Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis. — CFSMEATLAS
Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis.
Hendrix, Jolien, Fanning, Lara, Wyns, Arne et al. · European journal of clinical investigation · 2025 · DOI
Quick Summary
Researchers analyzed 37 studies comparing how the bodies of ME/CFS and fibromyalgia patients handle stress hormones compared to healthy people. They found that ME/CFS patients have higher levels of adrenaline at rest and unusual responses to exercise and position changes—suggesting their nervous system doesn't regulate stress hormones normally. These findings point to a specific biological problem in ME/CFS that might be treatable.
Why It Matters
This study identifies specific biological markers of adrenergic dysfunction in ME/CFS that are distinct from fibromyalgia, supporting the concept that ME/CFS involves genuine neurobiological abnormalities rather than being psychosomatic. These findings suggest potential therapeutic targets—such as adrenergic regulation—that could lead to new treatments tailored specifically to ME/CFS pathophysiology.
Observed Findings
ME/CFS patients had elevated baseline adrenaline levels in blood compared to healthy controls.
ME/CFS patients showed exaggerated increases in multiple adrenergic receptors (α2A, β2) and COMT enzyme after exercise.
ME/CFS patients had a greater noradrenaline response to orthostatic (position change) testing.
Fibromyalgia patients showed a diminished adrenaline response to exercise, differing from ME/CFS.
No significant baseline adrenergic differences were found in fibromyalgia patients.
Inferred Conclusions
Sympathetic nervous system dysfunction is more centrally involved in ME/CFS pathophysiology than in fibromyalgia.
The adrenergic abnormalities in ME/CFS are particularly evident during stress responses (exercise, position changes) rather than at rest.
Adrenergic dysregulation represents a targetable biological mechanism that may distinguish ME/CFS from other chronic pain conditions.
The distinctly different adrenergic profiles between ME/CFS and fibromyalgia suggest these are separate pathophysiological conditions despite symptom overlap.
Remaining Questions
Do these adrenergic abnormalities persist over time or change with disease progression in ME/CFS patients?
What This Study Does Not Prove
This study does not prove that adrenergic dysfunction causes ME/CFS or explain why these abnormalities develop. It cannot establish whether correcting these adrenergic abnormalities will improve patient symptoms, nor does it identify which specific adrenergic interventions would be beneficial. Correlation between biomarkers and disease mechanisms does not necessarily indicate causation.