Iron deficiency is common in cardiorespiratory diseases and appears to contribute to a worse outcome. This human physiology study will examine the extent to which human skeletal muscle metabolism and exercise physiology are impaired by iron deficiency.

This is a prospective double-blind randomised controlled study of the effect of endogenous iron status on skeletal muscle metabolism and exercise physiology. 32 healthy volunteers will take part, half of whom will be iron-deficient. The study involves a screening visit and two half-day visits during which assessments are performed. 50% of each group will be randomised to receive iron-repletion with ferric carboxymaltose at the end of the first experimental visit before returning to repeat identical assessments around one week later. This approach will make it possible to explore whether baseline differences in skeletal muscle metabolism are explained by differences in iron status per se, whilst controlling for any learning effect during participation in the study.

Inclusion Criteria:

• Willing and able to give informed consent for participation in the study
• Men and women aged 18 years or older and generally in good health
• For iron-deficient volunteers: ferritin ≤ 15 microg/L and transferrin saturation < 16%
• For iron-replete volunteers: ferritin ≥ 20 microg/L and transferrin saturation ≥ 20%

Exclusion Criteria:

• Haemoglobin < 8.0 g/dL
• Haemoglobinopathy
• Iron overload, defined as ferritin > 300 microg/L
• Hypoxaemia (SpO2 < 94%) or significant co-morbidity that may affect haematinics, metabolic or ventilatory responses
• Iron supplementation or blood transfusion within the previous 6 weeks
• Pregnancy or breast feeding
• Inability to exercise isolated calf muscle using a pedal or on a bicycle ergometer
• Contraindication to magnetic resonance spectroscopy exposure such as metallic implant
• Contraindication to receiving intravenous ferric carboxymaltose