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Adenosine 5′-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans

Ilja CW Arts1*, Erik JCM Coolen12, Martijn JL Bours1, Nathalie Huyghebaert3, Martien A Cohen Stuart4, Aalt Bast2 and Pieter C Dagnelie1

Author Affiliations

1 Department of Epidemiology, Maastricht University, P.O. Box 616, Maastricht, MD, 6200, The Netherlands

2 Department of Toxicology, Maastricht University, P.O. Box 616, Maastricht, MD, 6200, The Netherlands

3 Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, Ghent, B-9000, Belgium

4 Department of Agrotechnology and Food Sciences, Laboratory of Physical Chemistry and Colloid Science, Wageningen University, P.O. Box 8038, Wageningen, EK, 6700, The Netherlands

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Journal of the International Society of Sports Nutrition 2012, 9:16  doi:10.1186/1550-2783-9-16

Published: 17 April 2012



Nutritional supplements designed to increase adenosine 5′-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioavailable. We investigated whether acute supplementation with oral ATP administered as enteric-coated pellets led to increased concentrations of ATP or its metabolites in the circulation.


Eight healthy volunteers participated in a cross-over study. Participants were given in random order single doses of 5000 mg ATP or placebo. To prevent degradation of ATP in the acidic environment of the stomach, the supplement was administered via two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine), or via a naso-duodenal tube. Blood ATP and metabolite concentrations were monitored by HPLC for 4.5 h (naso-duodenal tube) or 7 h (pellets) post-administration. Areas under the concentration vs. time curve were calculated and compared by paired-samples t-tests.


ATP concentrations in blood did not increase after ATP supplementation via enteric-coated pellets or naso-duodenal tube. In contrast, concentrations of the final catabolic product of ATP, uric acid, were significantly increased compared to placebo by ~50% after administration via proximal-release pellets (P = 0.003) and naso-duodenal tube (P = 0.001), but not after administration via distal-release pellets.


A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability.

ATP; Metabolism; Nutritional supplement; Bioavailability; Gastrointestinal transit; Multi-particulate supplement