BiomarkerPEM-relevant

Biomarkers

270 studies in the atlas

Identifying reliable biomarkers for ME/CFS is a major research priority. Studies have explored cytokine profile differences, altered gene expression patterns, metabolomics signatures, autoantibodies against G-protein coupled receptors, and blood-based indicators from immune-system and energy-metabolism research. Multi-omics approaches — combining proteomics, transcriptomics, and metabolomics — have shown promise in identifying patient subgroups and distinguishing ME/CFS from other conditions. A reliable diagnostic biomarker would address one of the most significant clinical challenges in ME/CFS: the absence of an objective laboratory test for diagnosis.

What we know

Multiple candidate biomarkers have been identified, including NK cell cytotoxicity, cytokine profiles, and metabolomic signatures
Two-day CPET provides an objective functional measure, though it is not a blood-based biomarker
Several blood-based diagnostic assays are under development, including impedance-based and proteomic approaches
No single biomarker has yet been validated for clinical diagnostic use

What remains uncertain

Whether a single biomarker or a panel approach will prove most effective
Biomarker results may vary by disease duration, severity, and subtype
The Ron Davis lab impedance assay showed initial promise but awaits independent replication at scale
Whether Long COVID biomarker research will accelerate ME/CFS biomarker discovery

What is emerging

Which candidate biomarkers will survive large-scale validation
Whether biomarkers can predict disease trajectory or treatment response
The timeline to a clinically available diagnostic test
Whether different ME/CFS subtypes require different biomarker panels

Start here

E0 ConsensusPEM required

Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.

Davis, Leah, Higgs, Maisy, Snaith, Ailsa et al.·Frontiers in neuroscience·2025

This review examined research showing that ME/CFS, Gulf War Syndrome, and fibromyalgia may share similar problems with how the body produces energy and handles stress at the cellular level. Scientists found that these three conditions show signs of disrupted fat metabolism, energy production difficulties, and increased cellular damage from oxidative stress. Better understanding these shared biological problems could help doctors diagnose these conditions faster and develop treatments that target the root causes rather than just treating symptoms.

Research Momentum

258 publications over 36 years. Recent trend: steady (17/year over the last 3 years).

Top Studies

60 of 270, sorted by evidence level and year

Biomarkers

What we know

What remains uncertain

What is emerging

Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.

Research Momentum

Top Studies

Neuroendocrine signature of ME/CFS: Meta-analytic evidence for bioactive cortisol deficit and exaggerated feedback sensitivity.

Machine learning and multi-omics in precision medicine for ME/CFS.

Chronic Fatigue Syndrome: Diagnosis, Treatment, and Future Direction.

Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic review and meta-analysis.

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.

A systematic review and meta-analysis of urinary biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Frontiers in chronic fatigue syndrome research: An analysis of the top 100 most influential articles in the field.

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Insights into Metabolite Diagnostic Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

A systematic review of metabolomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID).

A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease.

A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID).

[Myalgic encephalomyelitis or chronic fatigue syndrome].

Inflammatory proteins are altered in chronic fatigue syndrome-A systematic review and meta-analysis.

The clinical value of cytokines in chronic fatigue syndrome.

Metabolic abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a mini-review.

The European ME/CFS Biomarker Landscape project: an initiative of the European network EUROMENE.

Myalgic Encephalomyelitis: Symptoms and Biomarkers.

The genetics and epigenetics of fatigue.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.

Dysregulation of lipid metabolism, energy production, and oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome, Gulf War Syndrome and fibromyalgia.

Biomarkers over Time: From Visual Contrast Sensitivity to Transcriptomics in Differentiating Chronic Inflammatory Response Syndrome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Metabolic neuroimaging of myalgic encephalomyelitis/chronic fatigue syndrome and Long-COVID.

Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium.

Identifying microRNAs Possibly Implicated in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Review.

DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients.

Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.

Cytokine signatures in chronic fatigue syndrome patients: a Case Control Study and the effect of anakinra treatment.

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Metabolic features of chronic fatigue syndrome

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial.

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

3D Virtual Reality Performance Metrics as a Future Fatigue Biomarker in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Phosphoproteomic analysis reveals differential associations between liver-spleen disharmony and qi-blood deficiency syndromes in chronic fatigue syndrome.

Development and validation of blood-based diagnostic biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using EpiSwitch® 3-dimensional genomic regulatory immuno-genetic profiling.

Mapping the complexity of ME/CFS: Evidence for abnormal energy metabolism, altered immune profile, and vascular dysfunction.

Variation in Repeated Handgrip Strength Testing Indicates Submaximal Force Production in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome.

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.

Age-specific alterations of the gut mycobiome in patients with myalgic encephalomyelitis/chronic fatigue syndrome and identification of potential diagnostic biomarkers.

Haptoglobin phenotypes and structural variants associate with post-exertional malaise and cognitive dysfunction in myalgic encephalomyelitis.

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis.

SMPDL3B a novel biomarker and therapeutic target in myalgic encephalomyelitis.

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome.

Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery.

Sex and disease severity-based analysis of steroid hormones in ME/CFS.

Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank.

Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls.

Circulating miRNAs Expression in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression.

Unsupervised Cluster Analysis Reveals Distinct Subtypes of ME/CFS Patients Based on Peak Oxygen Consumption and SF-36 Scores.

Comparative Analysis of Extracellular Vesicles in Patients with Severe and Mild Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Revisiting IgG Antibody Reactivity to Epstein-Barr Virus in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Its Potential Application to Disease Diagnosis.

Biomarkers in the diagnostic algorithm of myalgic encephalomyelitis/chronic fatigue syndrome.

Autoimmune gene expression profiling of fingerstick whole blood in Chronic Fatigue Syndrome.

Multimodal MRI of myalgic encephalomyelitis/chronic fatigue syndrome: A cross-sectional neuroimaging study toward its neuropathophysiology and diagnosis.

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.