Skip to main content
Top
Published in: Journal of the International Society of Sports Nutrition 1/2014

Open Access 01-12-2014 | Research article

Oral adenosine-5’-triphosphate (ATP) administration increases blood flow following exercise in animals and humans

Authors: Ralf Jäger, Michael D Roberts, Ryan P Lowery, Jordan M Joy, Clayton L Cruthirds, Christopher M Lockwood, John A Rathmacher, Martin Purpura, Jacob M Wilson

Published in: Journal of the International Society of Sports Nutrition | Issue 1/2014

Login to get access

Abstract

Introduction

Extracellular adenosine triphosphate (ATP) stimulates vasodilation by binding to endothelial ATP-selective P2Y2 receptors; a phenomenon, which is posited to be accelerated during exercise. Herein, we used a rat model to examine how different dosages of acute oral ATP administration affected the femoral blood flow response prior to, during, and after an exercise bout. In addition, we performed a single dose chronic administration pilot study in resistance trained athletes.

Methods

Animal study: Male Wistar rats were gavage-fed the body surface area, species adjusted human equivalent dose (HED) of either 100 mg (n=4), 400 mg (n=4), 1,000 mg (n=5) or 1,600 mg (n=5) of oral ATP as a disodium salt (Peak ATP®, TSI, Missoula, MT). Rats that were not gavage-fed were used as controls (CTL, n=5). Blood flow was monitored continuously: a) 60 min prior to, b) during and c) 90 min following an electrically-evoked leg-kicking exercise. Human Study: In a pilot study, 12 college-aged resistance-trained subjects were given 400 mg of ATP (Peak ATP®, TSI, Missoula, MT) daily for 12 weeks, and prior to an acute arm exercise bout at weeks 1, 4, 8, and 12. Ultrasonography-determined volumetric blood flow and vessel dilation in the brachial artery was measured at rest, at rest 30 minutes after supplementation, and then at 0, 3, and 6 minutes after the exercise.

Results

Animal Study: Rats fed 1,000 mg HED demonstrated significantly greater recovery blood flow (p < 0.01) and total blood flow AUC values (p < 0.05) compared to CTL rats. Specifically, blood flow was elevated in rats fed 1,000 mg HED versus CTL rats at 20 to 90 min post exercise when examining 10-min blood flow intervals (p < 0.05). When examining within-group differences relative to baseline values, rats fed the 1,000 mg and 1,600 mg HED exhibited the most robust increases in blood flow during exercise and into the recovery period. Human study: At weeks 1, 8, and 12, ATP supplementation significantly increased blood flow, along with significant elevations in brachial dilation.

Conclusions

Oral ATP administration can increase post-exercise blood flow, and may be particularly effective during exercise recovery.
Appendix
Available only for authorised users
Literature
1.
go back to reference Agteresch HJ, Dagnelie PC, van den Berg JW, Wilson JH: Adenosine triphosphate: established and potential clinical applications. Drugs. 1999, 58 (2): 211-232.CrossRefPubMed Agteresch HJ, Dagnelie PC, van den Berg JW, Wilson JH: Adenosine triphosphate: established and potential clinical applications. Drugs. 1999, 58 (2): 211-232.CrossRefPubMed
2.
go back to reference Bannwarth B, Allaert F-A, Avouac B, Rossignol M, Rozenberg S, Valat J-P: A randomized, double-blind, placebo controlled study of oral adenosine Triphosphate in subacute low back pain. J Rheumatol. 2005, 32: 1114-1117.PubMed Bannwarth B, Allaert F-A, Avouac B, Rossignol M, Rozenberg S, Valat J-P: A randomized, double-blind, placebo controlled study of oral adenosine Triphosphate in subacute low back pain. J Rheumatol. 2005, 32: 1114-1117.PubMed
3.
go back to reference Jordan AN, Jurca R, Abraham EH, Salikhova A, Mann JK, Morss GM, Church TS, Lucia A, Earnest CP: Effects of oral ATP supplementation on anaerobic power and muscular strength. Med Sci Sports Exerc. 2004, 36 (6): 983-990.CrossRefPubMed Jordan AN, Jurca R, Abraham EH, Salikhova A, Mann JK, Morss GM, Church TS, Lucia A, Earnest CP: Effects of oral ATP supplementation on anaerobic power and muscular strength. Med Sci Sports Exerc. 2004, 36 (6): 983-990.CrossRefPubMed
4.
go back to reference Rathmacher JA, Fuller JC, Baier SM, Abumrad NN, Angus HF, Sharp RL: Adenosine-5'-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. J Int Soc Sports Nutr. 2012, 9 (1): 48-PubMedCentralCrossRefPubMed Rathmacher JA, Fuller JC, Baier SM, Abumrad NN, Angus HF, Sharp RL: Adenosine-5'-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. J Int Soc Sports Nutr. 2012, 9 (1): 48-PubMedCentralCrossRefPubMed
5.
go back to reference Sprague RE, Bowles EA, Achilleus D, Ellsworth ML: Erythrocyte as controllers of perfusion distribution in the microvasculature skeletal muscle. Acta Physiol. 2011, 202: 285-292.CrossRef Sprague RE, Bowles EA, Achilleus D, Ellsworth ML: Erythrocyte as controllers of perfusion distribution in the microvasculature skeletal muscle. Acta Physiol. 2011, 202: 285-292.CrossRef
6.
go back to reference Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, Fuller JC, De Souza EO, Baier SM, Wilson SMC, Rathmacher JA: Effects of oral adenosine-5'-triphosphate (ATP) supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutr Metab (Lond). 2013, 10: 57-CrossRef Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, Fuller JC, De Souza EO, Baier SM, Wilson SMC, Rathmacher JA: Effects of oral adenosine-5'-triphosphate (ATP) supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutr Metab (Lond). 2013, 10: 57-CrossRef
7.
go back to reference May C, Weigl L, Karel A, Hohenegger M: Extracellular ATP activates ERK1/ERK2 via a metabotropic P2Y1 receptor in a Ca2+ independent manner in differentiated human skeletal muscle cells. Biochem Pharmacol. 2006, 71 (10): 1497-1509.CrossRefPubMed May C, Weigl L, Karel A, Hohenegger M: Extracellular ATP activates ERK1/ERK2 via a metabotropic P2Y1 receptor in a Ca2+ independent manner in differentiated human skeletal muscle cells. Biochem Pharmacol. 2006, 71 (10): 1497-1509.CrossRefPubMed
8.
go back to reference Rosenmeier JB, Hansen J, Gonźalez-Alonso J: Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle. J Physiol. 2004, 558: 351-365.PubMedCentralCrossRefPubMed Rosenmeier JB, Hansen J, Gonźalez-Alonso J: Circulating ATP-induced vasodilatation overrides sympathetic vasoconstrictor activity in human skeletal muscle. J Physiol. 2004, 558: 351-365.PubMedCentralCrossRefPubMed
9.
go back to reference Rosenmeier JB, Yegutkin GG, Gonźalez-Alonso J: Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle. J Physiol. 2008, 586: 4993-5002.PubMedCentralCrossRefPubMed Rosenmeier JB, Yegutkin GG, Gonźalez-Alonso J: Activation of ATP/UTP-selective receptors increases blood flow and blunts sympathetic vasoconstriction in human skeletal muscle. J Physiol. 2008, 586: 4993-5002.PubMedCentralCrossRefPubMed
10.
go back to reference Kichenin K, Seman M: Chronic oral administration of ATP modulates nucleoside transport and purine metabolism in rats. J Pharmacol Exp Ther. 2000, 294 (1): 126-133.PubMed Kichenin K, Seman M: Chronic oral administration of ATP modulates nucleoside transport and purine metabolism in rats. J Pharmacol Exp Ther. 2000, 294 (1): 126-133.PubMed
11.
go back to reference Reagan-Shaw S, Nihal M, Ahmad N: Dose translation from animal to human studies revisited. FASEB J. 2008, 22 (3): 659-661.CrossRefPubMed Reagan-Shaw S, Nihal M, Ahmad N: Dose translation from animal to human studies revisited. FASEB J. 2008, 22 (3): 659-661.CrossRefPubMed
12.
go back to reference Mohr T, Akers TK, Wessman HC: Effect of high voltage stimulation on blood flow in the rat hind limb. Phys Ther. 1987, 67 (4): 526-533.PubMed Mohr T, Akers TK, Wessman HC: Effect of high voltage stimulation on blood flow in the rat hind limb. Phys Ther. 1987, 67 (4): 526-533.PubMed
13.
go back to reference Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R: Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery. J Am Coll Cardiol. 2002, 39: 257-265.CrossRefPubMed Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R: Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery. J Am Coll Cardiol. 2002, 39: 257-265.CrossRefPubMed
14.
go back to reference Kichenin K, Decollogne S, Angignard J, Seman M: Cardiovascular and pulmonary response to oral administration of ATP in rabbits. J Appl Physiol. 2000, 88: 1962-1968.CrossRefPubMed Kichenin K, Decollogne S, Angignard J, Seman M: Cardiovascular and pulmonary response to oral administration of ATP in rabbits. J Appl Physiol. 2000, 88: 1962-1968.CrossRefPubMed
15.
go back to reference Arts IC, Coolen EJ, Bours MJ, Huyghebaert N, Stuart MA, Bast A, Dagnelie PC: Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans. J Int Soc Sports Nutr. 2012, 9 (1): 16-PubMedCentralCrossRefPubMed Arts IC, Coolen EJ, Bours MJ, Huyghebaert N, Stuart MA, Bast A, Dagnelie PC: Adenosine 5'-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans. J Int Soc Sports Nutr. 2012, 9 (1): 16-PubMedCentralCrossRefPubMed
16.
go back to reference Yegutkin GG: Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008, 1783: 673-694.CrossRefPubMed Yegutkin GG: Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008, 1783: 673-694.CrossRefPubMed
17.
go back to reference Strohmeier GR, Lencer WI, Patapoff TW, Thompson LF, Carlson SL, Moe SJ, Carnes DK, Mrsny RJ, Madara JL: Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia. J Clin Invest. 1997, 99: 2588-2601.PubMedCentralCrossRefPubMed Strohmeier GR, Lencer WI, Patapoff TW, Thompson LF, Carlson SL, Moe SJ, Carnes DK, Mrsny RJ, Madara JL: Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia. J Clin Invest. 1997, 99: 2588-2601.PubMedCentralCrossRefPubMed
18.
go back to reference Rapaport E, Fontaine J: Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. Proc Natl Acad Sci U S A. 1989, 86 (5): 1662-1666.PubMedCentralCrossRefPubMed Rapaport E, Fontaine J: Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. Proc Natl Acad Sci U S A. 1989, 86 (5): 1662-1666.PubMedCentralCrossRefPubMed
19.
go back to reference Rapaport E, Fontaine J: Generation of extracellular ATP in blood and its mediated inhibition of host weight loss in tumor-bearing mice. Biochem Pharmacol. 1989, 38 (23): 4261-4266.CrossRefPubMed Rapaport E, Fontaine J: Generation of extracellular ATP in blood and its mediated inhibition of host weight loss in tumor-bearing mice. Biochem Pharmacol. 1989, 38 (23): 4261-4266.CrossRefPubMed
20.
go back to reference Calbet JA, Lundby C, Sander M, Robach P, Saltin B, Boushel R: Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans. Am J Physiol Regul Integr Comp Physiol. 2006, 291 (2): R447-R453.CrossRefPubMed Calbet JA, Lundby C, Sander M, Robach P, Saltin B, Boushel R: Effects of ATP-induced leg vasodilation on VO2 peak and leg O2 extraction during maximal exercise in humans. Am J Physiol Regul Integr Comp Physiol. 2006, 291 (2): R447-R453.CrossRefPubMed
21.
go back to reference Sureda A, Pons A: Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?. Med Sport Sci. 2012, 59: 18-28.CrossRefPubMed Sureda A, Pons A: Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?. Med Sport Sci. 2012, 59: 18-28.CrossRefPubMed
22.
go back to reference Tang JE, Lysecki PJ, Manolakos JJ, MacDonald MJ, Tarnopolsky MA, Phillips SM: Bolus arginine supplementation affects neither muscle blood flow nor muscle protein synthesis in young men at rest or after resistance exercise. J Nutr. 2011, 141 (2): 195-200.CrossRefPubMed Tang JE, Lysecki PJ, Manolakos JJ, MacDonald MJ, Tarnopolsky MA, Phillips SM: Bolus arginine supplementation affects neither muscle blood flow nor muscle protein synthesis in young men at rest or after resistance exercise. J Nutr. 2011, 141 (2): 195-200.CrossRefPubMed
23.
go back to reference Alvares TS, Conte CA, Paschoalin VM, Silva JT, Meirelles Cde M, Bhambhani YN, Gomes PS: Acute l-arginine supplementation increases muscle blood volume but not strength performance. Appl Physiol Nutr Metab. 2012, 37 (1): 115-126.CrossRefPubMed Alvares TS, Conte CA, Paschoalin VM, Silva JT, Meirelles Cde M, Bhambhani YN, Gomes PS: Acute l-arginine supplementation increases muscle blood volume but not strength performance. Appl Physiol Nutr Metab. 2012, 37 (1): 115-126.CrossRefPubMed
Metadata
Title
Oral adenosine-5’-triphosphate (ATP) administration increases blood flow following exercise in animals and humans
Authors
Ralf Jäger
Michael D Roberts
Ryan P Lowery
Jordan M Joy
Clayton L Cruthirds
Christopher M Lockwood
John A Rathmacher
Martin Purpura
Jacob M Wilson
Publication date
01-12-2014
Publisher
BioMed Central
DOI
https://doi.org/10.1186/1550-2783-11-28

Other articles of this Issue 1/2014

Journal of the International Society of Sports Nutrition 1/2014 Go to the issue