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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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© 2026 ME/CFS Atlas

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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345 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

161–180 of 345 studies

E2 ModerateCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis--a new potential diagnostic biomarker.

Allen, John, Murray, Alan, Di Maria, Costanzo et al.·Physiological measurement·2012

This study tested a new way to measure how the heart and blood vessels respond when people stand up, using a painless light-based sensor on the ears, fingers, and toes. Researchers found that people with ME/CFS had a weaker blood vessel response to standing compared to healthy controls, which could potentially be used as an objective test to help diagnose ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Impaired blood pressure variability in chronic fatigue syndrome--a potential biomarker.

Frith, J, Zalewski, P, Klawe, J J et al.·QJM : monthly journal of the Association of Physicians·2012

ME/CFS is often associated with problems in the autonomic nervous system, which controls heart rate and blood pressure. This study measured how heart rate and blood pressure respond to position changes in 68 ME/CFS patients and 68 healthy controls. The researchers found that ME/CFS patients showed abnormal patterns in blood pressure variability that could potentially be used as a diagnostic test.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome.

Beaumont, Alison, Burton, Alexander R, Lemon, Jim et al.·PloS one·2012

This study examined whether problems with the heart's automatic nervous system (which controls heart rate) are connected to cognitive difficulties in ME/CFS patients. Researchers measured heart rate variability—the natural variation in time between heartbeats—while 30 ME/CFS patients and 40 healthy controls performed thinking tasks. ME/CFS patients showed slower thinking speeds and unusual heart rate patterns, and their reduced heart rate variability was linked to their cognitive slowness.

Autonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM not requiredCross-Sectional

Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes.

Okamoto, Luis E, Raj, Satish R, Peltier, Amanda et al.·Clinical science (London, England : 1979)·2012

This study looked at patients with POTS (a condition where heart rate increases too much when standing) to see how many also have ME/CFS and whether they are different from POTS patients without ME/CFS. The researchers found that most POTS patients experience severe fatigue, and about two-thirds also meet ME/CFS criteria. Those with both conditions had stronger heart rate increases when standing and signs of greater stress hormone activity.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredLongitudinal

Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study.

Jones, D E J, Gray, J, Frith, J et al.·Journal of internal medicine·2011

This study followed ME/CFS patients over 4 years to see how their fatigue changed. Researchers found that while some patients improved and others got worse, the overall severity of fatigue stayed relatively stable for most people. Importantly, fatigue was most closely linked to standing-related symptoms (dizziness, lightheadedness) and mood changes like depression and anxiety.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Sleep-wake behavior in chronic fatigue syndrome.

Rahman, Khairunnessa, Burton, Alexander, Galbraith, Sally et al.·Sleep·2011

Researchers wanted to know if ME/CFS is caused by problems with the body's internal biological clock. They studied 15 people with ME/CFS and 15 healthy controls for 5 days, measuring sleep patterns, daily activity, stress hormone levels, and heart function. While people with ME/CFS reported worse fatigue, sleep problems, and pain, the researchers found no differences in actual sleep patterns or biological rhythms between the groups.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome.

Miwa, Kunihisa, Fujita, Masatoshi·Clinical cardiology·2011

This study found that ME/CFS patients who experience dizziness or fainting when standing up (orthostatic intolerance) have smaller hearts and pump less blood with each beat compared to ME/CFS patients without these symptoms and healthy people. The researchers used ultrasound imaging to measure heart size and function in different groups and discovered that about half of ME/CFS patients with orthostatic intolerance had unusually small left heart chambers.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis.

Barnden, Leighton R, Crouch, Benjamin, Kwiatek, Richard et al.·NMR in biomedicine·2011

This study used specialized brain imaging (MRI) to compare 25 people with ME/CFS to 25 healthy controls, looking at brain structure and how it related to fatigue severity and other symptoms. Researchers found that people with ME/CFS showed differences in brainstem volume (a critical part of the brain controlling basic functions) that correlated with how long fatigue had lasted, and unusual patterns in how blood pressure related to brainstem structure. These findings suggest ME/CFS may involve damage to a specific brain region that disrupts the body's automatic control systems.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Physical activity intensity but not sedentary activity is reduced in chronic fatigue syndrome and is associated with autonomic regulation.

Newton, J L, Pairman, J, Hallsworth, K et al.·QJM : monthly journal of the Association of Physicians·2011

This study looked at how much people with ME/CFS move around during the day compared to healthy people. Researchers found that people with ME/CFS do less intense physical activity (like brisk walking or exercise) than healthy controls, even though they spend similar amounts of time sitting. The study also found that reduced physical activity was linked to problems with heart rate regulation in ME/CFS patients.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Comorbid health conditions in women with syncope.

Ulas, Umit H, Chelimsky, Thomas C, Chelimsky, Gisela et al.·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·2010

This study looked at hospital records of over 305,000 patients admitted for fainting (syncope) to see which health conditions were more common in women versus men. Researchers found that women were more likely to have several conditions related to nervous system problems that control blood pressure and heart rate, including chronic fatigue syndrome, migraines, and postural tachycardia syndrome (a condition where heart rate increases abnormally when standing). These autonomic conditions were especially common in women of reproductive age.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Orthostatic symptoms predict functional capacity in chronic fatigue syndrome: implications for management.

Costigan, A, Elliott, C, McDonald, C et al.·QJM : monthly journal of the Association of Physicians·2010

This study found that ME/CFS patients have much greater difficulty with daily activities compared to healthy people. Among ME/CFS patients, those who experience dizziness or lightheadedness when standing up (orthostatic symptoms) had the most trouble with physical functioning. The researchers suggest that treating these standing-related symptoms might help patients do more in their daily lives.

Autonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM not requiredCase-Control

Impaired cardiovascular response to standing in chronic fatigue syndrome.

Hollingsworth, Kieren G, Jones, David E J, Taylor, Roy et al.·European journal of clinical investigation·2010

This study found that people with ME/CFS have abnormal heart function when standing up, and their heart and muscle cells struggle to produce energy efficiently. Researchers used specialized scans to measure energy metabolism in the heart and muscles, and found that about one-third of ME/CFS patients showed significant heart energy problems. When standing, ME/CFS patients had stronger heart contractions and more symptoms compared to healthy controls, suggesting their bodies are working much harder to maintain blood flow.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Reduced heart rate variability predicts poor sleep quality in a case-control study of chronic fatigue syndrome.

Burton, A R, Rahman, K, Kadota, Y et al.·Experimental brain research·2010

People with ME/CFS often report poor sleep quality. This study measured heart rate patterns during sleep in 20 patients with ME/CFS and 20 healthy controls, finding that ME/CFS patients had much lower heart rate variability (natural changes in heart rate) during sleep. The researchers concluded that this reduced variability—suggesting the nervous system stays "on high alert" even at night—is closely linked to their sleep problems.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome.

Miwa, Kunihisa, Fujita, Masatoshi·Internal medicine (Tokyo, Japan)·2009

This study found that many ME/CFS patients experience heart-related symptoms like shortness of breath, chest pain, fainting, and dizziness. Using heart imaging tests, researchers discovered that about one-third of ME/CFS patients had smaller-than-normal hearts that pump less blood than expected, which may contribute to their fatigue and other symptoms.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

A comparison of dysautonomias comorbid with cyclic vomiting syndrome and with migraine.

Chelimsky, Gisela, Madan, Shruti, Alshekhlee, Amer et al.·Gastroenterology research and practice·2009

This study compared people with cyclic vomiting syndrome (CVS) to people with migraine headaches to see if they have the same associated conditions. Researchers looked at 21 CVS patients, 46 migraine patients, and 36 healthy controls, testing for 12 different conditions including orthostatic intolerance (feeling dizzy when standing), fibromyalgia, and chronic fatigue. While CVS and migraine shared many of the same comorbidities, CVS patients had significantly more cases of complex regional pain syndrome, suggesting these conditions may not be as similar as previously thought.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCross-Sectional

Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder.

Maes, Michael, Mihaylova, Ivanka, Kubera, Marta et al.·Neuro endocrinology letters·2009

This study found that people with ME/CFS have significantly lower levels of Coenzyme Q10 (CoQ10), a substance that helps cells produce energy, compared to healthy people. Nearly 45% of ME/CFS patients had CoQ10 levels below what was found in any of the healthy control group. Low CoQ10 was connected to worse fatigue, problems with heart and blood pressure regulation, and difficulty with thinking and memory.

Autonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM not requiredObservational

Lower ambulatory blood pressure in chronic fatigue syndrome.

Newton, Julia L, Sheth, Amish, Shin, Jane et al.·Psychosomatic medicine·2009

This study measured blood pressure patterns over 24 hours in people with ME/CFS, healthy volunteers, and people with a liver disease that also causes fatigue. The researchers found that ME/CFS patients had lower blood pressure than healthy people and their blood pressure did not drop as much during sleep as it normally should. Higher fatigue levels were linked to these abnormal blood pressure patterns.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredObservational

Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome.

Hoad, A, Spickett, G, Elliott, J et al.·QJM : monthly journal of the Association of Physicians·2008

This study looked at whether people with ME/CFS have a condition called POTS (postural orthostatic tachycardia syndrome), which causes the heart to beat much faster when standing up. Researchers tested 59 ME/CFS patients and compared them to 52 healthy people, measuring heart rate changes when they stood up. They found that 27% of ME/CFS patients had POTS, compared to only 9% of healthy controls, suggesting this condition is common but often missed in ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Enhanced vagal withdrawal during mild orthostatic stress in adolescents with chronic fatigue.

Wyller, Vegard Bruun, Barbieri, Riccardo, Thaulow, Erik et al.·Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·2008

This study looked at how the nervous system controls heart rate in adolescents with ME/CFS, particularly during mild physical stress (tilting on a table). Researchers found that teenagers with ME/CFS showed an unusual heart rate pattern—their bodies shifted too quickly toward stress-mode responses compared to healthy teens. This suggests their autonomic nervous system, which normally helps regulate heart rate and blood pressure, may not be working properly.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome.

Galland, Barbara C, Jackson, Pamela M, Sayers, Rachel M et al.·Pediatric research·2008

This study looked at how the hearts and blood vessels of children and teenagers with ME/CFS respond when they stand up or are tilted upright. Researchers compared 26 young people with ME/CFS to similar healthy controls using a tilt table test. They found that children with ME/CFS were much more likely to experience dizziness and abnormal heart rate responses during the test, suggesting their bodies struggle to regulate blood pressure and heart function when upright.

Autonomic Nervous System

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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.