Review Suggests Ferritin May Influence MS Progression and Repair

Emerging evidence suggests ferritin, a biomarker associated with iron storage, may have a more complex role in multiple sclerosis (MS), potentially serving as both an indicator of disease progression and a marker of remyelination capacity. Newly presented findings from a literature review at the 2026 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting held May 27-29 in Charlotte, indicated that elevated ferritin levels may correlate with neurodegeneration and chronic inflammatory activity in MS, but low ferritin levels may impair myelin repair mechanisms.¹

The review, led by Nikitha Sheth, a medical student at University of Missouri-Kansas City School of Medicine, examined published evidence spanning nearly 4 decades to assess whether ferritin could function as a clinically meaningful biomarker for monitoring MS progression and guiding management strategies. Although conclusions remain preliminary, investigators argued that routine ferritin assessment may warrant greater attention in clinical practice.

Ferritin’s Potential Dual Role in MS

Iron homeostasis has increasingly become an area of interest in neurodegenerative disease research with ferritin contributing to oligodendrocyte biology and myelin maintenance. Dysregulated iron metabolism has been implicated in oxidative stress, inflammation, and neurodegeneration pathologic processes relevant to progressive MS.² According to the review, elevated ferritin levels were associated with increased MS progression in several studies, potentially reflecting heightened inflammatory activity and iron-mediated oxidative injury.

Conversely, the authors noted that insufficient iron stores may also carry clinical consequences. Here, they highlighted evidence surrounding iron deficiency without anemia (IDWA), defined as low serum ferritin despite preserved hemoglobin levels. All told, low ferritin was associated with impaired myelination and symptoms commonly reported by patients with MS, including fatigue and anxiety.¹

Investigators noted that some studies described more favorable disease trajectories among patients with IDWA who received long-term iron supplementation, though these observations remain hypothesis-generating and require validation in prospective cohorts.¹

Review Methodology

The literature review analyzed studies published between 1989 and 2026 using databases including PubMed. Search terms included iron metabolism, ferritin, multiple sclerosis, and iron deficiency without anemia.¹

Studies evaluating elevated ferritin concentrations (>200 µg/L in women; >300 µg/L in men) and low ferritin concentrations (<30 µg/L) among patients with MS were included. Two independent reviewers performed study selection and data extraction, with disagreements resolved by consensus. Overall, 11 studies met inclusion criteria.

Across those studies, higher ferritin concentrations appeared associated with greater MS progression, while low ferritin levels were linked to defective myelination. Intravenous iron supplementation was reportedly associated with improved myelination-related outcomes in some populations. Because the review synthesized heterogeneous observational data rather than pooled outcomes in a meta-analysis, causality cannot be established.

Study Limitations

The authors emphasized several limitations, including the small evidence base and variability among included studies. Only 11 studies satisfied inclusion criteria, and standardized outcome measures, effect sizes, or risk-of-bias analyses were not reported.

Additionally, ferritin is an acute-phase reactant and may increase in response to systemic inflammation independent of iron status, potentially complicating interpretation in chronic inflammatory diseases such as MS.

Prospective longitudinal studies will likely be necessary before ferritin monitoring could be incorporated into formal MS management guidelines. The investigators concluded that further research should examine outcomes among patients undergoing routine ferritin assessment and determine optimal ferritin ranges that support repair without contributing to iron toxicity.¹

Ferritin’s Expanding Relevance Across Neurology

Interest in ferritin monitoring extends beyond MS and has increasingly emerged across several neurologic disorders associated with iron dysregulation. In restless legs syndrome (RLS), for example, updated clinical guidelines emphasize routine ferritin and transferrin saturation assessment as part of standard disease management, with defined thresholds guiding oral and intravenous iron supplementation.³

Although ferritin monitoring has not yet been incorporated into formal MS management recommendations, the authors suggested the evolving role of iron biomarkers in other neurologic diseases may support further investigation into whether similar strategies could eventually help identify patients at risk for impaired remyelination, worsening inflammation, or progressive disease activity in MS.¹

REFERENCES
1. Sheth N, Ragab A, Mahmoud R. Ferritin as a dual-edged biomarker in multiple sclerosis: a literature review of its role in progression, remyelination, and clinical monitoring. Presented at: 2026 Consortium of Multiple Sclerosis Centers Annual Meeting; May 27-29; Charlotte, NC. ABSTRACT LBA
2. Stephenson E, Nathoo N, Mahjoub Y, Dunn JF, Yong VW. Iron in multiple sclerosis: roles in neurodegeneration and repair. Nat Rev Neurol. 2014;10(8):459-468. doi:10.1038/nrneurol.2014.118
3. Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2025;21(1):137-152. doi:10.5664/jcsm.11390