E2 ModeratePreliminaryPEM unclearCross-SectionalPeer-reviewedMachine draft
Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia.
Azimi, Ghazaleh, Elremaly, Wesam, Elbakry, Mohamed et al. · International journal of molecular sciences · 2025 · DOI
Quick Summary
This study measured a protein called FGF-21 in the blood of people with ME/CFS, fibromyalgia, and both conditions combined, then compared how their symptoms and thinking abilities differed based on their FGF-21 levels. The researchers found that FGF-21 levels—not just the diagnosis alone—were better at predicting which symptoms and cognitive problems each person would experience. This suggests FGF-21 could become a useful blood test to help doctors understand and treat these conditions more precisely.
Why It Matters
Currently, ME/CFS and fibromyalgia lack objective diagnostic biomarkers, making clinical subtypes and treatment selection difficult. If FGF-21 can reliably identify patient subtypes with different symptom profiles and treatment needs, it could enable precision medicine approaches and help develop targeted therapies. This work addresses a critical gap in understanding biological heterogeneity within these overlapping syndromes.
Observed Findings
- Elevated FGF-21 levels were more frequently observed in ME and ME+FM groups compared to controls.
- Low FGF-21 levels were associated with worse perceived post-exertional malaise in fibromyalgia patients and greater immune/autonomic symptoms in ME patients.
- High FGF-21 levels correlated with better cognitive performance in ME but paradoxically with greater fatigue in ME+FM patients.
- FGF-21-based stratification revealed distinct symptom and cognitive profiles that were not apparent when using diagnosis alone.
- Discrepancies between subjective PEM questionnaires (DSQ) and detailed post-exertional malaise assessment (DPEMQ) highlight limitations of current assessment tools.
Inferred Conclusions
- FGF-21 may serve as a valuable biomarker for identifying clinically meaningful subtypes within ME and fibromyalgia based on metabolic/stress-response patterns.
- FGF-21-based stratification is more predictive of specific symptom profiles than categorical diagnosis alone, supporting a precision medicine approach.
- Objective biomarkers like FGF-21 could guide personalized treatment development rather than using syndrome diagnosis as the sole basis for therapy.
- The heterogeneity of FGF-21 across all patient groups suggests ME and fibromyalgia represent biologically diverse conditions requiring subtype-specific interventions.
What This Study Does Not Prove
This study does not prove that FGF-21 causes the observed symptoms—it only shows association at one time point. The cross-sectional design cannot establish causation or determine whether FGF-21 changes drive symptoms or respond to them. FGF-21 may also be a marker of other underlying biological processes rather than the direct mechanism of disease.
Tags
Symptom:Post-Exertional MalaiseCognitive DysfunctionPainFatigue
Biomarker:MetabolomicsBlood Biomarker
Method Flag:PEM Not DefinedExploratory OnlyMixed Cohort
Metadata
- DOI
- 10.3390/ijms26167670
- PMID
- 40868993
- Review status
- Machine draft
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 10 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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