An observational human study investigating the effect of anabolic androgenic steroid use on the transcriptome of skeletal muscle and whole blood using RNA-Seq.

BACKGROUND: The effects of Anabolic Androgenic Steroids (AAS) are largely illustrated through Androgen Receptor induced gene transcription, yet RNA-Seq has yet to be conducted on human whole blood and skeletal muscle. Investigating the transcriptional signature of AAS in blood may aid AAS detection and in muscle further understanding of AAS induced hypertrophy. METHODS: Males aged 20-42 were recruited and sampled once: sedentary controls (C), resistance trained lifters (RT) and resistance trained current AAS users (RT-AS) who ceased exposure ≤ 2 or ≥ 10 weeks prior to sampling. RT-AS were sampled twice as Returning Participants (RP) if AAS usage ceased for ≥ 18 weeks. RNA was extracted from whole blood and trapezius muscle samples. RNA libraries were sequenced twice, for validation purposes, on the DNBSEQ-G400RS with either standard or CoolMPS PE100 reagents following MGI protocols. Genes were considered differentially expressed with FDR < 0.05 and a 1.2- fold change. RESULTS: Cross-comparison of both standard reagent whole blood (N = 55: C = 7, RT = 20, RT-AS ≤ 2 = 14, RT-AS ≥ 10 = 10, RP = 4; N = 46: C = 6, RT = 17, RT-AS ≤ 2 = 12, RT-AS ≥ 10 = 8, RP = 3) sequencing datasets, showed that no genes or gene sets/pathways were differentially expressed between time points for RP or between group comparisons of RT-AS ≤ 2 vs. C, RT, or RT-AS ≥ 10. Cross-comparison of both muscle (N = 51, C = 5, RT = 17, RT-AS ≤ 2 = 15, RT-AS ≥ 10 = 11, RP = 3) sequencing (one standard & one CoolMPS reagent) datasets, showed one gene, CHRDL1, which has atrophying potential, was upregulated in RP visit two. In both muscle sequencing datasets, nine differentially expressed genes, overlapped with RT-AS ≤ 2 vs. RT and RT-AS ≤ 2 vs. C, but were not differentially expressed with RT vs. C, possibly suggesting they are from acute doping alone. No genes seemed to be differentially expressed in muscle after the long-term cessation of AAS, whereas a previous study found long term proteomic changes. CONCLUSION: A whole blood transcriptional signature of AAS doping was not identified. However, RNA-Seq of muscle has identified numerous differentially expressed genes with known impacts on hypertrophic processes that may further our understanding on AAS induced hypertrophy. Differences in training regimens in participant groupings may have influenced results. Future studies should focus on longitudinal sampling pre, during and post-AAS exposure to better control for confounding variables.

Association between basketball playing position and ACTN3 R577X polymorphism in athletes of first division Brazilian Basketball League.

INTRODUCTION: Genetic-association studies have shown that some polymorphisms are associated with different aspects of athletic performance, including very specific features, such as players' position in team sports, like soccer, rugby, and Australian football. However, this type of association has not been investigated in Basketball yet. The present study analyzed the association of ACTN3 R577X, AGT M268T, ACE I/D and BDKRB2+9/-9 polymorphisms with the position of basketball players. METHODS: One hundred fifty-two male athletes from 11 teams of the first division of Brazilian Basketball League and 154 male Brazilian controls were genotyped. The analyses of the ACTN3 R577X and AGT M268T were performed by the allelic discrimination method, while ACE I/D and BDKRB2+9/-9 by conventional PCR followed by electrophorese in agarose gel. RESULTS: The results showed a significant effect of height on all positions and an association between the genetic polymorphisms analyzed and basketball positions. In addition, a significantly higher frequency of ACTN3 577XX genotype was observed in Point Guards. Also, compared to Point Guard, ACTN3 RR and RX were more prevalent in the Shooting Guard and Small Forward group and RR genotype was also more prevalent in the Power Forward and Center group. CONCLUSION: The main finding of our study was the positive association of ACTN3 R577X polymorphism and basketball playing position, and a suggestion of genotypes related to strength/power performance with post players and genotypes related to endurance performance with point guard players.

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

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

The MMAAS Project: An Observational Human Study Investigating the Effect of Anabolic Androgenic Steroid Use on Gene Expression and the Molecular Mechanism of Muscle Memory.

OBJECTIVE: It remains unknown whether myonuclei remain elevated post anabolic-androgenic steroid (AAS) usage in humans. Limited data exist on AAS-induced changes in gene expression. DESIGN: Cross-sectional/longitudinal. SETTING: University. PARTICIPANTS: Fifty-six men aged 20 to 42 years. INDEPENDENT VARIABLES: Non-resistance-trained (C) or resistance-trained (RT), RT currently using AAS (RT-AS), of which if AAS usage ceased for ≥18 weeks resampled as Returning Participants (RP) or RT previously using AAS (PREV). MAIN OUTCOME MEASURES: Myonuclei per fiber and cross-sectional area (CSA) of trapezius muscle fibers. RESULTS: There were no significant differences between C (n = 5), RT (n = 15), RT-AS (n = 17), and PREV (n = 6) for myonuclei per fiber. Three of 5 returning participants (RP1-3) were biopsied twice. Before visit 1, RP1 ceased AAS usage 34 weeks before, RP2 and RP3 ceased AAS usage ≤2 weeks before, and all had 28 weeks between visits. Fiber CSA decreased for RP1 and RP2 between visits (7566 vs 6629 µm 2 ; 7854 vs 5677 µm 2 ) while myonuclei per fiber remained similar (3.5 vs 3.4; 2.5 vs 2.6). Respectively, these values increased for RP3 between visits (7167 vs 7889 µm 2 ; 2.6 vs 3.3). CONCLUSIONS: This cohort of past AAS users did not have elevated myonuclei per fiber values, unlike previous research, but reported AAS usage was much lower. Training and AAS usage history also varied widely among participants. Comparable myonuclei per fiber numbers despite decrements in fiber CSA postexposure adheres with the muscle memory mechanism, but there is variation in usage relative to sampling date and low numbers of returning participants.

Integrating Whole Blood Transcriptomic Collection Procedures Into the Current Anti-Doping Testing System, Including Long-Term Storage and Re-Testing of Anti-Doping Samples.

Introduction: Recombinant human erythropoietin (rHuEPO) administration studies involving transcriptomic approaches have demonstrated a gene expression signature that could aid blood doping detection. However, current anti-doping testing does not involve collecting whole blood into tubes with RNA preservative. This study investigated if whole blood in long-term storage and whole blood left over from standard hematological testing in short-term storage could be used for transcriptomic analysis despite lacking RNA preservation. Methods: Whole blood samples were collected from twelve and fourteen healthy nonathletic males, for long-term and short-term storage experiments. Long-term storage involved whole blood collected into Tempus™ tubes and K2EDTA tubes and subjected to long-term (i.e., ‒80°C) storage and RNA extracted. Short-term storage involved whole blood collected into K2EDTA tubes and stored at 4°C for 6‒48 h and then incubated at room temperature for 1 and 2 h prior to addition of RNA preservative. RNA quantity, purity, and integrity were analyzed in addition to RNA-Seq using the MGI DNBSEQ-G400 on RNA from both the short- and long-term storage studies. Genes presenting a fold change (FC) of >1.1 or < ‒1.1 with p ≤ 0.05 for each comparison were considered differentially expressed. Microarray analysis using the Affymetrix GeneChip® Human Transcriptome 2.0 Array was additionally conducted on RNA from the short-term study with a false discovery ratio (FDR) of ≤0.05 and an FC of >1.1 or < ‒1.1 applied to identify differentially expressed genes. Results: RNA quantity, purity, and integrity from whole blood subjected to short- and long-term storage were sufficient for gene expression analysis. Long-term storage: when comparing blood tubes with and without RNA preservation 4,058 transcripts (6% of coding and non-coding transcripts) were differentially expressed using microarray and 658 genes (3.4% of mapped genes) were differentially expressed using RNA-Seq. Short-term storage: mean RNA integrity and yield were not significantly different at any of the time points. RNA-Seq analysis revealed a very small number of differentially expressed genes (70 or 1.37% of mapped genes) when comparing samples stored between 6 and 48 h without RNA preservative. None of the genes previously identified in rHuEPO administration studies were differently expressed in either long- or short-term storage experiments. Conclusion: RNA quantity, purity, and integrity were not significantly compromised from short- or long-term storage in blood storage tubes lacking RNA stabilization, indicating that transcriptomic analysis could be conducted using anti-doping samples collected or biobanked without RNA preservation.

Risk factors and future directions for preventing and diagnosing exertional rhabdomyolysis.

Exertional rhabdomyolysis may occur when an individual is subjected to strenuous physical exercise. It is occasionally associated with myoglobinuria (i.e. "cola-colored" urine) alongside muscle pain and weakness. The pathophysiology of exertional rhabdomyolysis involves striated muscle damage and the release of cellular components into extracellular fluid and bloodstream. This can cause acute renal failure, electrolyte abnormalities, arrhythmias and potentially death. Exertional rhabdomyolysis is observed in high-performance athletes who are subjected to intense, repetitive and/or prolonged exercise but is also observed in untrained individuals and highly trained or elite groups of military personnel. Several risk factors have been reported to increase the likelihood of the condition in athletes, including: viral infection, drug and alcohol abuse, exercise in intensely hot and humid environments, genetic polymorphisms (e.g. sickle cell trait and McArdle disease) and epigenetic modifications. This article reviews several of these risk factors and proposes screening protocols to identify individual susceptibility to exertional rhabdomyolysis as well as the relevance of proteomics for the evaluation of potential biomarkers of muscle damage.

Anti-doping and other sport integrity challenges during the COVID-19 pandemic.

The coronavirus disease (COVID-19) pandemic has had an unprecedent impact on the world of sport and society at large. Many of the challenges with respect to integrity previously facing competitive sport have been accentuated further during the pandemic. Threats to the integrity of sporting competition include traditional doping, issues of technological fairness, and integration of transgender and intersex athletes in elite sport. The enforced lull in competitive sport provides an unprecedented opportunity for stakeholders in sport to focus on unresolved integrity issues and develop and implement long-lasting solutions. There needs to be a concerted effort to focus on the many technological innovations accelerated by and perfected during COVID-19 that have enabled us to work from home, such as teaching students on-line, applications for medical advice, prescriptions and referrals, and treating patients in hospitals/care homes via video links and use these developments and innovations to enhance sport integrity and anti-doping procedures. Positive sports integrity actions will require a considered application of all such technology, as well as the inclusion of "omics" technology, big data, bioinformatics and machine learning/artificial intelligence approaches to modernize sport. Applications include protecting the health of athletes, considered non-discriminative integration of athletes into elite sport, intelligent remote testing to improve the frequency of anti-doping tests, detection windows, and the potential combination with omics technology to improve the tests' sensitivity and specificity in order to protect clean athletes and deter doping practices.

Analysis of Anti-Doping Rule Violations That Have Impacted Medal Results at the Summer Olympic Games 1968-2012.

INTRODUCTION: Since 2004, the International Olympic Committee (IOC) store all samples collected at summer Olympic Games (OG) for retrospective re-analysis with more advanced analytical techniques to catch doping athletes. METHODS: All announced Anti-Doping Rule Violations (ADRVs) from IOC re-tests of the 2004, 2008 and 2012 OG (via IOC, International Federations and Athletics Integrity Unit public data) and other ADRVs confirmed to impact OG results from 1968 to 2012 (via the list of Doping Irregularities on olympedia.org) were collated to investigate how many medals have been impacted by ADRVs, when the ADRV was identified relative to the OG in question and its cause. RESULTS: One hundred and thirty-four medals were impacted by ADRVs but only 26% of these ADRVs were identified at the time of the OG. Most ADRVs impacting medal results (74%) were identified retrospectively, either from events prior to the OG (17%) or via IOC re-tests of samples from 2004, 2008 and 2012 (57%). ADRVs impacting medal results from these re-tests took a mean of 6.8 ± 2.0 years to be announced relative to the end of the OG in which the medal was originally won. Exogenous Anabolic Androgenic Steroid metabolites were present in 90% of all athlete (n = 142) samples from IOC re-tests with dehydrochloromethyltestosterone and stanozolol accounting for 79% of detected substances. Athletics (n = 64) and weightlifting (n = 62) were the most affected sports. CONCLUSION: This analysis shows the frequency of targeted pre-OG Out-of-Competition testing should increase. We advocate for long-term sample storage to continue and additionally incorporate novel and potentially complementary technologies/sample matrices.

Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement.

Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.

Doping practices in international weightlifting: analysis of sanctioned athletes/support personnel from 2008 to 2019 and retesting of samples from the 2008 and 2012 Olympic Games.

BACKGROUND: The pervasiveness of doping and findings of anti-doping corruption threaten weightlifting's position at the 2024 Olympic Games. Analysing the practices of doping in weightlifters could identify patterns in doping that assist in future detection. METHODS: We analysed publicly available data on sanctioned athletes/support personnel from the International Weightlifting Federation between 2008 and 2019 and announced retrospective Anti-Doping Rule Violations (ADRVs) from the 2008 and 2012 Olympic Games. RESULTS: There were 565 sanctions between 2008 and 2019 of which 82% related to the detection of exogenous Anabolic Androgenic Steroid (AAS) metabolites and markers indicating endogenous AAS usage. The detection of exogenous AAS metabolites, markers of endogenous AAS usage and other substance metabolites varied by IWF Continental Federation (p ≤ 0.05) with Europe (74%, 11%, 15%) and Asia (70%, 15%, 15%) showing a higher detection of exogenous AAS compared to Pan America (37%, 30%, 33%) and Africa (50%, 17%, 33%). When looking at the 10 most detected substances, the nations with the highest number of sanctions (range 17-35) all had at least one overrepresented substance that accounted for 38-60% of all detected substances. The targeted re-analysis of samples from the 2008 and 2012 Olympic Games due to the discovery of long-term metabolites for exogenous AAS resulted in 61 weightlifters producing retrospective ADRVs. This includes 34 original medallists (9 gold, 10 silver and 15 bronze), the highest of any sport identified by Olympic Games sample re-testing. The exogenous AAS dehydrochloromethyltestosterone and stanozolol accounted for 83% of detected substances and were present in 95% of these samples. CONCLUSION: Based on these findings of regional differences in doping practices, weightlifting would benefit from the targeted testing of certain regions and continuing investment in long-term sample storage as the sensitivity and specificity of detection continues to improve.

Previous experience, aerobic capacity and body composition are the best predictors for Olympic distance triathlon performance: Predictors in amateur triathlon.

OBJECTIVE: Present study examines predictors of the overall race time and disciplines in the Olympic distance triathlon. METHODS: Thirty-nine male and six female triathletes were evaluated for anthropometric, physiological, genetic, training, clinical and circadian characteristics. Body composition, maximum capacity for oxygen uptake (V˙O2max), maximum aerobic velocity (MAV), anaerobic threshold (AT), triathlon experience (TE) and XX genotype for α-actinin 3 affected total race time (p<0.05). RESULTS: Total race time can be predicted by MAV (ß = -0.430, t = -3.225, p = 0.003), TE (ß = -0.378, t = -3.605, p = 0.001), and percentage of lean mass (%LM) (ß = -0.332, t = -2.503, p = 0.017). Swimming can be predicted by MAV (ß = -0.403, t = -3.239, p = 0.002), TE (ß = -0.339, t = -2.876, p = 0.007), and AT%V˙O2max (ß = 0.281, t = 2.278, p = 0.028). Cycling can be predicted by MAV (ß = -0.341, t = -2.333, p = 0.025), TE (ß = -0.363, t = -3.172, p = 0.003), and %LM (ß = -0.326, t = -2.265, p = 0.029). In running split, MAV (ß = -0.768, t = -6.222, p < 0.001) was the only parameter present in the best multiple linear regression model. CONCLUSION: The most important variables in multiple regression models for estimating performance were MAV, TE, AT and %LM.

Association between ACTN3 and acute mountain sickness.

BACKGROUND: During the process of acclimatization, when our organism needs to adjust several metabolic processes in the attempt of establishing a better oxygenation, it is normal that individuals present some symptoms that can lead to the disease of the mountain. However, not everyone presents such symptoms and individuals native of high altitudes regions present genetic differences compared to natives of low altitudes which can generate a better acute adaptation. One of these differences is the higher proportion of type I muscle fibers, which may originate from the R577X polymorphism of the ACTN3 gene. The aim of this study was to compare the response of individuals with different ACTN3 genotypes at simulated 4500 m altitude on the presence of Acute Mountain Sickness (AMS) symptoms. Twenty-three volunteers (RR = 7, RX = 8, XX = 8) spent 4 hours exposed to a simulated altitude of 4500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2, heart rate and the symptoms of AMS were analyzed immediately before entering the chamber and at each hour of exposure. Statistical analysis was performed using IBM SPSS Statistics 21 software. RESULTS: Our results point to an association between AMS symptoms and the presence of R allele from R577X polymorphism. CONCLUSION: We conclude that individuals with at least one R allele of the R577X polymorphism seems to be more susceptible to the effects of hypoxia during the acclimatization process and may develop AMS symptoms.

Angiotensin-Converting Enzyme Related-Polymorphisms on Inflammation, Muscle and Myocardial Damage After a Marathon Race.

Muscle damage is one of the most important factors that affect muscle fatigue during endurance exercise. Recent evidence suggests that the renin-angiotensin system impacts on skeletal muscle wasting. The aim of this study was to determine association between the AGT Met235Thr, ACE I/D and BDKRB2 -9/+9 polymorphisms with inflammation, myocardial and muscle injury induced by endurance exercise. Eighty-one Brazilian male runners participated in this study and completed the International Marathon of Sao Paulo. Muscle and myocardial damage markers (alanine transaminase, ALT, aspartate transaminase, AST, lactic dehydrogenase, LDH, creatine kinase, CK, Troponin, pro BNP, myoglobin, and CK-MB) and inflammatory mediators (IL-6, IL-8, IL-10, IL12p70, IL1ß, and TNF-α) were determined one day before, immediately after, one day after, and three days after the event. Muscle damage was also determined fifteen days after race and angiotensinogen (AGT) Met235Thr, angiotensin-converting enzyme (ACE) I/D, and Bradykinin B2 receptor (BDKRB2) -9/+9 polymorphisms were determined. Marathon race participation induced an increase in all muscle damage and inflammatory markers evaluated (p < 0.0001). The muscle damage markers, troponin and pro BNP, CK and LDH and inflammatory markers, IL-6, IL-8, IL-1ß and IL-10 were also higher in ACE II genotype immediately after race, compared to DD genotype. The percentage of runners higher responders (>500U/I) to CK levels was higher for II genotypes (69%) compared to DD and ID genotypes (38% and 40%, respectively) immediately after. Troponin, pro BNP and IL-1ß, IL-8 levels were also elevated in AGT MM genotype compared to TT genotype athletes after and/or one day after race. BDKRB2 -9/-9 had pronounced response to LDH, CK, CK-MB and ALT and AST activities, myoglobin, troponin, IL-6, IL-8 levels immediately, one day and/or three days after race. The percentage of runners higher responders (>500U/I) to CK levels was greater for -9-9 and -9+9 genotypes (46 and 48%, respectively) compared to +9+9 genotypes (31%) immediately after. ACE II, AGT MM, and BDKRB2 -9-9 genotypes may increase the susceptibility to inflammation, muscle injury after endurance exercise and could be used to predict the development of clinical conditions associated with muscle damage and myocardial injury.

Angiotensin-converting enzyme related-polymorphisms on inflammation, muscle and myocardial damage after a marathon race

ABSTRACT: Muscle damage is one of the most important factors that affect muscle fatigue during endurance exercise. Recent evidence suggests that the renin-angiotensin system impacts on skeletal muscle wasting. The aim of this study was to determine association between the AGT Met235Thr, ACE I/D and BDKRB2 -9/+9 polymorphisms with inflammation, myocardial and muscle injury induced by endurance exercise. Eighty-one Brazilian male runners participated in this study and completed the International Marathon of Sao Paulo. Muscle and myocardial damage markers (alanine transaminase, ALT, aspartate transaminase, AST, lactic dehydrogenase, LDH, creatine kinase, CK, Troponin, pro BNP, myoglobin, and CK-MB) and inflammatory mediators (IL-6, IL-8, IL-10, IL12p70, IL1ß, and TNF-α) were determined one day before, immediately after, one day after, and three days after the event. Muscle damage was also determined fifteen days after race and angiotensinogen (AGT) Met235Thr, angiotensin-converting enzyme (ACE) I/D, and Bradykinin B2 receptor (BDKRB2) -9/+9 polymorphisms were determined. Marathon race participation induced an increase in all muscle damage and inflammatory markers evaluated (p < 0.0001). The muscle damage markers, troponin and pro BNP, CK and LDH and inflammatory markers, IL-6, IL-8, IL-1ß and IL-10 were also higher in ACE II genotype immediately after race, compared to DD genotype. The percentage of runners higher responders (>500U/I) to CK levels was higher for II genotypes (69%) compared to DD and ID genotypes (38% and 40%, respectively) immediately after. Troponin, pro BNP and IL-1ß, IL-8 levels were also elevated in AGT MM genotype compared to TT genotype athletes after and/or one day after race. BDKRB2 -9/-9 had pronounced response to LDH, CK, CK-MB and ALT and AST activities, myoglobin, troponin, IL-6, IL-8 levels immediately, one day and/or three days after race. The percentage of runners higher responders (>500U/I) to CK levels was greater for -9-9 and -9+9 genotypes (46 and 48%, respectively) compared to +9+9 genotypes (31%) immediately after. ACE II, AGT MM, and BDKRB2 -9-9 genotypes may increase the susceptibility to inflammation, muscle injury after endurance exercise and could be used to predict the development of clinical conditions associated with muscle damage and myocardial injury. (AU)

Association Between Hematological Parameters and Iron Metabolism Response After Marathon Race and ACTN3 Genotype.

α-Actinin-3 (ACTN3 R577X, rs.1815739) polymorphism is a genetic variation that shows the most consistent influence on metabolic pathway and muscle phenotype. XX genotype is associated with higher metabolic efficiency of skeletal muscle; however, the role of ACTN3 polymorphism in oxygen transport and utilization system has not yet been investigated. Therefore, the aim of this study was to determine the influence of ACTN3 polymorphisms on hematological and iron metabolism response induced by marathon race. Eighty-one Brazilian amateur male endurance runners participated in the study. Blood samples and urine were collected before; immediately after; and 1, 3, and 15 days after the marathon race. Urine, hematological parameters, iron metabolism, and ACTN3 genotyping analyses were performed. The marathon race induced a decrease in erythrocytes, Hb, and Ht, and an increase in hematuria, creatinine, myoglobin, red cell distribution width, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, direct and indirect bilirubin and erythropoietin. Moreover, an elevation immediately or 1 day after the marathon race follows a reduction 3 or 15 days after the marathon race were observed on transferrin saturation and iron and transferrin levels. Hematological parameters and iron metabolism changes induced by marathon race were not observed in XX genotypes. Hematuria and decreased erythrocytes, Hb, Ht, and iron and transferrin levels were observed only in RR and/or RX genotypes but not in XX genotypes. The percentage of runners with hematuria, leukocyturia, iron deficiency, creatinine, myoglobin, and bilirubin imbalance was higher in RR compared to XX genotypes. ACTN3 polymorphism is associated with iron metabolism and hematological responses after endurance exercise. Despite these results being based on a small sample, they highlight a protective role of the XX genotype on hematological and renal changes induced by long-distance exercise. Therefore, these findings should be further replicated.

Association between hematological parameters and iron metabolism response after marathon race and ACTN3 genotype

αlpha-Actinin-3 (ACTN3 R577X, rs.1815739) polymorphism is a genetic variation that shows the most consistent influence on metabolic pathway and muscle phenotype. XX genotype is associated with higher metabolic efficiency of skeletal muscle; however, the role of ACTN3 polymorphism in oxygen transport and utilization system has not yet been investigated. Therefore, the aim of this study was to determine the influence of ACTN3 polymorphisms on hematological and iron metabolism response induced by marathon race. Eighty-one Brazilian amateur male endurance runners participated in the study. Blood samples and urine were collected before; immediately after; and 1, 3, and 15 days after the marathon race. Urine, hematological parameters, iron metabolism, and ACTN3 genotyping analyses were performed. The marathon race induced a decrease in erythrocytes, Hb, and Ht, and an increase in hematuria, creatinine, myoglobin, red cell distribution width, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, direct and indirect bilirubin and erythropoietin. Moreover, na elevation immediately or 1 day after the marathon race follows a reduction 3 or 15 days after the marathon race were observed on transferrin saturation and iron and transferrin levels. Hematological parameters and iron metabolism changes induced by marathon race were not observed in XX genotypes. Hematuria and decreased erythrocytes, Hb, Ht, and iron and transferrin levels were observed only in RR and/or RX genotypes but not in XX genotypes. The percentage of runners with hematuria, leukocyturia, iron deficiency, creatinine, myoglobin, and bilirubin imbalance was higher in RR compared to XX genotypes. ACTN3 polymorphism is associated with iron metabolism and hematological responses after endurance exercise. Despite these results being based on a small sample, they highlight protective role of the XX genotype on hematological and renal changes induced by long-distance exercise. Therefore, these findings should be further replicated.(AU)

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

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