Supplementation of 225 mg per day of enteric-coated ATP supplementation for 15 days resulted in increased total bench press lifting volume as well as within-group repetitions to failure on set one of three with 70% of 1RM [3]. Moreover, 15 days of 400 mg per day of ATP supplementation reduced learn more muscle fatigue and enabled a higher force output during repeated high-intensity

bouts of exercise [4]. More recently, 12 weeks of 400 mg of oral ATP disodium salt supplementation in resistance-trained athletes utilizing a periodized resistance-training program (RT) resulted in significant increases in lean body mass, muscle thickness, total strength and vertical jump power [5]. ATP also reduced protein breakdown and limited the loss of strength and power during an Wortmannin cost overreaching cycle [5]. Three distinct mechanisms-of-action have been proposed for orally administered ATP’s ergogenic benefits: 1) ATP can increase blood flow, resulting in improved oxygen and nutrient delivery to the muscle [5] 2) ATP may increase muscular excitability [6]; 3) ATP can trigger signaling cascades for metabolic adaptation related to neuromuscular activity (phosphorylation of ERK1/2) (see Figure  1) [7]. However, it is unlikely that oral ATP administration will directly increase intramuscular ATP stores. Figure 1 Proposed mechanism-of-action of oral ATP administration.

Erythrocytes eFT-508 purchase function as an oxygen sensor, contributing to the regulation of skeletal muscle blood flow and oxygen delivery, by releasing ATP in proportion to the number of unoccupied oxygen binding sites in the hemoglobin molecule. ATP release results in vasodilation and greater blood flow to the working musculature, thereby enhancing nutrient and oxygen delivery. Thus, during exercise under hypoxic conditions, ATP is released from the red blood cells via pannexin channels. ATP then binds to the purinergic receptors on the endothelial cells [5].

The endothelial cells then produce endothelium-derived hyperpolarizing factor, prostacyclin, and nitric oxide, all of which serve to relax the smooth muscle of the vasculature (see Figure  1) [5]. Infused ATP has BCKDHB been shown to increase blood flow by stimulating endothelial ATP-selective P2Y2 receptors and increasing muscle sympathetic vasoconstrictor activity [8]. The vasodilatory and sympatholytic effects of exogenous ATP are mediated via ATP itself rather than its dephosphorylated metabolites [9]. Chronic oral administration of ATP in rats increased portal vein ATP concentration and nucleoside uptake by erythrocytes, which resulted in an increase in ATP synthesis in the erythrocytes [10]. To our knowledge, however, no studies have delineated if oral ATP administration enhances the blood flow response to exercise.