Ventilatory acclimatisation is beneficial for high-intensity exercise at altitude in elite cyclists.

AIM: The aim of this study was to examine the relationship between ventilatory adaptation and performance during altitude training at 2700 m. METHODS: Seven elite cyclists (age: 21.2 ± 1.1 yr, body mass: 69.9 ± 5.6 kg, height 176.3 ± 4.9 cm) participated in this study. A hypoxic ventilatory response (HVR) test and a submaximal exercise test were performed at sea level prior to the training camp and again after 15 d at altitude (ALT15). Ventilation (VE), end-tidal carbon-dioxide partial pressure (PETCO2) and oxyhaemoglobin saturation via pulse oximetry (SpO2) were measured at rest and during submaximal cycling at 250 W. A hill climb (HC) performance test was conducted at sea level and after 14 d at altitude (ALT14) using a road of similar length (5.5-6 km) and gradient (4.8-5.3%). Power output was measured using SRM cranks. Average HC power at ALT14 was normalised to sea level power (HC%). Multiple regression was used to identify significant predictors of performance at altitude. RESULTS: At ALT15, there was a significant increase in resting VE (10.3 ± 1.9 vs. 12.2 ± 2.4 L·min(-1)) and HVR (0.34 ± 0.24 vs. 0.71 ± 0.49 L·min(-1)·%(-1)), while PETCO2 (38.4 ± 2.3 vs. 32.1 ± 3.3 mmHg) and SpO2 (97.9 ± 0.7 vs. 94.0 ± 1.7%) were reduced (P < .05). Multiple regression revealed ΔHVR and exercise VE at altitude as significant predictors of HC% (adjusted r(2) = 0.913; P = 0.003). CONCLUSIONS: Ventilatory acclimatisation occurred during a 2 wk altitude training camp in elite cyclists and a higher HVR was associated with better performance at altitude, relative to sea level. These results suggest that ventilatory acclimatisation is beneficial for cycling performance at altitude.

Is three-dimensional anthropometric analysis as good as traditional anthropometric analysis in predicting junior rowing performance?

With the use of three-dimensional whole body scanning technology, this study compared the 'traditional' anthropometric model [one-dimensional (1D) measurements] to a 'new' model [1D, two-dimensional (2D), and three-dimensional (3D) measurements] to determine: (1) which model predicted more of the variance in self-reported best 2000-m ergometry rowing performance; and (2) what were the best anthropometric predictors of ergometry performance, for junior rowers competing at the 2007 and 2008 Australian Rowing Championships. Each rower (257 females, 16.3 ± 1.4 years and 243 males, 16.6 ± 1.5 years) completed a performance and demographic questionnaire, had their mass, standing and sitting height physically measured and were landmarked and scanned using the Vitus Smart® 3D whole body scanner. Absolute and proportional anthropometric measurements were extracted from the scan files. Partial least squares regression analysis, with anthropometric measurements and age as predictor variables and self-reported best 2000-m ergometer time as the response variable, was used to first compare the two models and then to determine the best performance predictors. The variance explained by each model was similar for both male [76.1% (new) vs. 73.5% (traditional)] and female [72.3% (new) vs. 68.6% (traditional)] rowers. Overall, absolute rather than proportional measurements, and 2D and 3D rather than 1D measurements, were the best predictors of rowing ergometry performance, with whole body volume and surface area, standing height, mass and leg length the strongest individual predictors.

Improved race performance in elite middle-distance runners after cumulative altitude exposure.

We quantified the effect of an extended live high-train low (LHTL) simulated altitude exposure followed by a series of training camps at natural moderate altitude on competitive performance in seven elite middle-distance runners (Vo2max 71.4 +/- 3.4 mL.min-1.kg-1, mean +/- SD). Runners spent 44 +/- 7 nights (mean +/- SD) at a simulated altitude of 2846 +/- 32 m, and a further 4 7- to 10-d training at natural moderate altitude (1700-2200 m) before racing. The combination of simulated LHTL and natural altitude training improved competitive performance by 1.9% (90% confidence limits, 1.3-2.5%). Middle-distance runners can confidently use a combination of simulated and natural altitude to stimulate adaptations responsible for improving performance.

A protocol for measuring the direct effect of cycling on neuromuscular control of running in triathletes.

The direct effects of cycling on movement and muscle recruitment patterns (neuromuscular control) during running are unknown but critical to success in triathlon. We outline and test a new protocol for investigating the direct influence of cycling on neuromuscular control during running. Leg movement (three-dimensional kinematics) and muscle recruitment (surface electromyography, EMG) were compared between a control run (no prior exercise) and a 30-min transition run that was preceded by 20 min of cycling. We conducted three experiments investigating: (a) the repeatability (between-day reliability) of the protocol; (b) the ability of the protocol to investigate, in highly trained national or international triathletes, the direct influence of cycling on neuromuscular control during running independent of neuromuscular fatigue; and (c) the ability of the protocol to provide a control, or baseline, measure of neuromuscular control (determined using a measure of stability) without causing fatigue. Kinematic and EMG measures of neuromuscular control during running showed moderate to high repeatability: mean coefficients of multiple correlation for repeatability of EMG and kinematics were 0.816 +/- 0.014 and 0.911 +/- 0.031, respectively. The protocol provided a robust baseline measure of neuromuscular control during running without causing neuromuscular fatigue (coefficients of multiple correlation for stability of EMG and kinematics were 0.827 +/- 0.023 and 0.862 +/- 0.054), while EMG and force data provided no evidence of fatigue. The protocol outlined here is repeatable and can be used to measure any direct influence of cycling on neuromuscular control during running.

Practical precooling: effect on cycling time trial performance in warm conditions.

The purpose of this study was to compare the effects of two practical precooling techniques (skin cooling vs. skin + core cooling) on cycling time trial performance in warm conditions. Six trained cyclists completed one maximal graded exercise test (VO2(peak) 71.4 +/- 3.2 ml x kg(-1) x min(-1)) and four approximately 40 min laboratory cycling time trials in a heat chamber (34.3 degrees C +/- 1.1 degrees C; 41.2% +/- 3.0% rh) using a fixed-power/variable-power format. Cyclists prepared for the time trial using three techniques administered in a randomised order prior to the warm-up: (1) no cooling (control), (2) cooling jacket for 40 min (jacket) or (3) 30-min water immersion followed by a cooling jacket application for 40 min (combined). Rectal temperature prior to the time trial was 37.8 degrees C +/- 0.1 degrees C in control, similar in jacket (37.8 degrees C +/- 0.3 degrees C) and lower in combined (37.1 degrees C +/- 0.2 degrees C, P < 0.01). Compared with the control trial, time trial performance was not different for jacket precooling (-16 +/- 36 s, -0.7%; P = 0.35) but was faster for combined precooling (-42 +/- 25 s, - .8%; P = 0.009). In conclusion, a practical combined precooling strategy that involves immersion in cool water followed by the use of a cooling jacket can produce decrease in rectal temperature that persist throughout a warm-up and improve laboratory cycling time trial performance in warm conditions.

Influence of nutrient intake after weigh-in on lightweight rowing performance.

PURPOSE: The aim of the present study was to compare the effectiveness of different nutritional recovery strategies between weigh-in and racing on 2000-m rowing ergometer performance among oarsmen undertaking short-term weight loss before competition. METHODS: Competitive rowers (N = 12) completed four ergometer trials, each separated by 48 h. No weight restrictions were imposed for the first trial (TR1). Thereafter, athletes were required to reduce their body mass by 5.2% in the 24 h before trial 2 (TR2), again reaching this body mass before the final two trials (TR3 and TR4). Athletes were provided with one of three nutritional recovery strategies in the 2 h between weigh-in and racing in a counterbalanced fashion according to a Latin square design: fluid (2.8 kJ.kg(-1), 0.0 g.kg(-1) carbohydrate, 0.6 mg.kg(-1) sodium, 28.5 mL.kg(-1) fluid; FLU), carbohydrate/sodium (45.3 kJ.kg(-1), 2.2 g.kg(-1) carbohydrate, 32.9 mg.kg(-1) sodium, 7.2 mL.kg(-1) fluid; CHO), and a combination of water and carbohydrate/sodium (44.8 kJ.kg(-1), 2.3 g.kg(-1) carbohydrate, 33 mg.kg(-1) sodium, 28.5 mL.kg(-1) fluid; COM). RESULTS: Performance was slower for CHO compared with both COM (mean difference, 4.13; 95% CI, 1.37-6.88 s; P = 0.003) and FLU (2.88; 95% CI, 0.13-5.63 s; P = 0.039). However, FLU was not significantly slower than COM (1.24; 95% CI, -1.41 to 3.90 s; P = 0.474). CONCLUSIONS: The present investigation has shown that although carbohydrate and sodium intake may be important in the recovery period between weigh-in and 2000-m rowing ergometer performance, fluid intake has a greater influence on performance among lightweight male rowers who undertake short-term weight loss to achieve specified body-mass limits.

Preparation of former heavyweight oarsmen to compete as lightweight rowers over 16 weeks: three case studies.

To strengthen the depth of lightweight rowing talent, we sought to identify experienced heavyweight rowers who possessed physique traits that predisposed them to excellence as a lightweight. Identified athletes (n = 3) were monitored over 16 wk. Variables measured included performance, anthropometric indices, and selected biochemical and metabolic parameters. All athletes decreased their body mass (range 2.0 to 8.0 kg), with muscle mass accounting for a large proportion of this (31.7 to 84.6%). Two athletes were able to maintain their performance despite reductions in body mass. However, performance was compromised for the athlete who experienced the greatest weight loss. In summary, smaller heavyweight rowers can successfully make the transition into the lightweight category, being nationally competitive in their first season as a lightweight.

Impact of two different body mass management strategies on repeat rowing performance.

PURPOSE: The present study was conducted to examine the impact of acute weight loss on repeat 2000-m rowing ergometer performance during a simulated multiday regatta, and to compare two different body mass management strategies between races. METHODS: Competitive rowers (N = 16) were assigned to either a control (CON), partial recovery (REC(partial)), or complete recovery (REC(complete)) group. Volunteers completed four trials, each separated by 48 h. No weight restrictions were imposed for the first trial. Thereafter, athletes in REC(partial) and REC(complete) were required to reduce their body mass by 4% in the 24 h before trial 2, again reaching this body mass before the final two trials. No weight restrictions were imposed on CON. Aggressive nutritional recovery strategies were used in the 2 h following weigh-in for all athletes. These strategies were maintained for the 12-16 h following racing for REC(complete) with the aim of restoring at least three quarters of the original 4% body mass loss. Postrace recovery strategies were less aggressive in REC(partial); volunteers were encouraged to restore no more than half of their initial 4% body mass loss. RESULTS: Acute weight loss increased time to complete the first "at-weight" performance trial by a small margin (mean 3.0, 95% CI -0.3 to 6.3 s, P = 0.07) when compared with the CON response. This effect decreased when sustained for several days. Aggressive postrace recovery strategies tended to eliminate the effect of acute weight loss on subsequent performance. CONCLUSION: Acute weight loss resulted in a small performance compromise that was reduced or eliminated when repeated over several days. Athletes should be encouraged to maximize recovery in the 12-16 h following racing when attempting to optimize subsequent performance.

Impact of acute weight loss and/or thermal stress on rowing ergometer performance.

PURPOSE: The impact of acute weight loss on rowing performance was assessed when generous nutrient intake was provided in 2 h of recovery after making weight. METHODS: Competitive rowers (N = 17) completed four ergometer trials, each separated by 48 h. Two trials were performed after a 4% body mass loss in the previous 24 h (WT) and two were performed after no weight restrictions, that is, unrestricted (UNR). In addition, two trials (1 x WT, 1 x UNR) were in a thermoneutral environment (NEUTRAL, mean 21.1 +/- SD 0.7 degrees C, 29.0 +/- 4.5% RH) and two were in the heat (HOT 32.4, +/- 0.4 degrees C, 60.4 +/- 2.7% RH). Trials were performed in a counterbalanced fashion according to a Latin square design. Aggressive nutritional recovery strategies (WT 2.3 g x kg(-1) carbohydrate, 34 mg x kg(-1) Na, 28.4 mL x kg(-1) fluid; UNR ad libitum) were employed in the 2 h after weigh-in. RESULTS: Both WT (mean 2.1, 95% CI 0.7-3.4 s; P = 0.003) and HOT (4.1, 2.7 - 5.4 s; P < 0.001) compromised 2000-m time-trial performance. Whereas WT resulted in hypohydration, the associated reduction in plasma volume explained only part of the performance compromise observed (0.2 s for every 1% decrement) Moreover, WT did not influence core temperature or indices of cardiovascular function. CONCLUSIONS: Acute weight loss compromised performance, despite generous nutrient intake in recovery, although the effect was small. Performance decrements were further exacerbated when exercise was performed in the heat.

Sleep disturbance at simulated altitude indicated by stratified respiratory disturbance index but not hypoxic ventilatory response.

At high altitudes, the clinically defined respiratory disturbance index (RDI) and high hypoxic ventilatory response (HVR) have been associated with diminished sleep quality. Increased RDI has also been observed in some athletes sleeping at simulated moderate altitude. In this study, we investigated relationships between the HVR of 14 trained male endurance cyclists with variable RDI and sleep quality responses to simulated moderate altitude. Blood oxygen saturation (SpO2%), heart rate, RDI, arousal rate, awakenings, sleep efficiency, rapid eye movement (REM) sleep, non-REM sleep stages 1, 2 and slow wave sleep as percentages of total sleep time (%TST) were measured for two nights at normoxia of 600 m and one night at a simulated altitude of 2,650 m. HVR and RDI were not significantly correlated with sleep stage, arousal rate or awakening response to nocturnal simulated altitude. SpO2 was inversely correlated with total RDI (r = -0.69, P = 0.004) at simulated altitude and with the change in arousal rate from normoxia (r = -0.65, P = 0.02). REM sleep response to simulated altitude correlated with the change, relative to normoxia, in arousal (r = -0.63, P = 0.04) and heart rate (r = -0.61, P = 0.04). When stratified, those athletes at altitude with RDI >20 h(-1) (n = 4) and those with <10 h(-1) (n = 10) exhibited no difference in HVR but the former had larger falls in SpO2 (P = 0.05) and more arousals (P = 0.03). Neither RDI (without stratification) nor HVR were sufficiently sensitive to explain any deterioration in REM sleep or arousal increase. However, the stratified RDI provides a basis for determining potential sleep disturbance in athletes at simulated moderate altitude.

Body-mass management of Australian lightweight rowers prior to and during competition.

PURPOSE: Although the body-mass management strategies of athletes in high-participation weight-category sports such as wrestling have been thoroughly investigated, little is known about such practices among lightweight rowers. This study examined the body-mass management practices of lightweight rowers before competition and compared these with current guidelines of the International Federation of Rowing Association (FISA). Quantification of nutrient intake in the 1-2 h between weigh-in and racing was also sought. METHODS: Lightweight rowers (N = 100) competing in a national regatta completed a questionnaire that assessed body-mass management practices during the 4 wk before and throughout a regatta plus recovery strategies after weigh-in. Biochemical data were collected immediately after weigh-in to validate questionnaire responses. Responses were categorized according to gender and age category (Senior B or younger than 23 yr old, i.e., U23, Senior A or OPEN, i.e., open age limit) for competition. RESULTS: Most athletes (male U23 76.5%, OPEN 92.3%; female U23 84.0%, OPEN 94.1%) decreased their body mass in the weeks before the regatta at rates compliant with FISA guidelines. Gradual dieting, fluid restriction, and increased training load were the most popular methods of body-mass management. Although the importance of recovery after weigh-in was recognized by athletes, nutrient intake and especially sodium (male U23 5.3 +/- 4.9, OPEN 7.7 +/- 5.9; female U23 5.7 +/- 6.8, OPEN 10.2 +/- 5.4 mg x kg(-1)) and fluid intake (male U23 12.1 +/- 7.1, OPEN 13.5 +/- 8.1; female U23 9.4 +/- 7.4, OPEN 14.8 +/- 6.9 mL x kg(-1)) were below current sports nutrition recommendations. CONCLUSION: Few rowers were natural lightweights; the majority reduced their body mass in the weeks before a regatta. Nutritional recovery strategies implemented by lightweight rowers after weigh-in were not consistent with current guidelines.

Hypoxic ventilatory response is correlated with increased submaximal exercise ventilation after live high, train low.

This study tested the hypothesis that live high, train low (LHTL) would increase submaximal exercise ventilation (V(E)) in normoxia, and the increase would be related to enhanced hypoxic ventilatory response (HVR). Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxia (LHTLc, n = 12), 20 nights of intermittent hypoxia (4x5-night 'blocks' of hypoxia interspersed by two nights of normoxia, LHTLi, n = 10), or control (CON, n = 11). LHTLc and LHTLi slept 8-10 h per night in normobaric hypoxia (2,650 m), and CON slept under ambient conditions (600 m). Resting, isocapnic HVR (DeltaV(E)/Deltablood oxygen saturation) was measured in normoxia before (PRE) and after 15 nights (N15) hypoxia. Submaximal cycle ergometry was conducted PRE and after 4, 10, and 19 nights of hypoxia (N4, N10, and N19 respectively). Mean submaximal exercise V(E) was increased (P < 0.05) from PRE to N4 in LHTLc [74.4 (5.1) vs 80.0 (8.4) l min(-1); mean (SD)] and in LHTLi [69.0 (7.5) vs 76.9 (7.3) l min(-1)] and remained elevated in both groups thereafter, with no changes observed in CON at any time. Prior to LHTL, submaximal V(E) was not correlated with HVR, but this relationship was significant at N4 (r = 0.49, P = 0.03) and N19 (r = 0.77, P < 0.0001). Additionally, the increases in submaximal V(E) and HVR from PRE to N15-N19 were correlated (r = 0.51, P = 0.02) for the pooled data of LHTLc and LHTLi. These results suggest that enhanced hypoxic chemosensitivity contributes to increased exercise V(E) in normoxia following LHTL.

Intermittent normobaric hypoxia does not alter performance or erythropoietic markers in highly trained distance runners.

This study was designed to test the hypothesis that intermittent normobaric hypoxia at rest is a sufficient stimulus to elicit changes in physiological measures associated with improved performance in highly trained distance runners. Fourteen national-class distance runners completed a 4-wk regimen (5:5-min hypoxia-to-normoxia ratio for 70 min, 5 times/wk) of intermittent normobaric hypoxia (Hyp) or placebo control (Norm) at rest. The experimental group was exposed to a graded decline in fraction of inspired O2: 0.12 (week 1), 0.11 (week 2), and 0.10 (weeks 3 and 4). The placebo control group was exposed to the same temporal regimen but breathed fraction of inspired O2 of 0.209 for the entire 4 wk. Subjects were matched for training history, gender, and baseline measures of maximal O2 uptake and 3,000-m time-trial performance in a randomized, balanced, double-blind design. These parameters, along with submaximal treadmill performance (economy, heart rate, lactate, and ventilation), were measured in duplicate before, as well as 1 and 3 wk after, the intervention. Hematologic indexes, including serum concentrations of erythropoietin and soluble transferrin receptor and reticulocyte parameters (flow cytometry), were measured twice before the intervention, on days 1, 5, 10, and 19 of the intervention, and 10 and 25 days after the intervention. There were no significant differences in maximal O2 uptake, 3,000-m time-trial performance, erythropoietin, soluble transferrin receptor, or reticulocyte parameters between groups at any time. Four weeks of a 5:5-min normobaric hypoxia exposure at rest for 70 min, 5 days/wk, is not a sufficient stimulus to elicit improved performance or change the normal level of erythropoiesis in highly trained runners.

Effects of live high, train low hypoxic exposure on lactate metabolism in trained humans.

We determined the effect of 20 nights of live high, train low (LHTL) hypoxic exposure on lactate kinetics, monocarboxylate lactate transporter proteins (MCT1 and MCT4), and muscle in vitro buffering capacity (betam) in 29 well-trained cyclists and triathletes. Subjects were divided into one of three groups: 20 consecutive nights of hypoxic exposure (LHTLc), 20 nights of intermittent hypoxic exposure [four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia (LHTLi)], or control (Con). Rates of lactate appearance (Ra), disappearance (Rd), and oxidation (Rox) were determined from a primed, continuous infusion of l-[U-14C]lactic acid tracer during 90 min of steady-state exercise [60 min at 65% peak O2 uptake (VO(2 peak)) followed by 30 min at 85% VO(2 peak)]. A resting muscle biopsy was taken before and after 20 nights of LHTL for the determination of betam and MCT1 and MCT4 protein abundance. Ra during the first 60 min of exercise was not different between groups. During the last 25 min of exercise at 85% VO(2 peak), Ra was higher compared with exercise at 65% of VO(2 peak) and was decreased in LHTLc (P < 0.05) compared with the other groups. Rd followed a similar pattern to Ra. Although Rox was significantly increased during exercise at 85% compared with 65% of VO(2 peak), there were no differences between the three groups or across trials. There was no effect of hypoxic exposure on betam or MCT1 and MCT4 protein abundance. We conclude that 20 consecutive nights of hypoxia exposure decreased whole body Ra during intense exercise in well-trained athletes. However, muscle markers of lactate metabolism and pH regulation were unchanged by the LHTL intervention.

Effect of altitude on second-generation blood tests to detect erythropoietin abuse by athletes.

BACKGROUND AND OBJECTIVES: ON- and OFF-model scores derived from blood parameters sensitive to erythropoiesis have been shown to be a useful tool to identify athletes who are currently injecting erythropoietin to enhance performance or those who have recently stopped doing so. We investigated changes in blood parameters and model scores during and after exposure to terrestrial and simulated altitudes. DESIGN AND METHODS: We retrospectively evaluated changes in hematologic data collected from 19 elite cyclists who lived and trained 2690 m above sea level for 26-31 days, from six elite Kenyan runners who lived 2100 m above sea level but descended to compete at sea level competitions, and from 39 well-trained subjects who resided at sea level but slept at a simulated altitude of 2650-3000 m for 20-23 days of either consecutive or intermittent nightly exposure. RESULTS: Upon ascent to a terrestrial altitude, ON- and OFF-model scores increased immediately, mainly because of an increase in hemoglobin concentration. Scores had not returned fully to baseline three weeks after return to sea level, because of the persistence of the raised hemoglobin concentration for the ON and OFF scores and a fall in reticulocyte percentage for OFF scores. Effects were smaller or negligible for simulated altitude. For Kenyan runners, ON- and OFF-model scores decreased within seven days of descent to sea level. INTERPRETATION AND CONCLUSIONS: Our results reinforce the notion that caution should be exercised when interpreting blood results from athletes who have recently been exposed to either terrestrial or simulated altitude, and appropriate allowance should be made for the effect of altitude on blood model scores.

The effect of common hematologic abnormalities on the ability of blood models to detect erythropoietin abuse by athletes.

BACKGROUND AND OBJECTIVES: Algorithms that combine scores from multiple blood parameters are demonstrably effective in highlighting recombinant human erythropoietin (rHuEPO) administration, and have been used to deter rHuEPO use by athletes. These models are sensitive to atypical levels of blood parameters encountered during altered states of red cell production. Because hematologic abnormalities can also result in unusual blood profiles, the aim of this study was to document the incidence and magnitude of such abnormalities in an elite athlete population. DESIGN AND METHODS: We screened blood samples obtained from 413 female and 739 male elite athletes from 12 countries for known hematologic abnormalities, and compared the algorithm scores for these athletes with those of their healthy counterparts. We also established the magnitude of blood parameters required for model scores to exceed cut-offs associated with rHuEPO use. RESULTS: We found that 0.7% of male and 2.4% of female athletes were iron deficient either with our without anemia. An additional 1.4% of males and 1.0% of females had hemoglobinopathies. On average these athletes' model scores were at or below the score of their healthy counterparts. The greatest influence on our models was hemoglobin concentration. Values of other parameters must exceed normal ranges by a substantial margin in order for model scores to approach levels associated with rHuEPO use. INTERPRETATION AND CONCLUSIONS: The hematologic disorders we encountered in elite athletes were not associated with model scores that exceeded the nominal cut-offs that we have previously recommended to delineate rHuEPO use. We did not find any abnormalities among elite endurance athletes that were associated with high model scores.

ACTN3 genotype is associated with human elite athletic performance.

There is increasing evidence for strong genetic influences on athletic performance and for an evolutionary "trade-off" between performance traits for speed and endurance activities. We have recently demonstrated that the skeletal-muscle actin-binding protein alpha-actinin-3 is absent in 18% of healthy white individuals because of homozygosity for a common stop-codon polymorphism in the ACTN3 gene, R577X. alpha-Actinin-3 is specifically expressed in fast-twitch myofibers responsible for generating force at high velocity. The absence of a disease phenotype secondary to alpha-actinin-3 deficiency is likely due to compensation by the homologous protein, alpha-actinin-2. However, the high degree of evolutionary conservation of ACTN3 suggests function(s) independent of ACTN2. Here, we demonstrate highly significant associations between ACTN3 genotype and athletic performance. Both male and female elite sprint athletes have significantly higher frequencies of the 577R allele than do controls. This suggests that the presence of alpha-actinin-3 has a beneficial effect on the function of skeletal muscle in generating forceful contractions at high velocity, and provides an evolutionary advantage because of increased sprint performance. There is also a genotype effect in female sprint and endurance athletes, with higher than expected numbers of 577RX heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggests that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggests that the R577X polymorphism may have been maintained in the human population by balancing natural selection.

Second-generation blood tests to detect erythropoietin abuse by athletes.

BACKGROUND AND OBJECTIVES: We previously developed blood tests that were introduced at the Sydney 2000 Olympic Games to identify athletes injecting recombinant human erythropoietin (rHuEPO). The aim of this study was to re-analyse our existing database to develop models with heightened sensitivity, using wherever possible blood parameters measurable with appropriate standards of analytical performance. DESIGN AND METHODS: The principal database for this study was derived from a double-blind trial in which 57 recreational athletes were administered either rHuEPO or placebo. Standard discriminant analysis was used to derive two ON models (ON-hes and ON-he) and two OFF models (OFF-hr and OFF-hre) sensitive to accelerated and decelerated erythropoiesis respectively, utilising concentrations of hemoglobin (h), erythropoietin (e) and serum transferrin receptor (s), as well as percent reticulocytes (r). The ability of our models to detect rHuEPO administration was assessed by comparing model scores of subjects in the administration trial with the model scores of 1152 elite athletes from 12 countries. RESULTS: The ability of the new models to detect rHuEPO administration was generally higher than that of our previous models, particularly during phases when low doses of rHuEPO were used, and after injections had ceased. INTERPRETATION AND CONCLUSIONS. The increased stability of the new blood parameters facilitates transport of samples to central laboratories, and the heightened sensitivity of the new models makes them better than existing models for federations wishing to screen samples for urine testing and to identify and target suspect athletes for out-of-competition testing. However procedures should be incorporated that respect an elevated model score caused by genetic, health or environmental circumstances.

Development of reference ranges in elite athletes for markers of altered erythropoiesis.

BACKGROUND AND OBJECTIVES: Our previous research developed two statistical models that are useful indicators of current (ON-model) or recently discontinued (OFF-model) recombinant human erythropoietin (rHuEPO) use by athletes. The component variables of the ON-model are hematocrit (Hct), reticulocyte hematocrit (RetHct), serum erythropoietin (EPO), percent macrocytes (%Macro), and soluble transferrin receptor (sTfr), whilst the OFF-model uses only the first three variables. Genetics and training modalities of elite athletes may conceivably produce unusual values for blood parameters related to erythropoiesis. The aims of this study were to develop reference ranges in elite athletes for key hematologic parameters as well as ON- and OFF-models scores, and to evaluate the effect of ethnicity, gender, residence at moderate altitude (approximately 2000 m) and within-individual variation on the variables and model scores. DESIGN AND METHODS: Over a period of three weeks, 413 female and 739 male elite athletes from 12 countries visited laboratories to provide three blood samples for analysis of blood parameters sensitive to erythropoiesis. For each parameter and for the ON- and OFF-model scores, we used mixed modeling to establish the range within which we could be 95% certain that the value for a randomly chosen athlete would fall, taking into account various random effects (variation within and between subjects and laboratories) and fixed effects (means for different levels of ethnicity, age, sport, altitude of residency). We performed similar analyses for changes in the ON- and OFF-model scores between the three visits. RESULTS: Most fixed effects were accompanied by clear-cut, small to moderate differences in several parameters. However, residency at moderate altitude was accompanied by a much higher hematocrit than residency nearer sea level, with the mean (and 95% confidence limits) for the difference being 2.3 (0.9 to 3.7) and 1.8 (0.1 to 3.5) units for males and females, respectively. Males at altitude also demonstrated a moderately higher ON-model score. Otherwise the influence of these effects was small for ON-, OFF- and changes in model scores. INTERPRETATION AND CONCLUSIONS: Assessment of an athlete's blood parameters and ON- and OFF-model scores may need adjustment for training modalities and other characteristics of the subject. Changes in model scores (together with monitoring of urine samples for the presence of rHuEPO) provide a promising approach to detection of rHuEPO abuse, because they are less sensitive to subject characteristics and less variable than raw model scores.