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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

21–40 of 260 studies

E0 ConsensusPEM requiredHigher confidenceGuidelineEditor reviewed

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management.

Bateman, Lucinda, Bested, Alison C, Bonilla, Hector F et al.·Mayo Clinic proceedings·2021

This article brings together 21 expert doctors who specialize in ME/CFS to share the best ways to diagnose and treat this complex illness. The experts explain that most people with ME/CFS don't get properly diagnosed, and many receive treatments that can actually make them worse. They provide clear, practical guidance that general doctors can use to help ME/CFS patients feel better and improve their quality of life.

ME/CFS (general)

E0 ConsensusPEM unclearHigher confidenceMeta-AnalysisEditor reviewed

Elevated Perceived Exertion in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis.

Barhorst, Ellen E, Andrae, William E, Rayne, Tessa J et al.·Medicine and science in sports and exercise·2020

This study reviewed 37 research papers that measured how hard exercise feels to people with ME/CFS and fibromyalgia compared to healthy people. The researchers found that people with these conditions consistently felt that exercise required significantly more effort, even when their heart rates and physical performance were similar to healthy controls. This difference was large and consistent across most studies, suggesting that something about how the brain perceives effort may be affected in these illnesses.

ME/CFS (general)

E0 ConsensusPEM requiredModerate confidenceCommentaryEditor reviewed

Graded exercise therapy does not restore the ability to work in ME/CFS - Rethinking of a Cochrane review.

Vink, Mark, Vink-Niese, Friso·Work (Reading, Mass.)·2020

This study examined whether graded exercise therapy (GET)—a treatment that gradually increases physical activity—actually helps people with ME/CFS return to work. The researchers found that while previous reviews claimed GET improved tiredness, these claims were based on unreliable self-reported outcomes in studies with serious flaws. When looking at objective measures and real-world outcomes, GET did not help people work better and may have harmed at least half of patients.

ME/CFS (general)

E0 ConsensusPEM unclearHigher confidenceMeta-AnalysisEditor reviewed

Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis.

Franklin, John Derek, Atkinson, Greg, Atkinson, Janet M et al.·International journal of sports medicine·2019

This research review analyzed 32 studies comparing how much oxygen people with ME/CFS can use during maximum exercise compared to healthy people. On average, people with ME/CFS used about 5 milliliters less oxygen per kilogram of body weight per minute than healthy controls—a meaningful difference that likely affects real-world functioning. This reduced oxygen capacity is one of the measurable physical differences between ME/CFS patients and healthy individuals.

ME/CFS (general)

E0 ConsensusPEM requiredModerate confidenceSystematic-ReviewEditor reviewed

Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review.

Vink, Mark, Vink-Niese, Alexandra·Health psychology open·2018

This study re-examined a major 2017 review that had concluded graded exercise therapy (GET) was helpful for ME/CFS. The researchers found serious problems with that review's methods and conclusions. They concluded there is no reliable evidence that GET works for ME/CFS, and safety concerns were not properly reported in the original trials.

ME/CFS (general)

E0 ConsensusPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Exercise and the Athlete With Infectious Mononucleosis.

Shephard, Roy J·Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine·2017

This review examines how infectious mononucleosis (a viral illness caused by Epstein-Barr virus) affects young athletes and whether it can lead to chronic fatigue syndrome. The main finding is that with proper diagnosis and a few weeks of rest followed by gradual return to activity, most athletes recover fully within 2-3 months, and serious complications like splenic rupture are rare.

ME/CFS (general)

E0 ConsensusPEM requiredPreliminaryMeta-AnalysisEditor reviewed

Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis.

Loy, Bryan D, O'Connor, Patrick J, Dishman, Rodney K·Medicine and science in sports and exercise·2016

This review of seven studies looked at how a single exercise session affects fatigue in people with ME/CFS. The combined results showed that exercise increased fatigue more in people with ME/CFS compared to healthy controls. Importantly, fatigue got worse over time—it was most noticeable 4 or more hours after exercise ended, rather than immediately during or right after the activity stopped.

ME/CFS (general)

E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Fear of movement and avoidance behaviour toward physical activity in chronic-fatigue syndrome and fibromyalgia: state of the art and implications for clinical practice.

Nijs, Jo, Roussel, Nathalie, Van Oosterwijck, Jessica et al.·Clinical rheumatology·2013

Many people with ME/CFS and fibromyalgia avoid physical activity because they fear it will make their symptoms worse—a concern that is often justified by their experience. This review looked at how common this fear and avoidance are, how they affect people's lives, and what treatments work best. The research found that fear of movement is very prevalent in both conditions and is linked to worse symptoms and lower quality of life.

ME/CFS (general)

E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome.

Nijs, Jo, Meeus, Mira, Van Oosterwijck, Jessica et al.·European journal of clinical investigation·2012

This review examined whether ME/CFS involves a nervous system that becomes overly sensitive to pain and other sensations. Researchers found that people with ME/CFS do show heightened responses to various types of stimuli—including touch, pressure, heat, and electrical stimulation—across multiple body areas. Importantly, this nervous system sensitivity tends to get worse, not better, after exercise or stress, suggesting a fundamental difference in how the central nervous system responds in ME/CFS.

ME/CFS (general)

E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome.

Nijs, Jo, Aelbrecht, Senne, Meeus, Mira et al.·Disability and rehabilitation·2011

This review looked at multiple studies comparing people with ME/CFS to healthy people who don't exercise much. The research found that people with ME/CFS are generally less active in their daily lives and have weaker muscles than similar healthy controls. However, the studies disagreed somewhat about exercise capacity, though overall the evidence suggests people with ME/CFS have reduced ability to exercise.

ME/CFS (general)

E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

The chronic fatigue syndrome--an update.

Wyller, Vegard Bruun·Acta neurologica Scandinavica. Supplementum·2007

ME/CFS is a serious condition where extreme fatigue is the main symptom and gets worse with activity rather than better with rest. This review of scientific research shows that ME/CFS affects more women than men, likely involves problems with the immune system and muscles, and that certain talk therapies and exercise programs have shown benefit in clinical trials. Most patients improve over time, though complete recovery is rare, especially in adults.

ME/CFS (general)

E0 ConsensusPEM requiredModerate confidenceSystematic-ReviewEditor reviewed

Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review.

Meeus, Mira, Nijs, Jo, Meirleir, Kenny De·European journal of pain (London, England)·2007

This review looked at 25 scientific studies about chronic pain in ME/CFS patients. Most people with ME/CFS experience widespread pain along with fatigue, but there is no clear agreement on how to define or measure this pain. The review found that pain is common and disabling, but we still don't know exactly what causes it or how to treat it effectively.

ME/CFS (general)

E0 ConsensusPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications.

Nijs, Jo, Meeus, Mira, De Meirleir, Kenny·Manual therapy·2006

Many people with ME/CFS experience muscle and joint pain that can be even more bothersome than the fatigue itself. This review found that while some people with ME/CFS have naturally flexible joints, this doesn't seem to cause their pain. However, the way people think about their pain—such as catastrophizing or assuming the worst—plays a big role in how much pain they feel. The body's response to exercise appears to create extra stress on muscles in ME/CFS patients, which explains why exercise can make pain worse rather than better.

ME/CFS (general)

E0 ConsensusPEM unclearPreliminaryEditorialEditor reviewed

A status report on chronic fatigue syndrome.

Natelson, Benjamin H, Lange, Gudrun·Environmental health perspectives·2002

This review examines why people develop ME/CFS, a condition marked by extreme tiredness and other symptoms that doctors struggle to explain. The authors suggest that ME/CFS likely isn't caused by a single thing, but rather by several different problems—including brain issues, difficulty handling stress, and concerns about making symptoms worse through activity. They note that while severe infections can trigger ME/CFS, the condition seems to persist through different biological mechanisms than the original infection itself.

ME/CFS (general)

E1 ReplicatedPEM not requiredPreliminaryRCTEditor reviewed

A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study.

Kan, Juntao, Cheng, Junrui, Hu, Chun et al.·Frontiers in nutrition·2021

Researchers tested whether a supplement containing two plant extracts (cistanche and ginkgo) could help adults with ME/CFS. Over 60 days, people taking the supplement reported improvements in fatigue, memory, sleep quality, and ability to exercise compared to those taking a placebo. The treatment also lowered certain chemicals in the blood (ammonia and lactic acid) that may be linked to fatigue.

ME/CFS (general)

E1 ReplicatedPEM requiredModerate confidenceObservationalEditor reviewed

Telephone-administered versus live group cognitive behavioral stress management for adults with CFS.

Hall, Daniel L, Lattie, Emily G, Milrad, Sara F et al.·Journal of psychosomatic research·2017

This study tested whether teaching stress management skills over the telephone worked as well as learning them in a live group setting for people with ME/CFS. Both formats helped reduce stress, but only the in-person group also improved physical symptoms like post-exertional malaise, chills, fever, and sleep quality. This suggests that meeting face-to-face may have extra benefits beyond just learning the techniques themselves.

ME/CFS (general)

E1 ReplicatedPEM requiredModerate confidenceRCTEditor reviewed

Fatigue Exacerbation by Interval or Continuous Exercise in Chronic Fatigue Syndrome.

Sandler, Carolina X, Lloyd, Andrew R, Barry, Benjamin K·Medicine and science in sports and exercise·2016

This study compared how people with ME/CFS feel after two types of exercise: high-intensity interval training (short bursts of harder exercise) and steady, continuous moderate exercise. Both types of exercise caused fatigue to worsen slightly afterward, but there was no meaningful difference between them. The findings suggest that high-intensity exercise might be safe to study further as part of graded exercise therapy programs.

ME/CFS (general)

E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Provision of social support to individuals with chronic fatigue syndrome.

Jason, Leonard A, Roesner, Nicole, Porter, Nicole et al.·Journal of clinical psychology·2010

This study tested whether having a student volunteer visit weekly to help with household tasks and errands could improve symptoms in people with ME/CFS. Participants were randomly assigned to receive either 4 months of buddy support or no intervention. People who received the buddy help reported significantly less fatigue and more energy than those who didn't, though there were no differences in physical functioning or stress levels.

ME/CFS (general)

E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Malaguarnera, Michele, Gargante, Maria Pia, Cristaldi, Erika et al.·Archives of gerontology and geriatrics·2008

Researchers tested whether a supplement called acetyl L-carnitine (ALC) could help reduce fatigue in older adults (over 70 years old) who met criteria for chronic fatigue syndrome. After treatment, patients showed meaningful improvements in physical tiredness, mental fatigue, sleep problems, and thinking ability. The supplement appeared to be safe and well-tolerated.

ME/CFS (general)

E2 ModeratePEM requiredModerate confidenceLongitudinalEditor reviewed

Post-discharge sequelae of Lassa fever survivors in Nigeria: an analysis of the LASCOPE prospective cohort.

Guichard, Eva, Juchet, Sylvain, Etafo, Ijeoma Chukwudumebi et al.·The Lancet. Infectious diseases·2026

This study followed 882 people who recovered from Lassa fever (a serious viral infection) after hospital discharge to see what long-term symptoms they experienced. Most survivors felt better within about 3 weeks after leaving the hospital, with the most common lingering symptoms being tiredness, headaches, and difficulty with physical activity. The good news is that serious complications like hearing loss were rare, affecting only 2% of survivors.

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.