Accelerated CMC workflows to enable speed to clinic in the COVID-19 era: A multi-company view from the biopharmaceutical industry.

The COVID-19 pandemic has placed unprecedented pressure on biopharmaceutical companies to develop efficacious preventative and therapeutic treatments, which is unlikely to abate in the coming years. The importance of fast progress to clinical evaluation for treatments, which tackle unmet medical needs puts strain on traditional product development timelines, which can take years from start to finish. Although previous work has been successful in reducing phase 1 timelines for recombinant antibodies, through utilization of the latest technological advances and acceptance of greater business risk or costs, substantially faster development is likely achievable without increased risk to patients during initial clinical evaluation. To optimize lessons learned from the pandemic and maximize multi-stakeholder (i.e., patients, clinicians, companies, regulatory agencies) benefit, we conducted an industry wide benchmarking survey in September/October 2021. The aims of this survey were to: (i) benchmark current technical practices of key process and product development activities related to manufacturing of therapeutic proteins, (ii) understand the impact of changes implemented in COVID-19 accelerated Ab programs, and whether any such changes can be retained as part of sustainable long-term business practices and (iii) understand whether any accelerative action(s) taken have (negatively) impacted the wider development process. This article provides an in-depth analysis of this data, ultimately highlighting an industry perspective of how biopharmaceutical companies can sustainably adopt new approaches to therapeutic protein development and production.

A critical review of citrulline malate supplementation and exercise performance.

As a nitric oxide (NO) enhancer, citrulline malate (CM) has recently been touted as a potential ergogenic aid to both resistance and high-intensity exercise performance, as well as the recovery of muscular performance. The mechanism has been associated with enhanced blood flow to active musculature, however, it might be more far-reaching as either ammonia homeostasis could be improved, or ATP production could be increased via greater availability of malate. Moreover, CM might improve muscle recovery via increased nutrient delivery and/or removal of waste products. To date, a single acute 8 g dose of CM on either resistance exercise performance or cycling has been the most common approach, which has produced equivocal results. This makes the effectiveness of CM to improve exercise performance difficult to determine. Reasons for the disparity in conclusions seem to be due to methodological discrepancies such as the testing protocols and the associated test-retest reliability, dosing strategy (i.e., amount and timing), and the recent discovery of quality control issues with some manufacturers stated (i.e., citrulline:malate ratios). Further exploration of the optimal dose is therefore required including quantification of the bioavailability of NO, citrulline, and malate following ingestion of a range of CM doses. Similarly, further well-controlled studies using highly repeatable exercise protocols with a large aerobic component are required to assess the mechanisms associated with this supplement appropriately. Until such studies are completed, the efficacy of CM supplementation to improve exercise performance remains ambiguous.

The Effect of Acute Caffeine Ingestion on Cognitive Dual Task Performance during Assessment of Static and Dynamic Balance in Older Adults.

The present work aimed to evaluate the effect of 3 mg·kg-1 caffeine consumption on the standing and dynamic balance performance of older adults and sought to establish if caffeine ingestion can modulate the influence of a cognitive dual task on balance performance. Twelve apparently healthy participants (8 females) aged >65 years (72 ± 3.7 years) completed the study. Bipedal postural sway, four square step test, timed up and go, Y-balance (anterior reach only) and force-time characteristics of sit-to-stand performance were used to assess standing and dynamic balance. Attention and working memory were assessed using a serial 3s and 7s subtraction task during seated rest and completion of the bipedal standing assessment and Y-balance test. This battery of assessments was completed on two separate occasions, once following the consumption of a non-ergogenic placebo and again following the consumption of 3 mg·kg-1 caffeine. The administration of treatments was randomised, counterbalanced and double-blind. Caffeine reduced performance in the bipedal standing balance assessments, evidenced by an increase in COPML, COPPath, COPVelocity. Performance during the dynamic balance tests was unaffected, other than rate of force development during the sit-to-stand, which was improved following caffeine ingestion. The introduction of a cognitive dual task had either limited effects, or improved facets of bipedal standing balance, whilst performance during the dynamic balance task was significantly reduced. In both balance assessments, there was evidence for a reduction in the performance of the cognitive task when both the balance and cognitive tests were performed simultaneously, with this effect not modulated by caffeine consumption. These findings refute the idea that caffeine ingestion may have positive effects on balance performance. However, despite a caffeine-induced reduction in bipedal standing balance, it is unlikely that caffeine ingestion would exacerbate fall risk given the limited effects in the dynamic balance tests. Future work should establish if these effects are generalisable to older frail participants and if caffeine can modulate the detrimental effects of an acute exercise bout on balance performance.

Lower tumorigenesis without life extension in rats receiving lifelong deep ocean minerals.

Naturally occurring tumor in animals receiving high minerals from deep oceans (DOM: hardness 600 mg/L) from 6 months of age until natural death was firstly assessed in 200 Sprague Dawley rats, randomized into four groups: Control (C), DOM (D), Fructose (F), and Fructose + DOM (FD). Fructose drink contained 11% fructose. Tumor incidence (necropsy at death) in the D group was ~40% lower than that in the C group (P < .05), together with lower body mass gain and greater locomotive activity during their initial 18 months (P < .05) but not during later life. X-ray image analysis on abnormal solid tissue among survivors at 18 and 24 months of age confirms a similar trend, exhibiting ~50% and ~65% lower tumor incidence than the C and F groups, respectively. Reduced-to-oxidized glutathione ratio (GSH/GSSG) declined with age for the first three quarters of life on all groups (P < .05), followed by a resurgence during end-life among survivors at 24 months. This resurgence is markedly associated with lower tumor expansion but unrelated with DOM supplementation. Our results demonstrate valuable application of minerals and trace elements from deep oceans, as a vastly available natural source, on tumor suppression during normal aging.

The Efficacy of Administering Fruit-Derived Polyphenols to Improve Health Biomarkers, Exercise Performance and Related Physiological Responses.

Polyphenols are secondary metabolites involved in a myriad of critical processes in plants. Over recent decades, special attention has been paid to the anti-oxidative role of fruit-derived polyphenols in the human diet, with evidence supporting the contribution of polyphenols in the prevention of numerous non-communicable disease outcomes. However, due to the low concentration in biological fluids in vivo, the antioxidant properties of polyphenols seem to be related to an enhanced endogenous antioxidant capacity induced via signaling through the nuclear respiratory factor 2 pathway. Polyphenols also seem to possess anti-inflammatory and antioxidant properties and have been shown to enhance vascular function via nitric oxide mediated mechanisms. Consequently, there is rationale to support fruit-derived polyphenol supplementation to enhance exercise performance, possibly via improved muscle perfusion. Fruit-derived polyphenol supplementation in exercise studies have included a variety of fruits, e.g., New Zealand blackcurrant, pomegranate, and cherry, in the form of extracts (multicomponent or purified), juices and infusions to varying degrees of benefit. For example, research has yet to link the health-related benefits of black elderberry (Sambucus nigra L.) ingestion to exercise performance in spite of the purported health benefits associated with black elderberry provision in vitro and in vivo models, which has been attributed to their high antioxidant capacity and polyphenol content. This review summarizes the existing evidence supporting a beneficial effect of fruit-derived polyphenols on various biological processes and outlines the potential for black elderberry ingestion to improve nitric oxide production, exercise performance, and the associated physiological responses before-, during- and post-exercise.

Post-exercise Supplementation of Sodium Bicarbonate Improves Acid Base Balance Recovery and Subsequent High-Intensity Boxing Specific Performance.

The aim of this study was to assess the effects of post-exercise sodium bicarbonate (NaHCO3) ingestion (0.3 g.kg-1 body mass) on the recovery of acid-base balance (pH, HCO 3 - , and the SID) and subsequent exercise performance in elite boxers. Seven elite male professional boxers performed an initial bout of exhaustive exercise comprising of a boxing specific high-intensity interval running (HIIR) protocol, followed by a high-intensity run to volitional exhaustion (TLIM1). A 75 min passive recovery then ensued, whereby after 10 min recovery, participants ingested either 0.3 g.kg-1 body mass NaHCO3, or 0.1 g.kg-1 body mass sodium chloride (PLA). Solutions were taste matched and administered double-blind. Participants then completed a boxing specific punch combination protocol, followed by a second high-intensity run to volitional exhaustion (TLIM2). Both initial bouts of TLIM1 were well matched between PLA and NaHCO3 (ICC; r = 0.94, p = 0.002). The change in performance from TLIM1 to TLIM2 was greater following NaHCO3 compared to PLA (+164 ± 90 vs. +73 ± 78 sec; p = 0.02, CI = 45.1, 428.8, g = 1.0). Following ingestion of NaHCO3, pH was greater prior to TLIM2 by 0.11 ± 0.02 units (1.4%) (p < 0.001, CI = 0.09, 0.13, g = 3.4), whilst HCO 3 - was greater by 8.8 ± 1.5 mmol.l-1 (26.3%) compared to PLA (p < 0.001, CI = 7.3, 10.2, g = 5.1). The current study suggests that these significant increases in acid base balance during post-exercise recovery facilitated the improvement in the subsequent bout of exercise. Future research should continue to explore the role of NaHCO3 supplementation as a recovery aid in boxing and other combat sports.

The Influence of Caffeine Expectancies on Simulated Soccer Performance in Recreational Individuals.

Caffeine (CAF) has been reported to improve various facets associated with successful soccer play, including gross motor skill performance, endurance capacity and cognition. These benefits are primarily attributed to pharmacological mechanisms. However, evidence assessing CAF's overall effects on soccer performance are sparse with no studies accounting for CAF's potential psychological impact. Therefore, the aim of this study was to assess CAF's psychological vs. pharmacological influence on various facets of simulated soccer performance. Utilising a double-dissociation design, eight male recreational soccer players (age: 22 ± 5 years, body mass: 78 ± 16 kg, height: 178 ± 6 cm) consumed CAF (3 mg/kg/body mass) or placebo (PLA) capsules, 60 minutes prior to performing the Loughborough Intermittent Shuttle Test (LIST) interspersed with a collection of ratings of perceived exertion (RPE), blood glucose and lactate, heart rate and performing the Loughborough Soccer Passing Test (LSPT). Whole-body dynamic reaction time (DRT) was assessed pre- and post- LIST, and endurance capacity (TLIM) post, time-matched LIST. Statistical analysis was performed using IBM SPSS (v24) whilst subjective perceptions were explored using template analysis. Mean TLIM was greatest (p < 0.001) for synergism (given CAF/told CAF) (672 ± 132 s) vs. placebo (given PLA/told PLA) (533 ± 79 s). However, when isolated, TLIM was greater (p = 0.012) for CAF psychology (given PLA/told CAF) (623 ± 117 s) vs. pharmacology (given CAF/told PLA) (578 ± 99 s), potentially, via reduced RPE. Although DRT performance was greater (p = 0.024) post-ingestion (+5 hits) and post-exercise (+7 hits) for pharmacology vs. placebo, psychology and synergism appeared to improve LSPT performance vs. pharmacology. Interestingly, positive perceptions during psychology inhibited LSPT and DRT performance via potential CAF over-reliance, with the opposite occurring following negative perceptions. The benefits associated with CAF expectancies may better suit tasks that entail lesser cognitive-/skill-specific attributes but greater gross motor function and this is likely due to reduced RPE. In isolation, these effects appear greater vs. CAF pharmacology. However, an additive benefit may be observed after combining expectancy with CAF pharmacology (i.e. synergism).

Oral Ingestion of Deep Ocean Minerals Increases High-Intensity Intermittent Running Capacity in Soccer Players after Short-Term Post-Exercise Recovery: A Double-Blind, Placebo-Controlled Crossover Trial.

This study examined whether deep ocean mineral (DOM) supplementation improved high-intensity intermittent running capacity after short-term recovery from an initial bout of prolonged high-intensity running in thermoneutral environmental conditions. Nine healthy recreational male soccer players (age: 22 ± 1 y; stature: 181 ± 5 cm; and body mass 80 ± 11 kg) completed a graded incremental test to ascertain peak oxygen uptake (V·O2PEAK), two familiarisation trials, and two experimental trials following a double-blind, repeated measures, crossover and counterbalanced design. All trials were separated by seven days and at ambient room temperature (i.e., 20 °C). During the 2 h recovery period after the initial ~60 min running at 75% V·O2PEAK, participants were provided with 1.38 ± 0.51 L of either deep ocean mineral water (DOM) or a taste-matched placebo (PLA), both mixed with 6% sucrose. DOM increased high-intensity running capacity by ~25% compared to PLA. There were no differences between DOM and PLA for blood lactate concentration, blood glucose concentration, or urine osmolality. The minerals and trace elements within DOM, either individually or synergistically, appear to have augmented high-intensity running capacity in healthy, recreationally active male soccer players after short-term recovery from an initial bout of prolonged, high-intensity running in thermoneutral environmental conditions.

Deep Ocean Minerals Minimize Eccentric Exercise-Induced Inflammatory Response of Rat Skeletal Muscle.

Background: We have previously shown an accelerated recovery from muscle fatigue in men challenged by prolonged exercise after oral deep ocean minerals (DOM) supplementation. Here, we hypothesized a decrease in eccentric exercise-induced muscle inflammation in rats regularly consuming DOM-containing drinks (hardness 600 mg/L and fructose 11%). Methods: Forty-seven male Sprague Dawley rats were randomized into 4 groups: Control (C, N = 12), Fructose (F, N = 12), Fructose+Exercise (FE, N = 12), and Fructose+Exercise+DOM (FED, N = 11). Since fructose is a commonly used ingredient in beverages, 11% of fructose was added as a vehicle of the study. Soleus muscles of rats were analyzed 24 h after an acute bout of downhill running following 9 weeks of DOM supplementation. Results: Leukocyte infiltration and TNF-α mRNA of muscle in the FE group were 5 times and 4 times greater the F group, respectively, (P < 0.05). Both markers in the FED group were significantly lower than those in the FE group (P < 0.05). IL-10 mRNA of muscle in the F group was >eight fold greater than the C group (P < 0.05). The reduced glutathione (GSH) of muscle in the F group was 34% lower than that in the C group (P < 0.05). However, GSH levels were similar for the C and FED groups. Conclusion: Prolonged fructose supplementation modulates inflammatory balance of rat skeletal muscle. The results of the study suggest that DOM can minimize eccentric exercise-induced inflammatory cytokine responses in rat skeletal muscle.

An exercise-induced improvement in isolated skeletal muscle contractility does not affect the performance-enhancing benefit of 70†µmol†l-1 caffeine treatment.

This study aimed to examine the effects of exercise-induced increases in skeletal muscle contractile performance on isolated skeletal muscle caffeine sensitivity in mice. CD1 mice (n=28; 30 weeks old) either served as controls or underwent 8 weeks of voluntary wheel running. Following the treatment intervention, whole soleus (SOL) or a section of the costal diaphragm (DIA) was isolated from each mouse and tested to determine the effect of 70 µmol l-1 caffeine on work loop power output. Although caffeine elicited a significant increase in power of both the SOL and the DIA relative to levels in a non-caffeine-treated control, the effect was not different between the experimental groups, despite the muscles of the trained group producing significantly greater muscle power. There was no significant relationship between training volume or baseline work loop power and the caffeine response. These results indicate that an exercise-induced increase in muscle performance did not influence the performance-enhancing effects of caffeine.

The effects of 8†weeks voluntary wheel running on the contractile performance of isolated locomotory (soleus) and respiratory (diaphragm) skeletal muscle during early ageing.

Decreased skeletal muscle performance with increasing age is strongly associated with reduced mobility and quality of life. Increased physical activity is a widely prescribed method of reducing the detrimental effects of ageing on skeletal muscle contractility. The present study used isometric and work loop testing protocols to uniquely investigate the effects of 8 weeks of voluntary wheel running on the contractile performance of isolated dynapenic soleus and diaphragm muscles of 38-week-old CD1 mice. When compared with untrained controls, voluntary wheel running induced significant improvements in maximal isometric stress and work loop power, a reduced resistance to fatigue, but greater cumulative work during fatiguing work loop contractions in isolated muscle. These differences occurred without appreciable changes in lactate dehydrogenase, citrate synthase, sarco-endoplasmic reticulum ATPase or myosin heavy chain expression synonymous with this form of training in younger rodent models. Despite the given improvement in contractile performance, the average running distance significantly declined over the course of the training period, indicating that this form of training may not be sufficient to fully counteract the longer-term ageing-induced decline in skeletal muscle contractile performance. Although these results indicate that regular low-intensity physical activity may be beneficial in offsetting the age-related decline in skeletal muscle contractility, future work focusing on the maintenance of a healthy body mass with increasing age and its effects on myosin-actin cross-bridge kinetics and Ca2+ handling is needed to clarify the mechanisms causing the improved contractile performance in trained dynapenic skeletal muscle.

Ingestion of Sodium Bicarbonate (NaHCO3) Following a Fatiguing Bout of Exercise Accelerates Postexercise Acid-Base Balance Recovery and Improves Subsequent High-Intensity Cycling Time to Exhaustion.

This study evaluated the ingestion of sodium bicarbonate (NaHCO3) on postexercise acid-base balance recovery kinetics and subsequent high-intensity cycling time to exhaustion. In a counterbalanced, crossover design, nine healthy and active males (age: 23 ± 2 years, height: 179 ± 5 cm, body mass: 74 ± 9 kg, peak mean minute power (Wpeak) 256 ± 45 W, peak oxygen uptake (V̇O2peak) 46 ± 8 ml.kg-1.min-1) performed a graded incremental exercise test, two familiarization and two experimental trials. Experimental trials consisted of cycling to volitional exhaustion (TLIM1) at 100% WPEAK on two occasions (TLIM1 and TLIM2) interspersed by a 90 min passive recovery period. Using a double-blind approach, 30 min into a 90 min recovery period participants ingested either 0.3 g.kg-1 body mass sodium bicarbonate (NaHCO3) or a placebo (PLA) containing 0.1 g.kg-1 body mass sodium chloride (NaCl) mixed with 4 ml.kg-1 tap water and 1 ml.kg-1 orange squash. The mean differences between TLIM2 and TLIM1 was larger for PLA compared with NaHCO3 (-53 ± 53 vs. -20 ± 48 s; p = .008, d = 0.7, CI =-0.3, 1.6), indicating superior subsequent exercise time to exhaustion following NaHCO3. Blood lactate [Bla-] was similar between treatments post TLIM1, but greater for NaHCO3 post TLIM2 and 5 min post TLIM2. Ingestion of NaHCO3 induced marked increases (p < .01) in both blood pH (+0.07 ± 0.02, d = 2.6, CI = 1.2, 3.7) and bicarbonate ion concentration [HCO3-] (+6.8 ± 1.6 mmo.l-1, d = 3.4, CI = 1.8, 4.7) compared with the PLA treatment, before TLIM2. It is likely both the acceleration of recovery, and the marked increases of acid-base after TLIM1 contributed to greater TLIM2 performance compared with the PLA condition.

Deep Ocean Mineral Supplementation Enhances the Cerebral Hemodynamic Response during Exercise and Decreases Inflammation Postexercise in Men at Two Age Levels.

Background: Previous studies have consistently shown that oral supplementation of deep ocean minerals (DOM) improves vascular function in animals and enhances muscle power output in exercising humans. Purpose: To examine the effects of DOM supplementation on the cerebral hemodynamic response during physical exertion in young and middle-aged men. Design: Double-blind placebo-controlled crossover studies were conducted in young (N = 12, aged 21.2 ± 0.4 years) and middle-aged men (N = 9, aged 46.8 ± 1.4 years). The counter-balanced trials of DOM and Placebo were separated by a 2-week washout period. DOM and Placebo were orally supplemented in drinks before, during, and after cycling exercise. DOM comprises desalinated minerals and trace elements from seawater collected ~618 m below the earth's surface. Methods: Cerebral hemodynamic response (tissue hemoglobin) was measured during cycling at 75% VO2max using near infrared spectroscopy (NIRS). Results: Cycling time to exhaustion at 75% VO2max and the associated plasma lactate response were similar between the Placebo and DOM trials for both age groups. In contrast, DOM significantly elevated cerebral hemoglobin levels in young men and, to a greater extent, in middle-aged men compared with Placebo. An increased neutrophil to lymphocyte ratio (NLR) was observed in middle-aged men, 2 h after exhaustive cycling, but was attenuated by DOM. Conclusion: Our data suggest that minerals and trace elements from deep oceans possess great promise in developing supplements to increase the cerebral hemodynamic response against a physical challenge and during post-exercise recovery for middle-aged men.

The effect of high-intensity cycling training on postural sway during standing under rested and fatigued conditions in healthy young adults.

PURPOSE: The purpose of this study was to investigate whether high-intensity cycling training leads to adapted responses of balance performance in response to exercise-induced muscle fatigue. METHODS: Eighteen healthy adults were assigned to either 3-weeks (n = 8, age 20.1 ± 2.6 years, height 177 ± 5 cm, mass 73.6 ± 5.1 kg) or 6-weeks (n = 10, age 24.3 ± 5.8 years, height 179 ± 6 cm, mass 81.0 ± 15.8 kg) of high-intensity training (HIT) on a cycle ergometer. The centre of pressure (COP) displacement in the anteroposterior (COPAP) direction and COP path length (COPL) were measured before and after the first and final high-intensity training sessions. RESULTS: Pre-training, exercise-induced fatigue elicited an increase in COPAP (3-weeks; p = 0.001, 6-weeks; p = 0.001) and COPL (3-weeks; p = 0.002, 6-weeks; p = 0.001) returning to pre-exercise levels within 10-min of recovery. Following 3-weeks of training, significant increases in COPAP (p = 0.001) and COPL (p = 0.002) were observed post-fatigue, returning to pre-exercise levels after 15-min of recovery. After 6-weeks of training no significant increases in sway (COPAP; p = 0.212, COPL; p = 0.998) were observed following exercise-induced fatigue. CONCLUSIONS: In summary, 3 weeks of HIT resulted in longer recovery times following fatigue compared to pre-training assessments. After 6 weeks of HIT, postural sway following fatigue was attenuated. These results indicate that HIT could be included in injury prevention programmes, however, caution should be taken during early stages of the overreaching process.

Evaluating the effects of caffeine and sodium bicarbonate, ingested individually or in combination, and a taste-matched placebo on high-intensity cycling capacity in healthy males.

This study evaluated the effects of ingesting sodium bicarbonate (NaHCO3) or caffeine individually or in combination on high-intensity cycling capacity. In a counterbalanced, crossover design, 13 healthy, noncycling trained males (age: 21 ± 3 years, height: 178 ± 6 cm, body mass: 76 ± 12 kg, peak power output (Wpeak): 230 ± 34 W, peak oxygen uptake: 46 ± 8 mL·kg(-1)·min(-1)) performed a graded incremental exercise test, 2 familiarisation trials, and 4 experimental trials. Trials consisted of cycling to volitional exhaustion at 100% Wpeak (TLIM) 60 min after ingesting a solution containing either (i) 0.3 g·kg(-1) body mass sodium bicarbonate (BIC), (ii) 5 mg·kg(-1) body mass caffeine plus 0.1 g·kg(-1) body mass sodium chloride (CAF), (iii) 0.3 g·kg(-1) body mass sodium bicarbonate plus 5 mg·kg(-1) body mass caffeine (BIC-CAF), or (iv) 0.1 g·kg(-1) body mass sodium chloride (PLA). Experimental solutions were administered double-blind. Pre-exercise, at the end of exercise, and 5-min postexercise blood pH, base excess, and bicarbonate ion concentration ([HCO3(-)]) were significantly elevated for BIC and BIC-CAF compared with CAF and PLA. TLIM (median; interquartile range) was significantly greater for CAF (399; 350-415 s; P = 0.039; r = 0.6) and BIC-CAF (367; 333-402 s; P = 0.028; r = 0.6) compared with BIC (313: 284-448 s) although not compared with PLA (358; 290-433 s; P = 0.249, r = 0.3 and P = 0.099 and r = 0.5, respectively). There were no differences between PLA and BIC (P = 0.196; r = 0.4) or between CAF and BIC-CAF (P = 0.753; r = 0.1). Relatively large inter- and intra-individual variation was observed when comparing treatments and therefore an individual approach to supplementation appears warranted.

Expectancy of ergogenicity from sodium bicarbonate ingestion increases high-intensity cycling capacity.

This study examined whether expectancy of ergogenicity of a commonly used nutritional supplement (sodium bicarbonate; NaHCO3) influenced subsequent high-intensity cycling capacity. Eight recreationally active males (age, 21 ± 1 years; body mass, 75 ± 8 kg; height, 178 ± 4 cm; WPEAK = 205 ± 22 W) performed a graded incremental test to assess peak power output (WPEAK), one familiarisation trial and two experimental trials. Experimental trials consisted of cycling at 100% WPEAK to volitional exhaustion (TLIM) 60 min after ingesting either a placebo (PLA: 0.1 g·kg(-1) sodium chloride (NaCl), 4 mL·kg(-1) tap water, and 1 mL·kg(-1) squash) or a sham placebo (SHAM: 0.1 g·kg(-1) NaCl, 4 mL·kg(-1) carbonated water, and 1 mL·kg(-1) squash). SHAM aimed to replicate the previously reported symptoms of gut fullness (GF) and abdominal discomfort (AD) associated with NaHCO3 ingestion. Treatments were administered double blind and accompanied by written scripts designed to remain neutral (PLA) or induce expectancy of ergogenicity (SHAM). After SHAM mean TLIM increased by 9.5% compared to PLA (461 ± 148 s versus 421 ± 150 s; P = 0.048, d = 0.3). Ratings of GF and AD were mild but ~1 unit higher post-ingestion for SHAM. After 3 min TLIM overall ratings of perceived exertion were 1.4 ± 1.3 units lower for SHAM compared to PLA (P = 0.020, d = 0.6). There were no differences between treatments for blood lactate, blood glucose, or heart rate. In summary, ergogenicity after NaHCO3 ingestion may be influenced by expectancy, which mediates perception of effort during subsequent exercise. The observed ergogenicity with SHAM did not affect our measures of cardiorespiratory physiology or metabolic flux.

Does a physiological concentration of taurine increase acute muscle power output, time to fatigue, and recovery in isolated mouse soleus (slow) muscle with or without the presence of caffeine?

High concentrations of caffeine and taurine are key constituents of many ergogenic supplements ingested acutely to provide legal enhancements in athlete performance. Despite this, there is little evidence supporting the claims for the performance-enhancing effects of acute taurine supplementation. In-vitro models have demonstrated that a caffeine-induced muscle contracture can be further potentiated when combined with a high concentration of taurine. However, the high concentrations of caffeine used in previous research would be toxic for human consumption. Therefore, this study aimed to investigate whether a physiological dose of caffeine and taurine would directly potentiate skeletal muscle performance. Isolated mouse soleus muscle was used to examine the effects of physiological taurine (TAU), caffeine (CAF), and taurine-caffeine combined (TC) on (i) acute muscle power output; (ii) time to fatigue; and (iii) recovery from fatigue, compared with the untreated controls (CON). Treatment with TAU failed to elicit any significant difference in the measured parameters. Treatment with TC resulted in a significant increase in acute muscle power output and faster time to fatigue. The ergogenic benefit posed by TC was not different from the effects of caffeine alone, suggesting no acute ergogenic benefit of taurine.

The effects of sodium bicarbonate (NaHCO3) ingestion on high intensity cycling capacity.

Ten healthy, non-cycling trained males (age: 21.2 ± 2.2 years, body mass: 75.9 ± 13.4 kg, height: 178 ± 6 cm, [Vdot]O2PEAK: 46 ± 10 ml · kg(-1) · min(-1)) performed a graded incremental exercise test, two familiarisation trials and six experimental trials. Experimental trials consisted of cycling to volitional exhaustion at 100%, 110% and 120% WPEAK, 60 min after ingesting either 0.3 g · kg(-1) body mass sodium bicarbonate (NaHCO3) or 0.1 g · kg(-1) body mass sodium chloride (placebo). NaHCO3 ingestion increased cycling capacity by 17% at 100% WPEAK (327 vs. 383 s; P = 0.02) although not at 110% WPEAK (249 vs. 254 s; P = 0.66) or 120% WPEAK (170 vs. 175 s; P = 0.60; placebo and NaHCO3 respectively). Heart rate (P = 0.02), blood lactate (P = 0.001), pH (P < 0.001), [HCO3 (-)], (P < 0.001), and base excess (P < 0.001) were greater in all NaHCO3 trials. NaHCO3 attenuated localised ratings of perceived exertion (RPEL) to a greater extent than placebo only at 100% WPEAK (P < 0.02). Ratings of abdominal discomfort and gut fullness were mild but higher for NaHCO3. NaHCO3 ingestion significantly improves continuous constant load cycling at 100% WPEAK due to, in part, attenuation of RPEL.