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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 6,206 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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1205 studies

E0 — Consensus655E1 — Replicated321E2 — Moderate2,807E3 — Preliminary2,423

ME/CFS4,041Long COVID224Post-infectious190Overlapping1,064

Required for diagnosis417Not specified / unclear2,252Not required3,537

Post-Exertional Malaise1,082Cognitive Dysfunction1,750Pain1,629Unrefreshing Sleep805Orthostatic Intolerance484

Cytokines821Gene Expression573Metabolomics478Neuroimaging472Autoantibodies460

Infection-Triggered1,182Long COVID Overlap604Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review272Meta-Analysis61RCT301

Peer-reviewed6,149Preprint3Unclear54

1021–1040 of 1,205 studies

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Chronic fatigue syndrome is associated with diminished intracellular perforin.

Maher, K J, Klimas, N G, Fletcher, M A·Clinical and experimental immunology·2005

This study found that people with ME/CFS have lower levels of a protein called perforin in their immune cells, particularly in natural killer cells. Perforin is a weapon that immune cells use to fight off infections and abnormal cells. The researchers suggest this deficiency might help explain why people with ME/CFS often have weakened immune function.

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.

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 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

Chronic fatigue syndrome. A brief review of functional disturbances and potential therapy.

Shephard, R J·The Journal of sports medicine and physical fitness·2005

This review examined what might cause ME/CFS and how to treat it. The authors found that many different factors have been suggested as causes—including overtraining, stress, hormonal problems, infections, and immune issues—but none consistently appears in all patients. They concluded that the best approach is to help patients gradually rebuild physical fitness through exercise, counseling, and encouragement, while avoiding the harmful cycle of doing less and becoming more deconditioned.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders?

Staines, Donald R·Medical hypotheses·2005

This paper proposes that ME/CFS and similar fatigue disorders may be caused by the immune system attacking special messenger molecules in the body called vasoactive neuropeptides. These molecules normally help control energy metabolism, nerve function, and immune responses. The authors suggest that when antibodies damage these molecules, it could explain the severe fatigue and other symptoms seen in ME/CFS.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Aetiology and pathogenesis of chronic fatigue syndrome: a review.

Mihrshahi, Robin, Beirman, Robyn·The New Zealand medical journal·2005

This review article examines what scientists currently understand about what causes ME/CFS and how the illness develops. The authors looked at research across four main areas: infections, immune system problems, hormonal and nervous system imbalances, and mental health factors. They suggest that ME/CFS likely results from a combination of these factors rather than a single cause.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome.

Kaushik, N, Fear, D, Richards, S C M et al.·Journal of clinical pathology·2005

Researchers compared blood cells from 25 ME/CFS patients with 25 healthy people to see if genes were turned on or off differently. They found 16 genes with different activity levels in ME/CFS patients—most were overactive. These changes suggest problems with immune cell activation, nerve function, and how cells produce energy, which could help explain why ME/CFS causes fatigue and other symptoms.

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 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 PreliminaryReviewPEM unclearReview-Narrative

Are attention deficit hyperactivity disorder and chronic fatigue syndrome allergy related? what is fibromyalgia?

Bellanti, Joseph A, Sabra, Aderbal, Castro, Henry J et al.·Allergy and asthma proceedings·2005

This review article explores whether allergies and immune system problems might play a role in three conditions: ADHD, chronic fatigue syndrome (CFS), and fibromyalgia. The authors suggest that while the exact causes of these disorders remain unknown, allergic reactions—including reactions to foods—may trigger or worsen symptoms in all three conditions. They propose that problems in the body's neuroendocrine-immune system (the network connecting the brain, hormones, and immune function) are central to understanding these illnesses.

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 PreliminaryReviewPEM not requiredReview-Narrative

Impairments of the 2-5A synthetase/RNase L pathway in chronic fatigue syndrome.

Nijs, Jo, De Meirleir, Kenny·In vivo (Athens, Greece)·2005

This study looks at a specific immune system pathway called the 2-5A synthetase/RNase L pathway that may be broken in ME/CFS patients. Researchers found that in ME/CFS, this pathway is overactive but also working improperly—it's being broken down into unusual pieces instead of functioning normally. This abnormal pathway appears connected to reduced natural killer cell function and problems with how cells die when they should.

E3 PreliminaryReviewPEM not requiredReview-Narrative

The role of enterovirus in chronic fatigue syndrome.

Chia, J K S·Journal of clinical pathology·2005

This review examines whether enteroviruses—common viruses that cause respiratory and stomach infections—might play a role in ME/CFS. Researchers found that these viruses can sometimes persist in the body long-term and produce symptoms similar to ME/CFS. Laboratory and animal studies showed that viral RNA (genetic material) can remain in muscles and cause ongoing inflammation, which matches what has been seen in tissue samples from ME/CFS patients.

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 PreliminaryMechanismPEM not requiredCross-Sectional

In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation.

Maes, Michael, Mihaylova, Ivana, Leunis, Jean-Claude·Neuro endocrinology letters·2005

This study found that people with ME/CFS have lower levels of omega-3 fatty acids (healthy fats found in fish) and higher levels of other types of fats compared to healthy people. These imbalances were linked to lower zinc levels and problems with immune cells called T cells, which help fight infection. The researchers suggest that omega-3 supplements might help ME/CFS patients.

E3 PreliminaryMechanismPEM not requiredMechanistic

Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome.

Wang, Xin Q, Takahashi, Takashi, Zhu, Shi-Jie et al.·Evidence-based complementary and alternative medicine : eCAM·2004

Researchers tested a Japanese herbal medicine called Hochu-ekki-to (TJ-41) in mice with an experimentally induced condition similar to ME/CFS. Mice treated with the herb showed better activity levels and survived longer than untreated mice, suggesting the herb may help reduce activity loss associated with chronic fatigue-like conditions.

E3 PreliminaryReviewPEM unclearReview-Narrative

[Systemic Mycoplasma blood infection in fibromyalgia and chronic fatigue syndrome].

Endresen, Gerhard K M·Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke·2004

This review examined whether bacteria called Mycoplasma found in the blood might be connected to fibromyalgia and chronic fatigue syndrome (ME/CFS). The author looked at existing research to understand if these bacteria could be a cause or contributing factor to these conditions. This was a summary of available evidence rather than a new experiment with patients.

E3 PreliminaryReviewPEM unclearReview-Narrative

[Chronic fatigue syndrome: a review].

Carlo-Stella, Nicoletta, Lorusso, Lorenzo, Candura, Stefano M et al.·Recenti progressi in medicina·2004

ME/CFS is a serious illness that causes extreme tiredness and disability, but many doctors don't recognize or diagnose it properly. This review explains what we know about ME/CFS, including possible causes like infections and immune system problems, and describes a research effort to collect biological samples from patients to better understand the disease.

E3 PreliminaryMechanismPEM not requiredMechanistic

Effect of Kuibitang on lipopolysaccharide-induced cytokine production in peripheral blood mononuclear cells of chronic fatigue syndrome patients.

Shin, Hye-Young, An, Nyeon-Hyoung, Cha, Yun-Jin et al.·Journal of ethnopharmacology·2004

This study tested whether Kuibitang (KBT), a traditional herbal treatment used in South Korea, could affect immune system chemicals in people with ME/CFS. Researchers added KBT to blood cells from CFS patients and healthy people, then stimulated those cells to see how they responded. They found that KBT reduced some inflammatory chemicals but increased others, suggesting it might help balance the abnormal immune responses seen in 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.