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

Journal Title (Medline/Pubmed accepted abbreviation): J. Int. Soc. Sports Nutr.
Year: 2012
Volume: 9
First Page: 16
Website: 10.1186/1550-2783-9-16

Summary of background and research design

Background: The energy source for cells is adenosine triphosphate (ATP). It is unknown if supplemental ATP is “bioavailable” or, in other words, if it can traverse the intestinal wall intact and make it into circulation. There is some evidence that ATP is not stable under the highly acidic environment in the stomach. Therefore, these scientists coated the ATP with a low pH-resistant enteric coating.

Hypothesis: Supplementation with ATP in enteric-coated pellets will increase the concentration of ATP and/or ATP metabolites in the blood stream.

Subjects: Healthy subjects, 6 females and 2 males, age 26.9 ± 5.9 y

Experimental design: randomized within the pellets (delivered during the first 3 wks) and the solution treatments (delivered in weeks 4 and 5), placebo-controlled, cross-over trial

1) 5000 mg ATP delivered via enteric coated pellets that are designed to release ATP in the proximal intestine (closer to the stomach)
2) 5000 mg ATP delivered via enteric coated pellets that are designed to release ATP in the distal intestine (closer to the colon)
3) 5000 mg ATP delivered via a naso-duodenal tube (a tube starting in the nose and reaching to the duodenum, or the upper part of the intestine)
4) A placebo (carboxymethylcellulose, no ATP) delivered via enteric coated pellets designed to release in the proximal intestine
5) A placebo (water) delivered via a naso-duodenal tube

Pellets were consumed with 200 mL water acidified to a pH of less than 5 with citric acid.

Protocol: Participants came to the laboratory on 5 occasions to complete all of the 5 treatments.  On weeks 1, 2, or 3 they received pellets and weeks 4 and 5 they received a naso-duodenal tube.  They arrived at the laboratory at 4:00 pm after fasting since 10:00 pm the night before.  Blood was collected 30, 20, and 10 min before administration of the ATP, and then at regular intervals to 270 min (naso-duodenal tube) or 420 min (pellets) for analysis of ATP concentration.  To assess the rate of pellet disintegration, lithium was added to the pellets and analyzed in the blood samples.  In order to calculate the amount of ATP in circulation, the area under the curve for ATP concentration vs. time was calculated. 
Summary of research findings
  • ATP concentrations did not increase in blood with any administration of ATP.
  • Concentrations of the ATP metabolites ADP, AMP, adenosine, adenine, inosine, hypoxanthine also did not change with administration of ATP.
  • Uric acid, the metabolite of ATP that is excreted in the urine, did increase in the blood as a result of ATP supplementation, especially the nasoduodenal tube and proximal release pellet methods of administration.
Key practice applications
ATP, as administered by supplement, was degraded in the small intestine and did not make it to the blood stream.  Therefore, it will likely not provide enhancements in performance or alertness.  This study administered 5000 mg of ATP, whereas most supplements for sale provide about 100-250 mg per dose.  Therefore, it is likely that the available supplements also do not increase the amount of ATP in the blood stream.  Uric acid has not been evaluated for ergogenic effects per se, but has been observed to have both positive (ex. antioxidant) and negative (ex. increase the risk for gout) health effects and would be interesting to evaluate in the future.
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