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Research Article

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

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Article: 16 | Published online: 01 Apr 2022
 

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Electronic supplementary material

The online version of this article (doi:10.1186/1550-2783-9-16) contains supplementary material, which is available to authorized users.

Copyright comment

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Electronic supplementary material

The online version of this article (doi:10.1186/1550-2783-9-16) contains supplementary material, which is available to authorized users.

Copyright comment

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Acknowledgements

This work was financially supported by the Graduate School VLAG.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

ICWA participated in the design and data analysis of the study, and drafted the manuscript, EJCMC carried out the human intervention study, participated in the data analysis and drafted the manuscript, MJLB participated in the design of the study and helped to draft the manuscript, NH produced the pellets and carried out the dissolution experiments, MACH participated in the design of the study and helped to draft the manuscript, AB participated in the design and conception of the study and helped to draft the manuscript, PCD conceived of the study, participated in the design and coordination of the study, and helped to draft the manuscript. All authors read and approved the final manuscript.