Oral bioavailability of ATP after prolonged administration

• Published in: British journal of nutrition Vol. 105; no. 3; pp. 357 - 366
• Main Authors: Coolen, Erik J. C. M., Arts, Ilja C. W., Bekers, Otto, Vervaet, Chris, Bast, Aalt, Dagnelie, Pieter C.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 14.02.2011
• Subjects: adenosine triphosphate; Adenosine Triphosphate - administration & dosage; Adenosine Triphosphate - blood; Adenosine Triphosphate - pharmacokinetics; administration & dosage; Administration, Oral; Adolescent; Adult; ATP; Bioavailability; Biological and medical sciences; Biological Availability; blood; blood plasma; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Enzymes; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; inflammation; kidneys; liver; Male; Metabolism and Metabolic Studies; Metabolites; Middle Aged; muscle contraction; nociception; oral administration; pellets; pharmacokinetics; receptors; Receptors, Purinergic; uric acid; Uric Acid - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Young Adult; Oral ATP administration; Human studies; Human; Vertebrata; Mammalia; Oral administration; Bioavailability; ATP
• ISSN: 0007-1145; 1475-2662; 1475-2662
• DOI: 10.1017/S0007114510003570

Purinergic receptors are important for the regulation of inflammation, muscle contraction, neurotransmission and nociception. Extracellular ATP and its metabolites are the main ligands for these receptors. Occasional reports on beneficial results of ATP administration in human and animal studies have suggested the bioavailability of oral ATP supplements. We investigated whether prolonged daily intake of oral ATP is indeed bioavailable. Thirty-two healthy subjects were randomised to receive 0, 250, 1250 or 5000 mg ATP per d for 28 d by means of enteric-coated pellets. In addition, on days 0 and 28, all thirty-two subjects received 5000 mg ATP to determine whether prolonged administration would induce adaptations in the bioavailability of ATP. ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations. On the basis of these findings, we seriously question the claimed efficacy of oral ATP at dosages even lower than that used in the present study.