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2018’s Next Big Stimulant DMAA Replacement! Show Me the Science!

Brian Turner

Posted on September 07 2018

By Robert A. Schinetsky

 2018 has been another banner year for the supplement industry -- rife with new products, industry drama, and the debut of novel ingredients. Chief among these new compounds is a next-gen stimulant that is being marketed in some pre workout and nootropic supplements as “the replacement for DMAA”.

 What is this new pre workout stimulant and does it live up to the hype?

 Let’s find out!

Dynamine -- The Next “Big Thing” 

 By now, you’ve no doubt seen an arsenal of products coming across the supplement wire touting a new ingredient called Dynamine, and along with this marketing material you’ve seen phrases such as “laser focus”, “intense energy,” and/or “relentless aggression.”

 So, what is Dynamine and what does it actually do?

 Dynamine is the trademarked name of methyliberine -- a methylurate (methyl uric acid) found predominantly in the kucha plant. Methyliberine can also be found in a few other botanical sources including:

          - Coffee robusta (not to be confused with coffee arabica-- your typical morning coffee)

          - Cocoa

          - Yerba mate

          - Cupuaçu

 Methylurates, such as Dynamine, and it’s equally well known cousin, TeaCrine, are similar is structure and function to methylxanthines (i.e. caffeine and theobromine), but vary a good bit, too.

 These minor structural differences between each of the respective compounds translates to big implications for your brain, CNS, and cardiovascular system, which we’ll get to in a moment.

 The chemical formula for Dynamine™ is 2-methoxy-1,7,9 Tetramethyluric acid, and when you compare that to the chemical formula for TeaCrine®’s -- 1,3,7,9 Tetramethyluric acid -- a few things will immediately jump off the page.

 Most notably, a methyl group on the “3-position” of the TeaCrine molecule has been removed and shifted onto one of the oxygens (2-oxo) on the pyrimidine ring.  In playing this game of methyl musical chairs, a “methoxy” group results.

 Why does this matter?

 The formation of a methoxy group increases lipid solubility as well as makes the molecule less hydrophilic. This is beneficial for users because less hydrophilic compounds can more easily cross the blood-brain barrier.

 Compound Solutions has speculated that because of this methoxy group, Dynamine should have a faster onset of action than TeaCrine.

 As such, Dynamine has been dubbed as the faster-acting and harder-hitting form of TeaCrine, also developed by Compound Solutions.

What Does Dynamine Do?

We’ll start this section by stating right off the bat that there is a severe lack of research regarding the pharmacokinetics of Dynamine. The following is based off of preliminary studies that have been conducted on Dynamine. To date, there have been no peer-reviewed studies published in notable journals on Dynamine and its effects in the human body.

That being said…

 Up top, we mentioned the movement of a methyl group, which then became a methoxy group. This transition should result in an easier transition of Dynamine across the blood-brain barrier and a more rapid onset of action (i.e. “harder hitting” and faster acting).

 Since Dynamine is a close relative of TeaCrine, and we know how TeaCrine affects the brain and body, we can begin to extrapolate the effects of Dynamine.

 Research has shown that TeaCrine (a.k.a theacrine) affects both the adenosine and dopamine systems. In doing so, it provides a mild stimulatory effect, as well as a calming effect.[1,2,3]

 Without getting to into the weeds with TeaCrine, it antagonizes adenosine receptors in a manner similar (though not as aggressively) to that of caffeine and increases dopamine production. This results in feeling more alert, less fatigued, and all around happier.

 Based on this, researchers theorize that Dyamine could potentially stimulate dopamine receptors more powerfully than TeaCrine and initiate greater downstream signaling of other important neurotransmitters such as norepinephrine, serotonin, and/or GABA.

 Preliminary, unpublished human studies on Dynamine have indicated that the onset of action enhanced energy, mood, and focus begins around 10-15 following ingestion and peaks around 45-60 minutes, with effects subsiding around the 3 hour mark -- similar to when the “high” of caffeine also subsides.

 Again, all of this is based on theory and conjecture, until conclusive proof is shown in published clinical studies.

 Additionally, similar to TeaCrine, Dynamine is believed to not impact the cardiovascular system, meaning no increase in heart rate, blood pressure, etc. when using it.

What is Wrong with TeaCrine?

 No doubt you’ve noticed we’ve made a few comparisons between Dynamine and its older brother TeaCrine

“Why is that?” you ask.

Well, that’s because both compounds work more or less the same. However, TeaCrine seemingly takes “forever” to really get going.

 Realistically speaking, TeaCrine’s onset of perceivable action doesn’t really occur until around 90-120 minutes post ingestion.

 This is one of the reasons that TeaCrine may not really be an ideal stimulant for pre workout supplements. Due to its delayed onset of action and incredibly long-lasting effects, TeaCrine is better suited to productivity / nootropic supplements, which is one of the reasons why we’ve included it in DopaRush.

The Problem with Dynamine

 When it comes to long-term safety and efficacy data, there is next to none. Furthermore, there has yet to be any published human data on Dynamine in regards to physical or mental performance. Research has shown that TeaCrine offers some benefit as a nootropic, and it does indeed synergize well with caffeine, but until there is independent testing done using Dynamine, everything you read about the ingredient and its effects is based on theory and conjecture.

 As such, why would you want to waste money on a new pre workout supplement using some next-gen ingredient that may or may not work?

 It simply doesn’t make sense.

 With that in mind, let’s quickly review two stimulants that have studied extensively, shown to be safe for human consumption, and have been shown time and again to improve physical and mental performance.

Caffeine -- THE Pre Workout Stimulant

 Caffeine was, is, and will continue to be the de facto pre workout stimulant. In fact, more safety and efficacy research continues to be published regarding this consummate physical and mental ergogenic.

 We’ve discussed caffeine at length a time or two before, but in case you haven’t read those articles or don’t remember all the reasons we discussed why caffeine is the best pre workout stimulant, here’s a quick refresher.

Caffeine 101

Caffeine is a naturally-occuring methylxanthine found in a number of plants, most notably coffee and tea. Caffeine is well known for its ability to obliterate fatigue and instill a sense of heightened alertness and focus.

 It does this through a variety of mechanisms. Chief among these, is caffeine’s role as an adenosine receptor antagonist. What this means, is that caffeine more or less “mimics” adenosine and enters the adenosine receptors. As a result, adenosine cannot bind to its receptor, and thus cannot induce feelings of fatigue.

 Additionally, caffeine also enhances dopamine signaling in the body and increases dopamine D2/D3 receptor availability, creating a larger, and more powerful release of this primetime neuro activating compound.

 The end result of these actions is a significantly more upbeat, alert, motivated, and focused individual.

 Now, let’s take a brief moment to recap how caffeine improves exercise performance.

Caffeine and Exercise Performance

 When it comes to athletic performance, caffeine seems to enhance just about every facet of training. Be it strength, power, time-to-exhaustion, or resistance to fatigue -- there’s nothing caffeine can’t seem to improve.[8,9,10]

 The question on your mind is...how does caffeine do this?

 Well, we’ve answered that in part by detailing its role as a dopaminergic agent and adenosine receptor antagonist, but caffeine’s benefits for performance don’t end there.

 Additional research has also shown that caffeine can increase cyclic AMP (cAMP) via inhibition of phosphodiesterase.

 In case you weren’t aware, phosphodiesterase (PDE) are a group of enzymes that operate as “energy regulators” of sorts, limiting the amount of energy you get produce at any one time. By negating the effects of those enzymes, it’s akin to removing the governor chip on your car. You body is not able to generate energy without restriction or limit.

 Researchers have also identified a number of other mechanisms through which caffeine can boost performance, including [8,9,11]:

- Reduces perception of fatigue and pain

- Boosts muscle glycogen resynthesis

- Enhances β-endorphin and catecholamine (for ex. norepinephrine) release

- Upregulates permeability and mobilization of intracellular calcium

- Boosts nerve conduction velocity

- Improves motor unit recruitment

- Increased permeability and mobilization of intracellular calcium

- Decreases uptake of intracellular calcium

 As you can see, caffeine is able to improve physical and mental performance through a myriad of mechanisms, which is why it’s classified as the pre workout stimulant.

 But, before we wrap things up, we can’t forget to briefly discuss the other thoroughly vetted pre workout stimulant in…

Synephrine

 Synephrine is a prominent beta adrenoceptor agonist found most notably in bitter orange, a.k.a. Citrus Aurantium. It shows the highest affinity for β-3 adrenoceptors, which allows users to experience the increased energy and calorie burning properties of the beta agonist class of compounds without the unfortunate drawbacks(elevated blood pressure, heart rate, etc.) of other beta receptor agonists, such is ephedrine.

  Numerous studies have demonstrated the safety and effectiveness of synephrine. Benefits attributed to the stimulant include:

- Increases metabolic rate

- Enhances lipolysis (liberating of stored fatty acids)

- Boosts fat oxidation (“fat burning”)

- Increases energy expenditure

- Enhances post exercise oxygen uptake

  Additionally, some studies suggest it may be useful for reducing food intake as well.

  And to top it all off, there’s even research showing synergism between synephrine and caffeine.[12] Essentially, combining caffeine with synephrine results in faster, more powerful repetitions all with no increase in lactate accumulation or perceived exertion![4]

  In other words, you can perform more intense work at a faster rate without experiencing additional fatigue that would typically accompany the increased work!

Takeaway

  At the end of the day, you have decide where your money is best spent:

 

               A. On a new ingredient that may or may not be safe, effective, or legal in the eyes of the FDA.

OR 

               B. On ingredients that have been put through rigorous testing and shown time and again to not only be safe, but effective.

 

  We know which option we’ll choose every time, and that’s why Advanced Molecular Labs Pre Workout utilizes only those ingredients which have been shown to be effective in humans. No other stimulants can match the mound of evidence that caffeine and synephrine have when it comes to improving performance, and until proven otherwise, any new stimulant that enters the supplement space is pure speculation and hype.

 

References

  1. Taylor L, Mumford P, Roberts M, 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. 2016;13:2. doi:10.1186/s12970-016-0113-3.
  2. Ziegenfuss, T. N., Habowski, S. M., Sandrock, J. E., Kedia, A. W., Kerksick, C. M., & Lopez, H. L. (2016). A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine(R)) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters. Journal of Dietary Supplements, 1–15. https://doi.org/10.1080/19390211.2016.1178678
  3. He Hui, Ma Dejian, Crone Laura Brooks, et al. Assessment of the Drug–Drug Interaction Potential Between Theacrine and Caffeine in Humans. Journal of Caffeine Research. July 2017, ahead of print. https://doi.org/10.1089/jcr.2017.0006
  4. 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
  5. Chang, D., Song, D., Zhang, J., Shang, Y., Ge, Q., & Wang, Z. (2018). Caffeine Caused a Widespread Increase of Resting Brain Entropy. Scientific Reports, 8(1), 2700. https://doi.org/10.1038/s41598-018-21008-6
  6. Niloofar Ale-Agha, Christine Goy, Judith Haendeler et al. CDKN1B/p27 is localized in mitochondria and improves respiration-dependent processes in the cardiovascular system—New mode of action for caffeine. PLOS Biology, 2018; 16 (6): e2004408 DOI: 10.1371/journal.pbio.2004408
  7. Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation. Bruno Gualano et al Journal of Applied Physiology 2017 123:1, 213-220
  8. Goldstein ER, Ziegenfuss T, Kalman D, et al. International society of sports nutrition position stand: caffeine and performance. J Int Soc Sports Nutr. 2010;7(1):5. doi:10.1186/1550-2783-7-5.
  9. Warren GL, Park ND, Maresca RD, McKibans KI, Millard-Stafford ML. Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis. Med Sci Sports Exerc. 2010;42(7):1375-1387. doi:10.1249/MSS.0b013e3181cabbd8.
  10. Grgic, J., Trexler, E. T., Lazinica, B., & Pedisic, Z. (2018). Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. Journal of the International Society of Sports Nutrition, 15(1), 11. http://doi.org/10.1186/s12970-018-0216-0
  11. Ratamess NA, Bush JA, Kang J, et al. The effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance. Journal of the International Society of Sports Nutrition. 2015;12:35. doi:10.1186/s12970-015-0096-5.
  12. Sidney J. Stohs, Harry G. Preuss, and Mohd Shara, “A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects,” Oxidative Medicine and Cellular Longevity, vol. 2011, Article ID 482973, 9 pages, 2011. https://doi.org/10.1155/2011/482973