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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.

© 2026 ME/CFS Atlas

ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,113 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by review quality. 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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260 studies

E0 — Consensus629E1 — Replicated320E2 — Moderate2,745E3 — Preliminary2,419

ME/CFS4,003Long COVID206Post-infectious189Overlapping1,031

Required for diagnosis410Not specified / unclear2,176Not required3,527

Post-Exertional Malaise1,039Cognitive Dysfunction1,709Pain1,606Unrefreshing Sleep785Orthostatic Intolerance468

Cytokines812Gene Expression566Metabolomics468Neuroimaging463Autoantibodies454

Infection-Triggered1,155Long COVID Overlap562Pediatric491Severe226

Strong Phenotyping427Sex-Stratified325Severe ME Included114

Systematic Review258Meta-Analysis59RCT300

Higher42Moderate2,570Preliminary3,224Weak277

Peer-reviewed6,056Preprint3Unclear54

141–160 of 260 studies

E2 ModeratePEM unclearModerate confidenceObservationalEditor reviewed

Physical activity before and after exercise in women with chronic fatigue syndrome.

Sisto, S A, Tapp, W N, LaManca, J J et al.·QJM : monthly journal of the Association of Physicians·1998

This study tracked the physical activity of 20 women with ME/CFS and 20 healthy volunteers for two weeks using a movement monitor worn at the waist. After all participants did a strenuous treadmill exercise test, researchers measured how their activity changed. Women with ME/CFS showed a noticeable drop in activity levels after the exercise, with the biggest decrease happening around days 12-14, and they took more rest breaks during the day.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome.

LaManca, J J, Sisto, S A, DeLuca, J et al.·The American journal of medicine·1998

This study looked at how exercise affects thinking and mental processing in people with ME/CFS compared to healthy people. Both groups did exhausting exercise on a treadmill, then took thinking tests right after and 24 hours later. People with ME/CFS performed worse on these thinking tests after exercise, particularly on tasks involving speed and attention, and their thinking stayed impaired the next day.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome.

Lane, R J, Barrett, M C, Woodrow, D et al.·Journal of neurology, neurosurgery, and psychiatry·1998

Researchers examined muscle samples from 105 ME/CFS patients to understand why they have abnormal responses to exercise, particularly high lactate levels. They found that patients with high lactate responses had fewer type 1 muscle fibres (which are energy-efficient), but this wasn't because they were inactive—it appeared to be a specific muscle problem related to ME/CFS itself.

ME/CFS (general)

E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

[Risk factors for ischemic heart disease in patients with chronic fatigue syndrome].

Vilikus, Z, Marecková, H, Janatková, I et al.·Sbornik lekarsky·1998

This study compared heart disease risk factors between people with ME/CFS and healthy controls. Researchers found that despite ME/CFS patients exercising less overall, they had no higher risk for heart disease than the control group. This suggests that reduced exercise activity in ME/CFS does not appear to increase cardiovascular risk in the way it might in other conditions.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Physical fatigability and exercise capacity in chronic fatigue syndrome: association with disability, somatization and psychopathology.

Fischler, B, Dendale, P, Michiels, V et al.·Journal of psychosomatic research·1997

This study looked at how people with ME/CFS respond to exercise by measuring whether they can reach their target heart rate during activity. Researchers found that many patients don't reach expected heart rates and that this relates to how disabled they feel in daily life. Interestingly, anxiety and depression didn't explain why people avoided strenuous exercise, suggesting that avoidance behavior in ME/CFS may have different causes than in other conditions.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Psychological symptoms, somatic symptoms, and psychiatric disorder in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting.

Wessely, S, Chalder, T, Hirsch, S et al.·The American journal of psychiatry·1996

This study followed over 1,900 people in primary care and found that most individuals with ME/CFS also had a current mental health condition like depression or anxiety. The researchers discovered that people with chronic fatigue were much more likely to have psychiatric disorders (60-78%) compared to those without fatigue (19-31%). While the study suggests a strong link between psychiatric conditions and ME/CFS, it does not explain whether one causes the other.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

An examination of the working case definition of chronic fatigue syndrome.

Komaroff, A L, Fagioli, L R, Geiger, A M et al.·The American journal of medicine·1996

Researchers studied 281 patients with severe, long-lasting fatigue to see how well the official definition of ME/CFS worked. They compared these patients to healthy people and people with similar conditions like multiple sclerosis and depression. The study found that certain symptoms—like muscle pain, post-exertion exhaustion, headaches, and flu-like symptoms—were very common in ME/CFS patients but rare in the other groups.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome.

Sisto, S A, LaManca, J, Cordero, D L et al.·The American journal of medicine·1996

Researchers tested how well women with ME/CFS could exercise compared to healthy controls by having them walk on a treadmill until exhaustion. Women with ME/CFS had lower aerobic fitness levels than healthy controls, but their hearts and lungs appeared to work normally. Importantly, the maximal exercise test did not cause a major flare-up of fatigue or other ME/CFS symptoms.

ME/CFS (general)

E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome.

MacDonald, K L, Osterholm, M T, LeDell, K H et al.·The American journal of medicine·1996

This study compared 47 people with ME/CFS to 47 matched healthy controls to identify what might trigger or contribute to the illness. Researchers found that people with ME/CFS were more likely to have exercised regularly before getting sick, and women with ME/CFS were more likely to have never had children. Depression was more common after ME/CFS developed, though it wasn't more common before illness onset.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

The impact of catastrophic beliefs on functioning in chronic fatigue syndrome.

Petrie, K, Moss-Morris, R, Weinman, J·Journal of psychosomatic research·1995

This study looked at whether how people think about ME/CFS affects how disabled they become. Researchers asked 282 people with ME/CFS what they thought would happen if they pushed themselves too hard, and sorted their answers into catastrophic (very negative) or non-catastrophic thinking. People who had catastrophic thoughts about pushing themselves were significantly more fatigued and more disabled in work, household tasks, sleep, socializing, and hobbies—even though they had been sick for similar lengths of time as others.

ME/CFS (general)

E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Repetitively negative changing T waves at 24-h electrocardiographic monitors in patients with the chronic fatigue syndrome. Left ventricular dysfunction in a cohort.

Lerner, A M, Lawrie, C, Dworkin, H S·Chest·1993

This study looked at heart activity recorded over 24 hours in ME/CFS patients compared to others. All 24 ME/CFS patients showed unusual patterns on their heart monitors (abnormal T waves), compared to only 22% of people without ME/CFS. Further testing found that 8 out of 60 ME/CFS patients had mild heart pumping problems that only showed up during exercise, even though their resting heart function appeared normal. The researchers suggest ME/CFS fatigue might be related to the heart not working well during normal daily activities.

ME/CFS (general)

E2 ModeratePEM unclearModerate confidenceReview-NarrativeEditor reviewed

Symptoms and signs of chronic fatigue syndrome.

Komaroff, A L, Buchwald, D·Reviews of infectious diseases·1991

This review summarizes what doctors have learned about chronic fatigue syndrome (ME/CFS) by studying approximately 510 patients. The hallmark features include a sudden illness-like onset, long-lasting exhaustion that severely limits daily activities, and a unique symptom called postexertional malaise—where patients feel much worse after physical or mental activity. Many patients also experience fever, sore throat, swollen lymph nodes, muscle pain, sleep problems, and difficulty concentrating.

ME/CFS (general)

E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

Aerobic work capacity in patients with chronic fatigue syndrome.

Riley, M S, O'Brien, C J, McCluskey, D R et al.·BMJ (Clinical research ed.)·1990

This study tested how much physical activity patients with ME/CFS could manage on a treadmill and compared them to healthy people and those with irritable bowel syndrome. Researchers found that ME/CFS patients got tired much faster, had higher heart rates during exercise, and felt like they were working much harder than the other groups—even though they weren't doing as much activity.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Cardiac function at rest and with exercise in the chronic fatigue syndrome.

Montague, T J, Marrie, T J, Klassen, G A et al.·Chest·1989

This study looked at heart function in 41 ME/CFS patients compared to healthy volunteers. While the hearts looked normal at rest, patients became exhausted during exercise much sooner than healthy people—their heart rates climbed more slowly and didn't reach the expected levels, even though their resting heart rhythms and structure were completely normal.

ME/CFS (general)

E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Molecular hydrogen as a treatment for ME/CFS: a mini-review of clinical evidence and mechanistic rationale.

Friedberg, Fred, LeBaron, Tyler W·Frontiers in medicine·2026

This review examines whether hydrogen-rich water might help ME/CFS patients. Hydrogen is a simple molecule that may reduce inflammation and improve energy production in cells—two problems linked to ME/CFS. Early studies show it may help reduce fatigue and improve daily functioning with few side effects, though the research is still very limited.

ME/CFS (general)

E3 PreliminaryPEM requiredPreliminaryReview-NarrativeEditor reviewed

Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae.

Gracidas, Carlos, Levy, Rakeem, Varon, Joseph et al.·Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·2026

This review suggests that ME/CFS and long COVID symptoms—including exhaustion, brain fog, and crashing after activity—may be caused by problems with how the body's energy-producing structures (mitochondria) work. The authors propose that treatments targeting three areas could help: improving the body's ability to handle lactate (a byproduct of exertion), increasing oxygen delivery to tissues, and helping the body burn fat for energy more efficiently, similar to how endurance athletes train.

ME/CFS (general)

E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.

Wang, Kun, Shen, Mengmeng, Tang, Hongguang et al.·Journal of ethnopharmacology·2025

Researchers tested a traditional Chinese medicine called Jingfang Granule (JFG) in mice with chronic fatigue syndrome. The treatment improved fatigue symptoms, helped mice recover weight and exercise capacity, and reduced harmful inflammation and oxidative stress in their bodies. The medicine appeared to work by boosting how efficiently cells produce energy through a key metabolic pathway.

ME/CFS (general)

E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

Creatine and post-viral fatigue syndrome: an update.

Ostojic, Sergej M, Candow, Daren G, Tarnopolsky, Mark A·Journal of the International Society of Sports Nutrition·2025

This review examines how creatine—a natural substance that helps muscles produce energy—might help people with post-viral fatigue syndrome (the prolonged exhaustion that can follow viral infections like COVID-19). The researchers found that people with this condition often have problems with how their body produces and uses energy, particularly in the mitochondria (the cell's power centers). They suggest that taking creatine supplements could help restore energy production and reduce symptoms like fatigue and brain fog.

ME/CFS (general)

E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation.

Jothi, Swathi, Insel, Michael, Claessen, Guido et al.·Physiological reports·2025

This study compared how bodies use oxygen during exercise in people with long COVID, ME/CFS, and healthy controls. Researchers found that both long COVID and ME/CFS patients had trouble getting oxygen into their muscles during exercise, which was the main reason they couldn't exercise as much as healthy people. If this muscle oxygen problem could be fixed, it might significantly improve exercise ability in both conditions.

ME/CFS (general)

E3 PreliminaryPEM requiredPreliminaryEditorialEditor reviewed

Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.

Kenny, Tiff-Annie·Therapeutic advances in drug safety·2025

This paper describes complex, long-lasting health problems that some people develop after vaccination, which resemble ME/CFS and Long COVID symptoms like fatigue, pain, brain fog, and heart rhythm issues. The author argues that current vaccine safety systems are not well-designed to detect or investigate these kinds of slow-developing, multisystem conditions because they work best for identifying immediate reactions like fever or allergies. The paper proposes changes to how we monitor vaccine safety—including better training for doctors, longer-term tracking of patients, and including patients' own descriptions of their symptoms—to catch these problems more effectively.

ME/CFS (general)

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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.