From Iron Deficiency to Overload: A Missing Link in the Mechanisms of Cardiac Autonomic Nervous System Dysfunction

The autonomic nervous system (ANS) plays a key role in cardiovascular regulation by maintaining hemodynamic and metabolic homeostasis through balanced sympathetic and parasympathetic activity. While autonomic dysfunction is classically associated with diabetes, neurodegenerative diseases, autoimmune neuropathies, and chronic cardiovascular conditions, growing evidence suggests that disturbances in iron metabolism represent an underrecognized contributor to cardiac autonomic dysregulation. This narrative review summarizes data from 107 studies on ANS disorders, including 49 investigating cardiovascular involvement. Reported abnormalities included reduced heart rate variability and baroreflex sensitivity, prolonged P-wave duration and QT dispersion, and deviations in non-invasive autonomic testing parameters. In iron overload states, these changes appear to be driven primarily by oxidative stress, whereas in iron deficiency they are likely mediated by tissue hypoxia. Importantly, several studies indicate that normalization of iron homeostasis may partially reverse autonomic dysfunction. This potentially reversible component underscores the clinical relevance of screening for and correcting iron imbalance not only to improve hematological status but also to reduce cardiovascular risk. Large-scale, multicenter studies using standardized autonomic assessment protocols are required to clarify prognostic implications and inform evidence-based clinical guidelines.