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

Ilja Cw Arts, Erik Jcm Coolen, Martijn Jl Bours, Nathalie Huyghebaert, Martien A Cohen Stuart, Aalt Bast, Pieter C Dagnelie, Ilja Cw Arts, Erik Jcm Coolen, Martijn Jl Bours, Nathalie Huyghebaert, Martien A Cohen Stuart, Aalt Bast, Pieter C Dagnelie

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.

Figures

Figure 1
Figure 1
Uric acid concentrations in healthy volunteers after oral ATP or placebo supplementation. A single dose of 5000 mg ATP or placebo was administered via proximal-release pellets, distal-release pellets, or naso-duodenal tube. Data are presented as percentage increase from the mean of three blood samples taken before administration. Values are means ± SEM, n = 8.
Figure 2
Figure 2
Release of ATP and metabolites from enteric coated supplement after dissolution testing. Release of ATP and its metabolites as a percentage of the release at 180 min for proximal-release pellets (closed symbols) and distal-release pellets (open symbols), after 120 min in 0.1 N HCl, and subsequently 60 min in buffer solutions with either pH 6.5 (proximal-release pellets) or 7.4 (distal-release pellets). Data were obtained by the reciprocating cylinder method (USP apparatus 3). Values are means ± SEM, n = 3.
Figure 3
Figure 3
Plasma lithium concentrations in healthy volunteers after administration of supplement containing 60 mg Li2CO3. A single dose of 5000 mg ATP or placebo with 60 mg Li2CO3 was administered via proximal-release pellets or distal-release pellets. Values are means ± SEM, n = 8.

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