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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

1101–1120 of 1,198 studies

E3 PreliminaryCommentaryPEM unclearEditorial

Future directions in exercise and immunology: regulation and integration.

Mackinnon, L T·International journal of sports medicine·1998

This editorial discusses how exercise affects the immune system and raises important questions for future research. It explores whether athletes' bodies are actually fighting infections less effectively, whether reducing certain immune responses might sometimes be helpful, and how exercise training might help people with conditions like chronic fatigue syndrome improve their immune function.

E3 PreliminaryMechanismPEM not requiredObservational

Elevated apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of protein kinase RNA.

Vojdani, A, Ghoneum, M, Choppa, P C et al.·Journal of internal medicine·1997

This study found that immune cells in ME/CFS patients are dying at higher rates than in healthy people. The researchers discovered that a molecule called PKR, which is produced in response to infections, is abnormally elevated in ME/CFS patients and may be triggering this excess cell death. When they blocked PKR in the lab, they were able to reduce cell death in about half of the ME/CFS samples, suggesting PKR might be a key player in ME/CFS disease.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome.

Plioplys, A V·Neurology·1997

Researchers investigated whether people with ME/CFS have antibodies (immune proteins) in their blood that attack muscles or the brain, which could explain fatigue and brain fog symptoms. They compared 10 ME/CFS patients with 10 healthy controls but did not find evidence of these harmful antibodies in either group.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Gender differences in host defense mechanisms.

Cannon, J G, St Pierre, B A·Journal of psychiatric research·1997

This review looks at why the immune system works differently in women compared to men. Women generally have stronger immune responses, which helps them fight infections better, but also makes them more likely to develop autoimmune diseases where the immune system attacks the body. Because ME/CFS affects mostly women, researchers wondered if these gender differences in immune function might help explain why the illness is so much more common in women.

E3 PreliminaryCohortPEM not requiredCase-Control

Chronic parvovirus B19 infection resulting in chronic fatigue syndrome: case history and review.

Jacobson, S K, Daly, J S, Thorne, G M et al.·Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·1997

This case study describes a young woman whose severe fatigue, fever, and other symptoms resembled ME/CFS, but were traced to a persistent parvovirus B19 infection. Doctors detected the virus in her blood using sensitive testing methods, even though her body had produced antibodies against it. When she received intravenous immunoglobulin treatment, her fever improved.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Cytokine production by adherent and non-adherent mononuclear cells in chronic fatigue syndrome.

Gupta, S, Aggarwal, S, See, D et al.·Journal of psychiatric research·1997

Researchers tested immune cells from people with ME/CFS to measure inflammation-related proteins called cytokines. They found that certain immune cells from ME/CFS patients produced higher levels of inflammatory proteins (TNF-alpha and IL-6) without any stimulation, but produced lower levels of a protective protein (IL-10) compared to healthy people. These imbalances might explain some of the symptoms people with ME/CFS experience.

E3 PreliminaryCohortPEM not requiredCross-Sectional

Profile of patients with chemical injury and sensitivity.

Ziem, G, McTamney, J·Environmental health perspectives·1997

This study looked at people who react strongly to everyday chemicals—like cleaning products, pesticides, and new materials—at levels that don't bother most people. Researchers gave these patients questionnaires and ran medical tests to understand their symptoms. They found that chemical sensitivity often overlaps with ME/CFS and fibromyalgia, and that several body systems (liver, nervous system, immune system) appear to be affected in these patients.

E3 PreliminaryMechanismPEM not requiredMechanistic

Biochemical evidence for a novel low molecular weight 2-5A-dependent RNase L in chronic fatigue syndrome.

Suhadolnik, R J, Peterson, D L, O'Brien, K et al.·Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research·1997

This study examined a specific immune system protein called RNase L in people with ME/CFS. Researchers found that people with ME/CFS had unusual forms of this protein that were different sizes and worked differently than those in healthy people, suggesting their antiviral defense system may be malfunctioning in a previously unknown way.

E3 PreliminaryReviewPEM unclearReview-Narrative

Chronic fatigue syndrome--aetiological aspects.

Dickinson, C J·European journal of clinical investigation·1997

This review examines why ME/CFS develops, looking at evidence from 40 years of research. The author discusses how ME/CFS may involve damage to the brain stem (the oldest part of the brain that controls basic functions like sleep and alertness), possibly from a previous viral infection. Brain imaging studies have found small patches of damage in the brain stems of some ME/CFS patients, similar to what is seen in other conditions like post-polio fatigue.

E3 PreliminaryReviewPEM unclearReview-Narrative

Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction.

Dröge, W, Holm, E·FASEB journal : official publication of the Federation of American Societies for Experimental Biology·1997

This study proposes that several diseases—including ME/CFS, HIV, cancer, and inflammatory bowel disease—share a common pattern: low levels of certain amino acids (cysteine and glutamine), weakened immune cells called natural killer cells, and muscle weakness. The researchers suggest these low amino acid levels may be both a cause and a consequence of muscle wasting, and that boosting cysteine might help treatment when combined with disease-specific therapies.

E3 PreliminaryMechanismPEM not requiredObservational

Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1 receptor type II secretion in chronic fatigue syndrome.

Cannon, J G, Angel, J B, Abad, L W et al.·Journal of clinical immunology·1997

This study examined whether people with ME/CFS have abnormal levels of immune signaling molecules (called interleukins) in their blood compared to healthy people. Researchers collected blood samples from women with ME/CFS and matched healthy controls at different points in their menstrual cycles, and tested how their immune cells responded to physical activity. The findings suggest that ME/CFS may involve differences in how the immune system communicates, possibly related to hormonal changes.

Immune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients.

See, D M, Broumand, N, Sahl, L et al.·Immunopharmacology·1997

This study tested whether two herbal supplements—echinacea and ginseng—could boost immune cells taken from healthy people and patients with ME/CFS or HIV/AIDS. Researchers found that both herbs increased the activity of natural killer cells and antibody-dependent immune responses in blood samples from all three groups. While the results suggest these herbs may help activate certain immune functions, this was a laboratory experiment using cells in a dish, not a study of people taking the supplements.

E3 PreliminaryReviewPEM unclearReview-Narrative

Viral arthritis.

Schnitzer, T J, Penmetcha, M·Current opinion in rheumatology·1996

This review examines how viral infections can cause joint pain and arthritis. Researchers found that several viruses—including hepatitis C, parvovirus B19, and those in certain vaccines—may trigger arthritis in some people. Interestingly, the study noted a negative association between parvovirus B19 and chronic fatigue syndrome, suggesting these conditions may not be closely linked.

E3 PreliminaryCohortPEM not required

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). I. A Pilot study of the new vitamin C infusion treatment with a volunteer CFS patient.

Kodama, M, Kodama, T, Murakami, M·In vivo (Athens, Greece)·1996

This pilot study tested whether high-dose vitamin C infusions, combined with a hormone called DHEA, could help one male ME/CFS patient who also had pneumonia-like symptoms. The patient received different types of infusions over 10 months, and his pneumonia-related symptoms improved when the new DHEA-enhanced vitamin C treatment was used alongside antibiotics. The researchers measured increased levels of certain hormones in his urine after treatment.

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome--psychiatric aspects].

Lemke, M R·Fortschritte der Neurologie-Psychiatrie·1996

This editorial discusses how ME/CFS involves both physical symptoms and mental health aspects that need to be understood together. The authors explain that while doctors have focused heavily on physical symptoms, psychiatric factors—such as stress, sleep problems, and how the body's stress system works—play an important role in the syndrome. An effective approach to ME/CFS requires doctors from different specialties to work together.

SleepImmune System

E3 PreliminaryReviewPEM unclearReview-Narrative

Infectious agents and immunological disturbances in relation to chronic fatigue syndrome.

Tripathy, B K, Agarwal, A K, Sangla, K S et al.·The Journal of the Association of Physicians of India·1996

This review article examines the connection between infections and immune system problems in ME/CFS. The authors looked at existing research to understand whether certain germs or viruses might trigger the condition, and how the immune system behaves differently in people with ME/CFS compared to healthy individuals.

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Development and application of HHV-6 antigen capture assay for the detection of HHV-6 infections.

Marsh, S, Kaplan, M, Asano, Y et al.·Journal of virological methods·1996

Researchers developed a new laboratory test to detect HHV-6, a common virus, in blood and body fluids. This test is faster, cheaper, and easier to use than older methods, and works reliably in clinical settings. They tested it on samples from healthy people, children with fever rashes, and patients with various conditions including chronic fatigue syndrome.

E3 PreliminaryReviewPEM unclearReview-Narrative

[Pathogenicity of fungi in the intestines--current status of the discussion].

Scheurlen, M·Fortschritte der Medizin·1996

Some people believe that yeast infections in the gut, particularly from a fungus called Candida, might cause chronic fatigue syndrome and other long-term illnesses by producing harmful toxins. However, experts disagree about whether this theory is actually true. This editorial explains that while the idea is interesting, there isn't enough solid scientific evidence yet to prove it works or to recommend yeast-fighting treatments based on this theory alone.

Gut MicrobiomeImmune System

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome.

Konstantinov, K, von Mikecz, A, Buchwald, D et al.·The Journal of clinical investigation·1996

Researchers found that about half of ME/CFS patients had antibodies (immune proteins) in their blood that attack a protein called lamin B1 found in the nucleus of cells. This suggests that ME/CFS may involve the immune system mistakenly attacking the body's own cells. This discovery provides evidence that autoimmunity—when the body's defense system malfunctions—may play a role in ME/CFS.

E3 PreliminaryMechanismPEM unclearObservational

Influence of immediate hypersensitivity skin reactions on delayed reactions in patients with chronic fatigue syndrome.

Steinberg, P, Pheley, A, Peterson, P K·The Journal of allergy and clinical immunology·1996

This study looked at how immediate allergic skin reactions (like those that happen within minutes of allergen exposure) might affect delayed allergic reactions (which develop over hours or days) in people with ME/CFS. Researchers were investigating whether the immune system's early response to allergens could influence its later response in this patient population. Understanding these connections may help explain why some ME/CFS patients experience unusual or prolonged allergic reactions.

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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.