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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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1202 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

101–120 of 1,202 studies

E0 ConsensusReviewPEM not requiredReview-Narrative

Fecal microbiota transplantation broadening its application beyond intestinal disorders.

Xu, Meng-Que, Cao, Hai-Long, Wang, Wei-Qiang et al.·World journal of gastroenterology·2015

This review explores how fecal microbiota transplantation (FMT)—transferring healthy gut bacteria from donors to patients—might help treat conditions beyond intestinal diseases, including chronic fatigue syndrome. The authors found that FMT has shown promise in improving insulin sensitivity in metabolic disease and has produced favorable results in case reports of patients with Parkinson's disease, multiple sclerosis, and chronic fatigue syndrome, suggesting that gut bacteria imbalance may contribute to these conditions.

E0 ConsensusReviewPEM unclearSystematic-Review

Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review.

Nijs, Jo, Nees, Andrea, Paul, Lorna et al.·Exercise immunology review·2014

When people with ME/CFS exercise, their immune system reacts differently than healthy people's immune systems do. This review looked at 23 studies comparing immune responses to exercise in ME/CFS patients versus healthy people. The key finding is that ME/CFS patients show stronger reactions in certain immune markers and more oxidative stress (damage from chemical imbalances), which may be connected to post-exertional malaise—the worsening of symptoms that happens after activity.

Immune SystemPost-Exertional Malaise

E0 ConsensusReviewPEM unclearReview-Narrative

Biological phenotypes underpin the physio-somatic symptoms of somatization, depression, and chronic fatigue syndrome.

Anderson, G, Berk, M, Maes, M·Acta psychiatrica Scandinavica·2014

This review examined research showing that the physical symptoms experienced in ME/CFS, depression, and somatization (medically unexplained symptoms) have real biological causes, not just psychological ones. The authors found that inflammation, immune system activation, and changes in how the body breaks down certain nutrients are linked to symptoms like fatigue, pain, and autonomic problems. Understanding these biological pathways may help explain why these conditions overlap and why symptoms feel so physically real.

E0 ConsensusReviewPEM not requiredReview-Narrative

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma.

Christley, Yvonne, Duffy, Tim, Everall, Ian Paul et al.·Current psychiatry reports·2013

This review examined how mental health symptoms like depression and cognitive problems (such as memory and concentration difficulties) commonly occur in ME/CFS patients. Researchers found that depression and ME/CFS often happen together but may involve different biological mechanisms in the body, particularly involving inflammation, immune system dysfunction, and stress hormone imbalances. Understanding these connections helps explain why ME/CFS patients struggle with both physical fatigue and mental health challenges.

E0 ConsensusReviewPEM not requiredReview-Narrative

Fecal microbiota transplantation: past, present and future.

Aroniadis, Olga C, Brandt, Lawrence J·Current opinion in gastroenterology·2013

This review examines fecal microbiota transplantation (FMT), a treatment that restores healthy gut bacteria by transferring stool from a healthy donor to a patient. While FMT works very well for a specific bacterial infection, researchers are exploring whether it might help with other conditions including gut disorders and diseases affecting other parts of the body, such as chronic fatigue syndrome. The authors emphasize that more research is needed before FMT can be widely used for conditions beyond its proven application.

E0 ConsensusReviewPEM not requiredReview-Narrative

Natural killer cells in patients with severe chronic fatigue syndrome.

Brenu, E W, Hardcastle, S L, Atkinson, G M et al.·Auto- immunity highlights·2013

This review examined how natural killer (NK) cells—a type of white blood cell that fights infections and abnormal cells—work differently in ME/CFS patients. The researchers found that people with ME/CFS often have unusual numbers of NK cells or reduced ability to fight infections, which may help explain why patients suffer from persistent symptoms and recurrent infections. Understanding these immune cell problems could eventually lead to better treatments.

E0 ConsensusReviewPEM not requiredReview-Narrative

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior.

Morris, Gerwyn, Anderson, George, Galecki, Piotr et al.·BMC medicine·2013

This study compares ME/CFS with sickness behavior—the tired, achy feeling you get when you have the flu. While ME/CFS and sickness behavior share some symptoms like fatigue and body pain, they are fundamentally different conditions. Sickness behavior is your body's helpful, temporary response to infection that goes away once you recover, whereas ME/CFS is a chronic disease that persists long-term and involves ongoing immune system problems.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome following infections in adolescents.

Katz, Ben Z, Jason, Leonard A·Current opinion in pediatrics·2013

This review examined teenagers who developed chronic fatigue syndrome (ME/CFS) after infections like mononucleosis. About 13% of teens had ME/CFS six months after infection, dropping to 7% at one year and 4% at two years. The good news is that teenagers generally recover better from post-infectious ME/CFS than adults do.

E0 ConsensusReviewPEM not requiredReview-Narrative

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

Kim, S E, Chang, L·Neurogastroenterology and motility·2012

Many patients with ME/CFS experience overlapping conditions like irritable bowel syndrome, fibromyalgia, and jaw pain. This review looked at what ME/CFS and similar conditions might have in common. The researchers found that these disorders likely share several underlying problems: how the body processes pain, changes in brain activity, possible past infections, immune system problems, and genetic factors that make some people more vulnerable.

E0 ConsensusReviewPEM unclearReview-Narrative

Biomarkers for chronic fatigue.

Klimas, Nancy G, Broderick, Gordon, Fletcher, Mary Ann·Brain, behavior, and immunity·2012

This review examines blood tests and biological markers that might help diagnose ME/CFS, since current diagnosis relies only on symptoms. The researchers found that multiple body systems—including the immune system, stress hormones, and nervous system—appear to be disrupted in ME/CFS patients. However, no single test yet reliably identifies the condition, suggesting ME/CFS may involve complex changes across several systems rather than one simple cause.

E0 ConsensusReviewPEM unclearReview-Narrative

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

Maes, Michael·Progress in neuro-psychopharmacology & biological psychiatry·2011

Depression and ME/CFS often occur together, and this study suggests they share common biological root causes involving inflammation and oxidative stress (damage to cells). While depression and ME/CFS look different clinically, they appear to involve similar underlying problems with the immune system, energy production, and antioxidant defenses. The authors argue these should be considered connected disorders rather than two separate conditions that happen to co-occur.

NeuroinflammationImmune System

E0 ConsensusReviewPEM not requiredMeta-Analysis

Meta analysis of Chronic Fatigue Syndrome through integration of clinical, gene expression, SNP and proteomic data.

Pihur, Vasyl, Datta, Somnath, Datta, Susmita·Bioinformation·2011

Researchers combined multiple types of biological data from ME/CFS patients and healthy controls to identify genes that may contribute to ME/CFS and its severity. They found 11 genes of potential importance, with one gene called WASF3 standing out as possibly influencing fatigue through a specific cellular pathway in the brain.

NeuroinflammationImmune System

E0 ConsensusReviewPEM not requiredReview-Narrative

Neuroaetiology of chronic fatigue syndrome: an overview.

Sanders, Patricia, Korf, Jakob·The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry·2008

This review examines several competing theories about what causes ME/CFS. The authors found that while viral infections, brain hormone imbalances, immune problems, and psychological factors are all proposed as causes, none has been definitively proven. The authors suggest that ME/CFS may not be one single disease, but rather several different conditions that produce similar symptoms, which could explain why treatments like cognitive behavioral therapy work for some patients but not others.

E0 ConsensusReviewPEM not requiredReview-Narrative

[Viral infections in chronic fatigue syndrome].

Sairenji, Takeshi, Nagata, Keiko·Nihon rinsho. Japanese journal of clinical medicine·2007

This review looked at research on whether viruses and other infections might trigger ME/CFS. Most people with ME/CFS report having a flu-like illness before their symptoms started, which led researchers to investigate if infections could cause long-term immune system problems. The authors summarized what scientists have learned about different viruses, bacteria-like organisms, and other microbes that might be involved in ME/CFS development.

E0 ConsensusReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome: biochemical examination of blood].

Hakariya, Yukiko, Kuratsune, Hirohiko·Nihon rinsho. Japanese journal of clinical medicine·2007

This review examined blood test abnormalities in ME/CFS patients. While standard blood tests often appear normal in CFS patients despite their many symptoms, specialized blood tests have found problems in the systems that control stress, hormones, and immune function. The authors suggest that ME/CFS may result from brain dysfunction caused by immune chemicals called cytokines or antibodies that attack the body's own cells.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology.

Cho, Hyong Jin, Skowera, Anna, Cleare, Anthony et al.·Current opinion in psychiatry·2006

This review examines what ME/CFS is and how it works in the body. The research shows that ME/CFS is a real condition separate from depression or anxiety, though the official way doctors diagnose it may need updating. Scientists have found signs that the nervous system, immune system, and genetics all play a role, but they still don't fully understand how these pieces fit together.

E0 ConsensusReviewPEM not requiredSystematic-Review

A systematic review and critical evaluation of the immunology of chronic fatigue syndrome.

Lyall, Marc, Peakman, Mark, Wessely, Simon·Journal of psychosomatic research·2003

Researchers reviewed all the studies looking at immune system problems in ME/CFS patients to see what patterns emerged. They found that results were mixed and often contradictory—some studies showed low natural killer cells, while others didn't, especially when looking at higher-quality research. The review suggests that how studies are designed and conducted can affect whether certain immune changes are found.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: reviewing the research findings.

Johnson, S K, DeLuca, J, Natelson, B H·Annals of behavioral medicine : a publication of the Society of Behavioral Medicine·1999

This review article examines what scientists have learned about ME/CFS by looking at many different studies. Researchers found that ME/CFS is complex—it likely involves multiple causes including viral infections, immune system problems, nervous system dysfunction, and possibly psychological factors. The article emphasizes that ME/CFS affects different people in different ways, suggesting that patients may benefit from being grouped by their symptoms and illness history rather than treated as one uniform condition.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome: an immunological perspective.

Vollmer-Conna, U, Lloyd, A, Hickie, I et al.·The Australian and New Zealand journal of psychiatry·1998

This review examines whether immune system problems might cause ME/CFS symptoms, particularly in the brain. The researchers found that while immune chemicals called cytokines are likely involved in ME/CFS, the results from studies measuring these chemicals in the blood have been mixed and unclear. They suggest that abnormal cytokine activity happening directly inside the brain—rather than in the bloodstream—may be more important for explaining the neurological symptoms patients experience.

E0 ConsensusReviewPEM not requiredReview-Narrative

Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.

Clauw, D J, Chrousos, G P·Neuroimmunomodulation·1997

This review examines fibromyalgia and chronic fatigue syndrome, two conditions with overlapping symptoms of pain and exhaustion that have been described throughout medical history under different names. The authors propose that both conditions stem from problems in the central nervous system—the brain and spinal cord—particularly in areas that control hormone levels, pain sensing, and automatic body functions. They suggest that immune system changes seen in these conditions are side effects rather than root causes.

Autonomic Nervous SystemImmune 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.