ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

481–500 of 746 studies

E3 PreliminaryMechanismPEM requiredMechanistic

Uncovering the genetic architecture of ME/CFS: a precision approach reveals impact of rare monogenic variation.

Birch, Camille L, Wilk, Brandon M, Gajapathy, Manavalan et al.·Journal of translational medicine·2025

Researchers studied the DNA of 31 people with ME/CFS from 25 families to find genetic causes of the illness. They found that about 39% of participants had gene mutations that could contribute to ME/CFS, and these mutations affected how bodies produce energy and handle stress. While the specific genes varied between patients, they all seemed to affect similar biological pathways, suggesting ME/CFS may be caused by different genetic problems that lead to the same symptoms.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome.

Glass, Katherine A, Giloteaux, Ludovic, Zhang, Sheng et al.·Clinical and translational medicine·2025

Researchers studied tiny particles called extracellular vesicles in the blood of ME/CFS patients before and after exercise. They found that in people with ME/CFS, these particles show signs of energy problems, immune overactivity, and cellular stress after exertion—changes that were linked to post-exertional malaise (the worsening of symptoms after activity). These findings suggest new targets for treatment that could help improve recovery and energy in ME/CFS.

BiomarkersPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Cerebrospinal fluid metabolomics, lipidomics and serine pathway dysfunction in myalgic encephalomyelitis/chronic fatigue syndroome (ME/CFS).

Baraniuk, James N·Scientific reports·2025

Researchers studied brain fluid from ME/CFS patients to understand what goes wrong with how their brains use energy. They found that ME/CFS patients have abnormal levels of certain molecules involved in energy production and brain cell function, and these problems got worse after exercise. The study suggests that ME/CFS may involve problems with how the brain processes nutrients and maintains its protective coating around nerve fibers.

Post-Exertional Malaise

E3 PreliminaryPEM required

Glymphatic System Dysregulation as a Key Contributor to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Nemat-Gorgani, Mohsen, Jensen, Michael Anthony, Davis, Ronald Wayne·International journal of molecular sciences·2025

Your brain has a cleaning system called the glymphatic system that removes toxic waste buildup, especially during sleep. This review suggests that this cleaning system may not be working properly in ME/CFS, which could explain symptoms like fatigue and brain fog. If the glymphatic system is involved in ME/CFS, new treatments designed to fix this cleaning process might help patients feel better.

SleepPost-Exertional Malaise

E3 PreliminaryMechanismPEM not requiredMechanistic

Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.

Wang, Kun, Shen, Mengmeng, Tang, Hongguang et al.·Journal of ethnopharmacology·2025

Researchers tested a traditional Chinese medicine called Jingfang Granule (JFG) in mice with chronic fatigue syndrome. The treatment improved fatigue symptoms, helped mice recover weight and exercise capacity, and reduced harmful inflammation and oxidative stress in their bodies. The medicine appeared to work by boosting how efficiently cells produce energy through a key metabolic pathway.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise.

Sharma, Sayan, Hodges, Lynette D, Peppercorn, Katie et al.·International journal of molecular sciences·2025

This study looked at how exercise affects the chemical switches on our genes (epigenetics) in ME/CFS patients, particularly during post-exertional malaise (PEM)—the exhaustion that worsens after physical activity. Researchers took blood samples from five ME/CFS patients before, immediately after, and 24-48 hours after an exercise test, and found distinct patterns of genetic changes that were specific to ME/CFS patients and not seen in healthy controls. These changes affected genes related to immune function, inflammation, and blood vessel health, suggesting the body's response to exercise in ME/CFS is fundamentally different at the molecular level.

BiomarkersImmune SystemPost-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Repeated Cardiopulmonary Exercise Testing of ME/CFS Patients.

Hodges, Lynette·Methods in molecular biology (Clifton, N.J.)·2025

This study explains how doctors use a special exercise test done twice (24 hours apart) to measure how ME/CFS affects the body's ability to exercise. The test shows that people with ME/CFS often cannot exercise as hard the second time, and their bodies don't use oxygen or produce power the way healthy people do. This helps prove that ME/CFS causes real, measurable changes in how the body functions.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.

Li, Gong-Hua, Han, Fei-Fei, Kalafatis, Efthymios et al.·International journal of molecular sciences·2025

This study found that both ME/CFS and Long COVID may share similar problems with how muscles process certain amino acids (building blocks of proteins). Using computer modeling, researchers identified that two specific metabolic pathways are underactive in muscle tissue. They then tested whether adding supplements containing aspartate and a related compound could help restore normal muscle metabolism, and suggest a combination treatment called LOLA as a potential future therapy.

Post-Exertional Malaise

E3 PreliminaryCommentaryPEM unclearEditorial

Skeletal muscle adaptations and post-exertional malaise in long COVID.

Charlton, Braeden T, Goulding, Richie P, Jaspers, Richard T et al.·Trends in endocrinology and metabolism: TEM·2025

This article reviews evidence that long COVID symptoms—especially worsening after activity (post-exertional malaise)—may be caused by problems with how muscles produce energy, damage to blood vessel function, and changes in muscle fiber types that make them rely more on less-efficient energy pathways. The authors suggest that physical or mental exertion may trigger rapid muscle damage and immune cell infiltration, which could explain why patients feel worse after activity.

Post-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.

Gupta, Gautam, Buonsenso, Danilo, Wood, John et al.·Comprehensive Physiology·2025

This review examines how Long Covid causes persistent symptoms affecting multiple body systems. The research suggests that SARS-CoV-2 virus may hide in body tissues, trigger ongoing immune problems, and damage how cells produce energy, which could explain fatigue and post-exertion crashes. These mechanisms appear similar to ME/CFS, suggesting the two conditions may share common biological pathways.

NeuroinflammationImmune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM requiredEditorial

Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.

Kenny, Tiff-Annie·Therapeutic advances in drug safety·2025

This paper describes complex, long-lasting health problems that some people develop after vaccination, which resemble ME/CFS and Long COVID symptoms like fatigue, pain, brain fog, and heart rhythm issues. The author argues that current vaccine safety systems are not well-designed to detect or investigate these kinds of slow-developing, multisystem conditions because they work best for identifying immediate reactions like fever or allergies. The paper proposes changes to how we monitor vaccine safety—including better training for doctors, longer-term tracking of patients, and including patients' own descriptions of their symptoms—to catch these problems more effectively.

Post-Exertional Malaise

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

MyGuide long COVID: An online self-management tool for people with long COVID.

Naik, Hiten, Pongratz, Kyla, Malbeuf, Michelle et al.·Internet interventions·2025

Researchers created MyGuide Long COVID, a free website where people with long COVID answer questions about their symptoms and receive personalized information and self-management tips. The website launched in August 2023 and attracted nearly 8,600 users in its first year, with the most popular topics being post-exertional malaise (worsening symptoms after activity) and general information about long COVID. This shows that a patient-centered online tool developed together with both doctors and people living with long COVID can successfully help patients manage their condition.

Post-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review.

Humer, Bart, Dik, Willem A, Versnel, Marjan A·Frontiers in immunology·2025

This review explores how a single severe infection might trigger long-term changes in the immune system that could lead to ME/CFS. After infection, immune cells can become 'trained' to overreact to future triggers, potentially causing the chronic symptoms patients experience. The researchers suggest this overactive immune response might explain why about 60% of ME/CFS patients remember getting sick before their symptoms started.

Immune SystemPost-Exertional Malaise

E3 PreliminaryPEM required

Managing Energy, and Shaping Care: Insights from Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Through Co-Production Workshops.

Thornton, Eleanor J, Hayes, Lawrence D, Goodwin, Dawn S et al.·The American journal of medicine·2025

This study asked people with ME/CFS and healthcare providers what they think about managing energy and daily activities. The researchers held online workshops where patients shared their experiences and suggestions for better care. Participants stressed that doctors need better training about ME/CFS, patients should be involved in their own care planning, and new tools like apps and sleep management could help improve how people manage their energy.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredPreprintPreprint

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·medRxiv : the preprint server for health sciences·2025

This study found that people with ME/CFS may have an overactive immune system that responds too strongly to germs and infections. The research showed problems with how the body produces energy and manages inflammation, and these problems got worse after exercise in ME/CFS patients but not in healthy people. The findings suggest multiple biological systems are working abnormally in ME/CFS, which could help doctors develop better treatments.

Energy MetabolismImmune SystemPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

Drosen, Molly E, Bulbule, Sarojini, Gottschalk, Gunnar et al.·Immunologic research·2025

Researchers gave mice a drug that overactivates a protein called mTOR and found it triggered muscle weakness, nerve damage, and worsening fatigue after exercise—similar to post-exertional malaise (PEM) in ME/CFS. The drug blocked a cellular cleanup system called autophagy, which led to inflammation and damage to the nerves controlling muscles. Mice engineered to have impaired autophagy showed similar problems, suggesting that broken autophagy may be involved in ME/CFS fatigue and exercise intolerance.

NeuroinflammationPost-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Measuring Biomarkers of Oxidative Stress in ME/CFS Patients.

Walker, Max·Methods in molecular biology (Clifton, N.J.)·2025

This study looked at whether certain molecules in the blood and immune cells could show signs of oxidative stress (cellular damage from harmful molecules called free radicals) in ME/CFS patients. The researchers tested two different markers before and after exercise: one test successfully measured protein damage, while another test designed to measure DNA damage was not sensitive enough to detect changes in this patient group.

BiomarkersPost-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Multimodal Telerehabilitation in Post COVID-19 Condition Recovery: A Series of 12 Cases.

Carpallo-Porcar, Beatriz, Beamonte, Esther Del Corral, Jiménez-Sánchez, Carolina et al.·Reports (MDPI)·2025

This study tested whether people recovering from COVID-19 could improve their symptoms through home-based exercise and education delivered via video appointments over 12 weeks. Most patients improved in fatigue, exercise capacity, and muscle strength, though breathlessness did not improve as much. The results suggest that remote rehabilitation programs delivered from home may be helpful for people with long COVID symptoms.

Post-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Post-exertional malaise - A functional brain aberration?

Bruun Bratholm Wyller, Vegard·Brain, behavior, and immunity·2024

This study explores whether post-exertional malaise (PEM)—the hallmark symptom of ME/CFS where activity makes symptoms worse—might be caused by problems in how the brain functions. Researchers examined brain activity patterns in ME/CFS patients to understand what happens after exertion. The findings suggest that brain function abnormalities could play a role in why patients experience this debilitating symptom.

Post-Exertional Malaise

E3 PreliminaryCohortPEM requiredCase-Control

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein-Barr Virus.

Tang-Siegel, Gaoyan G, Maughan, David W, Frownfelter, Milah B et al.·Case reports in genetics·2024

This study describes one patient with ME/CFS whose symptoms began after a severe viral infection (Epstein-Barr virus, which causes mononucleosis) 24 years ago. Researchers found that her cells had genetic mutations affecting the mitochondria—the 'power plants' that produce energy for our bodies—which may explain her extreme fatigue and difficulty recovering from physical activity. The study also found abnormal mitochondria circulating in her blood, suggesting that energy production problems may be contributing to her ME/CFS symptoms.

Post-Exertional Malaise

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Evidence browser

Uncovering the genetic architecture of ME/CFS: a precision approach reveals impact of rare monogenic variation.

Extracellular vesicle proteomics uncovers energy metabolism, complement system, and endoplasmic reticulum stress response dysregulation postexercise in males with myalgic encephalomyelitis/chronic fatigue syndrome.

Cerebrospinal fluid metabolomics, lipidomics and serine pathway dysfunction in myalgic encephalomyelitis/chronic fatigue syndroome (ME/CFS).

Glymphatic System Dysregulation as a Key Contributor to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Jingfang Granule promotes the tricarboxylic acid cycle to improve chronic fatigue syndrome by increasing the expression of Idh1 and Idh2.

Precision Medicine Study of Post-Exertional Malaise Epigenetic Changes in Myalgic Encephalomyelitis/Chronic Fatigue Patients During Exercise.

Repeated Cardiopulmonary Exercise Testing of ME/CFS Patients.

Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID.

Skeletal muscle adaptations and post-exertional malaise in long COVID.

Mechanistic Insights Into Long Covid: Viral Persistence, Immune Dysregulation, and Multi-Organ Dysfunction.

Complex chronic adverse events following immunization: a systemic critique and reform proposal for vaccine pharmacovigilance.

MyGuide long COVID: An online self-management tool for people with long COVID.

Advocating the role of trained immunity in the pathogenesis of ME/CFS: a mini review.

Managing Energy, and Shaping Care: Insights from Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Through Co-Production Workshops.

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Inactivation of ATG13 stimulates chronic demyelinating pathologies in muscle-serving nerves and spinal cord.

Measuring Biomarkers of Oxidative Stress in ME/CFS Patients.

Multimodal Telerehabilitation in Post COVID-19 Condition Recovery: A Series of 12 Cases.

Post-exertional malaise - A functional brain aberration?

Mitochondrial DNA Missense Mutations ChrMT: 8981A > G and ChrMT: 6268C > T Identified in a Caucasian Female with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Triggered by the Epstein-Barr Virus.

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