Abstract
Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case–control, clinical physiology study to explore the effects of iron deficiency on human metabolism, using exercise as a stressor. Thirteen iron-deficient (ID) individuals and thirteen iron-replete (IR) control participants each underwent 31P-magnetic resonance spectroscopy of exercising calf muscle to investigate differences in oxidative phosphorylation, followed by whole-body cardiopulmonary exercise testing. Thereafter, individuals were given an intravenous (IV) infusion, randomised to either iron or saline, and the assessments repeated ~ 1 week later. Neither baseline iron status nor IV iron significantly influenced high-energy phosphate metabolism. During submaximal cardiopulmonary exercise, the rate of decline in blood lactate concentration was diminished in the ID group (P = 0.005). Intravenous iron corrected this abnormality. Furthermore, IV iron increased lactate threshold during maximal cardiopulmonary exercise by ~ 10%, regardless of baseline iron status. These findings demonstrate abnormal whole-body energy metabolism in iron-deficient but otherwise healthy humans. Iron deficiency promotes a more glycolytic phenotype without having a detectable effect on mitochondrial bioenergetics.
Highlights
In subjects with profound iron-deficiency anaemia (IDA), maximal treadmill exercise time increased significantly with intravenous (IV) iron supplementation, and post-exercise venous blood lactate concentrations remained similar with successive experiments despite higher w orkloads[2]
The main finding of the present study is of abnormal whole-body metabolism in ID individuals, manifest as disturbed blood lactate kinetics during exercise, in the absence of any demonstrable impairment of skeletal muscle oxidative phosphorylation
Iron deficiency appears to promote a shift in favour of anaerobic glycolysis, reflected in sizeable changes in the threshold for anaerobic metabolism, and this effect is not mediated by differences in Hb concentration
Summary
The rate of decline in blood lactate concentration was diminished in the ID group (P = 0.005) IV iron increased lactate threshold during maximal cardiopulmonary exercise by ~ 10%, regardless of baseline iron status. These findings demonstrate abnormal wholebody energy metabolism in iron-deficient but otherwise healthy humans. In subjects with profound iron-deficiency anaemia (IDA), maximal treadmill exercise time increased significantly with intravenous (IV) iron supplementation, and post-exercise venous blood lactate concentrations remained similar with successive experiments despite higher w orkloads[2]. The use of oral iron over a protracted period inevitably leads to a rise in haemoglobin (Hb) concentration, which is a powerful confounding factor
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