High-level performances following low altitude training and tapering in warm environments in elite racewalkers.

Current guidelines for prolonged altitude exposure suggest altitude levels ranging from 2000 to 2500 m to optimize an increase in total hemoglobin mass (Hbmass). However, natural low altitude locations (<2000 m) remain popular, highlighting the interest to investigate any possible benefit of low altitude camps for endurance athletes. Ten elite racewalkers (4 women and 6 men) underwent a 4-week "live high-train high" (LHTH) camp at an altitude of 1720 m (PIO2 = 121 mmHg; 20.1°C; 67% relative humidity [RH]), followed by a 3-week tapering phase (20 m; PIO2 = 150 mmHg; 28.3°C; 53% RH) in preparation for the World Athletics Championships (WC). Venous blood samples were withdrawn weekly during the entire observation period. In addition, blood volumes were determined weekly by carbon monoxide rebreathing during altitude exposure and 2 weeks after return to sea level. High-level performances were achieved at the WC (five placings among the Top 10 WC races and three all-time career personal bests). A slight but significant increase in absolute (+1.7%, p = 0.03) and relative Hbmass (+2.3%, p = 0.02) was observed after 4-week LHTH. In addition, as usually observed during LHTH protocols, weekly training distance (+28%, p = 0.02) and duration (+30%, p = 0.04) significantly increased during altitude compared to the pre-LHTH period. Therefore, although direct causation cannot be inferred, these results suggest that the combination of increased training load at low altitudes with a subsequent tapering period in a warm environment is a suitable competition-preparation strategy for elite endurance athletes.

Yearly intrasubject variability of hematological biomarkers in elite athletes for the Athlete Biological Passport.

Confounding factors including exercise and environments challenge the interpretation of individual Athlete Biological Passports (ABPs). This study aimed to investigate the natural variability of hematological ABP parameters over 1 year in elite athletes compared with healthy control subjects and the validity of a multiparametric model estimating plasma volume (PV) shifts to correct individual ABP thresholds. Blood samples were collected monthly with full blood counts performed by flow cytometry (Sysmex XN analyzers) in 20 elite xc-skiers (ELITE) and 20 moderately trained controls. Individual ABP profiles were generated through Anti-Doping Administration & Management System Training, a standalone version of the ABP's adaptive model developed by the World Anti-Doping Agency. Additionally, eight serum parameters were computed as volume-sensitive biomarkers to run a multiparametric model to estimate PV. Variability in ELITE compared with controls was significantly higher for the Abnormal Blood Profile Scores (P = 0.003). Among 12 Atypical Passport Findings (ATPF) initially reported, six could be removed after correction of PV shifts with the multiparametric modeling. However, several ATPF were additionally generated (n = 19). Our study outlines a larger intraindividual variability in elite athletes, likely explained by more frequent exposure to extrinsic factors altering hematological biomarkers. PV correction for individual ABP thresholds allowed to explain most of the atypical findings while generating multiple new ATPF occurrences in the elite population. Overall, accounting for PV shifts in elite athletes was shown to be paramount in this study outlining the opportunity to consider PV variations with novel approaches when interpreting individual ABP profiles.

Indirect biomarkers of blood doping: A systematic review.

The detection of blood doping represents a current major issue in sports and an ongoing challenge for antidoping research. Initially focusing on direct detection methods to identify a banned substance or its metabolites, the antidoping effort has been progressively complemented by indirect approaches. The longitudinal and individual monitoring of specific biomarkers aims to identify nonphysiological variations that may be related to doping practices. From this perspective, the identification of markers sensitive to erythropoiesis alteration is key in the screening of blood doping. The current Athlete Biological Passport implemented since 2009 is composed of 14 variables (including two primary markers, i.e., hemoglobin concentration and OFF score) for the hematological module to be used for indirect detection of blood doping. Nevertheless, research has continually proposed and investigated new markers sensitive to an alteration of the erythropoietic cascade and specific to blood doping. If multiple early markers have been identified (at the transcriptomic level) or developed directly in a diagnostics' kit (at a proteomic level), other target variables at the end of the erythropoietic process (linked with the red blood cell functions) may strengthen the hematological module in the future. Therefore, this review aims to provide a global systematic overview of the biomarkers considered to date in the indirect investigation of blood doping.

Competitive performance as a discriminator of doping status in elite athletes.

As the aim of any doping regime is to improve sporting performance, it has been suggested that analysis of athlete competitive results might be informative in identifying those at greater risk of doping. This research study aimed to investigate the utility of a statistical performance model to discriminate between athletes who have a previous anti-doping rule violation (ADRV) and those who do not. We analysed performances of male and female 100 and 800 m runners obtained from the World Athletics database using a Bayesian spline model. Measures of unusual improvement in performance were quantified by comparing the yearly change in athlete's performance (delta excess performance) to quantiles of performance in their age-matched peers from the database population. The discriminative ability of these measures was investigated using the area under the ROC curve (AUC) with the 55%, 75% and 90% quantiles of the population performance. The highest AUC values across age were identified for the model with a 75% quantile (AUC = 0.78-0.80). The results of this study demonstrate that delta excess performance was able to discriminate between athletes with and without ADRVs and therefore could be used to assist in the risk stratification of athletes for anti-doping purposes.

A new multimodal paradigm for biomarkers longitudinal monitoring: a clinical application to women steroid profiles in urine and blood.

BACKGROUND: Most current state-of-the-art strategies to generate individual adaptive reference ranges are designed to monitor one clinical parameter at a time. An innovative methodology is proposed for the simultaneous longitudinal monitoring of multiple biomarkers. The estimation of individual thresholds is performed by applying a Bayesian modeling strategy to a multivariate score integrating several biomarkers (compound concentration and/or ratio). This multimodal monitoring was applied to data from a clinical study involving 14 female volunteers with normal menstrual cycles receiving testosterone via transdermal route, as to test its ability to detect testosterone administration. The study samples consisted of urine and blood collected during 4 weeks of a control phase and 4 weeks with a daily testosterone gel application. RESULTS: Integrating multiple biomarkers improved the detection of testosterone gel administration with substantially higher sensitivity compared with the distinct follow-up of each biomarker, when applied to selected urine and serum steroid biomarkers, as well as the combination of both. Among the 175 known positive samples, 38% were identified by the multimodal approach using urine biomarkers, 79% using serum biomarkers and 83% by combining biomarkers from both biological matrices, whereas 10%, 67% and 64% were respectively detected using standard unimodal monitoring. SIGNIFICANCE AND NOVELTY: The detection of abnormal patterns can be improved using multimodal approaches. The combination of urine and serum biomarkers reduced the overall number of false-negatives, thus evidencing promising complementarity between urine and blood sampling for doping control, as highlighted in the case of the use of transdermal testosterone preparations. The generation in a multimodal setting of adaptive and personalized reference ranges opens up new opportunities in clinical and anti-doping profiling. The integration of multiple parameters in a longitudinal monitoring is expected to provide a more complete evaluation of individual profiles generating actionable intelligence to further guide sample collection, analysis protocols and decision-making in clinics and anti-doping.

Longitudinal Profiling of Endogenous Steroids in Blood Using the Athlete Biological Passport Approach.

CONTEXT: Detection of endogenous anabolic androgenic steroids (EAAS), like testosterone (T), as doping agents has been improved with the launch of the Steroidal Module of the Athlete Biological Passport (ABP) in urine samples. OBJECTIVE: To target doping practices with EAAS, particularly in individuals with low level of biomarkers excreted in urine, by including new target compounds measured in blood. DESIGN: T and T/androstenedione (T/A4) distributions were obtained from 4 years of anti-doping data and applied as priors to analyze individual profiles from 2 T administration studies in female and male subjects. SETTING: Anti-doping laboratory. Elite athletes (n = 823) and male and female clinical trials subjects (n = 19 and 14, respectively). INTERVENTION(S): Two open-label administration studies were carried out. One involved a control phase period followed by patch and then oral T administration in male volunteers and the other followed female volunteers during 3 menstrual cycles with 28 days of daily transdermal T application during the second month. MAIN OUTCOME MEASURE(S): Serum samples were analyzed for T and A4 and the performance of a longitudinal ABP-based approach was evaluated for T and T/A4. RESULTS: An ABP-based approach set at a 99% specificity flagged all female subjects during the transdermal T application period and 44% of subjects 3 days after the treatment. T showed the best sensitivity (74%) in response to transdermal T application in males. CONCLUSIONS: Inclusion of T and T/A4 as markers in the Steroidal Module can improve the performance of the ABP to identify T transdermal application, particularly in females.

Variability of the urinary and blood steroid profiles in healthy and physically active women with and without oral contraception.

The steroidal module of the athlete biological passport (ABP) targets the use of pseudo-endogenous androgenous anabolic steroids in elite sport by monitoring urinary steroid profiles. Urine and blood samples were collected weekly during two consecutive oral contraceptive pill (OCP) cycles in 15 physically active women to investigate the low urinary steroid concentrations and putative confounding effect of OCP. In urine, testosterone (T) and epitestosterone (E) were below the limit of quantification of 1 ng/ml in 62% of the samples. Biomarkers' variability ranged between 31% and 41%, with a significantly lesser variability for ratios (except for T/E [41%]): 20% for androsterone/etiocholanolone (p < 0.001) and 25% for 5α-androstane-3α,17ß-diol/5ß-androstane-3α,17ß-diol (p < 0.001). In serum, markers' variability (testosterone: 24%, androstenedione: 23%, dihydrotestosterone: 19%, and T/A4: 16%) was significantly lower than in urine (p < 0.001). Urinary A/Etio increased by >18% after the first 2 weeks (p < 0.05) following withdrawal blood loss. In contrast, serum T (0.98 nmol/l during the first week) and T/A4 (0.34 the first week) decreased significantly by more than 25% and 17% (p < 0.05), respectively, in the following weeks. Our results outline steroidal variations during the OCP cycle, highlighting exogenous hormonal preparations as confounder for steroid concentrations in blood. Low steroid levels in urine samples have a clear negative impact on the subsequent interpretation of steroid profile of the ABP. With a greater analytical sensitivity and lesser variability for steroids in healthy active women, serum represents a complementary matrix to urine in the ABP steroidal module.

Future opportunities for the Athlete Biological Passport.

The Athlete Biological Passport (ABP) was introduced to complement the direct anti-doping approach by indirectly outlining the possible use of prohibited substances or methods in sports. The ABP proved its effectiveness, at least through a deterrent effect, even though the matrices used for longitudinal monitoring (urine and blood) are subject to many intrinsic (e.g., genetic) and extrinsic (e.g., environmental conditions) confounding factors. In that context, new and more specific biomarkers are currently under development to enhance both the sensitivity and the specificity of the ABP. Multiple strategies are presently being explored to improve this longitudinal monitoring, with the development of the current modules, the investigation of new strategies, or the screening of new types of doping. Nevertheless, due to the variability induced by indirect biomarkers, the consideration of confounding factors should continuously support this research. Beyond tremendous advances in analytical sensitivity, machine learning-based approaches seem inevitable to facilitate an expert interpretation of numerous biological profiles and promote anti-doping efforts. This perspective article highlights the current innovations of the Athlete Biological Passport that seem the most promising. Through different research axes, this short manuscript provides an opportunity to bring together approaches that are more widely exploited (e.g., omics strategies) and others in the early stages of investigation (e.g., artificial intelligence) seeking to develop the ABP.

Comparison of three different blood matrices for the quantification of endogenous steroids using UHPLC-MS/MS.

Urine is currently the matrix of choice for the detection of exogenous substances but also for the application of the steroidal module of the Athlete Biological Passport (ABP) consisting in a longitudinal monitoring of steroid biomarkers. To fill the limitations related to urine, the longitudinal monitoring of serum steroids concentration in the so-called 'blood steroid profile' has recently been proposed. Although serum samples are collected much less than urine samples, plasma derived from ABP whole blood samples used for the full blood count could be exploited for the quantification of endogenous steroids. Alternatively, dried blood spots (DBS) that are much easier to collect could also serve as matrix for the steroid profile. In this study, we compared the concentration levels of several endogenous steroids measured in three different blood matrices (serum, plasma and DBS) collected from 100 elite athletes participating in the 2019 Doha World Athletics Championships using UHPLC-MS/MS. Plasma and serum samples were collected by venipuncture, whereas DBS were generated from whole blood samples. Although steroids demonstrated a good agreement between the three matrices, a slight but acceptable underestimation (10%-20%) was observed in plasma compared with serum. The difference between DBS and the two other matrices was dependent of the bias between serum and plasma. We also showed that a generic HCT correction for DBS could be a valuable approach for quantitative measurements. This study demonstrates the possibility to use three different matrices for the quantification of endogenous steroids although the slight discrepancies should be considered for longitudinal evaluation.

Brain-muscle interplay during endurance self-paced exercise in normobaric and hypobaric hypoxia.

Purpose: Hypoxia is one major environmental factor, supposed to mediate central motor command as well as afferent feedbacks at rest and during exercise. By using a comparison of normobaric (NH) and hypobaric (HH) hypoxia with the same ambient pressure in oxygen, we examined the potential differences on the cerebrovascular and muscular regulation interplay during a self-paced aerobic exercise. Methods: Sixteen healthy subjects performed three cycling time-trials (250 kJ) in three conditions: HH, NH and normobaric normoxia (NN) after 24 h of exposure. Cerebral and muscular oxygenation were assessed by near-infrared spectroscopy, cerebral blood flow by Doppler ultrasound system. Gas exchanges, peripheral oxygen saturation, power output and associated pacing strategies were also continuously assessed. Results: The cerebral oxygen delivery was lower in hypoxia than in NN but decreased similarly in both hypoxic conditions. Overall performance and pacing were significantly more down-regulated in HH versus NH, in conjunction with more impaired systemic (e.g. saturation and cerebral blood flow) and prefrontal cortex oxygenation during exercise. Conclusions: The difference in pacing was likely the consequence of a complex interplay between systemic alterations and cerebral oxygenation observed in HH compared to NH, aiming to maintain an equivalent cerebral oxygen delivery despite higher adaptive cost (lower absolute power output for the same relative exercise intensity) in HH compared to NH.

Altitude and Erythropoietin: Comparative Evaluation of Their Impact on Key Parameters of the Athlete Biological Passport: A Review.

The hematological module of the Athlete's Biological Passport (ABP) identifies doping methods and/or substances used to increase the blood's capacity to transport or deliver oxygen to the tissues. Recombinant human erythropoietin (rhEPOs) are doping substances known to boost the production of red blood cells and might have an effect on the blood biomarkers of the ABP. However, hypoxic exposure influences these biomarkers similarly to rhEPOs. This analogous impact complicates the ABP profiles' interpretation by antidoping experts. The present study aimed to collect and identify, through a literature search, the physiological effects on ABP blood biomarkers induced by these external factors. A total of 43 studies were selected for this review. A positive correlation (R2 = 0.605, r = 0.778, p < 0.001) was identified between the hypoxic dose and the increase in hemoglobin concentration (HGB) percentage. In addition, the change in the reticulocyte percentage (RET%) has been identified as one of the most sensitive parameters to rhEPO use. The mean effects of rhEPO on blood parameters were greater than those induced by hypoxic exposure (1.7 times higher for HGB and RET% and 4 times higher for hemoglobin mass). However, rhEPO micro-doses have shown effects that are hardly distinguishable from those identified after hypoxic exposure. The results of the literature search allowed to identify temporal and quantitative evolution of blood parameters in connection with different hypoxic exposure doses, as well as different rhEPOs doses. This might be considered to provide justified and well-documented interpretations of physiological changes in blood parameters of the Athlete Biological Passport.

Similar Supine Heart Rate Variability Changes During 24-h Exposure to Normobaric vs. Hypobaric Hypoxia.

Purpose: This study aimed to investigate the differences between normobaric (NH) and hypobaric hypoxia (HH) on supine heart rate variability (HRV) during a 24-h exposure. We hypothesized a greater decrease in parasympathetic-related parameters in HH than in NH. Methods: A pooling of original data from forty-one healthy lowland trained men was analyzed. They were exposed to altitude either in NH (FIO2 = 15.7 ± 2.0%; PB = 698 ± 25 mmHg) or HH (FIO2 = 20.9%; PB = 534 ± 42 mmHg) in a randomized order. Pulse oximeter oxygen saturation (SpO2), heart rate (HR), and supine HRV were measured during a 7-min rest period three times: before (in normobaric normoxia, NN), after 12 (H12), and 24 h (H24) of either NH or HH exposure. HRV parameters were analyzed for time- and frequency-domains. Results: SpO2 was lower in both hypoxic conditions than in NN and was higher in NH than HH at H24. Subjects showed similarly higher HR during both hypoxic conditions than in NN. No difference in HRV parameters was found between NH and HH at any time. The natural logarithm of root mean square of the successive differences (LnRMSSD) and the high frequency spectral power (HF), which reflect parasympathetic activity, decreased similarly in NH and HH when compared to NN. Conclusion: Despite SpO2 differences, changes in supine HRV parameters during 24-h exposure were similar between NH and HH conditions indicating a similar decrease in parasympathetic activity. Therefore, HRV can be analyzed similarly in NH and HH conditions.

Prevalence Estimate of Blood Doping in Elite Track and Field Athletes During Two Major International Events.

In elite sport, the Athlete Biological Passport (ABP) was invented to tackle cheaters by monitoring closely changes in biological parameters, flagging atypical variations. The hematological module of the ABP was indeed adopted in 2011 by World Athletics (WA). This study estimates the prevalence of blood doping based on hematological parameters in a large cohort of track and field athletes measured at two international major events (2011 and 2013 WA World Championships) with a hypothesized decrease in prevalence due to the ABP introduction. A total of 3683 blood samples were collected and analyzed from all participating athletes originating from 209 countries. The estimate of doping prevalence was obtained by using a Bayesian network with seven variables, as well as "blood doping" as a variable mimicking doping with low-doses of recombinant human erythropoietin (rhEPO), to generate reference cumulative distribution functions (CDFs) for the Abnormal Blood Profile Score (ABPS) from the ABP. Our results from robust hematological parameters indicate an estimation of an overall blood doping prevalence of 18% in 2011 and 15% in 2013 (non-significant difference) in average in endurance athletes [95% Confidence Interval (CI) 14-22 and 12-19% for 2011 and 2013, respectively]. A higher prevalence was observed in female athletes (22%, CI 16-28%) than in male athletes (15%, CI 9-20%) in 2011. In conclusion, this study presents the first comparison of blood doping prevalence in elite athletes based on biological measurements from major international events that may help scientists and experts to use the ABP in a more efficient and deterrent way.

Positive expiratory pressure improves arterial and cerebral oxygenation in acute normobaric and hypobaric hypoxia.

Positive expiratory pressure (PEP) has been shown to limit hypoxia-induced reduction in arterial oxygen saturation, but its effectiveness on systemic and cerebral adaptations, depending on the type of hypoxic exposure [normobaric (NH) versus hypobaric (HH)], remains unknown. Thirteen healthy volunteers completed three randomized sessions consisting of 24-h exposure to either normobaric normoxia (NN), NH (inspiratory oxygen fraction, FiO2 = 13.6%; barometric pressure, BP = 716 mmHg; inspired oxygen partial pressure, PiO2 = 90.9 ± 1.0 mmHg), or HH (3,450 m, FiO2 = 20.9%, BP = 482 mmHg, PiO2 = 91.0 ± 0.6 mmHg). After the 6th and the 22nd hours, participants breathed quietly through a facemask with a 10-cmH2O PEP for 2 × 5 min interspaced with 5 min of free breathing. Arterial (SpO2, pulse oximetry), quadriceps, and cerebral (near-infrared spectroscopy) oxygenation, middle cerebral artery blood velocity (MCAv; transcranial Doppler), ventilation, and cardiovascular responses were recorded continuously. SpO2without PEP was significantly lower in HH (87 ± 4% on average for both time points, P < 0.001) compared with NH (91 ± 3%) and NN (97 ± 1%). PEP breathing did not change SpO2 in NN but increased it similarly in NH and HH (+4.3 ± 2.5 and +4.7 ± 4.1% after 6h; +3.5 ± 2.2 and +4.1 ± 2.9% after 22h, both P < 0.001). Although MCAv was reduced by PEP (in all sessions and at all time points, -6.0 ± 4.2 cm/s on average, P < 0.001), the cerebral oxygenation was significantly improved (P < 0.05) with PEP in both NH and HH, with no difference between conditions. These data indicate that PEP could be an attractive nonpharmacological means to improve arterial and cerebral oxygenation under both normobaric and hypobaric mild hypoxic conditions in healthy participants.

Fighting Doping in Elite Sports: Blood for All Tests!

In the fight against doping, detection of doping substances in biological matrices is paramount. Analytical possibilities have evolved and sanctioning a doping scenario by detecting forbidden bioactive compounds circulating unmodified in blood is nowadays very attractive. In addition, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) a decade ago as a new paradigm inferring the use of prohibited substances or methods through longitudinal profiling, or serial analyses of indirect biomarkers of doping, to be both scientifically and legally robust. After the introduction in 2008 of an hematological module (i.e., based on variations of blood variables) aiming to identify enhancement of oxygen transport and any form of blood transfusion or manipulation, a urinary steroidal module was additionally introduced in 2014 composed of concentrations and ratios of various endogenously produced steroidal hormones. Some evidence tends to discredit steroid profiles obtained from urine analyses to detect the use of endogenous androgenic anabolic steroids (EAAS), when administered exogenously, due to high rates of false negatives with short half-life and topical formulations rendering profile alteration only minimal or equivocal. On the other hand, steroid hormones quantification in blood showed a promising ability to detect testosterone doping and interesting complementarities to the ABP thanks to the most recent analytical techniques (UHPLC-HRMS or/and MS/MS). This perspective article explores the opportunities of blood samples to monitor not only hematological but also steroid profiles in elite athletes.

Worldwide distribution of blood values in elite track and field athletes: Biomarkers of altered erythropoiesis.

For the first time, blood samples were collected in all athletes participating in a major sporting event of the International Association of Athletics Federations (IAAF) (Athletics World Championships 2011, Daegu, Korea). All variables obtained from blood analyses were incorporated into the individual blood profiles of each athlete for the so-called athlete biological passport (ABP). This unprecedented data collection highlighted differences for a few blood biomarkers commonly measured and reported for the ABP on some group of athletes. Subsequently, blood tests analyses for all athletes were repeated during the following World Championships (2013, Moscow, Russia). Both sets of blood tests were then used to set up the distribution of blood values for track and field athletes considering potential confounding factors such as gender, age, discipline, origin of the athlete (continental classification), and time of blood collection. Implementation of well-defined distribution of blood values will allow to improve the estimation of blood doping prevalence among a specific population of athletes in track and field.

Do male athletes with already high initial haemoglobin mass benefit from 'live high-train low' altitude training?

NEW FINDINGS: What is the central question of this study? It has been assumed that athletes embarking on an 'live high-train low' (LHTL) camp with already high initial haemoglobin mass (Hbmass ) have a limited ability to increase their Hbmass further post-intervention. Therefore, the relationship between initial Hbmass and post-intervention increase was tested with duplicate Hbmass measures and comparable hypoxic doses in male athletes. What is the main finding and its importance? There were trivial to moderate inverse relationships between initial Hbmass and percentage Hbmass increase in endurance and team-sport athletes after the LHTL camp, indicating that even athletes with higher initial Hbmass can reasonably expect Hbmass gains post-LHTL. It has been proposed that athletes with high initial values of haemoglobin mass (Hbmass ) will have a smaller Hbmass increase in response to 'live high-train low' (LHTL) altitude training. To verify this assumption, the relationship between initial absolute and relative Hbmass values and their respective Hbmass increase following LHTL in male endurance and team-sport athletes was investigated. Overall, 58 male athletes (35 well-trained endurance athletes and 23 elite male field hockey players) undertook an LHTL training camp with similar hypoxic doses (200-230 h). The Hbmass was measured in duplicate pre- and post-LHTL by the carbon monoxide rebreathing method. Although there was no relationship (r = 0.02, P = 0.91) between initial absolute Hbmass (in grams) and the percentage increase in absolute Hbmass , a moderate relationship (r = -0.31, P = 0.02) between initial relative Hbmass (in grams per kilogram) and the percentage increase in relative Hbmass was detected. Mean absolute and relative Hbmass increased to a similar extent (P ≥ 0.81) in endurance (from 916 ± 88 to 951 ± 96 g, +3.8%, P < 0.001 and from 13.1 ± 1.2 to 13.6 ± 1.1 g kg-1 , +4.1%, P < 0.001, respectively) and team-sport athletes (from 920 ± 120 to 957 ± 127 g, +4.0%, P < 0.001 and from 11.9 ± 0.9 to 12.3 ± 0.9 g kg-1 , +4.0%, P < 0.001, respectively) after LHTL. The direct comparison study using individual data of male endurance and team-sport athletes and strict methodological control (duplicate Hbmass measures and matched hypoxic dose) indicated that even athletes with higher initial Hbmass can reasonably expect Hbmass gain post-LHTL.

Acute and chronic changes in baroreflex sensitivity in hypobaric vs. normobaric hypoxia.

Normobaric hypoxia (NH) is used as a surrogate for hypobaric hypoxia (HH). Recent studies reported physiological differences between NH and HH. Baroreflex sensitivity (BRS) decreases at altitude or following intense training. However, until now no study compared the acute and chronic changes of BRS in NH vs. HH. First, BRS was assessed in 13 healthy male subjects prior and after 20 h of exposure at 3450 m (study 1), and second in 15 well-trained athletes prior and after 18 days of "live-high train-low" (LHTL) at 2250 m (study 2) in NH vs. HH. BRS decreased (p < 0.05) to the same extent in NH and HH after 20 h of hypoxia and after LHTL. These results confirm that altitude decreases BRS but the decrease is similar between HH and NH. The persistence of this decrease after the cessation of a chronic exposure is new and does not differ between HH and NH. The previously reported physiological differences between NH and HH do not appear strong enough to induce different BRS responses.

Individual hemoglobin mass response to normobaric and hypobaric "live high-train low": A one-year crossover study.

The purpose of this research was to compare individual hemoglobin mass (Hbmass) changes following a live high-train low (LHTL) altitude training camp under either normobaric hypoxia (NH) or hypobaric hypoxia (HH) conditions in endurance athletes. In a crossover design with a one-year washout, 15 male triathletes randomly performed two 18-day LHTL training camps in either HH or NH. All athletes slept at 2,250 meters and trained at altitudes <1,200 meters. Hbmass was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre) and immediately after (post) each 18-day training camp. Hbmass increased similarly in HH (916-957 g, 4.5 ± 2.2%, P < 0.001) and in NH (918-953 g, 3.8 ± 2.6%, P < 0.001). Hbmass changes did not differ between HH and NH (P = 0.42). There was substantial interindividual variability among subjects to both interventions (i.e., individual responsiveness or the individual variation in the response to an intervention free of technical noise): 0.9% in HH and 1.7% in NH. However, a correlation between intraindividual ΔHbmass changes (%) in HH and in NH (r = 0.52, P = 0.048) was observed. HH and NH evoked similar mean Hbmass increases following LHTL. Among the mean Hbmass changes, there was a notable variation in individual Hbmass response that tended to be reproducible.NEW & NOTEWORTHY This is the first study to compare individual hemoglobin mass (Hbmass) response to normobaric and hypobaric live high-train low using a same-subject crossover design. The main findings indicate that hypobaric and normobaric hypoxia evoked a similar mean increase in Hbmass following 18 days of live high-train low. Notable variability and reproducibility in individual Hbmass responses between athletes was observed, indicating the importance of evaluating individual Hbmass response to altitude training.

Sleep Disordered Breathing During Live High-Train Low in Normobaric Versus Hypobaric Hypoxia.

Saugy, Jonas J., Laurent Schmitt, Sibylle Fallet, Raphael Faiss, Jean-Marc Vesin, Mattia Bertschi, Raphaël Heinzer, and Grégoire P. Millet. Sleep disordered breathing during live high-train low in normobaric versus hypobaric hypoxia. High Alt Med Biol. 17:233-238, 2016.-The present study aimed to compare sleep disordered breathing during live high-train low (LHTL) altitude camp using normobaric hypoxia (NH) and hypobaric hypoxia (HH). Sixteen highly trained triathletes completed two 18-day LHTL camps in a crossover designed study. They trained at 1100-1200 m while they slept either in NH at a simulated altitude of 2250 m or in HH. Breathing frequency and oxygen saturation (SpO2) were recorded continuously during all nights and oxygen desaturation index (ODI 3%) calculated. Breathing frequency was lower for NH than HH during the camps (14.6 ± 3.1 breath × min-1 vs. 17.2 ± 3.4 breath × min-1, p < 0.001). SpO2 was lower for HH than NH (90.8 ± 0.3 vs. 91.9 ± 0.2, p < 0.001) and ODI 3% was higher for HH than NH (15.1 ± 3.5 vs. 9.9 ± 1.6, p < 0.001). Sleep in moderate HH is more altered than in NH during a LHTL camp.