Wilson et al. recently suggested that oral ATP supplementation can significantly impact athletic performance, skeletal muscle hypertrophy and recovery; however, the study did not utilize methodologies to investigate the potential mechanism for the observed ergogenic effects. One of the proposed mechanisms of action of oral ATP administration is an increase in blood flow, resulting in improved oxygen and nutrient delivery to the muscle. Enhanced blood flow to an exercising skeletal muscle is expected to improve removal of metabolic waste products such as lactate and urea. Following exercise nutrient delivery and cell swelling play a vital role in the skeletal muscle adaptation response. Improvements in blood flow conceivably would allow for greater delivery of nutrients for skeletal muscle repair following a muscle damaging bout of training resulting in increases in muscle hypertrophy previously seen with oral ATP administration. The main finding of this study was that orally administered ATP as a disodium salt indeed increases blood flow in exercising animals and humans, most prominently during the recovery period from exercise. Significant improvements could be measured at a daily dose of 400 mg ATP in as little as one week in the human study.
Though the exact mechanism of oral ATP absorption is currently not fully understood, animal studies have shown that the chronic oral administration of ATP resulted in measurable changes in muscle metabolism, peripheral blood flow, and blood oxygenation[10, 14] and human studies have resulted in significant improvements in body composition and performance[4, 6]. Studies on the oral availability of ATP showed that it is unlikely that oral ATP administration will directly increase intramuscular ATP stores as a single dose of orally administered ATP in humans did not increase ATP concentrations in blood. The measurement of circulating free plasma ATP derived from oral ATP supplementation is very unlikely because exogenous free ATP is rapidly taken up by blood components or is rapidly metabolized. Kichenin et al. showed, in rats, that chronic oral administration of ATP increased portal vein ATP concentration and nucleoside uptake by erythrocytes, which resulted in an increase in ATP synthesis in the erythrocytes. In other animal studies the administration of oral ATP resulted in a rapid degradation through ectonucleotidase triphosphatase diphosphohydrolase 1 (CD39), present on the luminal side of intestinal enterocytes, which dephosphorylate ATP via ADP to AMP, after which ecto-5′-nucleotidase (CD73) degrades AMP to adenosine[16, 17]. Following absorption of adenosine and inorganic phosphate in the small intestine and the portal circulation these moieties are then incorporated into liver ATP pools, leading to expansions of these pools. Therefore, the systemic and oral administrations of ATP result in the expansions of liver, blood (red blood cells) and blood plasma (extracellular) pools of ATP which were shown for the first time by Rapaport et al.[18, 19].
Blood flow during exercise is indicative of nutrient (amino acids, glucose, etc.) and oxygen delivery rate. As such, increased blood flow will indicate greater nutrient availability for the working musculature, and, in theory, the muscle should have the capacity to recover more quickly between sets, maintain performance longer, and repair microtrauma more efficiently between training sessions. Wilson et al. hypothesized that the observed increases in lean body mass, markers of athletic performance, and resistance to an overreaching status with chronic ATP supplementation were due to enhanced blood flow leading to enhanced recovery, although this remained to be directly examined until the current study. However, despite increased blood flow during ATP infusion, oxygen consumption does not increase. Considering these two studies, it is possible that ATP is more efficacious for anaerobic versus aerobic based exercise. However, ATP’s efficacy in an endurance model remains to be investigated. Likewise, the exact mechanism whereby ATP increases post-exercise blood flow also remains to be determined, although others have hypothesized that this may be due to: a) ATP degradation products being taken up by erythrocytes and resynthesized into ATP; b) vasodilation of ATP degradation (i.e., adenosine) products; and/or c) adenosine-stimulated nitric oxide and prostacyclin synthesis and downstream signaling.
L-citrulline or L-arginine are amino acid precursors to nitric oxide and have been marketed as potential ergogenic aids based on their ability to increase blood flow to the exercising muscle. However, the daily dose needed to increase blood flow is high (6-24 g) and the ergogenic response may depend on the training status and health of the subjects. Whereas some studies involving untrained or moderately healthy subjects showed that nitric oxide donors could improve tolerance to aerobic and anaerobic exercise, no significant improvements were measured in healthy or highly-trained subjects[21, 23]. In contrast, oral ATP increases blood flow at mg doses and has been shown to increase lean body mass, strength and power in highly trained individuals. Therefore, oral ATP supplementation is an apparently efficacious method if the intent is increasing post-exercise blood flow and nutrient delivery.
Limitations of this study include the lack of control group and a rigorous control of other potentially confounding variables such as potential differences in exercise habits or baseline dietary habits and dietary supplement use in the human data. We propose future research to assess the effects of oral ATP administration on blood flow in a placebo-controlled crossover or parallel design.