Anaemia is a risk factor for functional decline and frailty in older adults including decreased physical performance and muscle strength, increased hospitalisation risk and mortality, falls, and poorer recovery from activities of daily living. Despite a major gap in human studies, research in animals has demonstrated an interrelationship between iron deficiency anaemia and deteriorated functional capacity and physical performance particularly in older adults. Iron deficiency and associated anaemia is a frequent accompanier of debilitating chronic diseases such as heart failure and chronic lung diseases. These conditions, more commonly seen in older patients, are strongly linked to deterioration in physical function, reduced skeletal muscle mass and quality, frailty, and poor quality of life. Exercise intolerance is also a common feature of these conditions as iron deficiency impairs the capacity of carrying oxygen leading to inability to sustain physical activities. Furthermore, the age-related decline in the muscle mass and quality (so called sarcopenia) and associated frailty has rapidly become a major health concern in the older adults particularly when accompanied by other chronic diseases. Recently, there has been an increasing interest in exploring the role of iron as a causative factor in the development of sarcopenia and related frailty.

In summary, there is a substantial gap of evidence whether Iron repletion leads to meaningful enhancements in the skeletal muscle function and physical performance in older adults suffering from iron deficiency anaemia. This study will investigate the impact of a standard care intervention (intravenous iron therapy) on muscular function and physical performance in older patients through a range of laboratory assessments.

The study will recruit two groups of stable patients (although likely with chronic diseases) with established iron deficiency anaemia through Aintree Hospital NHS Trust clinics. Fifty patients aged 60-85 years will be recruited into each group:

1. Intravenous iron therapy group: This group will receive intravenous iron calculated based on body weight and level of anaemia (hemoglobin concentration), as per the iron therapy's SPC
2. Active Control Group: This group will receive oral ferrous sulphate prescribed by their GP Randmisation: Simple randomisation/parallel assignment/single-blinded

Identified patients with iron deficiency anaemia will receive an invitation to participate in the study together with a Patient Information Sheet clearly explaining different aspects of the research project. Each participant will require to attend the School of Health Sciences' laboratories (Liverpool Hope University) on four different occasions (once before the intervention and three times after receiving the iron therapy) throughout a 3-year period to complete multiple assessments in relation to basic blood tests and musculoskeletal function and physical performance. In addition to this, participants in the first group will require to attend the Aintree Hospital NHS Trust clinics on one occasion to receive a single-dose intravenous iron.

The study will broadly investigate musculoskeletal function (health) and physical performance by means of muscle quality, muscle mass, muscle strength, muscle activation and fatigue levels, gait quality, muscle physiology (level of oxygen carried into the muscles), and functional questionnaires prior to, during, and after iron therapy. In addition to this, changes in patients' quality of life in each group will be assessed through administration of validated questionnaires.

The data will be analysed at the end of the study to identify any significant and clinically meaningful changes in the musculoskeletal function, physical performance, and health-related quality of life resulted from the iron therapy in each group while also comparing such changes between the two study groups.

Inclusion Criteria:

• Anaemia attributable to iron deficiency
• Haemoglobin < 120 g/L in women, Hb < 130 g/L in men
• Ferritin ≤100 ng/mL or ≤300 ng/mL if transferrin saturation (TSAT) ≤30%
• Age ≥ 60 to 85 years
• Ambulatory individuals
• Written informed consent

Exclusion Criteria:

• Patients already taking intravenous or oral iron
• BMI > 40 kg/m²
• Uncontrolled hypertension/ diabetes
• Potential medication interactions
• Hemochromatosis or iron storage disorders
• Recent treatment with IV antibiotics or red blood cell transfusion
• Dialysis dependent
• History of malignancy
• Pregnant or lactating women
• Severe hepatic and renal dysfunction
• Advanced cardiovascular disease and COPD
• Advanced Neuromuscular disorder
• Obvious cognitive disability and psychological illness
• Current treatment with systemic steroids or any other substantive medication
• Alcohol or any other drug abuse

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