Iron deficiency gets nearly all the attention in endurance sport. Ferritin screening, haemoglobin monitoring, dietary iron education — the conversation almost universally runs in one direction. But one in every 200 people of Northern European descent carries the genetic variant that causes iron accumulation, not depletion. And for those individuals, every iron supplement, every iron-rich diet recommendation, every well-intentioned intervention is quietly accelerating organ damage.
Hereditary haemochromatosis (HH) is caused primarily by mutations in the HFE gene — most commonly the C282Y variant (estimated carrier frequency 1 in 8 in Irish populations, 1 in 15 in Northern European populations broadly) and the H63D variant. Homozygous C282Y individuals (C282Y/C282Y) have a lifetime penetrance of 30–70% for clinical iron overload, meaning that many carriers will develop measurable iron accumulation without experiencing symptoms for decades. Compound heterozygotes (C282Y/H63D) have lower but non-negligible risk.
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The mechanism differs fundamentally from dietary iron absorption in non-HH individuals. Normally, hepcidin — a liver-derived peptide hormone — downregulates ferroportin (the iron exporter on enterocytes and macrophages) when body iron stores are adequate, limiting further absorption. In HH, HFE protein dysfunction impairs hepcidin upregulation in response to rising iron stores. The enterocytes continue absorbing dietary iron at an inappropriately high rate regardless of body iron status, producing a slow but relentless accumulation in the liver, heart, pancreas and joints.
The biochemical markers that signal iron overload are transferrin saturation >45% and serum ferritin >300 μg/L in men or >200 μg/L in women. In a standard pre-season sports medicine panel that includes ferritin as an overtraining and iron status marker, these elevations will appear — but they are commonly misattributed to inflammation or laboratory variation without HFE genotyping to identify the underlying cause.
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For endurance athletes, the presentation is complicated by several confounders. Exercise-induced hepcidin upregulation (lasting 3–6 hours post-exercise via interleukin-6 signalling) transiently raises iron absorption barriers — but this effect is insufficient to normalise iron balance in C282Y homozygotes. Elevated ferritin from training inflammation may mask early haemochromatosis if the clinician does not check transferrin saturation simultaneously. Conversely, heavy endurance training can produce dilutional pseudoanaemia (plasma volume expansion reducing haemoglobin concentration without true red cell deficit), which may prompt iron supplementation in someone who already has excess total body iron.
Roth and colleagues (2014, British Journal of Sports Medicine) reviewed iron metabolism in elite athletes and highlighted that the combination of high training volumes and dietary iron emphasis in endurance sport creates a risk environment where HH diagnoses are delayed. The consequences of undiagnosed iron overload — hepatic fibrosis progressing to cirrhosis, dilated cardiomyopathy, bronze diabetes (iron-induced pancreatic failure) and arthropathy — take decades to develop but are largely irreversible once established.
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The treatment for HH is phlebotomy (therapeutic venesection) — removing 450–500 mL of blood every 1–2 weeks until ferritin falls below 50 μg/L and transferrin saturation below 30%, then maintenance phlebotomy 3–4 times per year. The irony for endurance athletes: scheduled phlebotomy mimics altitude training by stimulating erythropoietin and new red blood cell production, temporarily reducing oxygen-carrying capacity before rebound to new equilibrium. Elite cyclists and distance runners with HH have, in fact, used scheduled phlebotomy therapeutically — an effect that regulators have noted in anti-doping contexts.
The diagnostic recommendation is straightforward: any athlete with unexplained fatigue, joint pain or elevated ferritin above 200 μg/L should have transferrin saturation measured. If that exceeds 45%, HFE genotyping should follow. Brissot and colleagues (2018, Nature Reviews Disease Primers) emphasise that early diagnosis and phlebotomy before organ damage occurs is associated with normal life expectancy, making genetic testing in at-risk populations both clinically and economically justified.
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For athletes monitoring iron status — whether screening for deficiency or evaluating ferritin levels that may warrant further investigation — the tool at winsport.uk/tools/health/iron-needs-calculator estimates your daily iron requirement based on training load, dietary pattern and loss factors, and flags ranges that warrant medical evaluation.
Have you had a full iron panel including transferrin saturation — or has your sports medicine testing focused only on ferritin and haemoglobin?