EPO for Cyclists: Comprehensive Guide to Medically Supervised Dosing

Estimated reading time: 9 minutes

In performance cycling, erythropoietin has been a controversial and widely debated topic. We’ve touched on the impact that the drug can have on well-trained cyclists powered by an 8-week research protocol. While the risks associated with EPO misuse are well-documented, recent research by experts at Centre for Human Drug Research (CHDR) has introduced a medically supervised EPO dosing protocol. This aims to optimize cycling performance while minimizing potential health risks.

Their 88-page Clinical Study Protocol titled “Recombinant human erythropoietin effects on cycling performance” should be mandatory reading for every athlete considering the use of EPO as well as their coaching and support staff.

In this article, we explain the detailed EPO dosing protocol developed by these researchers, shedding light on how to use EPO for cycling performance the right way.

Understanding the EPO Dosing Protocol

CHDR Researchers carefully designed and implemented an EPO dosing protocol, planning to replicate known practices in professional cycling while ensuring participant safety and adherence to ethical standards. Participants allocated to the rHuEPO (recombinant human erythropoietin) group received eight total doses throughout the study period.

Mean Doses and Placebos

The dosing regimen involved administering a mean rHuEPO dose, in the form of NeoRecormon, of 5000 IU per participant per week during the initial 4 weeks of the study. Subsequently, the dose was increased to 7000 IU per week for the remaining 4 weeks. To mitigate the risk of excessive hematological parameters, participants exceeding a 15% increase in hemoglobin compared to baseline or reaching a hematocrit concentration exceeding 52% were administered placebo injections on five occasions.

Total Average Doses & General Findings

The average administered rHuEPO dose throughout the study period was 48,000 IU, equivalent to an average of 6000 IU per week. This dosing strategy resulted in a substantial increase in hemoglobin concentration, with a mean elevation of 12% up to 10.2 mmol/L, and a 16% increase in hematocrit levels, reaching 50%. In contrast, participants in the placebo group exhibited relatively stable hemoglobin and hematocrit concentrations throughout the study.

Measures for Consistency

Participant diaries were maintained with meticulous documentation, helping to confirm adherence to the prescribed supplement regimen throughout the study period, ensuring consistency and reliability in administrating rHuEPO doses.

Moving on, we will delve further into the rationale behind this dosing strategy, its implications for cycling performance, and the broader context of medically supervised EPO dosing guidelines.

Breaking Down a Sample 8-Week Protocol

A sample 8-week protocol for NeoRecormon administration and supplementation could follow as such:

Week 1-4: NeoRecormon dosage ranging from 2000 to 10,000 IU per week (adjusted based on Hb and Ht measurements).

Week 5-8: Continued NeoRecormon dosage adjustments being made as necessary, with regular monitoring of hematological parameters.

Daily Supplementation: 50 mg vitamin C and 200 mg iron to optimize absorption and overall health.

Dosage Details with NeoRecormon Explained

The investigational drug used in the study was recombinant human erythropoietin (rHuEPO) NeoRecormon, containing the active substance Epoëtine beta. NeoRecormon was administered subcutaneously (into the fatty tissue under the skin) to participants adhering to a carefully designed dosing schedule, hoping to optimize hematological parameters while minimizing potential risks.

Dosage Rationale and Decision Tree

The dosing protocol for NeoRecormon was based on a comprehensive decision tree, devised to guide researchers in adjusting dosage according to individual participant characteristics and responses, particularly hemoglobin (Hb) concentration and hematocrit (Ht) levels. This decision tree was a visual aid to facilitate real-time decision-making regarding adjustments during the 8-week treatment period.

The decision tree outlined various scenarios based on Hb and Ht measurements before each administration of NeoRecormon or placebo. If a participant’s Ht exceeded 52%, indicating a high risk of hematologic complications, dosage administration was promptly interrupted to mitigate potential risks. Conversely, if Ht levels were below 52%, the decision tree directed researchers to assess the participant’s Hb concentration to determine the appropriate dosage of NeoRecormon.

Here are the steps of the decision tree in more detail:

• If the Ht level reached more than or equal to 52%, doping would stop. If Hb levels went under about 1.15X, dosing would also stop.
• If the Hb levels were above or equal to 1.10x, the dosing would remain at 2000IU/week.
• If things hadn’t moved along before 5 weeks, the dosing would reach 5000IU/week; if things hadn’t moved along after 5 weeks or more, the dosing would be raised to more than or equal to 6000IU/week, with a maximum dosage of 10,000IU/week.

The dosage of NeoRecormon ranged from 2000 to 10,000 IU per week, with the flexibility to adjust within this range based on each participant’s response to treatment. This dosage range was devised to ensure efficacy in raising Hb and Ht levels within the target range while minimizing the risk of adverse effects.

Benefit and Risk Assessment

NeoRecormon is a registered drug with a known safety profile, making it a suitable choice for use in research settings. However, researchers acknowledged the potential for side effects, including anaphylactoid reactions, albeit at a low incidence rate of ≤1 in 10,000 cases. With this in mind, all study drug administrations were conducted in a clinical setting under strict medical supervision, helping to mitigate the risks.

Monitoring Methodology

Participants were closely monitored throughout the study, with their medical conditions assessed regularly to ensure safety and well-being. Dosage adjustments were made as necessary based on hematological parameters and individual responses to treatment, guided by the decision tree algorithm.

By adhering to the prescribed dosing protocol, following the decision tree accurately, and implementing stringent safety measures, researchers aimed to optimize the efficacy and safety of NeoRecormon administration in enhancing cycling performance among participants.

Safety and Risk Assessment of NeoRecormon Usage

NeoRecormon, a recombinant human erythropoietin (rHuEPO), is commonly used in clinical settings to treat various medical conditions, including anemia associated with chronic kidney disease and cancer chemotherapy. Its safety profile has been extensively studied, with well-established dosing guidelines to ensure efficacy (in these medical contexts) while minimizing potential risks.

The Known Risks of rHuEPO & NeoRecormon

The risk most commonly associated with NeoRecormon relates to its potential to increase hematocrit and hemoglobin levels, which, if elevated excessively, can lead to complications such as thrombosis, hypertension, and cardiovascular events. However, when administered within the recommended dosage ranges, NeoRecormon is generally considered safe and effective for its intended medical purposes. Research has also shown that EPO performance enhancement is likely not as dangerous as anti-doping organizations would have the public believe.

Comparison to an Autologous Blood Pre-Donation Programme

The effects of NeoRecormon usage in patients participating in autologous blood pre-donation programs closely resemble those in healthy volunteers. In both scenarios, it was recognized to increase red blood cell production. The Summary of Product Characteristics (SmPC) for NeoRecormon in an autologous blood pre-donation program specifies a maximum recommended dose of 1200 IU/kg per week for subcutaneous administration, equivalent to 90,000 IU for a 75 kg individual.

In this EPO dosing protocol, which involves planned doses ranging from 2000 to 10,000 IU per week, NeoRecormon dosages are well below the maximum recommended limit. Therefore, the risk associated with NeoRecormon administration in the study is considered small and acceptable.

Mandatory Supplementation

To support the physiological effects of NeoRecormon administration and mitigate potential risks, participants were prescribed a mandatory daily supplementation of 50 mg of vitamin C (ascorbic acid) and 200 mg of iron (ferrofumarate) throughout the 8-week treatment period. These supplements help to optimize iron metabolism, erythropoiesis, and overall health during EPO therapy.

Medical Supervision and Harm Reduction Measures

Medical supervision during NeoRecormon administration closely monitors participants’ hematological parameters, vital signs, and overall health status, with detailed check-ups performed before every dose, meaning 8 checks throughout the process. Participants always received injections in a clinical setting under the direct supervision of a healthcare professional, guaranteeing proper administration and immediate management of any adverse reactions.

Harm reduction measures included:

• Weekly assessment of hematological parameters to detect and prevent excessive increases in Hb and Ht levels.
• Provision of mandatory vitamin C and iron supplementation to support erythropoiesis and minimize the risk of iron deficiency.
• Prompt discontinuation of NeoRecormon dosage if hematological parameters exceeded predefined thresholds or if adverse reactions occurred.

Blood Tests Conducted

During the study, participants also underwent weekly blood tests to monitor hematological parameters, including:

• Hemoglobin concentration
• Hematocrit levels
• Red blood cell count
• Platelet count
• Coagulation profile

These blood tests provided crucial information for assessing the safety and efficacy of NeoRecormon administration and guiding dosage adjustments as needed.

Implications for Sports Physicians and Self-Medicating Patients

For sports physicians encountering patients self-medicating with EPO or considering its use for performance enhancement, this research study provides valuable insights into what makes up a medically supervised dosing protocol with the right safety measures. The study underscores the importance of careful dosage levels, regular monitoring of hematological parameters, and adherence to supplementation regimens to mitigate potential risks and optimize benefits.

Criteria for Initial Dosages, Changes, or Discontinuation

The criteria that led the direction of adjustments included:

• Baseline hematological parameters (Hb and Ht levels)
• Response to initial dosages (e.g., rate of increase in Hb and Ht)
• Threshold values for Hb and Ht concentrations to prevent excessive elevations
• Occurrence of adverse reactions or symptoms suggestive of hematological complications

These criteria guided researchers in individualizing treatment regimens and ensuring participant safety throughout the study.

Risks and Side Effects Monitored

Researchers closely monitored participants for potential risks and side effects, including:

• Excessive increases in Hb and Ht levels leading to hematologic complications (e.g., thrombosis, hypertension).
• Anaphylactoid reactions or allergic responses to NeoRecormon injections.
• Iron deficiency or disturbances in iron metabolism due to increased erythropoiesis.

Regular assessment of hematological parameters and clinical evaluation allowed for early detection and management of adverse events, minimizing their impact on participant safety and well-being.

Conclusion

The dosage protocol discussed here sheds light on the potential use of EPO to enhance cycling performance under supervision, with our previous article showing that it could be effective in certain settings. This protocol is a great resource for individuals considering EPO use, emphasizing the importance of adherence to scientifically sound practices to optimize outcomes while prioritizing safety.

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