Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise

Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise Antonio Herbert Lancha Junior 0 1 Vitor de Salles Painelli 0 1 Bryan Saunders 0 1 Guilherme Giannini Artioli 0 1 0 Laboratory of Applied Nutrition and Metabolism, School of Physical Education and Sport, University of Sa ̃o Paulo , Av. Mello de Moraes, 65 Butanta, Sa ̃o Paulo, SP 05508-030 , Brazil 1 & Antonio Herbert Lancha Junior Intramuscular acidosis is a contributing factor to fatigue during high-intensity exercise. Many nutritional strategies aiming to increase intra- and extracellular buffering capacity have been investigated. Among these, supplementation of beta-alanine (*3-6.4 g/day for 4 weeks or longer), the rate-limiting factor to the intramuscular synthesis of carnosine (i.e. an intracellular buffer), has been shown to result in positive effects on exercise performance in which acidosis is a contributing factor to fatigue. Furthermore, sodium bicarbonate, sodium citrate and sodium/calcium lactate supplementation have been employed in an attempt to increase the extracellular buffering capacity. Although all attempts have increased blood bicarbonate concentrations, evidence indicates that sodium bicarbonate (0.3 g/kg body mass) is the most effective in improving high-intensity exercise performance. The evidence supporting the ergogenic effects of sodium citrate and lactate remain weak. These nutritional strategies are not without side effects, as gastrointestinal distress is often associated with the effective doses of sodium bicarbonate, sodium citrate and calcium lactate. Similarly, paresthesia (i.e. tingling sensation of the skin) is currently the only known side effect associated with beta-alanine supplementation, and it is caused by the acute elevation in plasma beta-alanine concentration after a single dose of beta-alanine. Finally, the co-supplementation of beta-alanine and sodium bicarbonate may result in additive - ergogenic gains during high-intensity exercise, although studies are required to investigate this combination in a wide range of sports. 1 Introduction High-intensity exercise requires maximal or near-maximal intensity efforts resulting in rapid changes in the intramuscular metabolic profile. These changes include substrate depletion [1] and metabolite accumulation and are accompanied by muscular fatigue [2]. Exercise-induced muscle fatigue, defined as the inability of the skeletal muscle to maintain a particular tension or a given exercise intensity [3], has been a focal point of research for many decades. However, the exact mechanisms that contribute to fatigue remain poorly understood; fatigue is a complex and multifactorial phenomenon that varies depending on the type, intensity and duration of the exercise. In the particular case of high-intensity short-duration exercise, several contributing factors appear to be of particular concern to the onset of muscle fatigue, including the accumulation of potassium ions (K?) in the interstitium of the muscle cell [4], decreased release/uptake of calcium ions (Ca2?) from/ to the sarcoplasmic reticulum [5], the depletion of energy substrates, and the accumulation of metabolites within the muscle cell [6]. Metabolite accumulation has long been considered one of the factors contributing to reduced exercise performance and capacity with the accumulation of hydrogen ions (H?), which causes acidification in the muscle, associated with muscle fatigue [2, 3, 7–10]. Analyses of muscle samples have consistently shown that pH values can decline from *7.1 (at rest) to *6.5 following high-intensity exercise to exhaustion [11–13]. The role of pH and the exact physiological mechanisms leading to fatigue remain controversial and are still under intense debate and investigation. Nonetheless, there is evidence to support the following roles of muscle acidosis in fatigue development: (1) competition of H? with Ca2? ions for the troponin binding site, impairing the ability of the contractile machinery to effectively operate [14, 15]; (2) inhibition of phosphorylcreatine resynthesis [16]; and (3) inhibition of key enzymes of the glycolytic pathway, such as glycogen phosphorylase and phosphofructokinase [17]. These effects may limit the ability of the muscle cells to cope with the high energy demand during exercise and result in a reduction in intensity and/or performance or complete cessation of exercise. The human body contains well-regulated mechanisms to maintain the intracellular and extracellular pH within the physiological range, including intracellular buffers, extracellular buffers, dynamic buffering systems, as well as respiratory and renal mechanisms for pH regulation [18, 19]. During high-intensity exercise, acid–base balance in muscle is mainly regulated by intracellular, extracellular and dynamic buffering (Fig. 1). Intracellular physicochemical buffering represents the immediate defence against the accumulation of H? (...truncated)