Orally Administered ATP (400mg) Increases Muscle Mass, Size and Performance Gains in Complex 12-Week Study With Previously Strength-Trained Subjects

Training till you drop? Well with some ATP 30 minutes before your workout it may take a couple of minutes / workout sessions more to "drop" ;-)

If you drive a Porsche that runs on super you would not put crude oil in the tank, would you? Well, why do you eat carbohydrates and fats then, when ATP, i.e. adenosine triphosphate, is the "fundamental energy unit" in our bodies? Why don't we guzzle ATP all day to run with the speed of light and lift with the force of an elephant? When? Well before, during and after a workout - sounds right, hah?

Ok, ok, we are not "meant" to do so, I know... but even if you managed to keep the "paleo logic" out of the equation for once, there would be another stumbling block. Oral ATP is - supposedly - not bioavailable, at least that's what many people think.

"ATP supplements are not orally bioavailable."

In fact, Arts et al. even used the words in the subheading of this paragraph as the title to the paper in which they describe the results of their 2012 randomized, placebo-controlled cross-over study that involved eight healthy volunteers who received 5,000mg of oral ATP per day (Art. 2012). In order to make sure that they did not simply use an inappropriate delivery route Art et al. even used three different delivery routes: Two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine), and a naso-duodenal tube. Increases in ATP were not measured with any of the preparations, though.

In previous studies even 5,000mg of ATP were "in and out" in 2x30 min and the 1250mg dosage (top) did not leave any significant impression, the only sign. effect was an increase in uric acid (not shown; Coolen. 2011)

Being aware of both this and a previous study on the effects of chronic oral ATP administration (5,000mg/day) by researchers from the same research group that concluded

"On the basis of these findings, we seriously question the claimed efficacy of oral ATP at dosages even lower than that used in the present study" (Coolen. 2011),

I was pretty surprised, when I hit upon a recent study in the Journal of the International Society of Sports Nutrition that says: Oral ATP supplementation works! ATP does - at least this is what the study suggests - "enhance muscular adaptations" and "prevent  decrements in performance following overreaching".

That certainly sounds like something ATP could do - if it actually made it to the muscle cells. So is it possible that the previous studies were flawed? Are we missing something? I guess so. Firstly, the results of any ATP measurements will depend on the ATP pool you chose to analyze or as Wilson et al. rightly point our:

"[T]he biological pool where ATP is measured will determine the results of bioavailability analysis. If sampled in venous portal blood, oral ATP is indeed bioavailable" (Wilson. 2013) 

Now exactly this, i.e. an analysis of the venous portal blood was what Coolen et al. didn't do. It is still interesting that there was a minor systemic increase with the highest dose of ATP in the Coolen, though. After all this tells us something about the absorption kinetics and thus the ideal time to ingest ATP supplements, which should accordingly be ~30min before a workout. And indeed, 30min is exactly the timespan between the ingestion of 400mg of ATP (in the form of ATP disodium) and the first set of the resistance training sessions in the Wilson study.

Overreaching tapering and ATP supplementation

Apropos, resistance training, the 24 subjects (3 dropouts during the study, so that N=21) were resistance trained men with a mean age of 23.4  ±  0.7 years and an average one-repetition maximum of 1.71 ± 0.04, 1.34 ± 0.03 and 2.05 ± 0.04 times their own bodyweight for squat, bench presses and deadlifts, respectively. Obviously none of them was taking steroids, other performance enhancing supplements, smoking pot ... you know the rest of the list ;-)

Contrary to strategic overreaching, which can be highly productive, there is nothing beneficial about overtraining. Unfortunately, it is pretty difficult to objectively determine where one ends and the other begins. Learn more about useful, less useful and totally useless markers I suggest you surf over to this previous SuppVersity article.

"The protocol was divided into three phases. Phase one consisted of a three times per week non-linear periodized RT program for weeks 1–8, modified from Kraemer et al. (2009). Phase two consisted of a two-week overreaching cycle during weeks 9–10. Finally, phase three consisted of participants tapering for weeks 11 and 12. Muscle mass and body composition were measured at baseline and at the end of weeks 4, 8, and 12. Muscle strength, vertical jump power, Wingate peak power (PP), creatine kinase (CK), C-reactive protein (CRP), free and total testosterone, and perceived recovery were measured at baseline and after weeks 4, 8, 9, 10 and 12." (Wilson. 2013)

I know that (at least some of) you are not really interested in these details, at least not before they have not had the following questions answered: "Ho much more muscle?", "How how much less fat?" and not just as popular "How much stronger?". I guess figure 1 should answer all these questions, doesn't it?

Figure 1: Changes in body composition and total strength after 4, 8 and 12 weeks (Wilson. 2013)

Now, of the changes Wilson et al. observed the slightly more pronounced increases in fat loss was clearly statistically non-significant. The rest of the parameters, on the other hand, showed statistically significant inter-group differences. Among these, I personally consider effect the ameliorative effects of the ATP supplementation had on the the strength decrements that occurred in the placebo group aver the overreaching most significant. Why? Well, only with the provision of ATP did the overreaching period lead to the strength (and thus performance) gains trainers and trainees expect.

Similarly beneficial effects were also observed for the protein breakdown. Despite being slightly increase in the regular training phase, the latter was significantly reduced by the ATP supplements, when the subjects were overreaching.

"We can speculate that under normal conditions of training, when glycogen levels are likely adequate those participants supplementing with ATP were able to maintain higher intensities, which would result in higher rates of protein breakdown. However, when exposed to greater training frequencies, glycogen levels are likely to be depleted, thus preventing higher intensities from being performed." (Wilson. 2013)

Against that background it should be obvious that the provision of ATP during phases of intense pre-season / pre-competition training could in fact boost the training outcome to new heights by bolstering the strength (and mass) increases during the taper after a typical pre-season overreaching phase.

If your training log tells you that you neither gained weight nor strength in the past two months, you'd just waste your money if you bought an ATP supplement before you fixed your broken workout and nutrition regimens. If you have no clue how to do that, I suggest you start with the Step-By-Step Guide to Your Own Workout Routine and set up a new routine that's in line with your social life, training status and current goals (open with IE or FF).

Bottom line: Irrespective of my initial (healthy ;-) skepticism, I must admit that the results Wilson et al. present in their most recent paper are not just impressive, they are also credible. With an excellent safety profile (none of the blood parameters Wilson et al. tested showed any abnormalities) and a mechanism of action that should offer synergies with the current staple supplements many of you are using, the provision of 400mg ATP ~30min before a workout (remember: In this case timing will probably matter) could actually produce visible changes to the figure and figures you see in the mirror and your training log, respectively.

If you are not pushing yourself hard enough, are chronically overtraining, don't have your diet in check, don't get enough sleep and have thus not made any gains in the past months, however, you better save your money and return to the drawing board to come up with a better training and nutrition plan, first.

References:

• Arts IC, Coolen EJ, Bours MJ, Huyghebaert N, Stuart MA, Bast A, Dagnelie PC. Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans. J Int Soc Sports Nutr. 2012 Apr 17;9(1):16. 
• Coolen EJ, Arts IC, Bekers O, Vervaet C, Bast A, Dagnelie PC. Oral bioavailability of ATP after prolonged administration. Br J Nutr. 2011 Feb;105(3):357-66. 
• Kraemer WJ, Hatfield DL, Volek JS, Fragala MS, Vingren JL, Anderson JM, Spiering BA, Thomas GA, Ho JY, Quann EE, Izquierdo M, Hakkinen K, Maresh CM: Effects of amino acids supplement on physiological adaptations to resistance training. Med Sci Sports Exerc. 2009, 41(5):1111–1121
• Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, Fuller JC, De Souza EO, Baier SM, Wilson SMC, Rathmacher JA. Effects of oral adenosine-5[prime]-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutrition & Metabolism 2013, 10:57.

Lack of Drive? Theacrine Will Get You Going - Every Day! Camellia Kucha Alkaloid Acts via Dopamine and Adenosine

Image 1: Coffee vs. tea, if it comes to the persistent dopaminergic "get going" effect it appears that a hitherto hardly known tea variety, Camellia Kucha has the edge on the #1 average westerner's #1 morning drink.

Caffeine is the #1 drug for anyone looking for that little extra of burst of energy and yet there are people who claim they would kill for their morning coffee, while others swear by having one cup right before bed to keep the blood sugar levels from dropping during the night. Whatever your personal preference may be, it probably did not escape your notice that cup no.10,000 does not exert the same magic as cup  no. 10, decades ago. The reason for that is a pretty rapid habituation effect, the extend of which varies remarkably from person to person.If you do belong to the vast majority of people for whom  the morning coffee has become more of an entrenched habit than an energizer, you will therefore probably be interested in the results of a recent study by Allison A. Feduccia and her colleagues from the Ernest Gallo Clinic and Research Center at the University of California at San Francisco, the School of Life Sciences at the San Yat-sen University in China and the Nutritional Science and Toxicology Department at the University of California (Feduccia. 2012).

Theacrine the non-sensitizing, no-tolerance locomotor activator from Camellia kucha

Feduccia et al. have been able to show that the intra-peritoneal administratoin of the human equivalent of 8mg/kg theacrine (1,2,7,9-tetramethyluric acid) a naturally occurring purine alkaloid with structural similarities to caffeine and established anti-inflammatory and analgesic (=pain reducing), as well as anti-depressant effects (Wang. 2010; Xie. 2009), boosts the physical activity of rodents by more than 130% (note: since i.p. injection have a higher bioavailability you better make the HED 10+mg/kg, if you want to see similar results; this is all the more true, in view of the fact that the lower 4mg/kg equivalent did not produce significant increases in motor activity in the study at hand).

Figure 1: Increase in locomotor activity after intra-peritoneal administration of the 24 or 48mg/kg Theacrine (human equivaled, HED: 4mg/kg or 8mg/kg; data adapted from Feduccia. 2012)

As the data in figure 1 shows the effects, which are mediated via adenosinergic (A1 and A2A) and dopaminergic (D1 & D2) pathways were pronounced yet not statistically significant in the low dose (human equivalent for 80kg ~ 320mg) group and highly significant (p < 0.01 ambulatory distance; p < 0.001 stereotypic counts) in the high dose group.

Nice, but what exactly is the advantage over caffeine?

In order to be able to give you a better idea of the actual effect size, as well as to underline the importance of the fact that even after 7 days of repeated administration, the locomotor activity counts did not change compared to day 1, I plotted data from a similar study on the effects of a low-dose of oral caffeine (HED ~280mg) on the locomotor activity of rats (Ball. 2009).

Figure 2: Ambulatory distance at day 1 and day 4 with and without daily administration of 3.5mg/kg caffeine (Ball. 2009).

As you can see in figure 2 the effects of caffeine are not only less pronounced, the sensitization effect is in fact so pronounced that after only 4 days, the rodents actually needed their daily dose of caffeine to get going - and even with it, their locomotor activity decreased by - 26% compared to baseline. Now compare that to the persistent +167% increase in locomotor activity (likewise measured by ambulatory distance) with theacrine and tell me which one would be more likely to get you through week after week of your demanding day work?

Update (05-20-2012): In response to questions on Facebook and the comment area, here on the SuppVersity, a brief summary of my formerly not mentioned, since unsuccessful attempts to identify whether or not you can buy this tea in the US or Europe. It appears as if, "Kucha" was a certain variety of the assamica variety of camellia sinensis. The latter is very commonly used in black teas, but the "Kucha" variety is probably the one with the highest theacrine content. According to Ye et al. it does contain 1.3-3.6% of the alkaloid in dried leaves - the exact content varied with season and the part of the leaves that was analyzed (Ye. 2003). If we assume a maximal extraction rate of ~80% in hot water, this would mean that a cup of tea brewed with a 2g bag could contain ~20,8-57,6mg of theacrine, which is obviously way too little to be effective. Which would make theacrine a potential candidate for a nutritional supplement - yet probably nothing you can ingest in significant amounts from your diet alone.

References:

• Ball KT, Poplawsky A. Low-dose oral caffeine induces a specific form of
  behavioral sensitization in rats. Pharmacol Rep. 2011 Nov;63(6):1560-3. PubMed
  PMID: 22358105.
• Feduccia AA, et al, Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: Involvement of adenosine and dopamine receptors, Pharmacol Biochem Behav (2012), doi:10.1016/j.pbb.2012.04.014
• F. Wang Y, Yang X, Zheng X, Li J, Ye C, Song X. Theacrine, a purine alkaloid with anti-inflammatory and analgesic activities. Fitoterapia 2010;81:627–31.
• Xie G, Wu M, Huang Y, Cao Y, Lai-dong L, He-liangl Z, et al. Experimental study of
  theacrine on antidepressant effects. Chin Pharmacol Bull 2009.
• Ye Chuangxing, Hiroshi A, Zheng Xinqiang, Wang Xiujuan, Gao Kun, Zhang Hongda. New discovery of pattern of purine alkaloids in wild tea trees. Zhongshan da xue xue Bao. Zi ran ke xue ban = Acta Scientiarum Naturalium Universitatis Sunyatseni. 2003, 42(1):62-65

Cirsimarin: An Almost Completely Overlooked Lipolytic Agent

It is interesting that, with the exception of USP Labs, who happen to have a talent to find "unorthodox" ingredients for their products, no supplement company has yet sourced an extract from Microtea debilis. After all, a similar extract ("similar" to the one used in USP Lab's Recreate) was found to

exert strong lipolytic properties being 20 times more potent than caffeine

in a 2005 study by Girotti et.al. (cf. Girotti, 2005 Fig.1, below)

Although the mechanism of action has not yet been fully investigated, a previous study by Hasrat et.al. found an antagonistic interaction with adenosine receptors similar to that of caffeine (Hasrat. 1997). The exact effect of Cirsimarin differs however from that of caffeine and the less pronounced effects Gingko biloba, so that the researchers conclude:

"This suggests that [...] the lipolytic activity of cirsimarin is related to another mechanism. [...] Studies to identify the precise mechanism of action of cirsimarin on lipolysis should involve phosphodiesterase inhibition." (Girotti, 2005)

This means that the mechanism of action (MOA) of cirsimarin would eventually be that of a phosphodiesterase inhibitor, which prevents the deactivation of cAMP- and cGMP-activity and thus increases energy uptake and -use of the cells.

Before you run to the supplement-shop of your choice and invest your peanuts into a bottle of Recreate, you should remember that lipolysis does not equal fat loss! If you do not force your body to consume the triglycerides it is breaking down inside the cells (preferably your muscles while your working out), its unlikely you will see results. So keep your diet in check, work out hard and maybe supplement with some lipolytic agent, such as Cirsimarin, the existence of which will hopefully be discovered by other supplement companies in the near future.