Classification of middle- and long-distance runners based upon their performance.

The scientific literature lacks consensus on classification of middle- and long-distance runners. This creates situations where the sample studied may not represent the target population and could produce misleading conclusions. Thus, we present an approach for a data-driven classification of middle- and long-distance runners according to their competition results. The best annual results of middle- and long-distance track runners participating at major (Olympics, World and European Championships) and national championships (Denmark, Sweden, Finland, Norway) were gathered for the 2012-2018 period. Overall, 1920 men's and 1808 women's performance results were gathered. The results were grouped accordingly. Quadratic discriminant analysis was applied to define the limits between the groups. Three basic categories could be proposed for classification: world class, international and national. Classification provides a realistic overview of performance standards and the number of athletes for different categories in middle- and long-distance track running in real-world settings. The performance-based classification provides data-driven and unified criteria for reporting standards on athletes' proficiency levels. It allows for more consistent reporting practices on the target population in research. In addition to scientific research, the classification could also be employed for a variety of practical purposes.

The need for an alternative method to determine intravascular volumes.

It is well described that numerous environmental factors, including exercise, modulate plasma volume (PV). These modulations prove problematic when a number of haematological markers are measured as a concentration in blood plasma. A primary example is haemoglobin concentration ([Hb]), a marker of erythropoiesis commonly used within medicine and also used to detect blood doping. Natural changes in PV can confound [Hb] values when a volume change is detected rather than a true change in haemoglobin mass (Hbmass) (e.g. volume expansion resulting in a [Hb] decrease and pseudo-anemia vs. Hbmass decline resulting in anaemia). Currently, there is no simple solution to correct for PV shifts, and this has proven problematic when monitoring volumetric health markers in clinical and anti-doping settings. This narrative review explores the influence that PV shifts have on volumetric biomarkers, such as [Hb]. The progressive expansion in PV observed during multi-day endurance events will be summarised, and the observed impact PV variance has on concentration-based markers will be quantified. From this, the need for alternative methods to correct [Hb] for volume fluctuations is highlighted. Available methods for calculating intravascular volumes are then discussed, with a focus on a recently developed approach using a panel of 'volume descriptive' biomarkers from a standard blood test. Finally, the practical applications of this novel PV blood test within both anti-doping and clinical settings will be examined.

The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load.

Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercise. This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p = 0.001) and recovery periods (p = 0.002) when compared to the baseline, while leptin decreased significantly during the race (p < 0.0001) and returned to baseline levels during the recovery period. Intra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%). With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. In healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation-like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity.

Application of the optimized CO-rebreathing method for determination of hemoglobin mass in patients with polycythemia vera.

Determination of red cell volume (RCV) might contribute to establishing the diagnosis of polycythemia vera (PV). A novel simplified method to detect RCV through CO rebreathing is nowadays applied in healthy young individuals but was not tested in a clinical or PV setting. The aim of the present study is to evaluate whether this spirometric approach is applicable in older subjects and contributes to PV diagnosis in a proof-of-concept approach. At first, RCV was determined by the optimized CO-rebreathing method in healthy subjects >50 years of age (n = 81, age 66 ± 9 years). Failure rate and age distribution of subjects who failed with CO rebreathing were analyzed. Then, RCV was measured in male PV patients (n = 7) and compared to healthy male controls (n = 35). RCV values in relation to several anthropometric references (body weight, body surface area (BSA), lean body mass (LBM)) were calculated to determine the sensitivity and specificity of established RCV thresholds when using optimized CO rebreathing. In healthy subjects, test failure rate was 9.9 %, but failure was not associated with age. Sensitivity and specificity (sens/spec) to detect PV was 100 %/83 % using the criteria of the PV study group. Using criteria based on BSA, sens/spec was 14 %/100 %. An arbitrary threshold of 50 ml/kg LBM yielded sens/spec of 100 %/97 %. In conclusion, this proof-of-concept indicates that optimized CO rebreathing is applicable in older subjects and allows determining RCV for the diagnosis of PV. Normalized values for RCV measures obtained from CO rebreathing are needed to grant sufficient sensitivity and/or specificity.

Variability of serum markers of erythropoiesis during 6 days of racing in highly trained cyclists.

The athlete biological passport for the fight against doping is currently based on longitudinal monitoring for abnormal changes in cellular blood parameters. Serum parameters related to altered erythropoiesis could be considered for inclusion in the passport. The aim of this study was to quantify the changes in such parameters in athletes during a period of intense exercise.12 highly trained cyclists tapered for 3 days before 6 days of simulated intense stage racing. Morning and afternoon blood samples were taken on most days and analysed for total protein, albumin, soluble transferrin receptor and ferritin concentrations. Plasma volume was determined via total haemoglobin mass measured by carbon-monoxide rebreathing. Percent changes in means from baseline and percent standard errors of measurement (analytical error plus intra-athlete variation) on each measurement occasion were estimated with mixed linear modelling of log-transformed measures. Means of all variables changed substantially in the days following the onset of racing, ranging from -13% (haemoglobin concentration) to +27% (ferritin). After the second day, errors of measurement were generally twice those at baseline. Plasma variables were affected by heavy exercise, either because of changes in plasma volume (total protein, albumin, haemoglobin), acute phase/inflammatory reactions (ferritin) or both (soluble transferrin receptor). These effects need to be taken into consideration when integrating a plasma parameter into the biological passport model for athletes.

The effect of a period of intensive exercise on the isoform test to detect growth hormone doping in sports.

OBJECTIVE: The major objective of this study was to investigate the effects of several days of intense exercise on growth hormone (hGH) testing using the World Anti-Doping Agencies hGH isoform differential immunoassays. Additionally the effects of circadian variation and exercise type on the isoform ratios were also investigated. STUDY DESIGN: 15 male athletes performed a simulated nine day cycling stage race. Blood samples were collected twice daily over a period of 15 days (stage race+three days before and after). hGH isoforms were analysed by the official WADA immunoassays (CMZ Assay GmbH). RESULTS: All measured isoform ratios were far below the WADA decision limits for an adverse analytical finding. Changes in the isoform ratios could not be clearly connected to circadian variation, exercise duration or intensity. CONCLUSIONS: The present study demonstrates that the hGH isoform ratios are not significantly affected by exercise or circadian variation. We demonstrated that heavy, long term exercise does not interfere with the decision limits for an adverse analytical finding.

The impact of long-haul air travel on variables of the athlete's biological passport.

INTRODUCTION: Dehydration, fluid shifts or changes in coagulation occurring during air travel can trigger distinct reactions in the haematological system. Athletes are concerned that these effects might impair sporting performance, increase the risk of thrombosis or cause abnormalities in blood values that might be mistaken for doping in the 'Athlete's biological passport' (ABP) a longitudinal monitoring of haematological variables in antidoping. The aim of the study was to investigate key variables of the ABP before and after a long-haul flight in athletes. METHODS: Fifteen endurance athletes were submitted to ABP blood samples in the morning before and after arrival of an 8 h flight. Two additional samples were obtained in the morning and the evening 3 days after the travel. Twelve nontravelling subjects served as controls. RESULTS: Haemoglobin concentration was higher before than after travel in athletes (+0.5 g/dL, P = 0.038), a similar pattern was observed 3 days after the travel. No difference was observed in the control group. Reticulocyte% did not show any significant changes in neither of the groups. CONCLUSION: The observed changes are in line with normal diurnal variations. There is no indication that travel will affect haematological variables in way that might be mistaken for blood doping.

Hypogonadism and anemia in an athlete.

We report the case of a highly trained endurance athlete (22-year-old) who developed anemia (Hb 9.5 mg/dl) over a period of 6 months. Iron deficient or haemolytic anemia, as well as chronic loss of blood, were excluded. Further, laboratory analyses revealed that this athlete exhibited very low levels of testosterone due to a partial hypogonadotropic hypogonadism. Following testosterone supplementation, red blood cell indices improved. Although hypogonadotropic hypogonadism is well known to be associated with reduced hematopoesis, it rarely causes anemia in athletes. This should be considered as a possible cause for anemia. Extreme training, unbalanced nutrition or the combination of both, have been shown to be causally involved in the development of secondary hypogonadotropic hypogonadism.

Changes in blood lactate concentrations during different treadmill exercise test protocols.

AIM: The purpose of this study was to compare the blood-lactate and heart rate response of three treadmill tests and to define a conversion algorithm. METHODS: Subjects included 19 long-distance runners. The first two tests had increments of 2 km/h every 3 (test3m) or 5 minutes (test5m). The third test (testFm) consisted of four consecutive 2000m-runs. The calculated individual-anaerobic-threshold (IAT) from test3m was defined as speed at the third step of testFm, speed-increments between the four steps were 0.25 m/s. RESULTS: Lactate threshold (LT) did not show significant differences. Speed at IAT in test3m (15.09|*plusmn*|2.29 km/h) was significantly higher than in test5m (14.74|*plusmn*|2.22 km/h), heart rates were nearly identical. Speed and heart rate at 2 mmol/L showed no significant differences. At lactate concentrations of 3 and 4 mmol/L, running-speeds in test3m were significantly higher than in test5m and testFm. Heart rate were the same in test3m and test5m but significantly higher in testFm. CONCLUSION: Taking test3m as basis for determining endurance-performance, an adjustment of test5m can be made by adding 1.8 mmol/l instead of 1.5 mmol/l to the LT to derive the IAT. TestFm shows similar results as test5m, however, standardization is difficult due to variable increment durations.

Stability and robustness of blood variables in an antidoping context.

INTRODUCTION: With the setting up of the newly Athlete's Biological Passport antidoping programme, novel guidelines have been introduced to guarantee results beyond reproach. We investigated in this context, the effect of storage time on the variables commonly measured for the haematological passport. We also wanted to assess for these variables, the within and between analyzer variations. METHODS: Blood samples were obtained from top level male professional cyclists (27 samples for the first part of the study and 102 for the second part) taking part to major stage races. After collection, they were transported under refrigerated conditions (2 °C < T < 12 °C), delivered to the antidoping laboratory, analysed and then stored at approximately 4 °C to conduct analysis at different time points up to 72 h after delivery. A mixed-model procedure was used to determine the stability of the different variables. RESULTS: As expected haemoglobin concentration was not affected by storage and showed stability for at least 72 h. Under the conditions of our investigation, the reticulocytes percentage showed a much better stability than previous published data (> 48 h) and the technical comparison of the haematology analyzer demonstrated excellent results. CONCLUSION: In conclusion, our data clearly demonstrate that as long as the World Anti-Doping Agency's guidelines are followed rigorously, all blood results reach the quality level required in the antidoping context.

The impact of acute gastroenteritis on haematological markers used for the athletes biological passport - report of 5 cases.

The haematological module of the "Athletes Biological Passport" (ABP) is used to detect blood doping through the longitudinal variation of blood variables, such as haemoglobin concentration (Hb). Sporting federations have opened disciplinary procedures against athletes based on ABP results. Suspicious athletes try to explain the variations in their blood values with dehydration caused by gastrointestinal (GI) problems. The aim of the present report is to describe haemoglobin concentration, a key variable of the ABP, during acute gastroenteritis in athletes. 5 athletes with severe gastroenteritis were studied in retrospective. Blood test results (Hb, white blood cell count (WBC) and differential, CRP) obtained on hospital admission for GI problems were compared to data obtained from the same athletes in states of good health on previous occasions. During GI problems, athletes displayed marked inflammatory constellations with increased CRP and typical WBC shifts. Hb was not affected and remained mostly unchanged. This is in line with basic physiologic fluid regulation, where plasma volume is kept constant, even under conditions of severe dehydration. It is therefore unlikely that fluid loss associated with gastroenteritis will cause athletes blood data to reach levels of abnormality that will be suspicious of blood doping.

Diurnal and exercise-related variability of haemoglobin and reticulocytes in athletes.

Haemoglobin (Hb) and Reticulocytes (Ret) are measured as indirect markers of doping in athletes. We studied the diurnal variation, the impact of exercise, fluid intake and ambient temperature in athletes on these parameters. Hourly venous blood samples were obtained from 36 male athletes of different disciplines (endurance (END) and non-endurance (NON-END)) over 12 h during a typical training day. Seven inactive subjects served as controls (CON). Hb and Ret were determined. A mixed model procedure was used to analyse the data. At baseline, Hb was similar for all groups, END showed lower Ret than NON-END and CON. Exercise showed a significant impact on Hb (+0.46 g/dl, p<0.001), the effect disappeared approximately 2 h after exercise. Hb decreased over the day by approximately 0.55 g/dl (p<0.01). There was no relevant effect on Ret. Fluid intake and ambient temperature had no significant effect. Hb shows significant diurnal- and exercise related variations. In an anti-doping context, most of these variations are in favour of the athlete. Blood samples taken after exercise might therefore provide reliable results and thus be used for the longitudinal monitoring of athletes if a timeframe for the re-equilibration of vascular volumes is respected.

Are 10 min of seating enough to guarantee stable haemoglobin and haematocrit readings for the athlete's biological passport?

Haemoglobin (Hb) and haematocrit (Hct) are measured as indirect markers of doping in athletes. We studied the effect of posture on these parameters in a typical antidoping setting. Venous blood samples were obtained from nine endurance athletes (six males, three females) and nine control subjects (six males, three females) immediately and after 5, 10, 15, 20 and 30 min after having adopted a seated position from normal daily activity. Hb (CV 0.72%) and Hct (CV 0.87%) were determined using an automated cell counter, plasma volume changes were calculated. Differences between the time points, gender and groups were calculated using a mixed-model procedure. Significant changes were observed in the first 10 min after sitting down but no further changes were noted between 10 and 30 min. Mean directional change for Hb and Hct between 0 min and the average of the period from 10 to 30 min was -2.4% (-0.35 g/dl) for Hb and -2.7% (-1.2%) for Hct. Plasma volume increased accordingly. Neither group nor gender had significant effects. Under typical conditions encountered during blood testing in doping control, a period of 10 min in a seated position is sufficient for the vascular volumes to re-equilibrate and to adapt to the new posture.

Post-transfusion stability of haemoglobin mass.

BACKGROUND AND OBJECTIVES: Total haemoglobin mass (tHb) as a direct parameter of the blood system and ultimate target of all blood transfusions has not been evaluated for its post-transfusion survival and stability. Therefore, the purpose of this study was to investigate the latter which may also be relevant from an anti-doping perspective as autologous blood transfusions remain impossible to detect. MATERIALS AND METHODS: The tHb was determined by the CO rebreathing method prior to and after donation of 1 unit of whole blood, as well as prior to and after reinfusion (weekly up to 56 days) of the erythrocyte concentrate in 10 men (28 +/- 7 years, 181 +/- 7 cm, 76 +/- 12 kg). RESULTS: The mean tHb content of the derived erythrocyte concentrate was 60 +/- 3 g, while the net tHb increases after transfusion of 51 g (95% confidence intervals 33-69 g) permitted proof of an elevated tHb for at least 56 days after transfusion. CONCLUSION: The results show that an elevated tHb induced by autologous transfusion allowed continuous identification although, as expected, a slow decrease of tHb has been revealed in the observation period. In reference to anti-doping, CO rebreathing permits proof of a supraphysiologically elevated tHb but possibly only if a stable baseline value is known.

Relations between haemoglobin mass, cardiac dimensions and aerobic capacity in endurance trained cyclists.

AIM: Chronic endurance exercise triggers increased cardiac dimensions, blood volumes and haemoglobin mass (Hb mass). Cardiac output and Hb mass are considered as independent contributors to aerobic performance. Therefore, increased Hb mass could counterbalance for a relative deficiency in cardiac adaptation. The purpose of the present study is to investigate relations between Hb mass and cardiac dimensions in a group of endurance athletes with respect to aerobic capacity. METHODS: Two groups of highly trained cyclists featuring high (HHB group, N.=13) and low (LHB group, N.=13) Hb mass (measured by a CO-rebreathing method) were compared for measures of aerobic performance, cardiac wall thickness, cavity size and left ventricular mass (determined by 2-D-echocardiography). Lean body mass (LBM) was chosen as anthropometrical reference for Hb mass. RESULTS: HHB featured higher cardiac wall thickness than LHB, but no difference appeared in cardiac cavity size, left ventricular mass and the performance parameters. Normalising Hb mass for body weight instead of LBM improved correlations between Hb mass and performance parameters. CONCLUSIONS: Our data provides new evidence for a connection between cardiac wall thickness and Hb mass in endurance athletes but no further evidence for a counterbalance between Hb mass and cardiac adaptation was found. Moreover, we postulate that Hb mass loses predictive value for aerobic performance when normalised for LBM.

Evaluation of anthropometrical reference parameters for hemoglobin mass in endurance athletes.

AIM: Blood volume and hemoglobin mass (tHb) are new emerging parameters in exercise physiology. The appropriate anthropometrical reference for these variables has not yet been investigated. In most current investigations, body weight is used in this context. The aim of the present study was therefore to evaluate three different anthropometrical parameters (body weight, body surface area [BSA] and lean body mass [LBM] with respect to tHb. METHODS: Sixty-five healthy male endurance athletes underwent a tHb determination (optimised CO rebreathing method) and anthropometrical evaluation (skinfold measurement) with estimation of body weight, LBM and BSA. Correlation analysis was performed; the correlations of the different anthropometrical reference ratios were compared and evaluated with regards to body composition. RESULTS: LBM showed the best correlation with tHb (R=0.81), although no significant differences between the three anthropometrical references were found (BSA R=0.76, body weight R=0.77). In contrast to tHb/body weight, tHb/LBM was independent of body fat content and thus body composition. CONCLUSION: The current study demonstrated no statistical difference between various anthropometrical references for tHb, which might be due to the anthropometrically homogenous study group of lean, endurance trained athletes. However, the significance dependence of body weight on body fat content indicates that this might not be the case in athletes of other somatotypes. It is therefore suggested that LBM instead of body weight should be used as anthropometrical reference when investigating tHb in athletes.

Cadence-power-relationship during decisive mountain ascents at the Tour de France.

The aim of the study was to report the relationship between cadence and power developed by professional cyclists during high mountain ascents of the Tour de France. From the 10 cyclists (30 +/- 4 years, 178 +/- 8 cm, 69 +/- 6 kg) involved in the study, 108 ascents were recorded and analyzed using a mobile power measurement device (SRM Training Systems, Jülich, Germany). Based on topographic characteristics, the ascents were categorized into 1st and Hors Category (HC) climbs. During the ascents of the 1st Category climbs, power output averaged 312 +/- 43 W (4.5 +/- 0.6 W/kg) with a mean cadence of 73 +/- 6 rpm and a mean duration of 37 : 41 +/- 16 : 16 min. Power output averaged 294 +/- 36 W (4.3 +/- 0.6 W/kg) at a mean cadence of 70 +/- 6 rpm during 57 : 40 +/- 10 : 32 min on HC climbs. The maximal mean power for long durations (1800 s) showed a mean power output of 327 W and 346 W for the 1st and HC climbs, respectively. The evaluation of the cadence-power output and the distance per pedaling cycle-power output relationship shows that high power outputs are mainly yielded by higher pedaling cadences and higher gears.