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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 6,205 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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214 studies

E0 — Consensus654E1 — Replicated321E2 — Moderate2,807E3 — Preliminary2,423

ME/CFS4,040Long COVID224Post-infectious190Overlapping1,064

Required for diagnosis417Not specified / unclear2,251Not required3,537

Post-Exertional Malaise1,082Cognitive Dysfunction1,749Pain1,628Unrefreshing Sleep805Orthostatic Intolerance484

Cytokines821Gene Expression573Metabolomics477Neuroimaging472Autoantibodies460

Infection-Triggered1,182Long COVID Overlap604Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review272Meta-Analysis61RCT301

Peer-reviewed6,148Preprint3Unclear54

141–160 of 214 studies

E3 PreliminaryReviewPEM unclearReview-Narrative

Dysregulation of cellular energetics in Gulf War Illness.

Raju, Raghavan Pillai, Terry, Alvin V·Toxicology·2021

Gulf War Illness affects about one-third of veterans from the 1991 Persian Gulf War and causes chronic fatigue, brain fog, pain, and immune problems similar to ME/CFS. This review examines evidence that the problem may stem from mitochondria (the energy-producing parts of cells) not working properly. The authors suggest that treatments targeting mitochondrial function could potentially help restore energy production and relieve symptoms.

Energy Metabolism

E3 PreliminaryMechanismPEM unclearMechanistic

Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts.

Missailidis, Daniel, Sanislav, Oana, Allan, Claire Y et al.·International journal of molecular sciences·2021

This study looked at how cells from ME/CFS patients use energy differently than healthy cells. Researchers found that ME/CFS cells are overproducing enzymes that break down fats, amino acids, and other nutrients to fuel their mitochondria (the cell's power plants), while their glycolysis (the main way cells normally produce energy) stays normal. This suggests ME/CFS cells may be forced to use alternative, less efficient pathways to generate the energy they need.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 'long-haulers'?

Wood, Emily, Hall, Katherine H, Tate, Warren·Chronic diseases and translational medicine·2021

This study reviews research on how mitochondria (the energy-producing centers in our cells) and oxidative stress (cellular damage from harmful molecules) may contribute to ME/CFS and long COVID symptoms. The authors examine whether antioxidant treatments could help restore energy production and reduce fatigue in these conditions. They highlight that many COVID-19 long-haulers develop symptoms that look very similar to ME/CFS, suggesting they may share underlying biological causes.

Energy Metabolism

E3 PreliminaryCommentaryPEM unclear

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome.

Komaroff, Anthony L, Lipkin, W Ian·Trends in molecular medicine·2021

This article compares myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with long COVID to see if they might share similar causes. The authors suggest that some people who develop long COVID symptoms—like persistent fatigue, cognitive problems, and pain—may experience similar biological problems to those seen in ME/CFS. Understanding these shared mechanisms could help doctors better treat both conditions.

Energy MetabolismLong COVID Overlap

E3 PreliminaryMechanismPEM not requiredMechanistic

Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats.

Hara, Yurie, Kume, Satoshi, Kataoka, Yosky et al.·Heliyon·2021

This study tested whether citric acid (a compound found in citrus fruits) changes the levels of energy-related chemicals in the blood of rats. Researchers found that giving citric acid increased levels of several metabolites involved in energy production—the opposite pattern seen in ME/CFS patients. This suggests citric acid might help restore normal energy metabolism, which could explain why some people report feeling less fatigued after consuming it.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Benefits of micronutrient supplementation on nutritional status, energy metabolism, and subjective wellbeing.

Maggini, Silvia, Óvári, Veronika, Ferreres Giménez, Inmaculada et al.·Nutricion hospitalaria·2021

Your body needs several vitamins and minerals—like vitamins A, D, E, folate, iron, zinc, and selenium—to make energy in your cells. Many people, even in wealthy countries, don't get enough of these nutrients. Studies show that taking a combination of these micronutrients, sometimes with coenzyme Q10, may help reduce fatigue, improve thinking, and make people feel better overall.

Energy Metabolism

E3 PreliminaryPEM unclear

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS.

Nacul, Luis, O'Boyle, Shennae, Palla, Luigi et al.·Frontiers in neurology·2020

This study proposes a framework for understanding how ME/CFS develops and changes over time, similar to other long-term illnesses. The authors suggest that ME/CFS progresses through stages—starting with genetic and environmental risk factors, moving through an early phase with high energy use and immune system problems, and potentially progressing to a later phase with low energy production and multiple system involvement. They emphasize that ME/CFS is not the same in every person or at every stage of illness, and that some people may improve if their body can restore better balance.

Energy MetabolismImmune System

E3 PreliminaryMechanismPEM unclearMechanistic

Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Schreiner, Philipp, Harrer, Thomas, Scheibenbogen, Carmen et al.·ImmunoHorizons·2020

This study explores how a virus called HHV-6 might trigger ME/CFS by examining what happens inside cells when the virus reactivates. The researchers found that when HHV-6 wakes up, it causes cells to switch into a protective mode that fights other viruses but seriously damages the cell's power plants (mitochondria) and energy-making abilities. Importantly, blood serum from ME/CFS patients showed similar patterns, suggesting HHV-6 reactivation may play a role in the disease.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Jerusalem artichoke (Helianthus tuberosus L.) as a medicinal plant and its natural products.

Sawicka, Barbara, Skiba, Dominika, Pszczółkowski, Piotr et al.·Cellular and molecular biology (Noisy-le-Grand, France)·2020

This review examined Jerusalem artichoke, a root vegetable, to understand its nutritional and health benefits. The researchers found that Jerusalem artichoke contains compounds that may help with blood sugar control, weight management, immune function, and several chronic conditions including chronic fatigue syndrome. However, this is a review of existing research rather than a new experiment testing these benefits in patients.

Energy MetabolismImmune System

E3 PreliminaryMechanismPEM not requiredMechanistic

Substrate utilisation of cultured skeletal muscle cells in patients with CFS.

Tomas, Cara, Elson, Joanna L, Newton, Julia L et al.·Scientific reports·2020

This study examined how muscle cells from ME/CFS patients use different fuels for energy compared to healthy people. Researchers found that ME/CFS muscle cells have trouble using glucose (a key fuel source) for energy, but can still use other fuels normally. This suggests the energy-producing problem in ME/CFS starts very early in the energy-making process, and may be caused by something genetic or chemical that persists even when cells are grown in a laboratory.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Spinach and quinoa - prospective food sources of biologically active substances].

Sidorova, Yu S, Petrov, N A, Shipelin, V A et al.·Voprosy pitaniia·2020

This review examined whether common foods like spinach and quinoa contain natural compounds that might help with chronic fatigue and other health problems. Researchers found that both foods contain substances called phytoecdysteroids and other active compounds that have been shown in animal studies to reduce fatigue, improve memory, and support overall health. The authors suggest these foods could be useful additions to supplements and specialized diets.

Energy Metabolism

E3 PreliminaryMechanismPEM not required

The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function.

Tomas, Cara, Elson, Joanna L, Strassheim, Victoria et al.·PloS one·2020

This study looked at how well the energy-producing parts of cells (mitochondria) work in people with ME/CFS compared to healthy people. Researchers found that both people with moderate and severe ME/CFS had problems with how their cells produce energy, but severely affected patients had additional problems with how their cells break down glucose for energy. This suggests that severe ME/CFS involves more widespread energy problems than moderate ME/CFS.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Sugars and Sweeteners: Structure, Properties and In Silico Modeling.

Janežič, Dušanka, Jäntschi, Lorentz, Bolboacă, Sorana D·Current medicinal chemistry·2020

This study reviews how different types of sugars and sweeteners affect health, including their possible links to chronic fatigue syndrome (ME/CFS). The researchers explain that each sugar and sweetener is processed differently by the body based on its chemical structure, and they used computer models to help understand and predict how these substances might affect health.

Energy Metabolism

E3 PreliminaryMechanismPEM not requiredMechanistic

Protective Effect of Hemin Against Experimental Chronic Fatigue Syndrome in Mice: Possible Role of Neurotransmitters.

Thakur, Vandana, Jamwal, Sumit, Kumar, Mandeep et al.·Neurotoxicity research·2020

Researchers studied a substance called hemin in mice to see if it could help with fatigue-like symptoms. Mice that were stressed for 21 days showed signs of exhaustion, weakness, and anxiety. When treated with hemin, these mice improved—they became more active, stronger, and less anxious. The improvements seemed to work through a specific pathway in the body related to an enzyme called HO-1.

Energy Metabolism

E3 PreliminaryCohortPEM unclear

Severe posterior hypometabolism but normal perfusion in a patient with chronic fatigue syndrome/myalgic encephalomyelitis revealed by PET/MRI.

Sahbai, S, Kauv, P, Abrivard, M et al.·European journal of nuclear medicine and molecular imaging·2019

This study examined a single ME/CFS patient's brain using advanced imaging technology (PET/MRI) that can show both brain activity and blood flow simultaneously. The researchers found that certain areas in the back of the patient's brain showed significantly lower metabolic activity (meaning cells were using less energy), but blood flow to those same areas appeared normal. This unusual pattern suggests that ME/CFS may involve a specific type of brain dysfunction that current standard brain scans might miss.

Energy Metabolism

E3 PreliminaryReviewPEM not requiredReview-Narrative

Astaxanthin: A Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging.

Sztretye, Mónika, Dienes, Beatrix, Gönczi, Mónika et al.·Oxidative medicine and cellular longevity·2019

This review examines astaxanthin, a powerful natural antioxidant found in marine organisms, and how it might help protect cells from damage caused by oxidative stress—an imbalance that occurs in ME/CFS and many other diseases. The authors explain how astaxanthin may work by targeting and protecting mitochondria, the energy-producing structures in our cells. They suggest this compound could potentially help prevent or slow disease progression and aging-related health problems.

Energy Metabolism

E3 PreliminaryMechanismPEM unclearMechanistic

The IDO Metabolic Trap Hypothesis for the Etiology of ME/CFS.

Kashi, Alex A, Davis, Ronald W, Phair, Robert D·Diagnostics (Basel, Switzerland)·2019

This study proposes a new theory about what might cause ME/CFS based on how the body processes an amino acid called tryptophan. The researchers suggest that if two proteins involved in tryptophan processing don't work properly together, the body could get stuck in a harmful state that causes ME/CFS symptoms. According to their mathematical model, if we could find a way to reset tryptophan levels back to normal, patients might recover.

Energy Metabolism

E3 PreliminaryMechanismPEM not requiredObservational

Mitochondrial complex activity in permeabilised cells of chronic fatigue syndrome patients using two cell types.

Tomas, Cara, Brown, Audrey E, Newton, Julia L et al.·PeerJ·2019

This study looked at whether the powerhouses of cells (mitochondria) work differently in ME/CFS patients compared to healthy people. Researchers tested muscle cells and immune cells from the blood using a special technique to measure how well different parts of the mitochondrial energy-production system functioned. Surprisingly, they found no significant differences between ME/CFS patients and healthy controls, suggesting that if mitochondria aren't working properly in ME/CFS, the problem may occur before it reaches the mitochondria itself.

Energy Metabolism

E3 PreliminaryReviewPEM unclearReview-Narrative

Understanding neuromuscular disorders in chronic fatigue syndrome.

Jammes, Yves, Retornaz, Frédérique·F1000Research·2019

This study examined how muscles work differently in people with ME/CFS. Researchers found that both the brain's ability to signal muscles and the muscles' ability to respond are impaired in ME/CFS patients. The muscles also appear to have trouble managing harmful molecules called free radicals, especially after exercise, and they may not be producing enough protective proteins that normally shield cells from damage.

Energy MetabolismPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Induced by Repeated Forced Swimming in Mice.

Ohba, Takuya, Domoto, Shinichi, Tanaka, Miyu et al.·Biological & pharmaceutical bulletin·2019

Researchers created a mouse model of ME/CFS by repeatedly forcing mice to swim, which produced fatigue-like behaviors similar to the human condition. They found that this stress reduced the activity of an important energy-producing enzyme called PDH in muscle cells. When they treated the mice with a drug that reactivates PDH, the fatigue-like symptoms improved, suggesting this enzyme may be a target for future ME/CFS treatments.

Energy Metabolism

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Or browse by topic

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.