Comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.
Morten et al, Frontiers of Neuroscience (2025)
Summary
- Metabolic Dysregulation in Chronic Conditions: The paper explores how Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Syndrome (GWS), and fibromyalgia share common metabolic disruptions, particularly in lipid metabolism and energy production, contributing to chronic fatigue and other symptoms.
- Increased Oxidative Stress: The paper emphasises the role of oxidative stress in these conditions, where an imbalance between free radicals and antioxidants leads to cellular damage and inflammation, further worsening symptoms.
- Need for Funding: The authors emphasise the need for international efforts and substancial funding to better understand the disease functions.
The following paper, ‘Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia,' was published in Frontiers of Neuroscience on the 10th of March by Morten et al.
This research was funded by the ME Association's Ramsay Research Fund.
Extracts
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War Syndrome (GWS), and Fibromyalgia (FM) are complex, chronic illnesses with overlapping clinical features. Symptoms that are reported across these conditions include post-exertional malaise (PEM), fatigue, and pain, yet the etiology of these illnesses remains largely unknown. Diagnosis is challenging in patients with these conditions as definitive biomarkers are lacking; patients are required to meet clinical criteria and often undergo lengthy testing to exclude other conditions, a process that is often prolonged, costly, and burdensome for patients.
The identification of reliable validated biomarkers could facilitate earlier and more accurate diagnosis and drive the development of targeted pharmacological therapies that might address the underlying pathophysiology of these diseases. Major driving forces for biomarker identification are the advancing fields of metabolomics and proteomics that allow for comprehensive characterization of metabolites and proteins in biological specimens.
Recent technological developments in these areas enable high-throughput analysis of thousands of metabolites and proteins from a variety of biological samples and model systems, that provides a powerful approach to unraveling the metabolic phenotypes associated with these complex diseases.
Emerging evidence suggests that ME/CFS, GWS, and FM are all characterized by disturbances in metabolic pathways, particularly those related to energy production, lipid metabolism, and oxidative stress. Altered levels of key metabolites in these pathways have been reported in studies highlighting potential common biochemical abnormalities. The precise mechanisms driving altered metabolic pathways in ME/CFS, GWS, and FM remain to be elucidated; however, the elevated oxidative stress observed across these illnesses may contribute to symptoms and offer a potential target for therapeutic intervention.
Investigating the mechanisms, and their role in the disease process, could provide insights into disease pathogenesis and reveal novel treatment targets.
As such, comprehensive metabolomic and proteomic analyses are crucial for advancing the understanding of these conditions in-order to identify both common, and unique, metabolic alterations that could serve as diagnostic markers or therapeutic targets.
Comment from Dr Karl Morten, PHD
Our review of the literature exploring how components of blood differ in ME/CFS, Fibromyalgia and Gulf War syndrome relative to healthy controls showed common themes emerging across all three patient groups. Evidence of increased oxidative stress, energy generation issues and abnormal lipid profiles were observed across all patient groups relative to controls.
This is suggesting that although the illness triggers might be different, there might be common causal elements which could be targeted with future treatments. One treatment might modulate symptoms in a wide range of conditions.
Our study also highlighted the concerning increase in Long Covid patients with over 16 million people predicted to develop Long Covid in the US during 2025. The number of patients who make a full recovery from Long Covid also appears worryingly low. Clearly research funding is desperately needed as we look to tease out which are the aberrant pathways to target with treatments.