Iron Dysregulation Linked to MS Progression, Review Finds

Disruptions in iron balance within the brain may play a key role in worsening multiple sclerosis (MS), according to a recent narrative review that examined how iron contributes to demyelination, inflammation, and neurodegeneration.1

Iron dysregulation significantly impacts MS progression, linking iron levels to neuroinflammation, demyelination, and potential therapeutic strategies. | Image credit: Yaruniv-Studio - stock.adobe.com

The review, published in Acta Neurobiologiae Experimentalis, explored decades of research on the relationship between iron metabolism and MS progression. Investigators reported that iron is essential for normal brain function, particularly for myelination and immune regulation, but both iron overload and deficiency appeared to exacerbate MS pathology.

“Central to the pathophysiology of MS is the dysregulation of iron homeostasis, which contributes to neuronal damage,” the authors wrote. “The alteration of iron metabolism and the associated oxidative damage highlight the importance of targeting iron-related pathways as potential therapeutic strategies in MS.”

MS is a chronic autoimmune condition that damages myelin and neurons in the central nervous system, leading to disability and cognitive decline. Although genetic and environmental factors are known contributors, the mechanisms underlying disease progression remain incompletely understood. Iron, a mineral required for oxygen transport, energy production, and immune function, is increasingly recognized as a potential driver of neurodegeneration when its regulation is disrupted.

A separate retrospective study from Oregon Health & Science University (OHSU) highlighted both the high prevalence of iron deficiency among women with MS and the clinical complexity of managing it.2 As the OHSU investigators concluded, “All women with multiple sclerosis should be evaluated for iron deficiency and investigated for cause if iron deficiency is found.” Future studies will be needed to clarify how diagnosing and treating iron deficiency might influence MS outcomes and quality of life.

Past imaging and tissue studies have suggested abnormal iron accumulation in gray matter and reduced levels in white matter among people with MS.1 These changes may impair remyelination, promote oxidative stress, and alter immune cell function. The review authors sought to synthesize evidence on how iron contributes to MS pathology and identify potential therapeutic implications.

The analysis highlighted several mechanisms linking iron dysregulation to MS progression:

• Oxidative stress: Excess iron can catalyze the production of reactive oxygen species, which damage neurons, oligodendrocytes, and the blood-brain barrier
• Ferroptosis: Iron overload may trigger ferroptosis, a type of cell death driven by lipid peroxidation, further accelerating demyelination
• Immune activation: Macrophages and microglia in MS lesions collect iron, polarizing toward a pro-inflammatory state that worsens neuroinflammation
• Iron deficiency: In contrast, low iron may impair T- and B-cell function, reducing immune regulation and potentially fueling autoimmune activity

Patient data also suggested that iron accumulation in the basal ganglia correlated with cognitive impairment and disability, while iron loss in white matter was associated with impaired remyelination capacity.

MS primarily affects young adults and is more common in women. The prevalence continues to rise globally, including in aging populations. The review underscored that iron-related mechanisms may influence both relapsing-remitting MS and progressive forms of the disease.

As a narrative literature review, the study synthesized findings from previously published work rather than presenting new clinical trial data. The authors acknowledged that variability in imaging methods, sample populations, and measurement techniques limited direct comparisons across studies. Additionally, the dual role of iron—as both essential and potentially harmful—complicates interpretation of results and highlights the need for controlled interventional research.

The findings suggest that monitoring and modulating iron levels may one day become part of comprehensive MS management. Oral or intravenous iron supplementation could address deficiency, while iron chelators and antioxidants may help limit overload and oxidative stress. However, the review emphasized that these strategies remain experimental and require further validation in prospective clinical studies.

Ultimately, the study reinforced the complexity of MS pathophysiology and the importance of precision medicine approaches.

“Maintaining the blood-brain barrier’s integrity and controlling the amount of iron in the brain are essential for halting the disease’s progression,” the authors concluded.

References

1. Kłodnicka K, Januszewski J, Forma A, et al. Iron in multiple sclerosis - from pathophysiology to disease progression - a narrative literature review. Acta Neurobiol Exp (Wars). 2025;85(2):75-93. doi:10.55782/ane-2025-2680

2. Patel S, Thawani R, Deloughery TG, et al. Iron deficiency is commonly observed in female multiple sclerosis (MS) patients with relapsed/refractory or primary progressive disease referred for biological therapies. Blood. 2022;140(suppl 1):11086-11087. doi:10.1182/blood-2022-170573