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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 6,145 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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729 studies

E0 — Consensus637E1 — Replicated320E2 — Moderate2,768E3 — Preliminary2,420

ME/CFS4,014Long COVID212Post-infectious189Overlapping1,045

Required for diagnosis412Not specified / unclear2,201Not required3,532

Post-Exertional Malaise1,055Cognitive Dysfunction1,723Pain1,612Unrefreshing Sleep793Orthostatic Intolerance474

Cytokines816Gene Expression567Metabolomics469Neuroimaging466Autoantibodies457

Infection-Triggered1,170Long COVID Overlap580Pediatric492Severe228

Strong Phenotyping435Sex-Stratified326Severe ME Included116

Systematic Review263Meta-Analysis60RCT300

Peer-reviewed6,088Preprint3Unclear54

681–700 of 729 studies

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Cirrhotic cardiomyopathy].

Osipenko, M F, Bikbulatova, E A·Klinicheskaia meditsina·2007

This review examines how liver cirrhosis (severe liver disease) affects the heart. The study found that patients with cirrhosis develop heart problems including thickened heart walls and weakened heart function, especially during physical activity. These heart changes may contribute to fatigue and reduced ability to work, but importantly, these problems can improve significantly after a liver transplant.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

Sense of effort during a fatiguing exercise protocol in chronic fatigue syndrome.

Wallman, Karen E, Sacco, Paul·Research in sports medicine (Print)·2007

This study asked whether people with ME/CFS feel more effort when doing physical tasks compared to healthy people. Researchers had both groups perform a repetitive arm exercise for 45 minutes while rating how hard it felt. People with ME/CFS reported significantly higher effort levels and produced more force than controls, even though the task was the same for everyone.

Post-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome--exercise and physical activity].

Greenberg, Shai, Frid, Mordechai·Harefuah·2006

People with ME/CFS often feel extremely tired and struggle with physical activity, experiencing worsening symptoms even after light exercise. This review found that ME/CFS patients typically have lower fitness levels, their hearts work harder during normal activity, and they take longer to recover than healthy people. The good news is that carefully guided exercise programs appear to be the most helpful treatment for improving energy levels, physical function, and daily life activities.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

[Possible mechanisms of chronic fatigue syndrome in multiple sclerosis].

Kasatkin, D S, Spirin, N N·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·2006

This review describes how fatigue in multiple sclerosis (MS) can happen in different ways: tiredness even at rest, exhaustion during activity, and fatigue linked to MS flare-ups. The authors explain that fatigue likely involves both brain-based and body-based mechanisms, and often occurs alongside depression and sleep problems, suggesting these conditions may share common biological causes related to brain chemicals like serotonin.

NeuroinflammationPost-Exertional Malaise

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 PreliminaryMechanismPEM unclearMechanistic

Altered central nervous system signal during motor performance in chronic fatigue syndrome.

Siemionow, Vlodek, Fang, Yin, Calabrese, Leonard et al.·Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology·2004

This study measured brain electrical activity in ME/CFS patients and healthy people while they performed repeated hand-squeezing exercises. The researchers found that ME/CFS patients showed different brain activity patterns—particularly increased slower brain waves and larger electrical signals related to movement control—especially when the exercises became tiring. These brain activity differences might help doctors develop better ways to diagnose ME/CFS.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Exercise lowers pain threshold in chronic fatigue syndrome.

Whiteside, Alan, Hansen, Stig, Chaudhuri, Abhijit·Pain·2004

This study looked at how exercise affects pain sensitivity in people with ME/CFS compared to healthy people. When healthy volunteers exercised, their pain threshold (the point at which they felt pain) went up, making them less sensitive to pain. However, in ME/CFS patients, the pain threshold actually decreased after exercise, meaning they became more sensitive to pain. This suggests that the body's natural pain-blocking system may not work properly in ME/CFS.

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Decreased fractal correlation in diurnal physical activity in chronic fatigue syndrome.

Ohashi, K, Bleijenberg, G, van der Werf, S et al.·Methods of information in medicine·2004

This study looked at how physical activity patterns differ between people with ME/CFS and healthy people throughout the day. Researchers used special mathematical tools to analyze activity data and found that people with ME/CFS have more sudden, abrupt stops in their activities during the day—possibly because fatigue forces them to rest unexpectedly. This pattern was not seen in healthy control subjects.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

Chronic fatigue syndrome: new evidence for a central fatigue disorder.

Georgiades, Evelina, Behan, Wilhelmina M H, Kilduff, Liam P et al.·Clinical science (London, England : 1979)·2003

This study investigated whether ME/CFS involves problems with how the brain regulates energy and effort perception. Researchers compared 12 ME/CFS patients and 11 healthy controls during exercise, measuring chemicals in the blood that help the brain function. ME/CFS patients felt more exhausted at every stage and had different levels of brain chemicals, particularly those related to serotonin and dopamine—systems that regulate mood, motivation, and perception of effort.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Activity rhythm degrades after strenuous exercise in chronic fatigue syndrome.

Ohashi, Kyoko, Yamamoto, Yoshiharu, Natelson, Benjamin H·Physiology & behavior·2002

This study looked at whether exhausting exercise disrupts the body's internal daily rhythm in people with ME/CFS. Researchers measured activity patterns in ME/CFS patients and healthy controls before and after a strenuous treadmill test. They found that ME/CFS patients' activity rhythms became abnormally lengthened (longer than 24 hours) after exercise, while healthy people's rhythms stayed normal—suggesting the body loses its ability to keep time after strenuous activity in ME/CFS.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Chronic fatigue syndrome: probable pathogenesis and possible treatments.

Evengård, Birgitta, Klimas, Nancy·Drugs·2002

ME/CFS is a serious illness affecting about 1 in 200 people in Western countries, causing extreme tiredness that lasts at least 6 months along with problems thinking clearly, poor sleep, and pain. While doctors don't yet know exactly what causes it, research shows the immune system is overactive and certain brain functions are disrupted. Currently, talking therapy (cognitive behavioural therapy) can help improve quality of life, but scientists are still searching for more effective treatments.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

The case definition of chronic fatigue syndrome.

Tan, Eng M, Sugiura, Kazumitsu, Gupta, Sudhir·Journal of clinical immunology·2002

This review discusses how ME/CFS is currently diagnosed using symptom-based criteria from 1994, which doesn't account for the fact that different patients have very different experiences. The authors suggest that ME/CFS might actually be four distinct subtypes based on which body system is most affected: nervous system (memory problems, headaches), endocrine system (poor sleep, post-exertion crashes), musculoskeletal system (muscle and joint pain), or immune/infection-related (sore throat, swollen lymph nodes). If researchers studied more similar groups of patients separately instead of mixing everyone together, they might get clearer and more consistent results.

Post-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

Cytokine responses to physical activity, with particular reference to IL-6: sources, actions, and clinical implications.

Shephard, Roy J·Critical reviews in immunology·2002

When people exercise, their muscles release a protein called IL-6 that helps control inflammation and manage energy. This review examines how the body produces different types of inflammatory signals during and after exercise, with IL-6 playing a central role. The authors note that people with ME/CFS have higher levels of these inflammatory proteins, though it's unclear whether these proteins actually cause the fatigue experienced by patients.

Immune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation.

Gaab, Jens, Hüster, Dominik, Peisen, Renate et al.·Psychosomatic medicine·2002

This study looked at how the stress-response system (a hormone system in the brain called the HPA axis) works in ME/CFS patients compared to healthy people. Researchers exposed both groups to different types of stress—mental stress, exercise, and a hormone test—and measured how their bodies responded. ME/CFS patients showed lower levels of a stress hormone called ACTH at baseline and during stress tests, but their cortisol levels were mostly normal, suggesting their stress system works differently rather than being broken.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Chronic fatigue syndrome: evaluation and treatment.

Craig, Timothy, Kakumanu, Sujani·American family physician·2002

ME/CFS is a serious condition marked by extreme tiredness that doesn't go away, along with muscle pain, swollen lymph nodes, and feeling worse after physical activity. Doctors diagnose it mainly by ruling out other illnesses, since there's no single blood test or physical sign that definitively confirms it. Treatment is personalized and may include exercise, sleep improvements, diet changes, and medications like antidepressants.

Post-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

Neural control of force output during maximal and submaximal exercise.

St Clair Gibson, A, Lambert, M L, Noakes, T D·Sports medicine (Auckland, N.Z.)·2001

This review challenges the common belief that muscle fatigue during exercise comes only from chemical changes in muscles themselves. Instead, the authors propose that the brain and nervous system actively control and limit how hard we can exercise to protect our bodies from damage. Interestingly, they note that people with ME/CFS experience fatigue even at rest, suggesting fatigue may be a protective signal from the nervous system rather than a simple muscle problem.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredObservational

Hormonal responses to exercise in chronic fatigue syndrome.

Ottenweller, J E, Sisto, S A, McCarty, R C et al.·Neuropsychobiology·2001

This study compared how the bodies of ME/CFS patients and healthy people respond to exercise, specifically looking at hormones—chemical messengers that regulate many body functions. Researchers found that ME/CFS patients had weaker responses in several key stress hormones (like adrenaline) immediately after exercise, but hormone levels returned to normal by the next day, suggesting that abnormal hormones may not be the main reason why ME/CFS patients feel worse after exertion.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM unclearMechanistic

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome.

Fulle, S, Mecocci, P, Fanó, G et al.·Free radical biology & medicine·2000

Researchers examined muscle tissue from ME/CFS patients and found signs of oxidative damage—a type of cellular wear and tear similar to rust forming on metal. The patients' muscles showed damage to DNA and fats in cells, and their bodies had ramped up production of protective chemicals called antioxidants to fight back against this damage. This suggests ME/CFS may cause real, measurable changes in how muscle cells function at a chemical level.

Post-Exertional Malaise

E3 PreliminaryCohortPEM not requiredCross-Sectional

"I could not lift my arm holding the fork...". Living with chronic fatigue syndrome.

Söderlund, A, Skoge, A M, Malterud, K·Scandinavian journal of primary health care·2000

This study asked 12 people with ME/CFS to describe what living with the illness is really like. They reported extreme exhaustion that goes far beyond normal tiredness, along with muscle weakness, pain, memory problems, sleep issues, and heightened sensitivity to light, sound, and smells. These symptoms made everyday activities like cooking, talking, and housework unpredictably difficult, which disrupted their social lives and relationships.

Post-Exertional Malaise

E3 PreliminaryCohortPEM unclearCase-Control

Managing chronic fatigue syndrome: overview and case study.

Jason, L A, Melrose, H, Lerman, A et al.·AAOHN journal : official journal of the American Association of Occupational Health Nurses·1999

This study explains 'envelope theory,' a practical approach where people with ME/CFS stay within their energy limits to avoid crashes and gradually build tolerance. By tracking energy levels over time, patients and doctors can better understand each person's unique patterns and what activities trigger setbacks.

Post-Exertional Malaise

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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.