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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

1021–1040 of 1,198 studies

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 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 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 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

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 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 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 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 not requiredReview-Narrative

Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health.

Gerrity, Timothy R, Papanicolaou, Dimitris A, Amsterdam, Jay D et al.·Neuroimmunomodulation·2004

This report summarizes what experts learned at a major research meeting about how immune system problems might be connected to ME/CFS. The experts found that people with ME/CFS do have immune system changes that look different from healthy people, but they couldn't determine whether these immune problems cause the illness or result from it. The researchers emphasized that understanding ME/CFS requires looking at multiple body systems working together, not just one system in isolation.

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 PreliminaryCohortPEM not requiredCase-Control

A case with chronic fatigue syndrome with positive antinuclear antibody followed by postpartum thyroiditis.

Itoh, Yasuhiko, Hamada, Hisamitsu, Igarashi, Tohru et al.·Modern rheumatology·2004

This case study describes a patient who had ME/CFS along with a positive antinuclear antibody (ANA)—a blood marker sometimes seen in autoimmune conditions. Five years after developing ME/CFS, the patient developed postpartum thyroiditis, an autoimmune thyroid condition that occurs after pregnancy. The doctors discussed how autoimmune conditions affecting the immune system might be connected to both ME/CFS and thyroid problems.

E3 PreliminaryReviewPEM not requiredReview-Narrative

Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation.

Famularo, Giuseppe, De Simone, Claudio, Trinchieri, Vito et al.·Annals of the New York Academy of Sciences·2004

This review discusses carnitine, a natural substance in the body that helps cells produce energy from fats. Carnitine levels are low in several conditions involving immune problems, including ME/CFS. The authors suggest that low carnitine may contribute to immune dysfunction and excessive inflammation, and that carnitine treatment might help restore normal immune function.

Energy MetabolismImmune System

E3 PreliminaryReviewPEM unclearReview-Narrative

[Physiopathologic relationship between interstitial cystitis and rheumatic, autoimmune, and chronic inflammatory diseases].

Lorenzo Gómez, María Fernanda, Gómez Castro, Susana·Archivos espanoles de urologia·2004

This review examined whether interstitial cystitis (a chronic bladder pain condition) shares common causes with autoimmune and inflammatory diseases like lupus, Sjögren's syndrome, and fibromyalgia. Researchers found that many patients with these conditions have similar symptoms and immune system abnormalities, and that some interstitial cystitis patients improve with anti-inflammatory medications. The study suggests these disorders may share underlying mechanisms, though the exact causes remain unknown.

E3 PreliminaryMechanismPEM not requiredCross-Sectional

High levels of type 2 cytokine-producing cells in chronic fatigue syndrome.

Skowera, A, Cleare, A, Blair, D et al.·Clinical and experimental immunology·2004

This study looked at immune cells in the blood of ME/CFS patients to see if they respond differently than in healthy people. Researchers found that ME/CFS patients had higher levels of immune cells that produce type 2 cytokines—signaling molecules associated with a particular type of immune response. This suggests the immune system in ME/CFS may be stuck in an unusual activation pattern.

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.

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 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 PreliminaryMechanismPEM not requiredMechanistic

Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome.

Steinau, Martin, Unger, Elizabeth R, Vernon, Suzanne D et al.·Journal of molecular medicine (Berlin, Germany)·2004

Researchers looked at immune cells from one ME/CFS patient and one healthy person to find differences in which genes were turned on or off. They found about 10 genes that behaved differently between the two people, with most differences present even before exercise. Many of these genes are involved in immune function, suggesting that ME/CFS may involve problems with how the immune system works.

E3 PreliminaryReviewPEM unclearReview-Narrative

Chronic fatigue syndrome (cfs).

Adler, Rolf H·Swiss medical weekly·2004

This review examines whether ME/CFS is a single illness or actually several different conditions. The authors found that ME/CFS involves multiple body systems—including the immune system, nervous system, hormones, and muscles—and that psychological factors also play a role. Rather than one disease, they suggest ME/CFS represents the body's emergency stress responses (fight-or-flight and shutdown) being inappropriately activated, and treatment should address the whole person, not just symptoms.

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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.