EPO Doping Offers No Benefit to Athletes, Only Possible Harm

Janis C. Kelly

December 06, 2012

The doping scandal that cost Lance Armstrong his 7 Tour de France cycling titles and raised the curtain on a sport apparently rife with secret use of recombinant human erythropoietin (rHuEPO) took an unexpected turn this week when Dutch researchers reported that EPO is unlikely to have much effect on elite athletes competing at Armstrong's level.

rHuEPO became a sports-doping drug of choice after it was shown to increase red blood cell mass and exercise capacity in patients with anemia from chronic kidney disease. This is in part a result of an increase in patients' maximal oxygen uptake (VO2max), one of the factors in endurance performance.

However, elite athletes are not debilitated renal failure patients. Their VO2max is already so high that adding rHuEPO has little effect, and marginal increases in VO2max have little effect on performance, according to J.A.A.C. Heuberger, BSc, from Leiden University in the Netherlands, and colleagues.

Endurance Improvements Unlikely

The authors report the results of their systematic literature review in an article published online December 6 in the British Journal of Clinical Pharmacology. Their review uncovered a paucity of studies testing rHuEPO in elite athletes. A few studies involved subjects described as "endurance trained recreational athletes," "well-trained individuals," or "healthy subjects." In addition, study participants varied in terms of endurance performance and fitness level. None of the studies reported on competitive cyclists.

"'[T]he better the athlete is trained, a similar increase in VO2max leads to a proportionally smaller increase in performance," the authors explain. "This also demonstrates that in world-class athletes, an increase in VO2max will have only limited effect on performance."

The authors note that in elite endurance athletes, VO2max can be 50% to 100% greater than those in normal healthy young people, but that VO2max plateaus in elite athletes while performance continues to improve. They suggest that this may be because of other factors involved in endurance such as high muscle capillary density, muscle metabolic adaptations such as increased mitochondria and oxidative enzymes, or more efficient biomechanics. Although moderately trained athletes can improve a variety of factors to increase endurance performance, elite athletes mainly improve endurance performance by changes in lactate threshold, lactate turn point, and work economy or efficiency. None of these is directly altered by erythropoietin.

This situation is compounded by the adverse event profile associated with rHuEPO.

Hypertension, Clots, Inflammation

According to the authors, this lack of benefit is accompanied by some significant risks for adverse effects including a rise in systolic blood pressure, increased risk for thrombotic events, increased blood viscosity, enhanced coagulation, endothelial activation and platelet reactivity, and inflammation.

The authors warn, "This combination of factors might increase the risk of thrombotic events in endurance performance athletes using rHuEPO. Increased [hematocrit levels] may lower cerebral blood flow and limit oxygen supply to the brain, predisposing to cerebral infarction. Thrombotic risks are underlined by a case report...where a professional cyclist presented with cerebral sinus thrombosis, thereafter confessing to 3 months of 2000 IU rHuEPO use every two days, in combination with 15 days of growth hormone and continuous high doses of vitamin A and E."

"Athletes and their medical staff may believe EPO enhances performance, but there is no evidence that anyone performed good experiments to check if EPO would actually improve performance in elite cyclists," lead author A.F. Cohen, MD, PhD, FFPM, FBPharmSoc, professor of clinical pharmacology, Leiden University Medical Centre, said in a press release.

The authors have disclosed no relevant financial relationships.

Br J Clin Pharmacol. Published online December 6, 2012. Abstract