Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial

Heuberger, Jules; Rotmans, Joris I.; Gal, Pim; Stuurman, Frederik E.; Westende, Juliëtte van 't; Post, Titiaan E.; Daniëls, Hans; Moerland, Matthijs; Veldhoven, Peter L J van; Kam, Marieke L. de; Ram, Herman; Hon, Olivier de; Posthuma, Jelle J.; Burggraaf, Jacobus; Cohen, Adam F.

doi:10.1016/s2352-3026(17)30105-9

Cited by 44 publications

(60 citation statements)

References 27 publications

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“…However, none of these studies showed whether these effects on surrogate biomarkers impacted actual performance. Because of this lack of information, a double-blind, randomized, placebo-controlled study in trained cyclists followed and showed that clinically more relevant tests, such as a time trial and uphill road race, were not affected by rHuEPO treatment [39]. Although there was again an effect of rHuEPOs on maximal exercise test variables, including V O 2max and P max (an increase of 5 and 3%, respectively), there was no evidence to suggest that these erythropoietin-induced effects improved actual cycling performance in trained cyclists.…”

Section: Resultsmentioning

confidence: 99%

Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects

Heuberger

Cohen

2018

Sports Med

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The World Anti-Doping Agency is responsible for maintaining a Prohibited List that describes the use of substances and methods that are prohibited for athletes. The list currently contains 23 substance classes, and an important reason for the existence of this list is to prevent unfair competition due to pharmacologically enhanced performance. The aim of this review was to give an overview of the available evidence for performance enhancement of these substance classes. We searched the scientific literature through PubMed for studies and reviews evaluating the effects of substance classes on performance. Findings from double-blind, randomized controlled trials were considered as evidence for (the absence of) effects if they were performed in trained subjects measuring relevant performance outcomes. Only 5 of 23 substance classes show evidence of having the ability to enhance actual sports performance, i.e. anabolic agents, β2-agonists, stimulants, glucocorticoids and β-blockers. One additional class, growth hormone, has similar evidence but only in untrained subjects. The observed effects all relate to strength or sprint performance (and accuracy for β-blockers); there are no studies showing positive effects on reliable markers of endurance performance. For 11 classes, no well-designed studies are available, and, for the remaining six classes, there is evidence of an absence of a positive effect. In conclusion, for the majority of substance classes, no convincing evidence for performance enhancement is available, while, for the remaining classes, the evidence is based on a total of only 266 subjects from 11 studies.

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Section: Resultsmentioning

confidence: 99%

Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects

Heuberger

Cohen

2018

Sports Med

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“…For the purpose of this study, blood and urine samples were used that were obtained in a double‐blind, randomized, placebo‐controlled, parallel, single‐center study on rHuEPO, in which 48 healthy male cyclists between 18 and 50 years of age were included. The design of this trial was described elsewhere . In short, the main inclusion criteria were maximum power‐to‐weight ratio during the maximal exercise test at screening exceeding 4 W/kg, Hb between 8.0 and 9.8 mmol/L (equivalent to 12.8–15.7 g/dL) and Ht below 48% at screening and not being subject to anti‐doping regulation or using medication that could potentially interact with the study drugs or study assessments.…”

Section: Methodsmentioning

confidence: 99%

Sensitivity and specificity of detection methods for erythropoietin doping in cyclists

Heuberger

Eenoo²,

Rotmans

et al. 2019

Drug Testing and Analysis

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Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti‐doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double‐blinded, placebo‐controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin β) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl‐PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl‐PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl‐PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings.

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“…The dosing regimen used in this study has been reported previously (Heuberger et al. ). In brief, each subject received a weekly dose of either rHuEPO or placebo (saline).…”

Section: Methodsmentioning

confidence: 99%

“…This study was part of a larger randomized, double‐blind, placebo‐controlled, parallel clinical trial in which we studied the effect of rHuEPO on cycling performance in well‐trained cyclists (Heuberger et al. ).…”

Section: Introductionmentioning

confidence: 99%

Recombinant human erythropoietin does not affect several microvascular parameters in well-trained cyclists

et al. 2018

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Recombinant human erythropoietin (rHuEPO) has been used as a performance‐enhancing agent by athletes in a variety of sports. The resulting increase in hematocrit levels leads to increased blood viscosity and can affect blood flow, potentially increasing the athlete's risk of developing health complications. However, the actual effects of using rHuEPO on microvascular blood flow and post‐occlusive reactive hyperemia are currently unknown. We therefore evaluated the effect of rHuEPO on the cutaneous microcirculation in well‐trained cyclists using laser speckle contrast imaging (LSCI). This study was part of a randomized, double‐blind, placebo‐controlled, parallel trial designed to investigate the effects of rHuEPO in 47 well‐trained adult cyclists (age 18–50 years). Subjects received a weekly dose of either rHuEPO or placebo for 8 weeks, and LSCI was performed at baseline, after a maximal exercise test in week 6, and before maximal exercise in week 8. Endpoints included basal blood flux, maximum post‐occlusion reperfusion, and time to return to baseline. Despite an increase in hematocrit levels in the rHuEPO‐treated group, we found no statistically significant difference in microvascular function measured between the rHuEPO‐treated group and the placebo group. Our results suggest that the increased hematocrit levels in rHuEPO‐treated well‐trained cyclists are not associated with changes in microvascular blood flow or post‐occlusive reactive hyperemia measured using LSCI.

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Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial

Cited by 44 publications

References 27 publications

Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects

Review of WADA Prohibited Substances: Limited Evidence for Performance-Enhancing Effects

Sensitivity and specificity of detection methods for erythropoietin doping in cyclists

Recombinant human erythropoietin does not affect several microvascular parameters in well-trained cyclists

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