Hepcidin Sequestration: The Hidden Cause of Anaemia in Endurance Athletes

Iron deficiency and iron deficiency anaemia (IDA) are among the most common clinical presentations in female athletes, particularly those in endurance sports like running and rowing. However, many athletes find that despite high-dose oral iron supplementation, their ferritin levels remain stubbornly low. The missing piece of the puzzle is hepcidin. Hepcidin is a small peptide hormone produced by the liver that acts as the master regulator of iron homeostasis. It functions by binding to ferroportin, the only protein that allows iron to exit cells and enter the bloodstream.

When hepcidin levels are high, ferroportin is degraded, and iron is 'locked' inside the gut cells (enterocytes) and macrophages, eventually being excreted rather than used. The biological trigger for hepcidin in athletes is exercise-induced inflammation. Specifically, the cytokine Interleukin-6 (IL-6) rises significantly during and after intense or prolonged exercise. IL-6 directly stimulates the liver to produce hepcidin. Studies show that hepcidin peaks approximately 3 to 6 hours after a workout and can stay elevated for up to 24 hours.

Conventional medicine typically suggests taking iron supplements once daily, often in the morning or evening without regard for training times. If an athlete trains in the morning and takes her iron supplement at lunch, she is attempting to absorb iron precisely when her hepcidin levels are at their peak, rendering the supplement useless and likely causing gastrointestinal distress. Furthermore, standard NHS blood tests often look only at haemoglobin, missing 'non-anaemic iron deficiency' where ferritin is low but haemoglobin is still within the normal range, yet performance and mitochondrial function are already compromised. To manage this, female athletes should adopt a chronobiological approach: taking iron either first thing in the morning before training (when hepcidin is naturally at its lowest) or waiting at least 24 hours after a particularly strenuous session. Alternate-day dosing has also been shown to be more effective than daily dosing, as it prevents the supplement itself from triggering a secondary hepcidin spike.

Dietary factors also play a role; consuming Vitamin C with iron and avoiding tannins (tea/coffee) or calcium at the same time is essential, but secondary to the hepcidin window. By understanding the inflammatory blockade, athletes can finally resolve chronic fatigue and optimize their oxygen-carrying capacity.