ATP – Is It a Useful Dietary Supplement?

Dear BLOG readers, Dear Peak customers,

I can well imagine that quite a few of you have heard or read something about ATP before. I’d guess that if you have, it was in connection with the use of creatine—am I right? For those of you who have never heard of ATP, today would be a good time to fill that knowledge gap. It’s worth it!

In today’s post, I’d like to introduce you to ATP as an important compound produced naturally by the body and then go on to discuss the extent to which you can benefit from ATP supplementation.

Enjoy!

 

ATP – The Most Important Energy-Rich Compound in Our Bodies

Of course, ATP is an abbreviation. It stands for “adenosine triphosphate” and is thus the most important high-energy compound involved in cellular metabolism.

In the context of energy metabolism, macronutrients (protein, carbohydrates, and fatty acids) are classified as macromolecules and thus serve as energy sources. The components of these macronutrients (glycerol, fatty acids, glucose, and amino acids) are used later in the metabolic process to provide or conserve energy. Among all high-energy compounds, ATP is the most important, as it is what makes a multitude of energy-consuming reactions at the cellular level possible in the first place. If you will, ATP is the final stop for supplied energy before it is ultimately consumed.

A compound as important as ATP is, of course, not only significant for our muscles; that is why ATP is found wherever energy must essentially be provided for physiological processes. ATP is ultimately formed (endogenously synthesized) in the mitochondrial matrix (the powerhouses of our cells)—that is, where oxidation (electron transfer) and thus the provision of energy take place.

ATP can be produced through:

• Oxidative decarboxylation of pyruvate (carbohydrates / glucose)
• β-oxidation of fatty acids
• Oxidation of amino acids

 

Which synthesis pathway is taken depends on substrate availability, but also on the duration and intensity of an exercise or energy demand.

At this point, it is important to briefly define the role of creatine. Creatine is part of the anaerobically mobilizable energy reserves that are drawn upon first when ATP is consumed. Creatine is synthesized by mitochondrial creatine kinase through the consumption of ATP, resulting in the formation of creatine phosphate. As described above, the phosphate can be transferred to ADP (depleted ATP), thereby generating new ATP.

Conclusion

After this introductory chapter, it should be clear to everyone what a central role ATP plays in energy metabolism and that muscular activity would not be possible without ATP. We have seen that any macromolecule can be metabolized into ATP. Indirectly, this should mean that a deficiency should not occur as long as substrates are available. This line of reasoning now brings us to the second central question of today’s article: to what extent can one benefit from using ATP as a dietary supplement?

 

Is ATP Supplementation Worthwhile?

Bioavailability

To get this out of the way first: there isn’t an abundance of reliable study data on ATP supplementation. In the available literature, one repeatedly encounters the overarching topic of “bioavailability”—which, strictly speaking, is the fundamental prerequisite for effectiveness (regardless, for now, of whether the effect is positive or negative).

Bioavailability is generally defined as the proportion of a nutrient that is actually available to the body after administration. A number of factors determine bioavailability (1):

• Activity of digestive enzymes
• Binding and absorption by the intestinal mucosa
• Transport through the intestinal wall into the bloodstream or the lymphatic system
• Systemic distribution
• Storage and metabolic–functional utilization

Is ATP bioavailable?

The direct administration of ATP (225 mg) as a gastro-resistant tablet resulted in a slight increase in strength performance in the 1-RM test, as well as a slightly delayed onset of fatigue (muscle failure) during exercise to the point of exhaustion, according to Jordan et al. (4). Apart from this observed effect, the researchers found only a slight overall increase in blood and plasma ATP concentrations as a result of the administration. This observation may suggest insufficient bioavailability. While ATP appears to work well in rabbits (5) and is evidently well absorbed, this seems to be less pronounced in human skeletal muscles. Animal studies (7, 8) have shown that orally administered ATP works primarily by accumulating in the blood; however, as Jordan et al. demonstrate, this does not appear to be the case in humans. Researchers have proposed several degradation mechanisms in the human digestive tract that come into play here and alter the ATP itself. Art et al. (17) also addressed the issue of oral bioavailability of ATP. To this end, they administered a single dose of as much as 5,000 mg of ATP to healthy subjects, sometimes using two types of enteric-coated, pH-sensitive capsules. Even with this high dose, the team did not observe a significant increase in whole-blood ATP concentration. Since no significant increase in adenosine levels was measured either, the researchers concluded that ATP was broken down into uric acid via xanthine oxidase (an enzyme). Indeed, plasma uric acid concentrations increased following ATP administration, which supports this hypothesis. Overall, the actual bioavailability of ATP was reported to be 16.6%, but the extent to which this might be improved with chronic administration was left as an “open question.” Coolen et al. (26), however, also found no increase in blood ATP concentration even with the administration of 5,000 mg of ATP over 28 days, though they did again observe an increase in uric acid levels. In conclusion, they state:

“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.”

Last but not least, Kichenin et al. (27) even observed a progressive decrease in plasma ATP levels with repeated oral administration in animal studies.

A Happy Ending?!
The studies by Jordan (4) and Wilson (24) now suggest a favorable outcome. Both research groups criticize previous studies, such as those by Coolen et al. (26), because venous blood was apparently NOT measured after ATP administration—and it is precisely THIS measurement that would likely indicate better bioavailability of orally administered ATP.

Conclusion
: When the scientific community is divided, we’re all caught in the middle, watching the ball go back and forth. What is certain is that measurement results (such as rising uric acid levels) suggest that at least a portion of all ingested ATP is not utilized as an energy source but is simply broken down. Breakdown into adenosine is also considered likely, although this is not to be viewed as a negative. The question of ATP’s actual bioavailability ultimately remains an unsolved mystery to this day, which is why we must focus on “genuine” ATP-mediated results to determine whether ATP supplementation is recommended or not.

 

Studies confirm that ATP has interesting effects

In their study, Rathmacher et al. (23) administered 400 mg of ATP (in non-enteric-coated tablets, but as a disodium salt for buffering) divided into 2 daily doses over 15 days to half of a test group consisting of 16 participants. The other half received a placebo. All participants performed 3 sets each on the leg extension machine, while strength and fatigue values were measured for all subjects. The results showed that, under the influence of ATP, peak torque improved starting with the second set, and muscle fatigue was reduced. However, these effects were not sufficient to ultimately demonstrate significant effects on strength performance. Rathmacher et al. attribute the observed effect not to ATP itself, but to its breakdown product, adenosine, which has been shown to cause vasodilation and increased blood flow (19–21). Another side effect is increased glucose and oxygen enrichment in the muscle (muscular substrate pool) (22).

Then, in 2013, the only study to date examining the effects of ATP on muscle mass was published. Wilson and colleagues (24) recruited trained participants and administered 400 mg of ATP or a placebo to them over 12 weeks, 30 minutes before each training session. The study consisted of three phases, beginning with periodized resistance training (weeks 1 through 8), followed by a two-week overreaching phase (weeks 9 and 10, with increased intensity and training frequency), and concluding with a two-week tapering phase (weeks 11 and 12). Strength values and muscle mass were measured at the start of the study and after 4, 8, and 12 weeks. As the study progressed, differences emerged in terms of strength performance (leg press: 12.9% vs. 4.4%; deadlift: 16.4% vs. 8.5%), vertical jump height (15.3% vs. 11.5%), and muscle mass, with the ATP group consistently showing better results. In addition, the ATP group exhibited reduced protein breakdown compared to the placebo group, as well as a statistically non-significant greater loss of fat mass. It was interesting to note that ATP helped not only to maintain muscle mass and strength levels, particularly during and after overreaching, but also to significantly increase them further. One explanation for the results regarding strength performance comes from Homsher et al. (25). It points to a change in Ca²⁺ influx, which can have a direct impact on muscular performance. Accelerated recovery thanks to ATP is suspected to be a possible effect of ATP, particularly in Phase 2, while increased substrate and oxygen availability are also cited here as possible causes of muscular changes (LBM and muscle thickness).

Conclusion

When administered 30 minutes before training in a dose of 400 mg, ATP performs significantly better than a placebo, both in terms of strength performance and changes in body composition. Exactly how this occurs is still being debated, with several interesting lines of inquiry.

 

Other Effects of ATP

Improved Well-Being Thanks to ATP Supplementation

It’s possible! The reason for this is its role as a neurotransmitter in the central and peripheral nervous systems, which has already been shown in studies to trigger the release of norepinephrine or serotonin (10–14).

Reduced Pain Perception Thanks to ATP

Possible, since adenosine—formed from ATP—inhibits pain transmission (14–16).

Indirectly Raising ATP Levels

Attempts by Herda et al. (3) to indirectly increase muscular ATP levels through the administration of adenyl pyrophosphoric acid, calcium pyruvate, mushroom extract (Cordyceps sinensis), and yohimbine HCl—with the aim of boosting strength and endurance performance in 24 healthy men—failed.

The situation is apparently different with the administration of certain extracts from peat and apples (elevATP™. Naturally funded by the manufacturer, the study by Reyes-Izquierdo et al. nevertheless shows a significant increase in blood ATP levels, no increase in plasma ATP, and a significant increase in intracellular muscle ATP levels during rest periods (most pronounced 120 minutes after administration). Furthermore, Joy et al. (29) report significant effects of administering this extract combination on muscle hypertrophy without simultaneously negatively affecting other blood markers. Jordan et al. (30) observed significant improvements in 1-RM strength values and vertical jump height.

Conclusion

Research is also already being conducted successfully on the approach of indirectly increasing ATP levels.

 

Dosage and Administration

There are indeed still strong objections that consider the genuine effects of ATP administration in doses of 225 mg per dose unlikely, given a total ATP pool of approximately 80 g in skeletal muscles. Even with 100% bioavailability, the likelihood of significant effects is considered too low, especially since adenosine—the active metabolite—has a very short half-life in human plasma (0.6 to 1.5 seconds) (9).

However, the studies available to date on trained subjects indicate that it does seem to work in some way. In these studies, genuine effects were observed with doses of 400 mg administered 30 minutes before exercise. Given the documented maximum increase in muscle ATP levels at rest after 120 minutes, the effects could ultimately be even more pronounced if ATP is taken at least 60 minutes before exercise; however, this is merely my personal interpretation at this point.

 

Safety

In the study by Wilson et al., no adverse changes were observed in blood cell counts, blood sugar, or liver and kidney function with 400 mg of ATP over 12 weeks. Coolen et al. (26) administered 5,000 mg daily to their subjects over 28 days and also found no concerning changes.

 

Summary

It’s truly a rollercoaster ride when dealing with ATP as a dietary supplement. The bottom line is that quite a few questions remain unanswered, starting with actual bioavailability, continuing through the exact mechanism of action, and finally extending to determining the optimal dosage, including the best time to take it.

What we do know: In the studies available so far, moderate to good results were observed with the use of ATP as an oral supplement. It’s definitely worth a try, although it’s likely that those of you who train particularly intensely and extensively will benefit the most.

I encourage everyone who decides to give it a try to share your experiences with me! Comment on this post or feel free to send me an email. I look forward to your feedback.

Best regards,

Holger Gugg

www.body-coaches.de

Sources

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• (2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441280/
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