Speedy Science with Hbspeed88 #2: Theacrine aka TeaCrine®

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Theacrine (TeaCrine®)

Welcome to the second installment of Speedy Science with hbspeed88! Today I’ll share the science behind a newer ingredient being featured in more and more supplements, theacrine. Theacrine is a caffeine-like molecule with a slightly different structure that makes it act much like caffeine does, but with a slightly changed pharmacological effect profile.

The theacrine molecule is found abundantly in the Camellia Kucha plant[1], and features the same double ringed structure as caffeine does with the exception of a double-bonded oxygen and another methyl (CH3) group.


Screen Shot 2016-01-05 at 7.17.23 PM.png

Sourced from: https://examine.com/supplements/theacrine/



First, lets start out by discussing why caffeine works the way it does. The primary mechanism by which caffeine works is by binding to adenosine receptors in the brain, subsequently blocking and inhibiting adenosine molecules from binding to its native receptor to spark the consequential signaling cascade. Caffeine has a similar structure to that of adenosine, making it act much like adenosine when binding to the adenosine receptor. When adenosine normally binds, it suppresses the central nervous system, making us feel tired and groggy. Caffeine keeps this from happening, helping us feel awake and focused.

Screen Shot 2016-01-05 at 7.17.00 PM.png

Sourced from: http://www.lchr.org/a/23/b7/adenosine.jpg
and Caffeine!



A bit more on adenosine for my science buffs

I’ll try to make this as laymen’s as possible, but understanding the mechanism of adenosine can aid in comprehending theacrine’s effects on adenosine. While there still is ongoing research with adenosine and the many roles that it plays in the body, one mechanism by which adenosine works is via inhibition of the adenylyl cyclase enzyme. As you can see in the signaling pathway[2], adenosine inhibits the G-protein complex upon binding to an adenosine receptor, subsequently inhibiting adenylyl cyclase and the formation of cyclic AMP. When cyclic AMP levels drop, the mechanism by which calcium gated ion channels in the brain become activated is hindered. This then slows the influx of calcium ions into the neuron, therefore suppressing the release of other neurotransmitters and creating a relaxed state in cells[2].



Screen Shot 2016-01-05 at 7.23.01 PM.png

Sourced from: THE BRAIN FROM TOP TO BOTTOM



Now let’s talk about how theacrine works and some of the studies that have been done on it.

Adenosine receptor antagonist (hinders function of receptor)

A study found that rats pre-treated with theacrine greatly weakened the effects of potent adenosine receptor agonists (chemicals that promote adenosine function), therefore suggesting theacrine’s involvement with adenosine receptors in the brain[3].

Dopaminergic function

The same study that looked at theacrine’s involvement in adenosinergic action also studied the effects of theacrine administration on dopamine activity. In this experiment, rats were injected with theacrine and then were treated with dopamine receptor antagonists. The results found that theacrine ingestion greatly increased the rats locomotion, and the following administration of dopamine receptor antagonists reduced the excitatory effect. These findings suggest theacrine’s involvement in dopaminergic transmission systems[3].

Effects on mood and fatigue

A placebo-controlled study was done on 10 male and 10 female subjects where they were administered with theacrine and caffeine, caffeine only, and a placebo on three separate days separated by a week. The subjects reported that feelings of well-being and energy were highest after taking the theacrine-containing supplement. Additionally, the theacrine-containing supplement had the lowest reports of lethargy and fatigue compared to the other two supplements[1].

Habituation and safety concerns with theacrine

We all know that caffeine is an extremely addictive drug that can cause a significant amount of dependance. On the contrary, a study funded by the patent-holder of TeaCrine® found that their version of theacrine was not only safe by clinical standards, but also lacked a habituative response in the subjects using up to 300mg a day for eight weeks[4].

Although the study may be a bit biased due to funding sources, I can anecdotally attest to the non-habituative effects of theacrine via my use of ATP Nutrition’s Perform Kinetics.

Anti-inflammatory, pain-relieving, and possible antioxidant effects

A study performed on mice found that theacrine reduced the inflammatory effects of paw and ear edema, a process mediated by inflammatory biomarkers like prostaglandins and histamines[5].

The study also found that pain thresholds were increased via a hot-plate and acetic acid writhing test after theacrine administration. It was suggested that theacrine may work by blocking or inhibiting central nervous system receptors and/or COX enzymes (inflammatory biomarker). Further study should elucidate these mechanisms[5].

Another study looked at the effect of theacrine on mice who were chronically stressed over an 18h period. Theacrine administration drastically reduced the amount of inflammatory and stress biomarkers in the mice’s plasma after the stress period, and even increased cellular antioxidant activity[6].


Products containing TeaCrine®
-ATP Perform Kinetics
-TheaTrim by Purus Labs
-Prime Nutrition Intra-MD EAA+
-Cellucor C4

References
[1] Kuhman, DJ et al. “Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women.” Nutrients 7:11 (2015): 9618-9632. Web.
[2] “MOLECULES THAT BUILD UP AND MAKE YOU SLEEP.” McGill University. Web.
[3] Feduccia, Allison et al. “Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors.” Pharmacology Biochemistry and Behavior 102:2 (2012): 241-248. Web.
[4] Hayward et al.: Safety of Teacrine®, a Non-Habituating, Naturally-Occurring Purine Alkaloid Over Eight Weeks of Continuous Use. Journal of the International Society of Sports Nutrition 2015 12(Suppl 1):p59. Web.
[5] Wang, Yuanyuan et al. “Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities.” Fitoterapia 81:6 (2010): 627-631. Web.
[6] Li, WX, et al. “Theacrine, a Purine Alkaloid Obtained from Camellia Assamica Var. Kucha, Attenuates Restraint Stress-provoked Liver Damage in Mice.” National Center for Biotechnology Information. J Agric Food Chem (2013). Web.
 

Pec.Major

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Great write up, much appreciated! :)
 
NoAddedHmones

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Is there any information available or your personal hypothesis as to why teacrine doesn't form a dependence like caffeine?
 
hbspeed88

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Great write up, much appreciated! :)
Thank you! Many more to come. All input is appreciated.

Is there any information available or your personal hypothesis as to why teacrine doesn't form a dependence like caffeine?
As far as I have read, I haven't seen any explained mechanisms for the appeared lack of tolerance build-up. Most of the papers suggest that theacrine should be researched further to elucidate any unsolved questions. You can speculate however, that it must have something to do with the altered structure to that of caffeine. That's about as far as you can guess up till this point. I'll be sure to post if I see any new science on it!
 
NoAddedHmones

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Thank you! Many more to come. All input is appreciated.



As far as I have read, I haven't seen any explained mechanisms for the appeared lack of tolerance build-up. Most of the papers suggest that theacrine should be researched further to elucidate any unsolved questions. You can speculate however, that it must have something to do with the altered structure to that of caffeine. That's about as far as you can guess up till this point. I'll be sure to post if I see any new science on it!
Thanks.

Based on your experimentation, how would you describe Teacrine effects in isolation? I have played around with it a fair bit and suffered nausea and generally uncomfortable feelings after about 150mg.
 
hbspeed88

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Thanks.

Based on your experimentation, how would you describe Teacrine effects in isolation? I have played around with it a fair bit and suffered nausea and generally uncomfortable feelings after about 150mg.
I personally have not used theacrine on it's own, only in products containing it with other ingredients. I'd be curious to see how it does with no other compounds.

I was looking through some Reddit posts today on some nootropics, and it dawned on me that there's typically no guarantees, especially with cognitive enhancers, stims, nootropics, etc. There's been products I've tried that receive all sorts of hype and have crazy stims in them, only to find that I'm yawning in the middle of my workout. Everyone reacts differently to these sorts of things; as formulators and supplement users, we have to look at trends and then decide what's best. The trend with theacrine is that for most people (and in studies), theacrine is shown to be an effective ingredient at elevating energy levels.
 
muscleupcrohn

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I personally have not used theacrine on it's own, only in products containing it with other ingredients. I'd be curious to see how it does with no other compounds.

I was looking through some Reddit posts today on some nootropics, and it dawned on me that there's typically no guarantees, especially with cognitive enhancers, stims, nootropics, etc. There's been products I've tried that receive all sorts of hype and have crazy stims in them, only to find that I'm yawning in the middle of my workout. Everyone reacts differently to these sorts of things; as formulators and supplement users, we have to look at trends and then decide what's best. The trend with theacrine is that for most people (and in studies), theacrine is shown to be an effective ingredient at elevating energy levels.
I've only really tried theacrine in place of caffeine (200mg instead of 200mg as a part of my daily energy/cognitive blend), and was a bit underwhelmed; I'd say 200mg caffeine > 200mg theacrine, although it may be worth mentioning that my blend includes theanine and ornithine, which are synergistic with caffeine (I'm not sure if this synergism carries over to theacrine or not).

I'm leaning towards saying that theacrine'a promise lies not in being a replacement for caffeine (as I'm not sure it outperforms it directly, and it's a lot more expensive) but as an addition to caffeine, perhaps to reduce or prevent caffeine tolerance.
 
hbspeed88

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I've only really tried theacrine in place of caffeine (200mg instead of 200mg as a part of my daily energy/cognitive blend), and was a bit underwhelmed; I'd say 200mg caffeine > 200mg theacrine, although it may be worth mentioning that my blend includes theanine and ornithine, which are synergistic with caffeine (I'm not sure if this synergism carries over to theacrine or not).

I'm leaning towards saying that theacrine'a promise lies not in being a replacement for caffeine (as I'm not sure it outperforms it directly, and it's a lot more expensive) but as an addition to caffeine, perhaps to reduce or prevent caffeine tolerance.
Interesting to hear. From what I've seen, your experiences are similar to others. Theacrine seems to be a good complement to caffeine.
 

kisaj

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I've tried theacrine solo and didn't notice anything. Perhaps added with caffeine makes the difference, but then I'd just take caffeine. Initially I think it needs more studies and anecdotal evidence because like mentioned, results were underwhelming.
 
hbspeed88

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I've tried theacrine solo and didn't notice anything. Perhaps added with caffeine makes the difference, but then I'd just take caffeine. Initially I think it needs more studies and anecdotal evidence because like mentioned, results were underwhelming.
Thanks for the input Kisaj. More studies for sure
 

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