Out or hypertension, since these require a prolonged period of severe increase [41]. On the other hand, high uric acid concentrations have also been associated with beneficial health effects. Uric acid may function as an antioxidant [42,43], and epidemiological studies have shown that healthy subjects with high uric acid concentrations are at a reduced risk for developing Parkinson’s disease, a condition suspected to be instigated by oxidative damage [44,45]. Furthermore, patients with multiple sclerosis are known to have lower uric acid concentrations than healthy volunteers, and raising the uric acid concentration by pharmacological means has been the subject of recent investigation [46]. Although increasing the uric acid concentration pharmacologically using ATP pellets might have benefits for certain individuals, these have to be weighed against increased risks of gout and possibly cardiovascular disease [36,38,39].Conclusions A single dose of oral ATP supplement is not bioavailable, whether administered as proximal-release or distal-release enteric coated pellets, or directly instilled in the smallintestine. This may explain why several studies did not find ergogenic effects of oral ATP supplementation. An on average 50 increase in uric acid concentration was found with the proximal-release pellets and with the naso-duodenal tube, suggesting that ATP or one of its metabolites is absorbed, but immediately metabolizedArts et al. Journal of the International Society of Sports Nutrition 2012, 9:16 http://www.jissn.com/content/9/1/Page 8 ofbefore becoming available to the body. Uric acid itself may have beneficial effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability.3.4.5. 6.Additional filesAdditional file 1: Figure S1. Individual increases in plasma uric acid concentrations following supplementation with 5000 mg ATP. ATP was administered at t = 0 as a solution through a naso-duodenal tube (A), proximal-release pellets (B), or distal-release pellets (C). Values represent the percentage increase from the mean baseline values that were determined in three samples collected at 30, 20 and 10 min before administration. The legend shows sex of subjects. Note the different scale of the x-axis in panel A. Additional file 2: Figure S2. Individual increases in plasma lithium concentrations after administration of supplement containing 60 mg Li2CO3. Plasma lithium concentrations (ng/ml) of 6 female and 2 male volunteers after (A) proximal-release pellets containing ATP, (B) proximal-release pellets containing placebo or (C) distal-release pellets containing ATP. Abbreviations AAS: Atomic absorption spectrophotometer; ADP: Adenosine 5-diphosphate; AMP: Adenosine 5-monophosphate; ATP: Adenosine 5-triphosphate; AUC: Area under the curve; CD73: Ecto-5-nucleotidase; carboxymethylcellulose; CNT: Concentrative nucleoside transporter; ENT: Equilibrative nucleoside transporter; PCA: Perchloric acid; TCA: Trichloroacetic acid. 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 HIV-1 integrase inhibitor 2 msds carried out the human intervention study, participated in the data analysis and drafted the manuscript, MJLB participated in the design of the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27527552 study and helped to draft the manuscript, NH produced the pellets and carried out the disso.
