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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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210 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 210 studies

E3 PreliminaryReviewPEM unclearReview-Narrative

Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues.

Romano, Graziella F, Tomassi, Simona, Russell, Alice et al.·Advances in psychosomatic medicine·2015

This review examines what scientists have learned about the biological causes of ME/CFS and fibromyalgia. Researchers have found that three main systems in the body appear to go wrong: inflammation (the body's immune response), oxidative stress (cellular damage from harmful molecules), and problems with hormones that control stress responses. These abnormalities may explain why patients experience fatigue, pain, memory problems, and mood changes.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Metabolism in chronic fatigue syndrome.

Armstrong, Christopher W, McGregor, Neil R, Butt, Henry L et al.·Advances in clinical chemistry·2014

This review examines how the body produces and uses energy in people with ME/CFS. Research suggests that people with ME/CFS have problems with how their bodies break down food and nutrients for energy, and their cells may not be using their energy factories (mitochondria) efficiently. The review highlights that metabolomics—a technique that measures thousands of molecules in the body at once—could be a powerful tool for understanding what goes wrong in ME/CFS.

Energy Metabolism

E3 PreliminaryMechanismPEM not requiredMechanistic

The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome.

Wang, Jia, Sun, Chengxin, Zheng, Yan et al.·Archives of pharmacal research·2014

Researchers tested a compound extracted from ginseng called WGPA-A in mice to see if it could help reduce fatigue. They found that mice given WGPA-A could swim longer before becoming tired, and the treatment reduced signs of cellular damage (oxidative stress) and improved the health of mitochondria—the energy-producing structures inside muscle cells. This suggests ginseng compounds might help fight fatigue by protecting cells from damage.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Carnitine derivatives: clinical usefulness.

Malaguarnera, Mariano·Current opinion in gastroenterology·2012

This review article discusses carnitine and its chemical cousins (acetyl-L-carnitine and propionyl-L-carnitine), which are natural substances your body uses to convert food into energy. The authors explain that these compounds may help with various conditions including chronic fatigue syndrome, depression, memory problems, and heart disease, and appear to be safe with few side effects.

Energy Metabolism

E3 PreliminaryMechanismPEM not requiredMechanistic

Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

Surapaneni, Dinesh Kumar, Adapa, Sree Rama Shiva Shanker, Preeti, Kumari et al.·Journal of ethnopharmacology·2012

Researchers tested a natural substance called shilajit in rats with fatigue symptoms similar to ME/CFS. The shilajit appeared to reduce fatigue-like behaviors and anxiety, and improved how well the rats' cells produced energy. This suggests shilajit might work by helping the body's stress response system and protecting mitochondria—the 'powerhouses' inside cells.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Kynurenine pathway Hypothesis: The nature of the chronic Fatigue syndrome (cFs) Revisited.

Blankfield, Adele·International journal of tryptophan research : IJTR·2011

This study examines a theory that ME/CFS might be related to problems with how the body processes an amino acid called tryptophan. The body normally breaks down tryptophan through a pathway called the kynurenine pathway, and the researchers suggest that abnormalities in this process could contribute to the symptoms of chronic fatigue syndrome.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances.

De Luca, Chiara, Raskovic, Desanka, Pacifico, Valeria et al.·International journal of environmental research and public health·2011

This review examines why some people develop severe reactions to chemicals, foods, and environmental exposures at levels that shouldn't cause harm. The authors argue these conditions—including ME/CFS, fibromyalgia, and multiple chemical sensitivity—are real biological disorders, not just psychological problems. They explore evidence that problems with how the body detoxifies and handles harmful substances, along with imbalances in antioxidant protection, may be key to understanding these diseases.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.

Gardner, Ann, Boles, Richard G·Progress in neuro-psychopharmacology & biological psychiatry·2011

For decades, doctors believed depression was caused by low serotonin levels in the brain, but research hasn't proven this is true. This review proposes that depression and related conditions like ME/CFS, fibromyalgia, and IBS may actually stem from problems with how cells produce energy (mitochondrial dysfunction) combined with inflammation in the body. The authors suggest that common depression medications work through multiple pathways—not just serotonin—and that targeting mitochondrial health might help treat these overlapping conditions.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Medication-induced mitochondrial damage and disease.

Neustadt, John, Pieczenik, Steve R·Molecular nutrition & food research·2008

Mitochondria are the energy-producing structures in our cells, and when they are damaged, they don't work properly. This review article explains that many common medications—including psychiatric drugs, cholesterol medications, and pain relievers like acetaminophen—can damage mitochondria, which may explain some of their harmful side effects. Since ME/CFS involves problems with energy production, understanding how medications damage mitochondria and how certain nutrients might help repair them could be important for patients.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome and neurotransmitters].

Miwa, Soichi, Takikawa, Osamu·Nihon rinsho. Japanese journal of clinical medicine·2007

This review examines how chemical messengers in the brain called neurotransmitters may be disrupted in ME/CFS. The researchers found that ME/CFS patients may have problems with serotonin and glutamate signaling, possibly triggered by viral infections or genetic differences. These imbalances could help explain why ME/CFS causes such persistent exhaustion.

Energy MetabolismImmune System

E3 PreliminaryReviewPEM not requiredReview-Narrative

Mechanisms of cancer-related fatigue.

Ryan, Julie L, Carroll, Jennifer K, Ryan, Elizabeth P et al.·The oncologist·2007

Cancer-related fatigue is extreme tiredness that happens during and after cancer treatment and significantly impacts quality of life, but doctors don't fully understand why it occurs. This review examines several possible causes, including problems with brain chemicals, muscle metabolism, hormonal balance, sleep-wake cycles, and inflammation in the body. Understanding these mechanisms could help develop better treatments for this distressing symptom.

Energy Metabolism

E3 PreliminaryCommentaryPEM unclearEditorial

Mitochondrial dysfunction and molecular pathways of disease.

Pieczenik, Steve R, Neustadt, John·Experimental and molecular pathology·2007

This article explains that many different diseases—including chronic fatigue syndrome—may share a common problem: damage to mitochondria, the energy-producing parts of our cells. When mitochondria don't work properly, they produce harmful molecules called reactive oxygen species that can further damage cells. The authors suggest that antioxidant treatments and specific urine tests might help doctors treat these conditions more effectively.

Energy Metabolism

E3 PreliminaryPEM unclear

The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study.

Teitelbaum, Jacob E, Johnson, Clarence, St Cyr, John·Journal of alternative and complementary medicine (New York, N.Y.)·2006

Researchers gave 41 patients with ME/CFS or fibromyalgia a natural sugar called D-ribose to see if it could help their symptoms. Two-thirds of patients reported feeling noticeably better, with improvements in energy, sleep, mental clarity, pain, and overall well-being. The supplement was well-tolerated with no serious side effects reported.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Proton and 31-phosphorus neurospectroscopy in the study of membrane phospholipids and fatty acid intervention in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis) and dyslexia.

Puri, Basant K·International review of psychiatry (Abingdon, England)·2006

This study describes advanced brain imaging techniques that can measure specific chemicals in the brain without surgery. These techniques help researchers understand how the brain uses fats and other building blocks to maintain healthy cell membranes. The authors explain how these imaging methods could be applied to study brain chemistry in ME/CFS and other conditions.

Energy Metabolism

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Gene expression correlates of unexplained fatigue.

Whistler, Toni, Taylor, Renee, Craddock, R Cameron et al.·Pharmacogenomics·2006

Researchers examined blood samples from hundreds of people to find which genes are connected to fatigue in ME/CFS. They looked at over 20,000 genes and found that 839 of them showed a relationship with fatigue levels. Many of these genes are involved in energy production and metabolism in the body, though about half of the genes they found don't yet have clear functions identified.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation.

Famularo, Giuseppe, De Simone, Claudio, Trinchieri, Vito et al.·Annals of the New York Academy of Sciences·2004

This review discusses carnitine, a natural substance in the body that helps cells produce energy from fats. Carnitine levels are low in several conditions involving immune problems, including ME/CFS. The authors suggest that low carnitine may contribute to immune dysfunction and excessive inflammation, and that carnitine treatment might help restore normal immune function.

Energy MetabolismImmune System

E3 PreliminaryMechanismPEM not requiredMechanistic

Integration of gene expression, clinical, and epidemiologic data to characterize Chronic Fatigue Syndrome.

Whistler, Toni, Unger, Elizabeth R, Nisenbaum, Rosane et al.·Journal of translational medicine·2003

This study looked at blood samples from people with ME/CFS to see if the disease might actually be several different conditions rather than one. Researchers found that when they grouped patients by how their illness started, certain genes were turned on or off differently. These genes are involved in how the body produces energy, particularly through breaking down sugars and other molecules. This suggests that ME/CFS patients may have different underlying problems with their body's energy production systems.

Energy Metabolism

E3 PreliminaryMechanismPEM unclearMechanistic

Hypothalamic digoxin, cerebral chemical dominance and myalgic encephalomyelitis.

Kurup, Ravi Kumar, Kurup, Parameswara Achutha·The International journal of neuroscience·2003

This study examined chemical pathways in the brains of 15 ME/CFS patients, focusing on how the body produces energy and manages stress. Researchers found that people with ME/CFS had lower levels of important protective molecules and higher levels of harmful byproducts, along with imbalances in brain chemicals that affect mood, energy, and pain. The study suggests these biochemical problems may be linked to how the brain is organized in people with ME/CFS.

Energy Metabolism

E3 PreliminaryMechanismPEM not requiredMechanistic

Isoprenoid pathway dysfunction in chronic fatigue syndrome.

Kurup, Ravi Kumar, Kurup, Parameswara Achutha·Acta neuropsychiatrica·2003

This study looked at a set of chemical processes in the body called the isoprenoid pathway in 15 people with ME/CFS. Researchers found that several key molecules and minerals were out of balance in ME/CFS patients compared to expected levels, including low magnesium, low energy-producing compounds in cells, and imbalanced brain chemicals. These patterns were associated with increased oxidative stress (cellular damage from unstable molecules) and problems with how the immune system presents viral antigens.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Nutritional strategies for treating chronic fatigue syndrome.

Werbach, M R·Alternative medicine review : a journal of clinical therapeutic·2000

This review examines whether nutritional deficiencies might play a role in ME/CFS and suggests that patients may benefit from supplementation. The authors identified several nutrients—including B vitamins, vitamin C, magnesium, and others—that appear to be lower in ME/CFS patients, likely due to the illness itself rather than poor diet. They recommend considering vitamin and mineral supplements as a trial treatment, since these supplements are generally safe and may help with both symptoms and recovery.

Energy Metabolism

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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.