g. meat, soy, mushrooms) [3] and in breast milk [4, 5]. Furthermore, capsules containing ATP are currently registered in France for the treatment of low back pain of muscular origin, and supplements containing ATP are marketed on the internet for various purposes including the restoration of energy. Oral ATP

supplements have beneficial effects in some but not all studies examining physical performance. In an experimental study by Jordan et al.[6], three groups of nine healthy Dorsomorphin men received ATP (150 or 225 mg) or placebo for 14 days. Physical performance and muscular strength were positively affected. Another study investigated the effects of supplementation with an ATP-containing registered drug for 30 days (Atépadène®, 90 mg daily) [7, 8]. The questionnaire-based outcome indicated that it provided benefit to patients with subacute low back pain. In contrast to these beneficial findings, Herda et al. [9] found no improvements in muscle strength, power output, or endurance after supplementation of 24 healthy men with a commercially available treatment intended to increase ATP. The authors suggested that the lack of an effect in this double-blind, placebo-controlled

crossover trial, might be caused by breakdown of ATP in the gastrointestinal tract. Because they did not collect blood samples from the participants, EX-527 the authors could not verify whether ATP concentrations in the blood circulation had been altered as a result of supplementation [9]. Evidence on the oral availability of ATP supplements is limited. In the study by Jordan et al. [6], no changes in whole blood and plasma ATP concentrations were learn more detected, but the dosages administered were modest (225 mg or less). Animal studies reporting alterations in cardiac, vascular and pulmonary function after 30 days of oral ATP supplementation, also found no increases in systemic concentrations of plasma or erythrocyte ATP [10, 11]. However, the concentration of ATP in plasma taken from the portal vein of rats increased rapidly

up to a 1000-fold after instillation of ATP in de small intestine [11]. The identification of a number of nucleoside transporters in the small intestine further suggested that orally administered ATP may be absorbed and utilized by the human body [12]. We have previously shown that ATP is bioavailable after intravenous administration in humans [13]. ATP concentrations in erythrocytes increased in a dose-dependent manner by ~60% after 24 h of continuous infusion. We now report the results of a randomized, placebo-controlled, cross-over trial in 8 healthy humans, designed to assess the oral bioavailability of an ATP nutritional supplement. The ATP was administered as a single dose that was high enough to enable its detection in whole blood (5000 mg). Furthermore, an acid-resistant enteric coating of the multi-particulate supplement was used to prevent the degradation of ATP in the acidic environment of the stomach.