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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,171 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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1198 studies

E0 — Consensus644E1 — Replicated320E2 — Moderate2,785E3 — Preliminary2,422

ME/CFS4,028Long COVID217Post-infectious189Overlapping1,051

Required for diagnosis415Not specified / unclear2,222Not required3,534

Post-Exertional Malaise1,067Cognitive Dysfunction1,737Pain1,621Unrefreshing Sleep800Orthostatic Intolerance479

Cytokines819Gene Expression568Metabolomics475Neuroimaging468Autoantibodies458

Infection-Triggered1,175Long COVID Overlap589Pediatric494Severe231

Strong Phenotyping439Sex-Stratified327Severe ME Included118

Systematic Review266Meta-Analysis60RCT300

Peer-reviewed6,114Preprint3Unclear54

1001–1020 of 1,198 studies

E3 PreliminaryReviewPEM not requiredReview-Narrative

Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines.

Zuckerman, Jane N·Journal of medical virology·2006

This review examines hepatitis B vaccines, which are widely used and have an excellent safety record across over 150 countries. The authors specifically addressed concerns about whether these vaccines cause chronic fatigue syndrome, and found no evidence of such a connection. The study looked at how well these vaccines work, why some people don't respond to them, and potential new ways to use them to treat hepatitis B infection.

E3 PreliminaryMechanismPEM not requiredMechanistic

Brain cytokines and the 5-HT system during poly I:C-induced fatigue.

Katafuchi, Toshihiko, Kondo, Tetsuya, Take, Sachiko et al.·Annals of the New York Academy of Sciences·2006

This study investigated how the brain's immune system might cause fatigue by looking at what happens when rats are exposed to a viral-like trigger. Researchers found that certain immune molecules in the brain (interferons) increased while a key fatigue-related brain chemical (serotonin) decreased. When they gave the rats a medication that boosted serotonin activity, the fatigue improved, suggesting that low serotonin in a specific brain region may play a role in fatigue.

E3 PreliminaryMechanismPEM not requiredObservational

Clinical activity of folinic acid in patients with chronic fatigue syndrome.

Lundell, Kathleen, Qazi, Sanjive, Eddy, Linda et al.·Arzneimittel-Forschung·2006

This study looked at 58 ME/CFS patients and found that most had weakened immune systems with low levels of a type of immune cell called B-lymphocytes, and most also had reactivated Epstein-Barr virus (EBV) infection. When researchers gave patients folinic acid (a form of vitamin B), about 81% reported feeling better. The findings suggest that folinic acid might help some ME/CFS patients and that immune problems may play a role in the illness.

E3 PreliminaryReviewPEM unclearReview-Narrative

Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a brief review and hypothesis.

Staines, Donald R·Clinical & developmental immunology·2006

This paper proposes that ME/CFS and similar conditions may develop when the immune system mistakenly attacks certain chemical messengers in the body called vasoactive neuropeptides (VNs). These VNs normally help control heart rate, breathing, temperature, memory, and mood. The authors suggest that after infections or other triggers, people's bodies may lose the ability to recognize these messengers as 'self,' leading to immune attacks that could cause the widespread symptoms seen in ME/CFS.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome.

Devanur, L D, Kerr, J R·Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology·2006

ME/CFS affects about 1 in 100 to 1 in 250 people worldwide and is diagnosed based on clinical symptoms after ruling out other diseases. Research shows that ME/CFS likely involves multiple factors: immune system problems, stress, infections (such as Epstein-Barr virus), and exposure to certain chemicals or toxins. Currently there is no proven cure, but treating underlying infections may help some patients.

E3 PreliminaryCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins.

Maes, Michael, Mihaylova, Ivana, Leunis, Jean-Claude·Neuro endocrinology letters·2006

This study found that people with ME/CFS have higher levels of immune antibodies (IgM) attacking damaged fats and proteins in their bodies. These antibodies target substances created when cells are damaged by oxidative stress—a harmful process where the body's natural defenses become imbalanced. The more severe someone's ME/CFS symptoms were, the higher their antibody levels tended to be.

BiomarkersImmune System

E3 PreliminaryMechanismPEM not requiredMechanistic

Beneficial effect of brewers' yeast extract on daily activity in a murine model of chronic fatigue syndrome.

Takahashi, Takashi, Yu, Fei, Zhu, Shi-Jie et al.·Evidence-based complementary and alternative medicine : eCAM·2006

Researchers gave mice a brewer's yeast extract to see if it could help restore activity levels in a mouse model of ME/CFS. Mice treated with the yeast extract showed significantly better activity levels compared to untreated mice, and the treated mice also had better survival rates. The study suggests that brewer's yeast extract may help by adjusting immune system responses that become imbalanced in ME/CFS.

E3 PreliminaryReviewPEM unclearReview-Narrative

Fibromyalgia, infection and vaccination: two more parts in the etiological puzzle.

Ablin, Jacob N, Shoenfeld, Yehuda, Buskila, Dan·Journal of autoimmunity·2006

This review examines whether infections and vaccinations might trigger fibromyalgia and related conditions like chronic fatigue syndrome. Researchers found that certain infections (like Lyme disease and hepatitis C) have been linked to fibromyalgia, and some people report symptoms starting after vaccinations, but antibiotics and antivirals don't appear to help treat fibromyalgia effectively. The authors suggest that vaccinations might act as one trigger among several factors that together cause these conditions.

E3 PreliminaryCohortPEM not requiredCase-Control

Four problems with the clinical control of interstitial pneumonia, or chronic fatigue syndrome, using the megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex.

Kodama, Mitsuo, Kodama, Toshiko·In vivo (Athens, Greece)·2006

This study describes a clinic's experience treating patients with interstitial pneumonia (a lung condition) using high-dose vitamin C infusions combined with hormones and antibiotics since 1996. The authors discuss four main challenges they encountered: deciding whether to continue treatment when patients seemed stable, dealing with bacteria becoming resistant to antibiotics, observing bone marrow damage in one patient, and noting one patient developed breast cancer during treatment.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Is human herpesvirus-6 a trigger for chronic fatigue syndrome?

Komaroff, Anthony L·Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology·2006

This study reviews evidence about whether a virus called human herpesvirus-6 (HHV-6) might cause ME/CFS. Researchers found that active HHV-6 infection appears more frequently in ME/CFS patients than in healthy people, and the virus may be connected to some of the nervous system and immune system problems seen in ME/CFS. However, not all ME/CFS patients test positive for active HHV-6, suggesting it may only trigger the illness in some people.

E3 PreliminaryMechanismPEM not requiredMechanistic

Identifying illness parameters in fatiguing syndromes using classical projection methods.

Broderick, Gordon, Craddock, R Cameron, Whistler, Toni et al.·Pharmacogenomics·2006

Researchers studied 111 women to find common patterns that distinguish ME/CFS patients from healthy controls by looking at both their symptoms and gene activity in blood cells. They used a statistical method to combine multiple pieces of information—like fatigue scores, quality of life measures, and which genes were active—rather than looking at single factors alone. The analysis identified key differences related to stress in cells, immune problems, and imbalanced minerals, particularly reflected in abnormal heart rate patterns during sleep.

E3 PreliminaryMechanismPEM not requiredMechanistic

Gene expression profile exploration of a large dataset on chronic fatigue syndrome.

Fang, Hong, Xie, Qian, Boneva, Roumiana et al.·Pharmacogenomics·2006

Researchers studied the genes that are turned on or off differently in people with ME/CFS compared to healthy controls. They looked at blood samples from 167 people and used computer analysis to identify 24 key genes and 11 biological pathways that appear to be involved in ME/CFS. These genes are involved in immune function, cell communication, and nerve activity—areas that scientists already suspect play a role in the illness.

E3 PreliminaryMechanismPEM not requiredMechanistic

Pathogenesis of parvovirus B19 infection: host gene variability, and possible means and effects of virus persistence.

Kerr, J R·Journal of veterinary medicine. B, Infectious diseases and veterinary public health·2005

This study examined how parvovirus B19 might trigger chronic fatigue syndrome (CFS) in some people. Researchers found that patients with prolonged symptoms after B19 infection had high levels of inflammatory chemicals in their blood, and identified certain genetic variations that may make some people more susceptible to developing CFS after B19 infection. They also discovered that the virus may persist in the body by hiding in human genes, and found that people carrying B19 virus DNA had altered expression of several genes involved in cell structure and immune function.

E3 PreliminaryCommentaryPEM unclearEditorial

Are vasoactive neuropeptide autoimmune fatigue-related disorders mediated via G protein-coupled receptors?

Staines, Donald·Medical hypotheses·2005

This paper proposes that ME/CFS might involve problems with special proteins on cell surfaces called G protein-coupled receptors (GPCRs), which normally help cells respond to stress and manage energy. The author suggests that certain immune molecules and genetic variations could damage these receptors, disrupting the cell's ability to produce energy and causing fatigue. This is a theoretical explanation rather than a proof based on patient data.

E3 PreliminaryMechanismPEM not requiredMechanistic

2',5'-Oligoadenylate size is critical to protect RNase L against proteolytic cleavage in chronic fatigue syndrome.

Frémont, Marc, El Bakkouri, Karim, Vaeyens, Freya et al.·Experimental and molecular pathology·2005

In ME/CFS, immune cells produce abnormal levels of proteins involved in fighting viral infections. This study found that a protective molecule called 2-5A can shield a key antiviral protein (RNase L) from being broken down by inflammatory enzymes. However, in ME/CFS patients, cells tend to produce smaller versions of 2-5A, which cannot provide this protection, leading to the accumulation of damaged RNase L protein.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Persistent nonallergic rhinosinusitis.

Staevska, Maria, Baraniuk, James N·Current allergy and asthma reports·2005

This review describes different types of nasal and sinus inflammation that are not caused by allergies. The authors propose a new way to organize these conditions based on whether they involve certain immune cells (eosinophils or neutrophils) or other mechanisms like hormonal changes. Interestingly, they mention that nonallergic rhinitis can occur in chronic fatigue syndrome (ME/CFS) and may involve nerve-related sensitivity.

E3 PreliminaryReviewPEM unclearReview-Narrative

Therapeutic and preventive interventions for postulated vasoactive neuropeptide autoimmune fatigue-related disorders.

Staines, Donald R·Medical hypotheses·2005

This article explores a theory that ME/CFS and related conditions like fibromyalgia might be caused by problems with special chemical messengers in the body called vasoactive neuropeptides. These chemicals normally help control blood vessels, inflammation, and immune function. The authors suggest that if this theory is correct, several treatments might help—including replacing these chemicals, using certain medications, or modifying genes—though they emphasize this is still speculative and unproven.

E3 PreliminaryCohortPEM not required

The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex.

Kodama, Mitsuo, Kodama, Toshiko·International journal of molecular medicine·2005

This study describes a treatment approach combining high-dose vitamin C infusions with hormonal supplements (DHEA and cortisol) in patients with interstitial pneumonia, which the authors propose may be related to ME/CFS. Over 9 years, the researchers tracked whether this treatment reduced flare-ups and prevented complications like cancer and depression. The treatment appeared to help reduce active pneumonia symptoms, though it did not prevent long-term scarring of the lungs.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Drug targets in stress-related disorders.

Covelli, Vito, Passeri, Maria Elena, Leogrande, Domenica et al.·Current medicinal chemistry·2005

This review examines how stress affects both the nervous and immune systems, and explores potential drug treatments for stress-related disorders. The authors discuss how the body's stress response systems can trigger or worsen conditions like chronic fatigue syndrome (CFS), and suggest that medicines targeting immune cell activity and inflammatory chemicals may help. They found that CFS patients have different immune patterns compared to depressed patients, which could guide future treatment approaches.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Cytokine production and modulation: comparison of patients with chronic fatigue syndrome and normal controls.

Tomoda, Akemi, Joudoi, Takako, Rabab, El-Mezayen et al.·Psychiatry research·2005

This study examined immune system chemicals called cytokines in people with ME/CFS compared to healthy volunteers. Researchers took blood cells from both groups and stimulated them in the laboratory to see how they would respond. They found that ME/CFS patients produced lower levels of certain immune chemicals, particularly one called TGF-beta1, which might play a role in the inflammation seen in ME/CFS.

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.