Whole-Blood and Peripheral Mononuclear Cell Transcriptional Response to Prolonged Altitude Exposure in Well-Trained Runners.

BACKGROUND: Recombinant human erythropoietin (rHuEpo) abuse by athletes threatens the integrity of sport. Due to the overlap in physiological response to rHuEpo and altitude exposure, it remains difficult to differentiate changes in hematological variables caused by rHuEpo or altitude, and therefore, other molecular methods to enhance anti-doping should be explored. OBJECTIVE: To identify the hematological and transcriptomic response to prolonged altitude exposure typical of practices used by elite athletes. DESIGN: Longitudinal study. SETTING: University of Cape Town and Altitude Training Centre in Ethiopia. PARTICIPANTS AND INTERVENTION: Fourteen well-trained athletes sojourned to an altitude training camp in Sululta, Ethiopia (∼2400-2500 m above sea level) for 27 days. Blood samples were taken before arrival, 24 hours, and 9, 16, and 24 days after arrival at altitude in addition to 24 hours and 6, 13, and 27 days upon return to sea level. MAIN OUTCOME MEASURES: Blood samples were analyzed for hemoglobin concentration, hematocrit, and reticulocyte percentage. The transcriptomic response in whole blood and peripheral blood mononuclear cells (PBMC) were analyzed using gene expression microarrays. RESULTS: A unique set of 29 and 10 genes were identified to be commonly expressed at every altitude time point in whole blood and PBMC, respectively. There were no genes identified upon return to sea level in whole blood, and only one gene within PBMC. CONCLUSIONS: The current study has identified a series of unique genes that can now be integrated with genes previously validated for rHuEpo abuse, thereby enabling the differentiation of rHuEpo from altitude exposure.

Metabolomic Profiling of Recombinant Erythropoietin (rHuEpo) in Trained Caucasian Athletes.

OBJECTIVE: Recombinant human erythropoietin (rHuEpo) is prohibited by the World Anti-Doping Agency but remains the drug of choice for many cheating athletes wishing to evade detection using current methods. The aim of this study was to identify a robust metabolomics signature of rHuEpo using an untargeted approach in blood (plasma and serum) and urine. DESIGN: Longitudinal study. SETTING: University of Glasgow. PARTICIPANTS: Eighteen male participants regularly engaged in predominantly endurance-based activities, such as running, cycling, swimming, triathlon, and team sports, were recruited. INTERVENTIONS: Each participant received 50 IU·kg -1 body mass of rHuEpo subcutaneously every 2 days for 4 weeks. Samples were collected at baseline, during rHuEpo administration (over 4 weeks) and after rHuEpo administration (week 7-10). The samples were analyzed using hydrophilic interaction liquid chromatography mass spectrometry. MAIN OUTCOME MEASURES: Significant metabolic signatures of rHuEpo administration were identified in all biofluids tested in this study. RESULTS: Regarding metabolomics data, 488 plasma metabolites, 694 serum metabolites, and 1628 urinary metabolites were identified. Reproducible signatures of rHuEpo administration across all biofluids included alterations of pyrimidine metabolism (orotate and dihydroorotate) and acyl-carnitines (palmitoyl-carnitine and elaidic carnitine), metabolic pathways that are associated with erythropoiesis or erythrocyte membrane function, respectively. CONCLUSIONS: Preliminary metabolic signatures of rHuEpo administration were identified. Future studies will be required to validate these encouraging results in independent cohorts and with orthogonal techniques, such as integration of our data with signatures derived from other "omics" analyses of rHuEpo administration (eg, transcriptomics).

Altitude Training and Recombinant Human Erythropoietin: Considerations for Doping Detection.

The benefit of training at altitude to enhance exercise performance remains equivocal although the most widely accepted approach is one where the athletes live and perform lower-intensity running at approximately 2300 m with high-intensity training at approximately 1250 m. The idea is that this method maintains maximal augmentations in total hemoglobin mass while reducing the performance impairment of high-intensity sessions performed at moderate altitude and thus preventing any detraining that can occur when athletes live and train at moderate altitude. This training regimen, however, is not universally accepted and some argue that the performance enhancement is due to placebo and training camp effects. Altitude training may affect an athlete's hematological parameters in ways similar to those observed following blood doping. Current methods of detection appear insufficient to differentiate between altitude training and blood doping making the interpretation of an athlete's biological passport difficult. Further research is required to determine the optimal method for altitude training and to enhance current detection methods to be able to differentiate better blood doping and altitude exposure.

The Performance Effects of Microdose Recombinant Human Erythropoietin Administration and Carbon Monoxide Rebreathing.

Frequent, low doses of recombinant human erythropoietin (rHuEpo) have been shown to increase the oxygen carrying capacity of an athlete and enhance endurance performance, although its effect on repeated sprint ability (RSA) remains unknown. If the mechanisms behind improved RSA performance reside within the augmented O2 carrying capacity, then carbon monoxide (CO) inhalation should inhibit RSA. Purpose: The aim of this study was to assess the effects on maximal oxygen uptake (V˙O2max) and RSA of two interventions known to differentially influence blood oxygen carrying capacity. Methods: Fourteen endurance-trained individuals were administered microdoses of rHuEpo (20-40 IUkg) or placebo twice per week for 7 wk using a randomized, crossover design. V˙O2max and RSA were measured at baseline and after rHuEpo administration. Total hemoglobin mass (tHb-mass) was measured twice at baseline (14 and 7 d before the first injection), three times during rHuEpo administration (10, 24, and 38 d after the first rHuEpo injection) and twice after the cessation of rHuEpo administration (7 and 21 d after the final injection) using the optimized CO rebreathing method. V˙O2max and RSA also were assessed in a separate cohort of 11.

Integration of Wearable Sensors Into the Evaluation of Running Economy and Foot Mechanics in Elite Runners.

Running economy, known as the steady-state oxygen consumption at a given submaximal intensity, has been proposed as one of the key factors differentiating East African runners from other running communities around the world. Kenyan runners have dominated middle- and long-distance running events and this phenomenon has been attributed, in part at least, to their exceptional running economy. Despite such speculation, there are no data on running mechanics during real-life situations such as during training or competition. The use of innovative wearable devices together with real-time analysis of data will represent a paradigm shift in the study of running biomechanics and could potentially help explain the outstanding performances of certain athletes. For example, the integration of foot worn inertial sensors into the training and racing of athletes will enable coaches and researchers to investigate foot mechanics (e.g., an accurate set of variables such as pitch and eversion angles, cadence, symmetry, contact and flight times or swing times) during real-life activities and facilitate feedback in real-time. The same technological approach also can be used to help the athlete, coach, sports physician, and sport scientist make better informed decisions in terms of performance and efficacy of interventions, treatments or injury prevention; a kind of "telesport" equivalent to "telemedicine." There also is the opportunity to use this real-time technology to advance broadcasting of sporting events with the transmission of real-time performance metrics and in doing so enhance the level of entertainment, interest, and engagement of enthusiasts in the broadcast and the sport. Such technological advances that are able to unobtrusively augment personal experience and interaction, represent an unprecedented opportunity to transform the world of sport for participants, spectators, and all relevant stakeholders.

The Effect of Sodium Alginate and Pectin Added to a Carbohydrate Beverage on Endurance Performance, Substrate Oxidation and Blood Glucose Concentration: A Systematic Review and Meta-analysis.

INTRODUCTION: Scientific and public interest in the potential ergogenic effects of sodium alginate added to a carbohydrate (CHO) beverage has increased in the last ~ 5 years. Despite an extensive use of this technology by elite athletes and recent research into the potential effects, there has been no meta-analysis to objectively elucidate the effects of adding sodium alginate to a CHO beverage on parameters relevant to exercise performance and to highlight gaps in the literature. METHODS: Three literature databases were systematically searched for studies investigating the effects of sodium alginate added to CHO beverage during prolonged, endurance exercise in healthy athletes. For the systematic review, the PROSPERO guidelines were followed, and risk assessment was made using the Cochrane collaboration's tool for assessing the risk of bias. Additionally, a random-effects meta-analysis model was used to determine the standardised mean difference between a CHO beverage containing sodium alginate and an isocaloric control for performance, whole-body CHO oxidation and blood glucose concentration. RESULTS: Ten studies were reviewed systematically, of which seven were included within the meta-analysis. For each variable, there was homogeneity between studies for performance (n = 5 studies; I2 = 0%), CHO oxidation (n = 7 studies; I2 = 0%) and blood glucose concentration (n = 7 studies; I2 = 0%). When compared with an isocaloric control, the meta-analysis demonstrated that there is no difference in performance (Z = 0.54, p = 0.59), CHO oxidation (Z = 0.34, p = 0.71) and blood glucose concentration (Z = 0.44, p = 0.66) when ingesting a CHO beverage containing sodium alginate. The systematic review revealed that several of the included studies did not use sufficient exercise intensity to elicit significant gastrointestinal disturbances or demonstrate any ergogenic benefit of CHO ingestion. Risk of bias was generally low across the included studies. CONCLUSIONS: This systematic review and meta-analysis demonstrate that the current literature indicates no benefit of adding sodium alginate to a CHO beverage during exercise. Further research is required, however, before firm conclusions are drawn considering the range of exercise intensities, feeding rates and the apparent lack of benefit of CHO reported in the current literature investigating sodium alginate.

Recent Improvements in Marathon Run Times Are Likely Technological, Not Physiological.

Every women's and men's world records from 5 km to the marathon has been broken since the introduction of carbon fibre plate (CFP) shoes in 2016. This step-wise increase in performance coincides with recent advancements in shoe technology that increase the elastic properties of the shoe thereby reducing the energy cost of running. The latest CFP shoes are acknowledged to increase running economy by more than 4%, corresponding to a greater than 2% improvement in performance/run time. The recently modified rules governing competition shoes for elite athletes, announced by World Athletics, that includes sole thickness must not exceed 40 mm and must not contain more than one rigid embedded plate, appear contrary to the true essence and credibility of sport as access to this performance-defining technology becomes the primary differentiator of sporting performance in elite athletes. This is a particular problem in sports such as athletics where the primary sponsor of the athlete is very often a footwear manufacturing company. The postponement of the 2020 Summer Olympics provides a unique opportunity for reflection by the world of sport and time to commission an independent review to evaluate the impact of technology on the integrity of sporting competition. A potential solution to solve this issue can involve the reduction of the stack height of a shoe to 20 mm. This simple and practical solution would prevent shoe technology from having too large an impact on the energy cost of running and, therefore, determining the performance outcome.

The Impact of Sodium Alginate Hydrogel on Exogenous Glucose Oxidation Rate and Gastrointestinal Comfort in Well-Trained Runners.

PURPOSE: The purpose of this study is to quantify the effect of adding sodium alginate and pectin to a carbohydrate (CHO) beverage on exogenous glucose (ExGluc) oxidation rate compared with an isocaloric CHO beverage. METHODS: Following familiarization, eight well-trained endurance athletes performed four bouts of prolonged running (105 min; 71 ± 4% of VO2max) while ingesting 175 mL of one of the experimental beverages every 15 min. In randomized order, participants consumed either 70 g.h-1 of maltodextrin and fructose (10% CHO; NORM), 70 g.h-1 of maltodextrin, fructose, sodium alginate, and pectin (10% CHO; ENCAP), 180 g.h-1 of maltodextrin, fructose, sodium alginate, and pectin (26% CHO; HiENCAP), or water (WAT). All CHO beverages had a maltodextrin:fructose ratio of 1:0.7 and contained 1.5 g.L-1 of sodium chloride. Total substrate oxidation, ExGluc oxidation rate, blood glucose, blood lactate, serum non-esterified fatty acid (NEFA) concentration, and RPE were measured for every 15 min. Every 30 min participants provided information regarding their gastrointestinal discomfort (GID). RESULTS: There was no significant difference in peak ExGluc oxidation between NORM and ENCAP (0.63 ± 0.07 and 0.64 ± 0.11 g.min-1, respectively; p > 0.5), both of which were significantly lower than HiENCAP (1.13 ± 0.13 g.min-1, p < 0.01). Both NORM and HiENCAP demonstrated higher total CHO oxidation than WAT from 60 and 75 min, respectively, until the end of exercise, with no differences between CHO trials. During the first 60 min, blood glucose was significantly lower in WAT compared with NORM and HiENCAP, but no differences were found between CHO beverages. Both ENCAP and HiENCAP demonstrated a higher blood glucose concentration from 60-105 min than WAT, and ENCAP was significantly higher than HiENCAP. There were no significant differences in reported GID symptoms between the trials. CONCLUSIONS: At moderate ingestion rates (i.e., 70 g.h-1), the addition of sodium alginate and pectin did not influence the ExGluc oxidation rate compared with an isocaloric CHO beverage. At very high ingestion rates (i.e., 180 g.h-1), high rates of ExGluc oxidation were achieved in line with the literature.

The validity and reliability of a novel isotope ratio infrared spectrometer to quantify 13C enrichment of expired breath samples in exercise.

The traditional method to measure 13CO2 enrichment in breath involves isotope ratio mass spectrometry (IRMS), which has several limitations such as cost, extensive training, and large space requirements. Here, we present the validity and reliability data of an isotope ratio infrared spectrometer (IRIS)-based method developed to combat these limitations. Eight healthy male runners performed 105 min of continuous running on a motorized treadmill while ingesting various carbohydrate beverages enriched with 13C and expired breath samples were obtained every 15 min in triplicates. A total of 213 breath samples were analyzed using both methods, whereas 212 samples were repeated using IRIS to determine test-retest reliability. Bland-Altman analysis was performed to determine systematic and proportional bias, and intraclass correlation coefficient (ICC) and coefficient of variation (CV) to assess level of agreement and magnitude of error. The IRIS method demonstrated a small but significant systematic bias to overestimate δ13CO2 (0.18‰; P < 0.05) compared with IRMS, without any proportional bias or heteroscedasticity and a small CV (0.5%). There was a small systematic bias during the test-retest of the IRIS method (-0.07‰; P < 0.05), no proportional bias, an excellent ICC (1.00), and small CV (0.4%). The use of the Delta Ray IRIS to determine 13C enrichment in expired breath samples captured during exercise has excellent validity and reliability when compared with the gold standard IRMS.NEW & NOTEWORTHY The use of IRIS to determine 13C enrichment in expired breath samples captured during exercise to determine exogenous glucose oxidation during exercise has excellent validity and reliability when compared with the gold standard IRMS.

Wearable and telemedicine innovations for Olympic events and elite sport.

Rapid advances in wearable technologies and real-time monitoring have resulted in major inroads in the world of recreational and elite sport. One such innovation is the application of real-time monitoring, which comprises a smartwatch application and ecosystem, designed to collect, process and transmit a wide range of physiological, biomechanical, bioenergetic and environmental data using cloud-based services. We plan to assess the impact of this wireless technology during Tokyo 2020, where this technology could help characterize the physiological and thermal strain experienced by an athlete, as well as determine future management of athletes during a medical emergency as a result of a more timely and accurate diagnosis. Here we describe some of the innovative technologies developed for numerous sports at Tokyo 2020 ranging from race walking (20 km and 50 km events), marathon, triathlon, road cycling (including the time trial event), mountain biking, to potentially team sports played outdoors. A more symbiotic relationship between sport, health and technology needs to be encouraged that harnesses the unique demands of elite sport (e.g., the need for unobtrusive devices that provide real-time feedback) and serves as medical and preventive support for the athlete's care. The implementation of such applications would be particularly welcome in the field of medicine (i.e., telemedicine applications) and the workplace (with particular relevance to emergency services, the military and generally workers under extreme environmental conditions). Laboratory and field-based studies are required in simulated scenarios to validate such emerging technologies, with the field of sport serving as an excellent model to understand and impact disease.

Addition of an Alginate Hydrogel to a Carbohydrate Beverage Enhances Gastric Emptying.

PURPOSE: This study aimed to examine the effect of altering osmolality or adding sodium alginate and pectin to a concentrated carbohydrate (CHO) beverage on gastric-emptying (GE) rate. METHODS: Boluses (500 mL) of three drinks were instilled double blind in eight healthy men while seated, GE was measured using the double sampling method for 90 min, and blood samples were collected regularly. Drinks consisted of glucose and fructose (MON; 1392 mOsmol·kg), maltodextrin and fructose (POLY; 727 mOsmol·kg), and maltodextrin, fructose, sodium alginate, and pectin (ENCAP; 732 mOsmol·kg) with each providing 180 g·L CHO (CHO ratio of 1:0.7 maltodextrin or glucose/fructose). RESULTS: Time to empty half of the ingested bolus was faster for ENCAP (21 ± 9 min) than for POLY (37 ± 8 min); both were faster than MON (51 ± 15 min). There were main effects for time and drink in addition to an interaction effect for the volume of test drink remaining in the stomach over the 90 min period, but there were no differences between MON and POLY at any time point. ENCAP had a smaller volume of the test drink in the stomach than MON at 30 min (193 ± 62 vs 323 ± 54 mL), which remained less up to 60 min (93 ± 37 vs 210 ± 88 mL). There was a smaller volume of the drink remaining in the stomach in ENCAP compared with POLY 20 min (242 ± 73 vs 318 ± 47 mL) and 30 min (193 ± 62 vs 304 ± 40 mL) after ingestion. Although there was a main effect of time, there was no effect of drink or an interaction effect on serum glucose, insulin or nonesterified fatty acid concentrations. CONCLUSION: The addition of sodium alginate and pectin to a CHO beverage enhances early GE rate but did not affect serum glucose, insulin, or nonesterified fatty acid concentration at rest.

The Use of Technology to Protect the Health of Athletes During Sporting Competitions in the Heat.

During the 2019 IAAF World Championships in Athletics in Doha and the 2020 Olympic Games in Tokyo, minimum daily temperatures are expected to be in excess of 30°C. Due to the metabolic demands of the sporting events and the high environmental temperatures, the risk of exertional heat stroke (EHS) is high. Careful planning by event organizers are needed to ensure that athletes are protected from irreversible long-term health damage, or even death during sporting competitions in the heat. Efforts typically have included standard medical plans, equipment, protocols, and expert medical teams. In addition, the importance of responding quickly to a hyperthermic athlete cannot be understated, as minimizing treatment time will greatly improve the chances of full recovery. Treatment time can be minimized by notifying medical personnel about the health status of the athlete and the extent of any pre-competition heat acclimatization. Technology that allows the live transmission of physiological, biomechanical, and performance data to alert medical personnel of potential indicators of EHS should be considered. Real time monitoring ecosystems need to be developed that integrate information from numerous sensors such as core temperature-monitoring "pills" to relay information on how an athlete is coping with competing in intense heat. Medical/support staff would be alerted if an athlete's responses were indicating signs of heat stress or EHS signs and the athlete could be withdrawn under exceptional circumstances. This technology can also help provide more rapid, accurate and dignified temperature assessment at the road/track side in medical emergencies.

Effects of EPO on Blood Parameters and Running Performance in Kenyan Athletes.

INTRODUCTION: Recombinant human erythropoietin (rHuEpo) administration enhances oxygen carrying capacity and performance at sea level. It remains unknown whether similar effects would be observed in chronic altitude-adapted endurance runners. The aim of this study was to assess the effects of rHuEpo on hematological and performance parameters in chronic altitude-adapted endurance runners as compared to sea level athletes. METHODS: Twenty well-trained Kenyan endurance runners (KEN) living and training at approximately 2150 m received rHuEpo injections of 50 IU·kg body mass every 2 d for 4 wk and responses compared with another cohort (SCO) that underwent an identical protocol at sea level. Blood samples were obtained at baseline, during rHuEpo administration and 4 wk after the final injection. A maximal oxygen uptake (V˙O2max) test and 3000-m time trial was performed before, immediately after and 4 wk after the final rHuEpo injection. RESULTS: Hematocrit (HCT) and hemoglobin concentration (HGB) were higher in KEN compared to SCO before rHuEpo but similar at the end of administration. Before rHuEpo administration, KEN had higher V˙O2max and faster time trial performance compared to SCO. After rHuEpo administration, there was a similar increase in V˙O2max and time trial performance in both cohorts; most effects of rHuEpo were maintained 4 wk after the final rHuEpo injection in both cohorts. CONCLUSIONS: Four weeks of rHuEpo increased the HGB and HCT of Kenyan endurance runners to a lesser extent than in SCO (~17% vs ~10%, respectively) and these alterations were associated with similar improvements in running performance immediately after the rHuEpo administration (~5%) and 4 wk after rHuEpo (~3%).