Does EPO Truly Enhance Cycling Performance? A Study with Real World Dosages

Estimated reading time: 9 minutes

Introduction

The use of erythropoietin (EPO) to enhance athletic performance, especially in competitive cycling, has been a contentious issue for over twenty years. Despite its widespread use and the controversies that come with it, there is still a lack of solid scientific evidence proving its effectiveness in improving performance among well-trained cyclists.

Jules Heuberger and his team at the Centre for Human Drug Research in the Netherlands set out to scientifically address this very question: Does EPO actually enhance performance for experienced riders? They conducted a double-blind, randomized, placebo-controlled trial—considered the “gold standard” of scientific research—with EPO dosages that mirror real-world usage in competitive cycling. This article shares their findings.

Understanding EPO and Its Effects

But first, It’s important to understand the background issues related to the use of EPO in sports, and specifically its impact on cycling performance.

Why Do We Think EPO Enhances Performance?

Many competitive athletes and observers believe EPO enhances athletic performance by boosting red blood cell production and oxygen delivery to muscles. Clinical rHuEPO is used to treat anemia, increasing red blood cell count in patients, implying it could do the same for athletes. This rationale has contributed to its status as a banned substance by most anti-doping agencies, starting with the International Olympic Committee in 1990.

However, despite this widespread belief and its illicit use among athletes, concrete scientific evidence supporting its performance-enhancing effects in well-trained cyclists is hard to find.

What are the Adverse Effects of EPO?

While many focus on EPO’s potential to increase red blood cell mass and oxygen-carrying capacity, others believe its misuse can lead to serious adverse effects. There have been countless statements made relating to cardiovascular complications such as hypertension, thrombosis, and increased risk of stroke, as well as hematologic disorders like polycythemia.

Additionally, some warn that improper administration or dosage of EPO can result in an imbalance in red blood cell production, leading to dangerous levels of hematocrit and viscosity, which in turn can increase the risk of blood clots and other cardiovascular events. However, as we’ve touched on in this series, EPO’s alleged dangers in performance cycling have been subject to scrutiny and studies, showing that sports agencies have often relied on unsubstantiated claims.

Understanding the Potential Risks of EPO Dosing in Athletes

While some consider EPO supplementation among the best performance-enhancing drugs for cycling, there are studies that support its potential to be dangerous.

Why Do We Think EPO Could Be Dangerous in Athletes?

While the extent of the risks associated with erythropoietin (EPO) use in athletes remains uncertain, evidence from literature reviews and studies in healthy and trained subjects provides insights into potential dangers.

Systolic Blood Pressure

In one study, the researchers noted a considerable rise in systolic blood pressure, both at rest and during submaximal exercise following EPO administration. Increases in blood pressure can predispose athletes to cardiovascular complications, including hypertension and an increased risk of thrombotic events.

Thrombotic Events

Evidence from literature reviews also highlights an elevated incidence of thrombotic events in patients treated with high doses of rHuEPO compared to those receiving a placebo. However, it is important to note that these studies typically utilized doses significantly higher than those commonly used in endurance performance studies. Factors such as increased blood viscosity, enhanced coagulation, endothelial activation, platelet reactivity, and inflammation may all contribute to these adverse events.

Impact with Exercise

It’s also important to consider the physiological changes induced by acute exercise. These impacts include reductions in plasma volume and blood volume accompanied by increased hematocrit, potentially exacerbating the risk of thrombotic events in endurance athletes––particularly under dehydrated and hyperthermic conditions.

Non-Conclusive

While these findings suggest potential dangers associated with EPO use in athletes, conclusive evidence is lacking. Definitive conclusions cannot be drawn without well-designed research studies specifically investigating the effects of EPO on performance and safety in elite cyclists.

Investigating the Effects and Safety of EPO in Well-Trained Cyclists

Heuberger and his colleagues designed a randomized, double-blind, placebo-controlled study to address the uncertainties surrounding the effects and safety of EPO use in well-trained cyclists. This study aims to rigorously investigate the impact of NeoRecormon, a form of synthetic recombinant human erythropoietin, on performance and safety parameters in elite cyclists.

The Basics of The Study

The study focused on the effects on well-trained cyclists, comprised of 48 healthy, medically stable subjects recruited via media advertisements and cycling associations. These individuals were selected to represent the elite in cycling, with a high level of physical fitness and training experience. The study protocol involved an 8-week period during which participants will be randomly assigned to receive either NeoRecormon or a placebo.

NeoRecormon was administered at doses of 2000, 5000, or between 6000 and 10,000 IU per week. The goal was to reach the target range, with adjustments made as necessary based on hemoglobin (Hb) or hematocrit (Ht) results.

The study spanned a total duration of 129 days, with the treatment period lasting 8 weeks. This timeline allowed for comprehensive assessments of performance and safety outcomes following the administration of NeoRecormon. Detailed assessments of performance metrics, including endurance, power output, and oxygen utilization, were conducted before and after the intervention period.

What Were the Study Objectives?

Primary Objectives

The study objective was to explore the effects of NeoRecormon on cycling performance in well-trained cyclists. This was achieved through various means, including separate performance assessments in exercise tests, competition settings, and the measurement of hematological markers via the Athlete Biological Passport. Blood flow measurements were also conducted to evaluate physiological responses to EPO administration.

Secondary Objectives

Secondary objectives included further exploration of NeoRecormon’s effects in a competitive road race setting, making it easier to determine its capacity among cycling performance-enhancing supplements and drugs. Other objectives included a comprehensive evaluation of its safety profile in well-trained cyclists and an assessment of doping detection methods for NeoRecormon use.

The Results of the Study

Did It Cause Any Adverse Effects?

The safety evaluation of rHuEPO treatment in well-trained cyclists revealed reassuring findings. Vital signs such as weight, heart rate, and blood pressure were similar between the two treatment groups, with observed adverse events being mild to moderate and comparable between groups. Notably, no severe adverse events (grade 3 or worse) were reported across either group.

While some endothelial function markers showed a slight increase with rHuEPO treatment, suggesting a potential increase in thrombogenicity, there were no clinical signs of adverse effects associated with rHuEPO administration.

Did It Enhance Performance?

In terms of performance enhancement, rHuEPO treatment led to improvements in laboratory-based maximal exercise tests, resulting in enhanced endurance and performance. However, its effects on submaximal exercise tests and road race performance were undetectable. Overall, the results of the study were less pronounced than the claims often found in popular literature and anecdotal accounts. This underscores the importance of evidence-based research in assessing the efficacy and safety of performance-enhancing interventions like EPO.

Understanding the Lack of Performance Results

The absence of significant performance enhancement effects observed in the study can be attributed to several factors:

Contextual Differences

EPO effects may be more pronounced in multi-stage events like the Tour de France, where endurance and recovery play critical roles, compared to single-day races like the Mont Ventoux race included in the study. The duration and intensity of the events may influence the detectability of EPO’s effects.

Study Size and Statistical Power

The study’s sample size may have been insufficient to detect subtle differences in performance outcomes, particularly in the road race setting. The complexity of measuring performance in real-world cycling competitions alongside the variability inherent in individual athlete performance may have limited the study’s statistical power to detect significant effects.

Small Magnitude of Benefits

It’s possible that the benefits of rHuEPO on performance, while present, are smaller than people tend to claim or believe, making them hard to discern without larger sample sizes or more sensitive measurement techniques.

Conclusions on EPO Safety and Performance Enhancement

Based on the findings of the double-blind controlled study, the safety of EPO use for enhancing cycling performance remains a topic of debate and caution. While no significant differences in adverse events were observed between the EPO and placebo groups, the study did reveal a concerning increase in endothelial markers, specifically E-selectin and P-selectin, associated with thrombogenicity and inflammation.

Risks Could be More Significant

These findings suggest a potential increase in cardiovascular risk associated with rHuEPO treatment, which may not have been adequately captured due to the low incidence of cardiovascular events in healthy athletes. The study’s limited power to detect such risks underscores the need for further research with larger sample sizes and longer follow-up periods.

Given the widespread and uncontrolled use of rHuEPO among athletes, the potential risks of cardiovascular events cannot be dismissed. Therefore, while EPO may offer performance-enhancing benefits, its use should be approached cautiously, and athletes should be aware of the potential risks associated with its administration.

Future Directions and Implications

Moving forward, it is imperative to conduct larger-scale studies with extended follow-up periods to comprehensively assess the safety and efficacy of EPO use in well-trained cyclists. Evidence-based policies and regulations must be implemented to mitigate the potential risks associated with the misuse of performance-enhancing substances, consciously not using hyperbole or exaggeration to demonize a substance.

Stay tuned for our next article, where we will discuss the step-by-step guide to designing your own 8-week EPO cycle based on the 68-page Clinical Study Protocol provided courtesy of the researchers at Centre for Human Drug Research.

Reference

Heuberger, J. A. A. C., Rotmans, J. I., Gal, P., Stuurman, F. E., van ’t Westende, J., Post, T. E., Daniels, J. M. A., Moerland, M., van Veldhoven, P. L. J., de Kam, M. L., Ram, H., de Hon, O., Posthuma, J. J., Burggraaf, J., & Cohen, A. F. (2017). Effects of erythropoietin on cycling performance of well trained cyclists: A double-blind, randomised, placebo-controlled trial. The Lancet Haematology, 4(8), e374–e386. https://doi.org/10.1016/S2352-3026(17)30105-9