400 mg ATP Supplementation Acutely Ergogenic - Gymrats' Max. Leg Workout Volume/Rep Number Increases by 24%

Needless to say that the study at hand cannot prove that, but it is logical to assume that similar increases in training volume would be observed for full squats and other lower body exercises. Moreover, Jordan et al. (2004) have observed significant improvements in all-out (1RM) bench press performance many of you would certainly appreciate.

There's little doubt that well-stocked ATP stores are essential for maximal exercise performance. Adenosine-5’-triphosphate (ATP) is, after all, the primary source of energy for muscle cells. Still, scientists have long assumed that the provision of exogenous ATP (orally) wouldn't trigger measurable performance increases because it (a) wouldn't even make it to the muscle but is metabolized before and/or (b) is rapidly resynthesized during exercise training, anyway.

As de Freitas et al. (2017) point out in their latest paper, "the first study to evaluate the effects of oral ATP administration was performed by Jordan et al. in 2004. In said study, the authors did not increase whole blood or plasma ATP concentrations and failed to improve any metric of performance measured via the anaerobic Wingate test either acutely or sub-chronically.

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What did improve (dose-dependently, with the high dose) in Jordan's study, however, was the 1RM (maximal weight) bench press performance of the subjects consuming 225mg ATP/day - acutely. Moreover, the group consuming 225 mg ATP performed more repetitions during 3 sets of bench press to fatigue with 70% of the 1 RM compared to the 150 mg ATP and placebo group.

Meanwhile, a number of studies have suggested ergogenic effects of ATP ranging from improved fatigue resilience to increased strength and size gains (Wilson 2013) - with the latter being a result that the light after the saw infamous HMB study, though, it did yet raise some serious questions about the methodological quality of the study design (Phillips 2017).

Overall, there's thus insufficient evidence to (a) say for sure whether oral ATP supplements work and whether they are (b) able to trigger statistically significant and practically relevant performance increases. The purpose of de Freitas et al.'s study was now to ...

"[...] investigate the effect of a single dose of ATP supplementation on lower-body resistance exercise performance and the physiological responses in recreationally resistance trained males [and check the hypothesis] that acute ATP supplementation will attenuate fatigue and result in greater resistance training volume and oxygen consumption" (de Freitas 2017).

In the absence of chronic supplementation, the study at hand will therefore not answer the question whether the previously referenced increases in long-term gains was a methodological artifice or not.

What's the mechanism, here? De Freitas et al. propose two different mechanisms. There's (a) an effect of extracellular ATP on muscle excitability - an effect that is mediated by the P2X4 receptor and subsequent increases in intracellular calcium influx (30). Alternatively, there's (b) a possible effect of extracellular ATP on vascular tissue, where it interacts with the P2Y receptor which will, as the authors point out,  "induce [the] production of endothelium-derived hyperpolarizing factor, prostacyclin, and nitric oxide by endothelial cells, relaxing the smooth muscle of the vasculature" This, in turn, may also explain the increase in oxygen delivery and uptake De Freitas et al. observed in the study at hand. Future studies will have to look at the underlying mechanism more closely. 

Still, with "recreationally resistance trained" subjects (N=11 men; age= 27.5±5.5 yrs, weight= 83.4±9.8 kg, height= 182±0.04 cm; squat 1-RM = 127.8±19.7 kg) and an effective dietary control (CHO 211,3± 55.8, PRO 149,7±81.1, FAT 54,13±21.7 all in grams/d), the randomized, double-blind study at hand provides evidence that the money you may spend on ATP supplements ain't a complete waste.

Figure 1: Supplementing 400 mg of ATP 30 minutes before a standardized (half-)squat workout significantly increased the total weight lifted (primary axis) and the total number of reps (secondary axis) in 11 recreationally trained men.

Compared to the placebo condition, the consumption of 400mg of ATP thirty minutes before a standardized resistance training workout consisting of 4 sets of half-squat until momentary muscular failure with a load corresponding to 80% of the 1RM and 2 minutes of rest between sets increased the total training volume of the subjects not just significantly, but also to a practically relevant extent (+24% | Placebo= 3995.7±1137.8, ATP= 4967.4±1497.9 Kg; p= 0.005) - one that could, at least, explain the previously cited increase in strength and size gains. After all, training volume is one of the few (more or less) certain correlates of training adaptation (Schoenfeld 2015) we know.

Fatigue resistance is apparently the main mechanism

The results also support the notion that ATP exerts any potential ergogenic effects by increasing subjects' fatigue resistance since statistically significant differences weren't observed for the total weight lifted, only, but also for the number of repetitions (Fig.2B: Placebo= 40± 11 vs ATP= 49.4± 11.5 Kg; p= 0.006). In that, it's worth mentioning that the effect sizes de Freitas et al. calculated were large for the number of repetitions (d= 0.83) and ranged from moderate to large in the total weight lifted (d= 0.73) - this makes the 24% difference the scientists detected even more interesting.

No effect of supplementation was found for blood pressure and excess post-exercise oxygen consumption. Lactate as well as the subjects' heart rates and relative and absolute oxygen uptake, on the other hand, showed a trend for (lactate) or statistically significant improvements in the 400mg ATP vs. placebo trial... that's not surprising, though, considering the fact that the training volume/number of reps increased significantly.

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So what's the verdict, then? The study at hand found an - at face value - realistic acute performance/volume increase. An improvement that's not just statistically significant, but also large enough to be of practical relevance for the average gymrat... assuming - and that's important - that a 24% increase in rep and weight-volume occurs everytime you're downing ATP before a workout!

If the former is the case and the repeated use of the supplement does not mitigate the effects, we can furthermore speculate that the consumption of 400mg of ATP 30 minutes before (timing may be crucial, here!) a workout could increase your training volume and thus the anabolic stimulus to an extent that will produce noticeable increases in both, size and strength gains, over time.

Until this hypothesis is confirmed in long(er)-term follow-up studies, the only thing we can now say w/ progressively increased certainty is that 400 mg ATP may acutely enhance the anaerobic performance in previously trained men who work out to failure - at high intensities | Comment!

References:

• de Freitas, et al. (2017) "A Single Dose Of Oral Atp Supplementation Improves Performance And Physiological Response During Lower Body Resistance Exercise In Recreational Resistance Trained Males." Journal of Strength and Conditioning Research Publish Ahead of Print | DOI: 10.1519/JSC.0000000000002198
• Jordan, A. N., Jurca, R., Abraham, E. H., Salikhova, A., Mann, J. K., Morss, G. M., ... & Earnest, C. P. (2004). Effects of oral ATP supplementation on anaerobic power and muscular strength. Medicine & Science in Sports & Exercise, 36(6), 983-990.
• Phillips, S. M., Aragon, A. A., Arciero, P. J., Arent, S. M., Close, G. L., Hamilton, D. L., ... & Ormsbee, M. J. (2017). Changes in Body Composition and Performance With Supplemental HMB‐FA+ ATP. The Journal of Strength & Conditioning Research, 31(5), e71-e72.
• Schoenfeld, B. J., Peterson, M. D., Ogborn, D., Contreras, B., & Sonmez, G. T. (2015). Effects of low-vs. high-load resistance training on muscle strength and hypertrophy in well-trained men. The Journal of Strength & Conditioning Research, 29(10), 2954-2963.
• Wilson, J. M., Joy, J. M., Lowery, R. P., Roberts, M. D., Lockwood, C. M., Manninen, A. H., ... & Rathmacher, J. A. (2013). Effects of oral adenosine-5′-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutrition & metabolism, 10(1), 57.