When the alarm clock goes off, if you’re like most people, you roll out of bed, and head straight to the kitchen for some coffee (or pre workout or energy drink) to get some needed caffeine to shake the cobwebs off and feel somewhat human.
With the energy-boosting stimulant coursing through your veins, you set about the rest of your morning routine and eventually make it to the office. A couple of hours later, the pep in absent from your step, your thinking feels a bit slower, and everything just seems to take more effort.
Why is this?
Well, part of it is due to the fact that you’re probably sleep deprived, but another part of it is that the energy rush from your morning hit of caffeine is wearing off...which only means one thing. It’s time to get another boost.
And, guess what?
In another three hours you’ll need another up and another...and the vicious cycle continues.
Such is the way when you’re running on caffeine.
You see, while caffeine has a half-life of around 5.5 hours, it’s pronounced effects usually start to wane around the 3-hour mark, which means if you want to keep feeling energized you need to keep “re-upping” on caffeine.
Rather than have to continue to fuel your day with caffeine, wouldn’t it be better if there was something that provided the same benefits of caffeine, but without the crash, tolerance build up, or constant need to “re up?”
You bet it would.
And it turns out, such a compound does exist, in TeaCrine.
What is TeaCrine?
TeaCrine (1,3,7,9-tetramethyluric acid) is a chemical cousin of caffeine that’s found predominantly in the leaves of the kucha plant as well as Cupuacu and Coffea robusta.
In addition to sharing a similar molecular structure to caffeine, Teacrine also exerts many of the same effects as caffeine (increased energy, alertness, mood, and motivation), but the manner in which it works is ever so slightly different.
The main difference between TeaCrine and caffeine is that it does NOT come with habituation, impact sleep, or impact the cardiovascular system -- all of which caffeine does.[1,2,3]
In fact, even after consuming 300mg of TeaCrine® everyday for 8 weeks straight, study subjects demonstrated no signs of dependency, tolerance build up, or withdrawal as is commonly experienced with other stimulants, such as caffeine.
What this means is that you do not need to continually “up the dose” with TeaCrine to keep experiencing the same boost in energy, mood, and focus day after day like you would with caffeine.
Plus, TeaCrine®’s half-life is ~20 hours, meaning its effects are incredibly long-lasting (much longer than caffeine) which makes it a great choice for those seeking sustained energy, focus, and mood-enhancement.
And, since it doesn’t impact sleep or the cardiovascular system, you can take it late in the day for those afternoon training/study sessions, but not have to worry about disrupted sleep when you finally decide to shut it down for the day.
How Does TeaCrine Work?
Antagonizes Adenosine Receptors
TeaCrine’s primary mechanism of action (much like caffeine) is through antagonism (inhibition) of adenosine receptors in the brain.
Adenosine is a neurotransmitter comprised of adenine and d-ribose. It’s found in every cell of the human body and serves a variety of important roles in the body, including the synthesis of DNA, RNA, and ATP.
But, most pertinent to our purposes here, adenosine acts as an agonist on the adenosine receptor in the brain. (FYI, “agonist” is just a fancy way of saying that when adenosine binds to the adenosine receptor, it turns the receptor “on.”)
When this happens, we feel tired and sluggish.
Furthermore as we “burn” ATP, adenosine starts building up in extracellular space, and when enough accumulates, it stimulates adenosine receptors which inhibits the release of several important neurotransmitters that are involved with wakefulness, alertness, and cognition. This is the brain’s way of “calming us down” and telling us it’s time to rest.
However, what if you want to prevent or side step the onset of fatigue?
Well, you’d want to use something that prevents adenosine from binding to its receptor, i.e. an adenosine receptor antagonist (inhibitor).
The most well-known adenosine receptor antagonist is caffeine. It binds orthosterically to the adenosine receptors, which is the molecular equivalent of “kicking in the front door” of a house to enter it. The binding action is why caffeine provides such a pronounced and immediate boost in energy.
TeaCrine, however, is a bit more stealthy. It binds to the adenosine receptor allosterically, which would be the equivalent of sneaking in through an open window. Binding in this manner provides a softer and smoother increase in energy in the body, and is part of the reason why TeaCrine comes with no crash or habituation (the same of which can’t be said for caffeine).
And due to the fact that caffeine and TeaCrine bind differently to the adenosine receptor (yet both still inhibit adenosine from binding), they are highly synergistic and stack incredibly well together, which will explain more about down below!
Enhances Dopamine Production
In addition to antagonizing the adenosine receptor, TeaCrine also enhances dopamine production (again similar to what caffeine does).[1,2]
Why is this important?
Dopamine is one of the “heavy hitter” neurotransmitters in the body that plays a role in movement, motivation, reward, and decision-making.
Basically, with more dopamine available, you’re more motivated and focus to accomplish your goal, whether it being crushing a new PR in training or finishing that big project at work.
Dopamine also serves as the precursor to the fat-burning catecholamines (such as noradrenaline and adrenaline) which increase brown fat thermogenesis and support weight loss.
Research from 2014 demonstrated that just a single 200mg dose of TeaCrine significantly improved feelings of energy and reduced fatigue.
Additionally, after seven days of use, subjects in the same study reported improvements in concentration, energy, motivation, and anxiety.
Analgesic & Anti-Inflammatory Effects
Additional studies also indicate that TeaCrine used at dosages between 8-32 mg/kg is capable of conferring dose-related anti-inflammatory and analgesic effects. Interestingly, the other hand, oral administration of caffeine at the same dosage rage (8-32 mg/kg) did not exhibit these effects.
What is the Optimal TeaCrine Dose?
TeaCrine is typically dosed between 50-200 milligrams when stacked with caffeine. When used by itself, it appears to be most effective when dosed between 125-200mg.
Is TeaCrine Safe?
Yes, TeaCrine is GRAS affirmed.
Furthermore, TeaCrine does NOT impact heart rate or blood pressure. And, the LD50 for TeaCrine® (the dose needed to kill 50% of a sample population) in mice is 810.6 mg/kg.
In humans, this equates to roughly 4g for an individual weighing approximately 170 pounds.
What Can I Stack with TeaCrine?
Due to the complementary actions on the adenosine receptors, the combination of caffeine and TeaCrine makes perfect sense as it provides the perfect combination of immediate and long-lasting energy.
In fact, a number of studies have demonstrated that the combination of caffeine + TeaCrine®[1,3,4,6,7]:
- Boosts mental and physical performance superior to caffeine alone
- Enhances energy, mood, and focus to a greater extent than just caffeine
- Increases energy levels for longer than taking caffeine alone
- Improves feelings of attentiveness, alertness, and focus
Furthermore, TeaCrine can enhance and prolong the effects of caffeine, allowing you to get “more” from a lower amount of caffeine. This is great for those who are stimulant sensitive and do not do well with high doses of caffeine.
In fact, recent research shows that a combination of 125mg TeaCrine + 150mg caffeine outperformed both 275mg caffeine alone or 275mg teacrine alone in measures of time-to-exhaustion, choice reaction time, and cognitive performance.
- Suggested Dose: 50-200mg TeaCrine + 100-300mg Caffeine (based on personal preference and tolerance)
If you’re looking for a caffeine-free stack to enhance mental energy, productivity, and cognition, the combination of TeaCrine and Acetyl L-Carnitine might just be the thing you’re looking for.
Acetyl-L-Carnitine (ALCAR) is well-known in the nootropic community for its mentally stimulating properties. The reason for this is that ALCAR readily crosses the blood-brain barrier where it improves mitochondrial function and energy production.
Furthermore, ALCAR can also increase levels of noradrenaline (norepinephrine) in the hippocampus -- the region of the brain involved in the formation of new memories and is also associated with learning.
And, to top it off, ALCAR also contributes to the production of the “learning neurotransmitter,” acetylcholine, by donating a methyl group which joins with a molecule of choline (which can be gotten from either choline bitartrate or alpha GPC -- both of which are in Mega Pre Red).
- Suggested Dose: 500-2000mg ALCAR + 100-150mg TeaCrine
Caffeine is the compound of choice for many individuals looking to increase energy, focus, and performance, which is why it’s a foundational ingredient in many of the best pre-workouts and fat burners on the market– including Primeval Labs Mega Pre Black and Pyretic Black.
And, as great as caffeine is, it isn’t perfect.
TeaCrine® offers an ideal partner to caffeine.
It offers longer-lasting energy than caffeine, yet doesn’t come with the habituation or disrupted sleep that caffeine does.
Combining the two might just be the best combination since peanut butter and jelly!
- 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(1):1-14. doi:10.1186/s12970-016-0113-3.
- Feduccia, A.A., Wang, Y., Simms, J.A., Yi, H.Y., Li, R., Bjeldanes, L., 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.
- Access O. Proceedings of the Fourteenth International Society of Sports Nutrition (ISSN) Conference and Expo. J Int Soc Sports Nutr. 2017;14(S2):31. doi:10.1186/s12970-017-0188-5.
- 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. doi:10.1089/jcr.2017.0006.
- Geethavani G, Rameswarudu M, Reddy R. Effect of Caffeine on Heart Rate and Blood Pressure. Int J Sci Res Publ. 2014;4(2):1-4.
- Wang Y, Yang X, Zheng X, Li J, Ye C, Song X. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities. Fitoterapia. 2010;81(6):627-631. doi:https://doi.org/10.1016/j.fitote.2010.03.008.
- 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):9618-32. Published 2015 Nov 19. doi:10.3390/nu7115484
- Habowski, S. M., Sandrock, J. E., Kedia, A. W., & Ziegenfuss, T. N. (2014). The effects of TeacrineTM, a nature-identical purine alkaloid, on subjective measures of cognitive function, psychometric and hemodynamic indices in healthy humans: a randomized, double-blinded crossover pilot trial. Journal of the International Society of Sports Nutrition, 11(S1), P49.
- National Center for Biotechnology Information. PubChem Compound Database; CID=60961, https://pubchem.ncbi.nlm.nih.gov/compound/60961
- “Adenosine.” ScienceDirect.com | Science, Health and Medical Journals, Full Text Articles and Books, www.sciencedirect.com/science/article/pii/S0099542808607510.
- Jacobson, K. A., & Gao, Z.-G. (2009). Adenosine. In L. R. B. T.-E. of N. Squire (Ed.) (pp. 83–95). Oxford: Academic Press. https://doi.org/https://doi.org/10.1016/B978-008045046-9.00627-6
- Sperlágh B, Vizi ES. The role of extracellular adenosine in chemical neurotransmission in the hippocampus and Basal Ganglia: pharmacological and clinical aspects. Curr Top Med Chem. 2011;11(8):1034-46.
- Magkos F, Kavouras SA. Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action. Crit Rev Food Sci Nutr. 2005;45(7-8):535-562. doi:10.1080/1040-830491379245.
- Smeland, O. B., Meisingset, T. W., Borges, K., & Sonnewald, U. (2012). Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. Neurochemistry International, 61(1), 100–107. https://doi.org/10.1016/j.neuint.2012.04.008
- Brennan BP, Jensen JE, Hudson JI, et al. A placebo-controlled trial of acetyl-L-carnitine and α-lipoic acid in the treatment of bipolar depression. J Clin Psychopharmacol. 2013;33(5):627–635. doi:10.1097/JCP.0b013e31829a83f5
- White H.L., Scates P.W. “Acetyl-L-carnitine as a precursor of acetylcholine.” Neurochemical Research 1990 Jun;15(6):597-601.