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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 6,188 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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742 studies

E0 — Consensus649E1 — Replicated321E2 — Moderate2,795E3 — Preliminary2,423

ME/CFS4,032Long COVID222Post-infectious189Overlapping1,058

Required for diagnosis416Not specified / unclear2,235Not required3,537

Post-Exertional Malaise1,074Cognitive Dysfunction1,744Pain1,625Unrefreshing Sleep802Orthostatic Intolerance482

Cytokines820Gene Expression570Metabolomics476Neuroimaging471Autoantibodies458

Infection-Triggered1,178Long COVID Overlap597Pediatric494Severe232

Strong Phenotyping443Sex-Stratified328Severe ME Included119

Systematic Review269Meta-Analysis61RCT301

Peer-reviewed6,131Preprint3Unclear54

381–400 of 742 studies

E2 ModerateCohortPEM not requiredCase-Control

Symptom fluctuations and daily physical activity in patients with chronic fatigue syndrome: a case-control study.

Meeus, Mira, van Eupen, Inge, van Baarle, Ellen et al.·Archives of physical medicine and rehabilitation·2011

This study tracked physical activity and daily symptoms in 67 women with ME/CFS compared to healthy women who were not very active. Researchers found that ME/CFS patients were generally less active overall, but surprisingly, on days when patients were more active, they experienced more symptoms and greater symptom fluctuations the same day and the next day. Conversely, patients had fewer symptom changes on days when they stayed more sedentary and spread their limited activity throughout the day.

Post-Exertional Malaise

E2 ModerateCohortPEM requiredLongitudinal

A natural history study of chronic fatigue syndrome.

Jason, Leonard A, Porter, Nicole, Hunnell, Jessica et al.·Rehabilitation psychology·2011

This 10-year study followed 32 people from the community who had been diagnosed with ME/CFS to see how their condition changed over time. Researchers found that most people with ME/CFS remained quite ill, though a few improved or developed other conditions. A key symptom called post-exertional malaise—where physical activity makes symptoms much worse—was the best marker that distinguished people with ME/CFS from others.

Post-Exertional Malaise

E2 ModerateCohortPEM requiredCross-Sectional

Reliability and validity of Short Form 36 Version 2 to measure health perceptions in a sub-group of individuals with fatigue.

Davenport, Todd E, Stevens, Staci R, Baroni, Katie et al.·Disability and rehabilitation·2011

This study tested whether a common health questionnaire (SF-36) could accurately measure how ME/CFS affects quality of life and symptom burden. Researchers gave the questionnaire to 16 people with ME/CFS and 14 healthy controls, then had them perform exercise tests to see how their symptoms changed. The SF-36 successfully captured differences between the two groups and predicted who would recover quickly after exercise.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredObservational

Sleep is not disrupted by exercise in patients with chronic fatigue syndromes.

Togo, Fumiharu, Natelson, Benjamin H, Cherniack, Neil S et al.·Medicine and science in sports and exercise·2010

Researchers studied whether exercise makes sleep worse in ME/CFS patients, since many report feeling much sicker after activity. They measured sleep quality using overnight sleep monitoring in ME/CFS patients and healthy controls, both before and after an exercise test. The main finding: exercise did not make sleep worse for ME/CFS patients, and about half actually slept better after exercising.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Classification of myalgic encephalomyelitis/chronic fatigue syndrome by types of fatigue.

Jason, Leonard A, Boulton, Aaron, Porter, Nicole S et al.·Behavioral medicine (Washington, D.C.)·2010

This study looked at 100 people with ME/CFS to see if they experience fatigue in different ways. Researchers used a questionnaire to measure five different types of fatigue and found that patients naturally fell into distinct groups based on their fatigue patterns. The results show that ME/CFS affects people differently—some experience mostly one type of fatigue heavily, while others have combinations of different fatigue types.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome.

Jones, D E J, Hollingsworth, K G, Taylor, R et al.·Journal of internal medicine·2010

This study looked at how muscles clear acid buildup after exercise in people with ME/CFS compared to healthy people. Researchers used a special MRI technique to measure this process and also checked the nervous system's ability to regulate heart rate. People with ME/CFS had much slower acid clearance from their muscles after exercise, and this slowness was linked to problems with their autonomic nervous system (the part that controls automatic body functions).

Post-Exertional Malaise

E2 ModerateCohortPEM requiredCross-Sectional

Postexertional malaise in women with chronic fatigue syndrome.

VanNess, J Mark, Stevens, Staci R, Bateman, Lucinda et al.·Journal of women's health (2002)·2010

This study looked at how women with ME/CFS recover from exercise compared to healthy women. After a single exercise test, 85% of healthy women felt completely back to normal within 24 hours, but none of the women with ME/CFS did—in fact, most took much longer to recover, experiencing worsening fatigue, pain, cognitive problems, and other symptoms. This research confirms that postexertional malaise is a real and serious condition that makes recovery from physical activity dramatically different for people with ME/CFS.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredObservational

Plasma IL-6, its soluble receptors and F2-isoprostanes at rest and during exercise in chronic fatigue syndrome.

Robinson, M, Gray, S R, Watson, M S et al.·Scandinavian journal of medicine & science in sports·2010

This study looked at specific markers of inflammation and oxidative stress (cellular damage) in people with ME/CFS compared to healthy individuals, both at rest and after exercise. Researchers found that a marker called F2-isoprostanes—which indicates oxidative stress—was consistently higher in ME/CFS patients. However, they did not find differences in inflammation markers like IL-6 between the two groups.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

Nitric oxide metabolite production during exercise in chronic fatigue syndrome: a case-control study.

Suárez, Andrea, Guillamó, Elisabet, Roig, Teresa et al.·Journal of women's health (2002)·2010

This study looked at a chemical called nitric oxide in the blood of people with ME/CFS and healthy controls before and after exercise. Researchers found that people with ME/CFS had much higher levels of this chemical in their blood after exercise compared to healthy people. The findings suggest that measuring nitric oxide response to exercise might help doctors diagnose ME/CFS in the future.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredObservational

Exercise tolerance testing in a prospective cohort of adolescents with chronic fatigue syndrome and recovered controls following infectious mononucleosis.

Katz, Ben Z, Boas, Steven, Shiraishi, Yukiko et al.·The Journal of pediatrics·2010

After infectious mononucleosis, some teenagers develop ME/CFS. Researchers compared how well teenagers with ME/CFS could exercise compared to teenagers who recovered normally from mono. Teenagers with ME/CFS showed lower oxygen use and heart efficiency during exercise tests, even though they looked the same as healthy teens in other ways.

Post-Exertional Malaise

E2 ModerateCohortPEM requiredObservational

Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta.

Nijs, J, Van Oosterwijck, J, Meeus, M et al.·Journal of internal medicine·2010

This study looked at what happens in the blood after people with ME/CFS exercise. Researchers compared 22 women with ME/CFS to 22 healthy women and measured specific immune markers (elastase, IL-1beta, and complement C4a) before and after two different types of exercise. Both types of exercise triggered postexertional malaise (a worsening of symptoms after activity) in the ME/CFS group, but surprisingly, the immune markers they measured didn't show significant changes in either group.

Immune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

Postinfectious fatigue in adolescents and physical activity.

Huang, Yue, Katz, Ben Z, Mears, Cynthia et al.·Archives of pediatrics & adolescent medicine·2010

This study followed 301 teenagers with infectious mononucleosis (mono) for 2 years, comparing those who developed chronic fatigue syndrome (CFS) with those who recovered normally. Adolescents with post-infection CFS reported much more severe fatigue and needed more daytime sleep than their peers, even though their overall activity levels looked similar on paper. The key finding suggests that teenagers with CFS after mono may be forcing themselves to stay active like their friends, but at a significant physical cost in terms of exhaustion and sleep needs.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study.

Paul, Lorna, Rafferty, Danny, Marshal, Rebecca·Disability and rehabilitation·2009

This study compared how much energy people with ME/CFS use when walking compared to healthy people. Researchers found that people with ME/CFS walk more slowly and use more energy per unit of distance covered, meaning their bodies have to work harder to move the same distance as healthy people.

Energy MetabolismPost-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

Chronic fatigue syndrome combines increased exercise-induced oxidative stress and reduced cytokine and Hsp responses.

Jammes, Y, Steinberg, J G, Delliaux, S et al.·Journal of internal medicine·2009

This study found that people with ME/CFS experience unusual stress on their cells during exercise, particularly involving harmful molecules called free radicals. Their bodies also fail to mount normal protective responses—both in terms of producing protective proteins (heat shock proteins) and inflammatory markers that healthy people produce during exertion. This combination of excessive cellular damage and insufficient protective response may explain why exercise is so difficult for people with ME/CFS.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Severe versus Moderate criteria for the new pediatric case definition for ME/CFS.

Jason, Leonard, Porter, Nicole, Shelleby, Elizabeth et al.·Child psychiatry and human development·2009

This study tested a new way to diagnose ME/CFS in children and teenagers, comparing those with the illness to those without it. The researchers found that the new diagnostic criteria could successfully identify who has ME/CFS and could also distinguish between children with more severe symptoms versus those with moderate symptoms. The study looked at six main symptom areas: fatigue, post-exertional malaise (getting worse after activity), sleep problems, pain, thinking/memory difficulties, and autonomic/immune system problems.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

The Energy Envelope Theory and myalgic encephalomyelitis/chronic fatigue syndrome.

Jason, Leonard, Muldowney, Kathleen, Torres-Harding, Susan·AAOHN journal : official journal of the American Association of Occupational Health Nurses·2008

This study tested the Energy Envelope Theory, which suggests that ME/CFS symptoms get worse when people spend more energy than they have available. Researchers asked people with ME/CFS to track their daily energy use compared to their available energy, and found that those who exceeded their energy budget experienced more severe fatigue, pain, depression, anxiety, and reduced quality of life. The findings support the idea that staying within your energy limits may help manage ME/CFS symptoms.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome.

Patrick Neary, J, Roberts, Andy D W, Leavins, Nina et al.·Clinical physiology and functional imaging·2008

This study measured oxygen levels in the brain during exercise in people with ME/CFS compared to healthy controls. People with ME/CFS became exhausted much faster, at lower exercise levels, and showed lower oxygen and blood volume in their brain during and after exercise, suggesting that reduced blood flow to the brain may be part of what causes exercise problems in ME/CFS.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Can submaximal exercise variables predict peak exercise performance in women with chronic fatigue syndrome?

Nijs, Jo, Demol, Seppe, Wallman, Karen·Archives of medical research·2007

Researchers tested whether measurements taken during moderate-intensity exercise could predict how much energy a person with ME/CFS could produce during their maximum effort. In 222 women with ME/CFS, oxygen use at moderate intensity correlated well with peak oxygen use, but the prediction had too much variation to be reliable for individual patients.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

A real-time assessment of the effect of exercise in chronic fatigue syndrome.

Yoshiuchi, Kazuhiro, Cook, Dane B, Ohashi, Kyoko et al.·Physiology & behavior·2007

This study looked at what happens to people with ME/CFS after they exercise, tracking their symptoms in real-time using a watch-like computer for a week before and two weeks after exercise. The main finding was that physical symptoms like pain and fatigue got worse in ME/CFS patients, but this didn't happen right away—it took about five days to appear. Interestingly, mental symptoms and thinking abilities didn't show the same delayed worsening pattern that physical symptoms did.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Differential diagnosis of chronic fatigue syndrome and major depressive disorder.

Hawk, Caroline, Jason, Leonard A, Torres-Harding, Susan·International journal of behavioral medicine·2006

This study compared people with ME/CFS, people with depression, and healthy controls to find which symptoms best tell these conditions apart. Researchers found that post-exertional malaise (worsening after activity), unrefreshing sleep, and memory problems were the strongest differences. When they used a combination of symptoms including fatigue duration and severity of various symptoms, they could correctly identify which group each person belonged to nearly 100% of the time.

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.