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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 6,145 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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206 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

61–80 of 206 studies

E2 ModerateCohortPEM unclear

Association of mitochondrial DNA variants with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms.

Hanson, Maureen R, Gu, Zhenglong, Keinan, Alon et al.·Journal of translational medicine·2016

This study looked at whether variations in mitochondrial DNA (the genetic material in the energy-producing parts of our cells) are linked to ME/CFS. Researchers compared genetic samples from ME/CFS patients and healthy people. While they didn't find that specific DNA variants caused the disease itself, they did discover that certain genetic variations were associated with specific symptoms and how severe those symptoms were.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?

Boles, Richard G, Zaki, Essam A, Kerr, Jonathan R et al.·Mitochondrion·2015

This study found that two specific variations in mitochondrial DNA (the energy-producing structures in our cells) appear more frequently in people with ME/CFS and several other conditions that cause fatigue, pain, or dysfunction. The researchers looked at people with a particular genetic background and found that having one or both of these DNA variations was linked to increased risk of developing these conditions. This suggests these genetic variations may be a shared risk factor across multiple illnesses.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

Irritable bowel syndrome may be associated with maternal inheritance and mitochondrial DNA control region sequence variants.

van Tilburg, Miranda A L, Zaki, Essam A, Venkatesan, Thangam et al.·Digestive diseases and sciences·2014

This study looked at whether irritable bowel syndrome (IBS) runs in families through the mother's side, and whether this pattern is linked to variations in mitochondrial DNA (the energy-producing structures in our cells). Researchers found that about 1 in 6 IBS patients had a family history suggesting maternal inheritance, and certain DNA variations were more common in these patients. This suggests that mitochondrial dysfunction may explain IBS symptoms in some people.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

Payne, B A I, Hateley, C L, Ong, E L C et al.·HIV medicine·2013

This study looked at fatigue in people living with HIV who were taking modern HIV medications and had their virus under control. Surprisingly, about half of these patients still reported significant fatigue, even though their HIV was suppressed and their immune systems were recovering. The researchers found that fatigue was often linked to problems with blood pressure control (orthostatic intolerance) and previous exposure to certain older HIV medications.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology.

Shungu, Dikoma C, Weiduschat, Nora, Murrough, James W et al.·NMR in biomedicine·2012

This study used specialized brain imaging to look for differences in how the brains of people with ME/CFS work compared to healthy people and those with depression or anxiety. Researchers found that people with ME/CFS had higher levels of lactate (a chemical produced when cells don't get enough oxygen) in their brain fluid and lower levels of a natural antioxidant that protects cells from damage. These findings suggest that oxidative stress—damage from harmful molecules—may be an important part of what causes ME/CFS.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

The assessment of the energy metabolism in patients with chronic fatigue syndrome by serum fluorescence emission.

Mikirova, Nina, Casciari, Joseph, Hunninghake, Ronald·Alternative therapies in health and medicine·2012

This study tested whether measuring a specific molecule in the blood called NAD(P)H could help diagnose and monitor ME/CFS. The researchers found that people with ME/CFS had lower levels of this energy-related molecule compared to healthy people, and this difference might be useful as a blood test marker for the disease.

Energy Metabolism

E2 ModerateCohortPEM unclearCross-Sectional

Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Booth, Norman E, Myhill, Sarah, McLaren-Howard, John·International journal of clinical and experimental medicine·2012

This study tested whether ME/CFS fatigue is caused by problems with how cells produce energy. Researchers measured energy production in immune cells from 138 ME/CFS patients and compared them to healthy controls, finding that all patients had measurable problems with their cellular energy factories (mitochondria) that matched how sick they felt. The study also found signs of tissue damage in the blood, suggesting these energy problems affect many cells throughout the body.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity.

Reuter, S E, Evans, A M·Journal of internal medicine·2011

This study found that people with ME/CFS have lower levels of certain fat-like molecules called acylcarnitines in their blood compared to healthy people. These molecules are important for cells to produce energy from fat. The researchers suggest this difference might be related to how the body processes fatty acids, and they propose that taking omega-3 fatty acids along with carnitine supplements might help improve symptoms.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome.

Smits, Bart, van den Heuvel, Lambert, Knoop, Hans et al.·Mitochondrion·2011

This study looked at whether measurements of mitochondria (the energy-producing parts of cells) can help distinguish ME/CFS from true mitochondrial diseases. The researchers found that while people with ME/CFS have fewer mitochondria overall, the mitochondria that are present work normally. In contrast, people with actual mitochondrial disorders have mitochondria that don't function well, even when mitochondrial numbers are considered.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

Chronic fatigue syndrome is associated with metabolic syndrome: results from a case-control study in Georgia.

Maloney, Elizabeth M, Boneva, Roumiana S, Lin, Jin-Mann S et al.·Metabolism: clinical and experimental·2010

This study found that people with ME/CFS are twice as likely to have metabolic syndrome—a cluster of conditions including high blood pressure, high blood sugar, excess belly fat, and abnormal cholesterol levels—compared to healthy people. The more metabolic factors someone had, the worse their fatigue tended to be. This suggests that metabolic problems may be connected to ME/CFS severity.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Visible and near-infrared spectral changes in the thumb of patients with chronic fatigue syndrome.

Sakudo, Akikazu, Kato, Yukiko Hakariya, Tajima, Seiki et al.·Clinica chimica acta; international journal of clinical chemistry·2009

Researchers used a special light-based scanning tool to examine the thumbs of ME/CFS patients and healthy people, looking for differences in blood and oxygen levels. They found that ME/CFS patients had higher oxygen-carrying proteins in their blood, less water in their tissues, and signs of faster energy use in their cells. These findings suggest that ME/CFS patients' bodies may be working harder than usual, even at rest.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Chronic fatigue syndrome and mitochondrial dysfunction.

Myhill, Sarah, Booth, Norman E, McLaren-Howard, John·International journal of clinical and experimental medicine·2009

This study tested whether people with ME/CFS have problems with how their cells produce energy. Researchers developed a blood test called the 'ATP profile' that measures five different factors related to mitochondrial function—the parts of cells responsible for energy production. They compared 71 patients with ME/CFS to 53 healthy controls and found a strong connection between mitochondrial dysfunction and illness severity, suggesting energy problems may underlie ME/CFS symptoms.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study.

Paul, Lorna, Rafferty, Danny, Marshal, Rebecca·Disability and rehabilitation·2009

This study compared how much energy people with ME/CFS use when walking compared to healthy people. Researchers found that people with ME/CFS walk more slowly and use more energy per unit of distance covered, meaning their bodies have to work harder to move the same distance as healthy people.

Energy MetabolismPost-Exertional Malaise

E2 ModerateCohortPEM not requiredCase-Control

Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome.

Sheedy, John R, Wettenhall, Richard E H, Scanlon, Denis et al.·In vivo (Athens, Greece)·2009

This study found that people with ME/CFS have higher levels of specific bacteria in their gut that produce a substance called D-lactic acid. These bacteria were found in much larger quantities in stool samples from ME/CFS patients compared to healthy people. The researchers suggest this excess D-lactic acid might help explain why some ME/CFS patients experience brain fog and cognitive problems.

Gut MicrobiomeEnergy Metabolism

E2 ModerateMechanismPEM not requiredMechanistic

Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome.

Pietrangelo, T, Mancinelli, R, Toniolo, L et al.·International journal of immunopathology and pharmacology·2009

Researchers examined muscle tissue from ME/CFS patients and found abnormalities in how genes are expressed—essentially, certain genetic instructions were turned up or down compared to healthy people. The biggest changes involved genes related to energy production in cells, muscle structure, and communication between nerves and muscles. These findings suggest that problems at the cellular level may explain why ME/CFS patients experience muscle weakness and fatigue.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

Hematologic and urinary excretion anomalies in patients with chronic fatigue syndrome.

Niblett, Suzanne H, King, Katrina E, Dunstan, R Hugh et al.·Experimental biology and medicine (Maywood, N.J.)·2007

Researchers compared blood and urine samples from 100 people with ME/CFS and 82 healthy controls to look for abnormalities. While standard blood tests appeared normal, closer examination found subtle differences in blood cell counts and patterns in how patients' bodies were processing and excreting amino acids (building blocks of protein) and other compounds in their urine.

Energy MetabolismImmune System

E2 ModerateCohortPEM not requiredCase-Control

Allostatic load is associated with symptoms in chronic fatigue syndrome patients.

Goertzel, Benjamin N, Pennachin, Cassio, de Souza Coelho, Lucio et al.·Pharmacogenomics·2006

This study looked at whether ME/CFS patients have higher 'allostatic load'—a measure of stress on the body's systems including metabolism, heart function, and hormones. Researchers compared 43 ME/CFS patients to 60 healthy controls and found that ME/CFS patients with higher allostatic load reported worse physical function, more body pain, and more frequent symptoms. The study suggests the body's stress response systems may play a role in ME/CFS severity.

Energy Metabolism

E2 ModerateCohortPEM unclearCross-Sectional

Urinary and plasma organic acids and amino acids in chronic fatigue syndrome.

Jones, Mark G, Cooper, Elizabeth, Amjad, Saira et al.·Clinica chimica acta; international journal of clinical chemistry·2005

Researchers tested blood and urine samples from ME/CFS patients and compared them to healthy people, those with depression, and those with rheumatoid arthritis. Previous studies claimed certain chemicals in urine were markers for ME/CFS, but this study could not confirm those earlier findings. However, the study did find some signs of inflammation and possible muscle changes that might explain why ME/CFS patients experience fatigue and muscle pain.

Energy Metabolism

E2 ModerateCohortPEM not requiredCross-Sectional

Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome.

Jones, Mark G, Goodwin, C Stewart, Amjad, Saira et al.·Clinica chimica acta; international journal of clinical chemistry·2005

Researchers tested whether people with ME/CFS have low levels of carnitine, a substance that helps muscles produce energy. They compared blood and urine samples from 31 ME/CFS patients with samples from healthy people and patients with other conditions. The study found no significant differences in carnitine levels between the groups, suggesting that low carnitine is not responsible for the fatigue experienced by ME/CFS patients.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

The distribution of white blood cell fat oxidation in health and disease.

Pendergast, D R, Fisher, N M, Meksawan, K et al.·Journal of inherited metabolic disease·2004

This study looked at how white blood cells use fat for energy in different groups of people, including those with ME/CFS. Researchers measured fat burning in blood cells from healthy controls, people with ME/CFS, people with other conditions, and athletes. They found that people with ME/CFS had unusually high fat oxidation in their white blood cells, while people with a genetic disorder (CPT II deficiency) had very low fat oxidation.

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.