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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 6,166 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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349 studies

E0 — Consensus643E1 — Replicated320E2 — Moderate2,781E3 — Preliminary2,422

ME/CFS4,025Long COVID216Post-infectious189Overlapping1,050

Required for diagnosis414Not specified / unclear2,218Not required3,534

Post-Exertional Malaise1,063Cognitive Dysfunction1,735Pain1,620Unrefreshing Sleep799Orthostatic Intolerance478

Cytokines818Gene Expression567Metabolomics473Neuroimaging468Autoantibodies458

Infection-Triggered1,174Long COVID Overlap587Pediatric493Severe231

Strong Phenotyping438Sex-Stratified326Severe ME Included118

Systematic Review265Meta-Analysis60RCT300

Peer-reviewed6,109Preprint3Unclear54

181–200 of 349 studies

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 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

Small heart syndrome in patients with chronic fatigue syndrome.

Miwa, Kunihisa, Fujita, Masatoshi·Clinical cardiology·2008

This study found that people with ME/CFS are more likely to have a smaller heart than healthy people. Researchers used chest X-rays and heart ultrasounds to measure heart size in 56 ME/CFS patients under age 50 and compared them to 38 healthy controls. Patients with both ME/CFS and a small heart also experienced more symptoms like dizziness when standing, cold feet, and heart rhythm irregularities.

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

E2 ModerateCohortPEM not requiredCross-Sectional

Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome.

Wyller, Vegard Bruun, Saul, J Philip, Walløe, Lars et al.·European journal of applied physiology·2008

This study looked at how the bodies of adolescents with ME/CFS respond to physical stress, specifically when lying down while pressure is applied to the legs and while squeezing a hand grip. Researchers found that ME/CFS patients had higher heart rates and stress hormone levels even at rest, and their cardiovascular system overreacted to the leg pressure test but underreacted during the hand grip exercise compared to healthy teenagers.

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 unclearCross-Sectional

Electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome.

Naschitz, Jochanan E, Slobodin, Gleb, Sharif, Dauod et al.·European journal of internal medicine·2008

This study found that ME/CFS and fibromyalgia, two conditions that seem similar on the surface, actually show different patterns on heart tests. People with ME/CFS had shorter QT intervals on their electrocardiogram (a measure of heart electrical activity) and had more dramatic blood pressure and heart rate changes during a tilting test compared to people with fibromyalgia. These differences suggest the two conditions may be distinct disorders rather than variants of the same illness.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Symptoms of autonomic dysfunction in chronic fatigue syndrome.

Newton, J L, Okonkwo, O, Sutcliffe, K et al.·QJM : monthly journal of the Association of Physicians·2007

This study looked at whether people with ME/CFS have problems with their autonomic nervous system (the part that controls automatic body functions like heart rate and blood pressure). Researchers used a questionnaire called COMPASS to measure autonomic symptoms in ME/CFS patients and healthy controls. They found that autonomic dysfunction symptoms were significantly more common in ME/CFS patients and were linked to how severe their fatigue was.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

[Estimation of fatigue state in patient with CFS using actigraph and R-R interval power spectrum analysis].

Tajima, Seiki, Kuratsune, Hirohiko, Yamaguti, Kouzi et al.·Nihon rinsho. Japanese journal of clinical medicine·2007

This study measured activity levels and sleep patterns in people with ME/CFS using wearable devices and heart rate analysis. Researchers found that ME/CFS patients had lower activity during waking hours, slept longer, experienced more frequent sleep disruptions, and showed abnormal nervous system activity during sleep compared to healthy people.

SleepAutonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study.

Boneva, Roumiana S, Decker, Michael J, Maloney, Elizabeth M et al.·Autonomic neuroscience : basic & clinical·2007

This study found that people with ME/CFS have a faster heart rate and less heart rate variability (natural changes in heartbeat speed) during sleep compared to healthy people. These differences suggest that the nervous system in ME/CFS patients stays more activated even during sleep, which may be related to chemical imbalances in the body.

SleepAutonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue.

Wyller, Vegard B, Saul, J P, Amlie, Jan P et al.·Clinical physiology and functional imaging·2007

This study looked at how the nervous system controls the heart and blood vessels in teenagers with ME/CFS when their bodies experience mild stress (tilting on a bed). Researchers found that adolescents with ME/CFS showed an exaggerated sympathetic nervous system response—meaning their "fight or flight" system kicked in too strongly compared to healthy teenagers. This suggests the body's automatic control of heart rate and blood pressure may not work normally in ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls.

Wyller, Vegard Bruun, Due, Reidar, Saul, J Philip et al.·The American journal of cardiology·2007

This study tested how the hearts of adolescents with ME/CFS respond to mild physical stress (tilting the body slightly upright for 15 minutes) compared to healthy teenagers. Researchers found that young people with ME/CFS had abnormal heart and blood vessel responses during this test—their hearts beat faster, their blood pressure increased more, and their stroke volume (amount of blood pumped per heartbeat) decreased more than in healthy controls. These differences suggest that ME/CFS involves problems with how the body regulates blood flow and heart function during even mild stress.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope.

Naschitz, Jochanan E, Mussafia-Priselac, Renata, Kovalev, Yulia et al.·The American journal of the medical sciences·2006

This study looked at whether people with ME/CFS, fibromyalgia, and dizziness breathe too fast when standing up, causing them to exhale too much carbon dioxide (a condition called hypocapnia). Researchers tested 585 people using a tilt table that slowly raises the upper body while measuring breathing patterns. They found that 9-27% of people with these conditions showed abnormal breathing on the tilt test, compared to 0-2% of healthy controls, suggesting this may be a real but not universal feature of these illnesses.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome.

Naschitz, Jochanan, Fields, Madeline, Isseroff, Hillel et al.·Journal of electrocardiology·2006

This study examined heart rhythm patterns in ME/CFS patients by measuring a specific electrical timing interval on EKGs (called the QT interval). Researchers found that people with ME/CFS had shorter QT intervals than healthy controls, both when lying down and during a head-up tilt test. This shortened interval appears to be linked to the autonomic nervous system problems common in ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Hyperventilation and amplified blood pressure response: is there a link?

Naschitz, J E, Mussafia-Priselac, R, Peck, E R et al.·Journal of human hypertension·2005

This study looked at whether rapid, shallow breathing (hyperventilation) causes blood pressure to rise when people change position, such as standing up. Researchers tested 320 patients with various conditions including ME/CFS using a tilt table test while measuring breathing CO2 levels. They found that hyperventilation during the test did not lead to higher blood pressure increases, suggesting that rapid breathing may not be the cause of blood pressure problems in these patient groups.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Cardiovascular reactivity in fibromyalgia: evidence for pathogenic heterogeneity.

Naschitz, Jochanan E, Rozenbaum, Michael, Fields, Madeline C et al.·The Journal of rheumatology·2005

This study looked at how the hearts of fibromyalgia patients respond to position changes (lying down versus standing up) compared to people with other conditions including ME/CFS. Researchers used a specialized test that measures heart rate patterns during a tilt test and analyzed the data with advanced mathematical methods. They found no single heart response pattern that was unique to fibromyalgia, suggesting that fibromyalgia patients have different types of heart responses rather than one shared pattern.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCase-Control

Orthostatic instability in a population-based study of chronic fatigue syndrome.

Jones, James F, Nicholson, Ainsley, Nisenbaum, Rosane et al.·The American journal of medicine·2005

This study tested whether people with ME/CFS have problems with their body's ability to regulate blood pressure and heart rate when changing positions (like standing up). Researchers compared 58 people with ME/CFS to 55 healthy people using a tilt table test. Surprisingly, they found that both groups had similar rates of these problems, suggesting that this particular type of autonomic dysfunction may not be a primary cause of ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCase-Control

Peripheral cholinergic function in humans with chronic fatigue syndrome, Gulf War syndrome and with illness following organophosphate exposure.

Khan, Faisel, Kennedy, Gwen, Spence, Vance A et al.·Clinical science (London, England : 1979)·2004

Researchers tested how blood vessels in the forearm respond to acetylcholine (a chemical messenger in the body) in people with ME/CFS, Gulf War illness, and pesticide exposure. They found that people with ME/CFS had an unusually strong vascular response to acetylcholine, but people with the other two conditions had normal responses. This suggests ME/CFS may involve a specific problem with how the body breaks down acetylcholine in blood vessels.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Use of time-frequency analysis to investigate temporal patterns of cardiac autonomic response during head-up tilt in chronic fatigue syndrome.

Yoshiuchi, Kazuhiro, Quigley, Karen S, Ohashi, Kyoko et al.·Autonomic neuroscience : basic & clinical·2004

This study looked at how the nervous system that controls heart rate and blood pressure responds when people stand up from lying down. Researchers tested people with ME/CFS (with and without a condition called POTS), and compared them to healthy volunteers. They found that even ME/CFS patients without POTS showed subtle differences in how their heart rate changed during the standing test, suggesting their autonomic nervous system may not work quite normally.

Autonomic Nervous System

E2 ModerateCohortPEM not requiredCross-Sectional

Patterns of cardiovascular reactivity in disease diagnosis.

Naschitz, J E, Rosner, I, Rozenbaum, M et al.·QJM : monthly journal of the Association of Physicians·2004

This study looked at how the heart and blood vessels respond to changes in body position (lying down versus standing up) in people with ME/CFS compared to healthy people and those with other conditions. Researchers used a simple test where patients lie down and then tilt upright while measuring heart rate and blood vessel changes. They found that people with ME/CFS have a distinctive pattern of heart and blood vessel responses that could help doctors identify the condition.

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.