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

“These changes include substrate depletion [1] and metabolite accumulation and are accompanied by muscular fatigue [2].”

“These changes include substrate depletion [1] and metabolite accumulation and are accompanied by muscular fatigue [2].”

“10 % [121].”

“beta-alanine level [31].”

“[4], decreased release/uptake of calcium ions (Ca) from/ to the sarcoplasmic reticulum [5], the depletion of energy substrates, and the accumulation of metabolites within the muscle cell [6].”

“In both reactions, there is a net consumption of H, which could indirectly spare blood bicarbonate and increase blood pH [113, 119], increasing lactate and H efflux from the muscle, therefore decreasing intramuscular H concentration [79, 80].”

“Importantly, the consistency of beta-alanine supplementation to improve exercise performance has been shown across individuals within the same exercise test [46, 54, 64].”

“However, it is important to highlight several individual studies, particularly those employing multiple bouts of supramaximal exercise, since exercise of this type may elicit higher muscle acidosis than continuous supramaximal exercise [85, 86].”

“This has gained some support from indirect evidence in studies with well-trained athletes who supplemented with betaalanine and showed no improvements in performance [48, 50, 59, 60].”

“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].”

“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].”

“This has led to a number of original investigations on a variety of supplements, including betaalanine, sodium bicarbonate, sodium citrate, sodium and calcium lactate, with several narrative, systematic and meta-analytic reviews published on these topics [21–27].”

“This is likely due to a high degree of inter-individual variability, which may have masked the true magnitude of effect in studies employing a solitary intervention trial [124].”

“Nonetheless, there is evidence to support the following roles of muscle acidosis in fatigue development: (1) competition of H with Ca 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) in…”

“[22] showed that sodium bicarbonate was effective at improving a 1-min all-out bout by 1.”

“Nonetheless, there is evidence to support the following roles of muscle acidosis in fatigue development: (1) competition of H with Ca 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) in…”

“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].”

“Some doubt has been raised concerning the efficacy of b-alanine on athletes since sprint-trained individuals have been shown to have an elevated buffering capacity compared with their non-trained and endurance-trained counterparts [65, 66].”

“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.”

“Incidence and severity of symptoms differ between individuals [65] and may also be influenced by dose, as McNaughton [76] reported increased gastrointestinal disturbance in all participants consuming doses above”

“by the enzyme carnosine synthase [32, 33].”

“Nonetheless, there is evidence to support the following roles of muscle acidosis in fatigue development: (1) competition of H with Ca 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) in…”

“5 following high-intensity exercise to exhaustion [11–13].”

“Indeed, there is now a growing body of evidence to support the effective use of beta-alanine among the elite athletic populations; athletes involved in 100- and 200-m freestyle swimming [67], 2000-m rowing [68–70] and 800-m running [55].”

“This has led to a number of original investigations on a variety of supplements, including betaalanine, sodium bicarbonate, sodium citrate, sodium and calcium lactate, with several narrative, systematic and meta-analytic reviews published on these topics [21–27].”

“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].”

“There is clear evidence that exercises shorter than 60 s are unaffected by beta-alanine [48–50].”

“No side effects were reported in other studies [105, 115].”

“Studies using multiple bouts of highintensity exercise have consistently shown performance improvements in excess of 8 % [57, 87, 88].”

“This has led to a number of original investigations on a variety of supplements, including betaalanine, sodium bicarbonate, sodium citrate, sodium and calcium lactate, with several narrative, systematic and meta-analytic reviews published on these topics [21–27].”

“on prolonged cycling time trial performance [53, 62], which is in line with the role of carnosine as an intramuscular buffer since fatigue during exercise of this duration is not associated with increasing acidosis.”

“In the blood, the chemical buffering system is primarily composed of bicarbonate (HCO3 ), which has the ability to bind H [20].”

“The increase in blood pH through sodium citrate supplementation facilitates a greater efflux of H and lactate from the active muscles via monocarboxylate transporter proteins that carry monocarboxylates across the cell membrane [100].”

“Studies using multiple bouts of highintensity exercise have consistently shown performance improvements in excess of 8 % [57, 87, 88].”

“In order to gain further insight into this emerging supplement, our research group investigated the acute effects of two different dosages of calcium lactate (150 and 300 mg/kg BM) on high-intensity intermittent performance in the form of three upper-body arm-crank bouts (this protocol has previously been shown to be…”

“This has led to a number of original investigations on a variety of supplements, including betaalanine, sodium bicarbonate, sodium citrate, sodium and calcium lactate, with several narrative, systematic and meta-analytic reviews published on these topics [21–27].”

“increased calcium release and reuptake from the sarcoplasmic reticulum), and excitation-contraction coupling [37, 39].”

“The lactate ingested is absorbed preferentially at the jejunum, through the sodium-coupled intestinal lactate transporter (sMCT), also known as the SLC5A8 [114–116].”

“The effects of sodium citrate on exercise have been well documented, with numerous original investigations assessing its ergogenic capacity [97–112].”

“Incidence and severity of symptoms differ between individuals [65] and may also be influenced by dose, as McNaughton [76] reported increased gastrointestinal disturbance in all participants consuming doses above”

“Several physiological functions have been attributed to carnosine in skeletal muscle, including antioxidant activity [36] and protection against protein glycation and carbonylation [37, 38].”

“Several studies have shown the efficacy of increased muscle carnosine content through beta-alanine supplementation on high-intensity exercises lasting 1–4 min; exercise performance and capacity have been improved in a variety of cycling [46, 51–54], running [55, 56], and repeated-bout upper- and lower-body protocols […”

“In addition, there is evidence to suggest that sodium bicarbonate is also beneficial to sport-specific performance in a variety of disciplines where the metabolic demands are predominantly anaerobic, such as judo, swimming, boxing and water polo [89–92].”

“83 [41, 42], making carnosine an obligatory physicochemical buffer.”

“3 mmol/L) [43, 44].”

“Several physiological functions have been attributed to carnosine in skeletal muscle, including antioxidant activity [36] and protection against protein glycation and carbonylation [37, 38].”

“This has led to a number of original investigations on a variety of supplements, including betaalanine, sodium bicarbonate, sodium citrate, sodium and calcium lactate, with several narrative, systematic and meta-analytic reviews published on these topics [21–27].”

“[84] showed a large inter-individual ergogenic response to sodium bicarbonate while also highlighting the negative impact that the associated side effects can have on performance.”

“Studies using multiple bouts of highintensity exercise have consistently shown performance improvements in excess of 8 % [57, 87, 88].”

“In addition, there is evidence to suggest that sodium bicarbonate is also beneficial to sport-specific performance in a variety of disciplines where the metabolic demands are predominantly anaerobic, such as judo, swimming, boxing and water polo [89–92].”

“5 following high-intensity exercise to exhaustion [11–13].”

“Carnosine is a cytoplasmic dipeptide abundantly found in excitable tissues, such as skeletal muscle [31], heart [34] and in some brain regions [35], although the highest concentrations of carnosine in humans are found in skeletal muscle.”

“Sodium bicarbonate supplementation has consistently caused blood alkalosis [12, 77, 78] accompanied by an increase in blood bicarbonate concentrations (for a review, see Carr et al.”

“Bicarbonate is a blood buffer that plays an important role in maintaining both extracellular and intracellular pH, despite its inability to permeate the sarcolemma [12, 74].”

“As a consequence of increased blood pH and HCO3 , there is a parallel increase in the intracellular/extracellular gradient of H, enhancing the activity of the lactate/H cotransporters [79–81], ultimately leading to a greater efflux of H and lactate out of the active muscles and into the circulation, where they are buf…”

“Once in the bloodstream, it can be taken up by several tissues, including skeletal muscle, where it is oxidised [117].”

“83 [41, 42], making carnosine an obligatory physicochemical buffer.”

“As a consequence of increased blood pH and HCO3 , there is a parallel increase in the intracellular/extracellular gradient of H, enhancing the activity of the lactate/H cotransporters [79–81], ultimately leading to a greater efflux of H and lactate out of the active muscles and into the circulation, where they are buf…”

“5 g/kg BM sodium citrate, with all incidences occurring within the first 60 min post-ingestion [103].”

“Moreover, plasma and intramuscular concentrations of L-histidine are substantially higher than beta-alanine [45].”

“Indeed, there is now a growing body of evidence to support the effective use of beta-alanine among the elite athletic populations; athletes involved in 100- and 200-m freestyle swimming [67], 2000-m rowing [68–70] and 800-m running [55].”

“5 g/kg did improve 3000-m running performance in male and female athletes [107] and 5000-m running performance in well-trained college runners [108].”

“3 g/kg BM sodium citrate on a variety of exercise protocols [97, 98, 102].”

“Carnosine is a cytoplasmic dipeptide abundantly found in excitable tissues, such as skeletal muscle [31], heart [34] and in some brain regions [35], although the highest concentrations of carnosine in humans are found in skeletal muscle.”

“No beneficial effects were shown on repeated bouts of\10 s in duration [96, 123].”

“In order to recover this equilibrium, a decrease of H in plasma occurs as well as a resultant increase in HCO3 , enhancing the extracellular buffering capacity [99].”

“3 mmol/L) [43, 44].”

“In both reactions, there is a net consumption of H, which could indirectly spare blood bicarbonate and increase blood pH [113, 119], increasing lactate and H efflux from the muscle, therefore decreasing intramuscular H concentration [79, 80].”

“In addition, there is evidence to suggest that sodium bicarbonate is also beneficial to sport-specific performance in a variety of disciplines where the metabolic demands are predominantly anaerobic, such as judo, swimming, boxing and water polo [89–92].”

“[101] showed peak values of pH and HCO3 - in blood 100–120 min following the ingestion of 0.”

“Both groups showed a similar improvement in total work done (*3 %) following supplementation [58], indicating that beta-alanine is equally efficient in untrained and athletic populations.”

“The effects of sodium citrate on exercise have been well documented, with numerous original investigations assessing its ergogenic capacity [97–112].”

“In light of the current evidence suggesting no major side effects other than paraesthesia during supplementation of 2–16 weeks in duration [46, 47, 73], athletes can safely”

“Several strategies have been adopted in order to minimise the discomfort associated with acute sodium bicarbonate supplementation, including multiday ingestion [94], chronic administration [95] and split-dose protocols [54, 96].”

“The effects of sodium citrate on exercise have been well documented, with numerous original investigations assessing its ergogenic capacity [97–112].”

“Several studies have shown the efficacy of increased muscle carnosine content through beta-alanine supplementation on high-intensity exercises lasting 1–4 min; exercise performance and capacity have been improved in a variety of cycling [46, 51–54], running [55, 56], and repeated-bout upper- and lower-body protocols […”

“As a consequence of increased blood pH and HCO3 , there is a parallel increase in the intracellular/extracellular gradient of H, enhancing the activity of the lactate/H cotransporters [79–81], ultimately leading to a greater efflux of H and lactate out of the active muscles and into the circulation, where they are buf…”

“3 g/kg BM sodium citrate on a variety of exercise protocols [97, 98, 102].”

“Alternatively, lactate can be taken up by hepatocytes, where it is converted into glucose [118].”

“Sodium bicarbonate supplementation has consistently caused blood alkalosis [12, 77, 78] accompanied by an increase in blood bicarbonate concentrations (for a review, see Carr et al.”

“Lactate supplementation has been suggested as a strategy capable of increasing extracellular buffering capacity [105, 113].”

“Repeated-bout high-intensity exercise may induce a greater severity of muscle acidosis, particularly in the latter bouts [86], leading to several studies that have investigated the effects of co-supplementation of beta-alanine and sodium bicarbonate on exercise of this type.”

“Furthermore, sodium citrate was equally unable to improve repeated 60-s sprints in moderately active males [111].”

“performance test, which results in even greater acidosis than leg cycling exercises [122], and theoretically would make our protocol more sensitive to detect the effects of calcium lactate ingestion on performance.”

“However, further research from this group has yielded contrasting evidence with no effect of an equivalent dose on 5-km time trial in trained male runners [109] or 1500-m performance in trained female middledistance runners [110] following 0.”

“3 g/kg BM sodium citrate on a variety of exercise protocols [97, 98, 102].”

“The only reported side effects from sodium/calcium lactate supplementation resulted from a recent study conducted in our laboratory [120].”

“Alternative synthesis from pathways in the gut [29] and kidney [30] might also account for some endogenous production of beta-alanine, although the very low fasting concentrations in blood [31] suggest that endogenous synthesis is rather low and does not constitute a significant source of beta-alanine for the tissues.”

“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].”

“The lactate ingested is absorbed preferentially at the jejunum, through the sodium-coupled intestinal lactate transporter (sMCT), also known as the SLC5A8 [114–116].”

“This has led to a number of original investigations on a variety of supplements, including betaalanine, sodium bicarbonate, sodium citrate, sodium and calcium lactate, with several narrative, systematic and meta-analytic reviews published on these topics [21–27].”

“Ingestion of sodium bicarbonate results in the release of HCO3 - within the stomach, which is swiftly neutralised by the H found in the stomach’s gastric juice, which leads to increased CO2 production, and may cause abdominal pain, flatulence, nausea, diarrhoea and even vomiting [93].”

“[4], decreased release/uptake of calcium ions (Ca) from/ to the sarcoplasmic reticulum [5], the depletion of energy substrates, and the accumulation of metabolites within the muscle cell [6].”

“Mechanism Acts as an extracellular (blood) buffer, aiding intracellular pH regulation by raising the extracellular pH, and HCO3concentrations (Katz et al., 1984; Lancha Junior et al., 2015).”

“Beta-alanine is the rate-limiting precursor to carnosine, an endogenous intracellular (muscle) buffer, and one of the immediate defenses against the accumulation of protons in the contracting musculature during exercise (Lancha Junior et al., 2015).”

“(cid:129) Interactions with the concurrent use of other performance supplements require consideration; at present, this has been investigated in relation to use with caffeine with unclear results (Burke, 2017). β -Alanine β -Alanineis arate-limiting precursor tocarnosine,an endogenous intracellular (muscle) pH buffer…”