contradiction has not been clarified.

Anti-inflammatory and antioxidant properties of theacrine, its effect on lipid metabolism and the liver, were also studied in preclinical models. However, these data were obtained in cells and animals and so far have no confirmation in clinical studies in humans.

• Adenosine system:reduction of fatigue signals.
• Dopamine system:effect on motivation and mood (data in animals).
• Other effects:anti-inflammatory and metabolic — only preclinical data.

Pharmacokinetics and differences from caffeine

The pharmacokinetics of theacrine in humans were studied by He et al. (2017). They showed that theacrine is eliminated from the body much more slowly than caffeine, and that when taken together with caffeine the exposure to theacrine (the area under the concentration curve) increases. That is, the two substances affect each other's metabolism.

The second difference, most often emphasized by manufacturers, is the absence of tolerance. In a study by Taylor et al. (2016) participants took theacrine daily for eight weeks, and the authors found no signs of a decrease in subjective effects characteristic of caffeine. At the same time, this is a single study, funded by the manufacturer, with a limited number of participants.

The third difference is the effect on the cardiovascular system. In the same study theacrine at doses of 200 and 300 mg per day did not cause clinically significant changes in heart rate and blood pressure. Caffeine, on the other hand, in people without tolerance can transiently raise blood pressure.

Finally, the subjective profile of action. Users describe the effect of theacrine as milder and longer-lasting, without a sharp “peak” and “crash.” However, these sensations are largely individual and depend on habituation to caffeine.

Where theacrine is used

Theacrine is most often found in pre-workout complexes, where it is combined with caffeine. The manufacturers' logic: caffeine provides a quick start, and theacrine prolongs the feeling of energy. Such formulas are aimed at those who train for a long time or want to avoid a sharp drop after caffeine.

The second niche is nootropic and “productivity” supplements for concentration, where theacrine is positioned as a mild agent for mental work. Small studies, in particular Kuhman et al. (2015) and Ziegenfuss et al. (2017), assessed subjective energy, concentration and mood with ambiguous but mostly positive subjective results.

The third niche is complexes for weight control and “fat burners.” Here the evidence base is weakest: there are no convincing data on the effect of theacrine on fat loss in humans.

As for athletic performance — strength, endurance, speed — the data are contradictory and mostly do not show an advantage of theacrine on its own. We discuss this in more detail in a separate article on the evidence base.

Editorial conclusions

Theacrine is a natural purine alkaloid from kucha tea, structurally close to caffeine but with different pharmacokinetics: it stays in the body longer and interacts with caffeine at the level of metabolism.

Its mechanism of action is associated with the adenosine and dopamine systems, but most of the data on mechanisms were obtained in animals. Clinical studies in humans are few and often funded by the manufacturer.

Claims about the absence of tolerance have some confirmation but require independent verification. Theacrine is an interesting but not yet fully studied substance.

We recommend continuing your acquaintance with the topic in our articles “The benefits of Theacrine for athletes: the evidence base,” “Side effects of Theacrine” and “How to take Theacrine: dosage, timing, duration.”

References

1. Zheng XQ, Ye CX, Kato M, Crozier A, Ashihara H. Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha). Phytochemistry. 2002;60(2):129–134.
2. Feduccia AA, Wang Y, Simms JA, et al. Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors. Pharmacol Biochem Behav. 2012;102(2):241–248.
3. Xu JK, Kurihara H, Zhao L, Yao XS. Theacrine, a special purine alkaloid with sedative and hypnotic properties from Cammelia assamica var. kucha in mice. J Asian Nat Prod Res. 2007;9(6–8):665–672.
4. Taylor L, Mumford P, Roberts M, et al. Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use. J Int Soc Sports Nutr. 2016;13:2.
5. He H, Ma D, Crone LB, et al. Assessment of the drug–drug interaction potential between theacrine and caffeine in humans. J Caffeine Res. 2017;7(3):95–102.
6. Kuhman DJ, Joyner KJ, Bloomer RJ. Cognitive performance and mood following ingestion of a theacrine-containing dietary supplement, caffeine, or placebo by young men and women. Nutrients. 2015;7(11):9618–9632.
7. Ziegenfuss TN, Habowski SM, Sandrock JE, et al. 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;14(1):9–24.