Erythropoietin (EPO)

The verdict

Our read at a glance.

Whether raising haemoglobin above normal improves endurance enough to justify a risk profile that regulators quantified in patients.

The signal

Both halves of this file are strong. Clinically, erythropoiesis-stimulating agents are approved for anaemia of chronic kidney disease and chemotherapy-induced anaemia, with extensive labelling and continuing trials. On performance, the effect is not disputed: raising red cell mass raises oxygen-carrying capacity and improves maximal oxygen uptake and endurance performance, which is why an entire anti-doping infrastructure including the athlete biological passport was built to detect it.

The unknown

Very little. The clinical trial programme that produced the boxed warning already answered the central question about what happens when haemoglobin is driven high, and there is no reason to expect a healthy athlete's vasculature to be exempt from the thrombotic consequences of raised haematocrit.

Our read

An unusual entry: the performance claim is true and the risk is quantified, both from the same well-run clinical programme. The trials that established the danger were the ones designed to find the benefit, and they found that pushing haemoglobin higher killed more people. Deliberately doing that to a healthy body while dehydrated is a thrombotic gamble with published odds.