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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 6,113 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

101–120 of 260 studies

E2 ModeratePEM requiredModerate confidenceLongitudinalEditor reviewed

Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms.

Sulheim, Dag, Hurum, Harald, Helland, Ingrid B et al.·BioPsychoSocial medicine·2012

This study followed 47 teenagers with ME/CFS over several months to see how they changed over time. Researchers found that most teens improved in their symptoms—including fatigue, pain, and brain fog—and these improvements happened at the same time their heart and nervous system function also improved. This suggests that problems with how the body regulates heart rate and blood pressure may be connected to ME/CFS symptoms.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study.

Nijs, Jo, Meeus, Mira, Heins, Marianne et al.·Disability and rehabilitation·2012

This study looked at whether fear of movement and worried thoughts about symptoms affect how well people with ME/CFS can climb stairs. Researchers found that people with higher fear of movement and catastrophic thinking took longer to complete the stair task. However, these fears did not predict how much physical activity people did in their daily lives over the following week.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

[Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units].

Ruiz, E, Alegre, J, García Quintana, A M et al.·Revista clinica espanola·2011

This study looked at 824 people with ME/CFS (91% women, average age 48) seen at two specialized clinics between 2008 and 2010. The researchers found that most people had severe fatigue that worsened with activity, sleep problems, and memory/concentration difficulties. Many also had anxiety, dry eyes (sicca syndrome), and fibromyalgia. On average, it took over 9 years for people to get a diagnosis after their symptoms started.

ME/CFS (general)

E2 ModeratePEM requiredModerate confidenceLongitudinalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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).

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM unclearPreliminaryObservationalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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.

ME/CFS (general)

E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Evaluation of maximal exercise performance, fatigue, and depression in athletes with acquired chronic training intolerance.

St Clair Gibson, A, Grobler, L A, Collins, M et al.·Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine·2006

This study looked at athletes who reported unusual tiredness and couldn't train like they normally could, even though their bodies seemed to work normally during fitness tests. Researchers found that these athletes' muscles and heart/lung capacity were just as strong as athletes without fatigue problems, but they had higher scores for depression and mood problems. The study suggests that the excessive tiredness these athletes felt might be connected to depression rather than a physical problem with their muscles or fitness.

ME/CFS (general)

E2 ModeratePEM unclearPreliminaryLongitudinalEditor reviewed

Time course of exercise induced alterations in daily activity in chronic fatigue syndrome.

Black, Christopher D, McCully, Kevin K·Dynamic medicine : DM·2005

This study tracked how much physical activity people with ME/CFS could do while following a walking program. Participants wore activity monitors for 4 weeks. They were able to meet their daily walking goals for the first 1-2 weeks, but then their activity levels dropped significantly and symptoms got worse, suggesting they had hit a limit their bodies could not sustain.

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.