ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

21–40 of 270 studies

E0 ConsensusReviewPEM unclearSystematic-Review

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

Huth, Teilah Kathryn, Eaton-Fitch, Natalie, Staines, Donald et al.·Journal of translational medicine·2020

Researchers reviewed 11 studies that measured tiny chemical molecules (metabolites) in the blood and urine of ME/CFS patients to see if problems with these chemicals might explain the illness. While they found some patterns—especially with chemicals related to amino acids (building blocks of proteins)—the results were inconsistent across different studies. The researchers concluded that we don't yet have enough evidence that metabolite problems cause ME/CFS.

Biomarkers

E0 ConsensusReviewPEM unclearSystematic-Review

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

Holden, Sean, Maksoud, Rebekah, Eaton-Fitch, Natalie et al.·Journal of translational medicine·2020

This review looked at 19 studies examining whether the power-generating structures in our cells (called mitochondria) work differently in people with ME/CFS compared to healthy people. While many studies found some differences in how these cellular power plants function, the results were inconsistent across different research groups, making it hard to draw clear conclusions about whether mitochondrial problems actually cause ME/CFS.

Biomarkers

E0 ConsensusReviewPEM not requiredSystematic-Review

The clinical value of cytokines in chronic fatigue syndrome.

Yang, Tiansong, Yang, Yan, Wang, Delong et al.·Journal of translational medicine·2019

This review examined whether immune system signaling molecules called cytokines could help doctors diagnose or treat ME/CFS. While researchers found that cytokines are abnormal in ME/CFS patients' blood and fluid around the brain, the current evidence shows these markers are not reliable enough to use alone for diagnosis. The review suggests that measuring multiple cytokines together might help doctors better understand what's happening in individual patients, but cytokines are not yet proven as effective treatment targets.

BiomarkersImmune System

E0 ConsensusReviewPEM unclearSystematic-Review

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

Corbitt, Matthew, Eaton-Fitch, Natalie, Staines, Donald et al.·BMC neurology·2019

Researchers reviewed 15 studies that measured immune signaling molecules called cytokines in people with ME/CFS compared to healthy people. Although many studies have looked at cytokines in ME/CFS, the results were too mixed and inconsistent to show that cytokines could be used as a reliable test for the condition or to confirm a clear role in causing the disease.

BiomarkersImmune System

E0 ConsensusReviewPEM not requiredMeta-Analysis

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

Strawbridge, Rebecca, Sartor, Maria-Laura, Scott, Fraser et al.·Neuroscience and biobehavioral reviews·2019

This research review looked at 42 studies measuring inflammatory proteins (substances in the blood linked to inflammation) in people with ME/CFS compared to healthy people. The researchers found that people with ME/CFS had higher levels of five specific inflammatory proteins, but twelve other proteins were similar to healthy controls. This suggests that inflammation may play a role in ME/CFS for some patients, but it's likely not the main problem for everyone with the condition.

BiomarkersImmune System

E0 ConsensusReviewPEM requiredReview-Narrative

[Myalgic encephalomyelitis or chronic fatigue syndrome].

Brinth, Louise, Nielsen, Henrik, Varming, Kim et al.·Ugeskrift for laeger·2019

ME/CFS is a serious condition that causes extreme tiredness affecting both mind and body, along with pain, sleep problems, difficulty thinking clearly, and a symptom called post-exertional malaise where activity makes symptoms worse. Research has found changes in patients' cells, hormones, immune systems, and how their bodies process energy, which could lead to better ways to diagnose and treat this condition.

BiomarkersEnergy MetabolismImmune SystemPost-Exertional Malaise

E0 ConsensusReviewPEM unclearReview-Narrative

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

Tomas, Cara, Newton, Julia·Biochemical Society transactions·2018

This review examines research showing that people with ME/CFS have problems with how their bodies use energy at a cellular level. Scientists have found several different metabolic abnormalities—issues with immune function, mitochondria (the cell's power plants), muscle acid buildup, and other energy-related problems—that could potentially be used as biomarkers (measurable signs) to diagnose the disease. However, no single test can yet reliably identify ME/CFS.

BiomarkersImmune System

E0 ConsensusReviewPEM unclearEvidence-Map

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

Scheibenbogen, Carmen, Freitag, Helma, Blanco, Julià et al.·Journal of translational medicine·2017

Researchers across Europe are working together to find biological markers (signs in blood or body tests) that could help diagnose ME/CFS and track how treatments work. This study reviewed all the biomarker research happening in Europe and created a database of what scientists are studying. The goal is to develop reliable tests that doctors could use in the future to diagnose ME/CFS and improve clinical trials.

Biomarkers

E0 ConsensusReviewPEM unclearReview-Narrative

Myalgic Encephalomyelitis: Symptoms and Biomarkers.

Jason, Leonard A, Zinn, Marcie L, Zinn, Mark A·Current neuropharmacology·2015

This review article examines what we know about ME/CFS symptoms and biological markers that could help diagnose the disease. The authors point out that ME/CFS is often confused with other conditions like early multiple sclerosis or Parkinson's disease because they share similar symptoms. They call for better standardized ways to diagnose ME/CFS and more large-scale studies to understand what's happening in the body during this illness.

Biomarkers

E0 ConsensusReviewPEM not requiredSystematic-Review

The genetics and epigenetics of fatigue.

Landmark-Høyvik, Hege, Reinertsen, Kristin V, Loge, Jon H et al.·PM & R : the journal of injury, function, and rehabilitation·2010

This study reviewed scientific literature to understand whether genetics (inherited traits) and epigenetics (chemical changes that affect how genes work) influence fatigue in people with ME/CFS and other conditions. The researchers found that while some biological systems appear to malfunction in people with persistent fatigue, no clear genetic or epigenetic markers have been reliably identified yet. The authors argue that future research needs to be larger, better-designed, and consider how genes, environment, and body systems work together.

Endocrine DisruptionBiomarkers

E1 ReplicatedTrialPEM unclearCase-Control

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

Roerink, Megan E, Knoop, Hans, Bronkhorst, Ewald M et al.·Journal of translational medicine·2017

Researchers compared immune signaling molecules (cytokines) in the blood of 50 women with ME/CFS to 48 healthy women and found two markers were elevated in the ME/CFS group: IL-12p40 and CSF-1. They also tested whether a drug called anakinra (which blocks inflammation) could help reduce these markers, but found it did not significantly change cytokine levels after 4 weeks of treatment.

BiomarkersImmune System

E1 ReplicatedCohortPEM unclearObservational

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Jose G. Montoya, Tyson H. Holmes, Jill N. Anderson et al.·Proceedings of the National Academy of Sciences (PNAS)·2017·n=192

Stanford researchers measured 51 cytokines in 192 ME/CFS patients and 392 healthy controls. Seventeen cytokines were significantly elevated in ME/CFS, with TGF-beta most strongly associated with disease severity. More severe patients had higher cytokine levels, suggesting immune activation scales with illness burden.

Severe MEBiomarkersImmune System

E1 ReplicatedCohortPEM requiredObservational

Metabolic features of chronic fatigue syndrome

Robert K. Naviaux, Jane C. Naviaux, Kefeng Li et al.·Proceedings of the National Academy of Sciences (PNAS)·2016·n=84

This study analyzed blood metabolites from 84 ME/CFS patients and 45 healthy controls using untargeted metabolomics. Researchers found 80% of the abnormal metabolites were decreased in ME/CFS patients, suggesting a hypometabolic state — the body running in energy conservation mode. The pattern resembled a 'dauer-like' state seen in organisms under stress.

BiomarkersEnergy Metabolism

E1 ReplicatedTrialPEM not requiredRCT

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

Natelson, Benjamin H, Vu, Diana, Mao, Xiangling et al.·The journal of pain·2015

This study tested whether a medication called milnacipran could reduce brain inflammation and pain in fibromyalgia patients. Researchers measured a chemical called lactate in the brain using a special MRI scan and found that fibromyalgia patients had higher levels than healthy people. After 8 weeks of treatment, patients taking milnacipran showed lower lactate levels and less pain compared to those taking placebo, suggesting the medication may work by reducing brain inflammation.

NeuroinflammationBiomarkers

E2 ModerateCohortPEM unclearLongitudinal

Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.

Palomo, Irene Mena, Cox, Brandon, Williams, Marshall V et al.·Journal of medical virology·2026

This study found that people with ME/CFS have higher levels of immune responses to three common viruses (EBV, HHV-6, and VZV) compared to healthy people. About 72% of ME/CFS patients showed antibodies to multiple viruses at the same time, versus only 31% of healthy controls. The antibody levels were higher in patients with moderate to severe fatigue, suggesting a possible connection between these viral reactivations and symptom severity.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCase-Control

Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.

Gülmez, Dilara, Siwy, Justyna, Kurz, Katharina et al.·Proteomics·2026

Researchers found a simple urine test that can accurately identify people with long COVID (PASC) by measuring tiny protein fragments in the urine. The test correctly identified long COVID patients 96% of the time compared to healthy people and those with ME/CFS. The urine signatures suggest that long COVID involves ongoing inflammation and changes in how the body breaks down and rebuilds connective tissue.

BiomarkersImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

Jones, Ansley E, Mira-Sanchez, Margarita, Khan, Zain et al.·Journal of intensive care medicine·2026

This study examined blood clotting patterns in 93 people who survived severe COVID-19 requiring hospitalization, testing them 15 months after discharge. Researchers observed that those with lingering post-COVID symptoms—particularly fatigue and post-exertional malaise (worsening after activity)—showed altered clotting characteristics on specialized blood tests, specifically higher fibrinogen levels. However, this is a single cross-sectional study and does not establish whether these clotting changes cause the symptoms or are simply associated with them.

BiomarkersLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki et al.·Open forum infectious diseases·2026

Researchers analyzed tiny cell particles called extracellular vesicles in blood samples from people with Long COVID, ME/CFS, and healthy controls. They observed that both Long COVID and ME/CFS groups had elevated levels of certain immune cell-derived particles and alterations in mitochondrial (energy-producing) markers within B cells and other immune cells, though the findings were not identical between groups. These preliminary results suggest there may be shared immune and metabolic changes in these conditions, but the meaning of these changes for patient health remains unclear and needs further study.

BiomarkersEnergy MetabolismImmune SystemLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Extracellular Vesicle Protein and MiRNA Signatures as Biomarkers for Post-Infectious ME/CFS Patients.

Seifert, Martina, Schäfers, Johannes, Douglas, Fiona F et al.·International journal of molecular sciences·2026

Researchers examined tiny packages of proteins and molecules (called extracellular vesicles) found in the blood of ME/CFS patients to see if they contain unique signatures that could help diagnose the disease. They found that certain proteins and a specific small molecule called hsa-let-7b-5p were different in ME/CFS patients compared to healthy people, and these differences were linked to worse fatigue, pain, and immune problems. This discovery suggests that blood tests measuring these substances could eventually help doctors diagnose ME/CFS and better understand who has the disease.

Biomarkers

E2 ModerateCohortPEM unclearLongitudinal

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Jones, Ansley E, Khan, Zain, McGroder, Claire F et al.·Critical care explorations·2026

This study followed people who were hospitalized with severe COVID-19 for 3 years after they left the hospital. About one-quarter of them continued to experience long COVID symptoms like fatigue, brain fog, and difficulty with physical activity. Surprisingly, when researchers measured inflammation and blood vessel markers in their blood, these markers were not elevated and did not explain why some people had ongoing symptoms.

BiomarkersImmune SystemPost-Exertional Malaise

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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.

The clinical value of cytokines in chronic fatigue syndrome.

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

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

[Myalgic encephalomyelitis or 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.

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.

Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.

Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.

Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors.

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Extracellular Vesicle Protein and MiRNA Signatures as Biomarkers for Post-Infectious ME/CFS Patients.

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

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