ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

461–480 of 742 studies

E3 PreliminaryReviewPEM unclearReview-Narrative

Creatine and post-viral fatigue syndrome: an update.

Ostojic, Sergej M, Candow, Daren G, Tarnopolsky, Mark A·Journal of the International Society of Sports Nutrition·2025

This review examines how creatine—a natural substance that helps muscles produce energy—might help people with post-viral fatigue syndrome (the prolonged exhaustion that can follow viral infections like COVID-19). The researchers found that people with this condition often have problems with how their body produces and uses energy, particularly in the mitochondria (the cell's power centers). They suggest that taking creatine supplements could help restore energy production and reduce symptoms like fatigue and brain fog.

Post-Exertional Malaise

E3 PreliminaryReviewPEM unclearReview-Narrative

Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Syed, Abu Mohammad, Karius, Alexander K, Ma, Jin et al.·Physiology (Bethesda, Md.)·2025

This review examines how mitochondria—the parts of cells that produce energy—may not be working properly in ME/CFS patients. The authors suggest that problems with energy production in cells could explain why people with ME/CFS feel severely exhausted after physical activity. They also note that similar energy problems appear in long COVID, which suggests both conditions may share a common underlying cause.

Severe MELong COVID OverlapPost-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 PreliminaryMechanismPEM requiredMechanistic

Gulf War Illness Induced Sex-Specific Transcriptional Differences Under Stressful Conditions.

Frank, Joshua, Tehrani, Lily, Gamer, Jackson et al.·International journal of molecular sciences·2025

Researchers studied how the immune system responds to physical stress in Gulf War veterans with Gulf War Illness (GWI), a condition similar to ME/CFS with fatigue, brain fog, and exhaustion. They found that men and women with GWI have different patterns of immune system activation during and after exercise, suggesting their bodies handle stress differently. These differences could help doctors develop better tests and treatments tailored to each person's sex.

BiomarkersImmune SystemPost-Exertional Malaise

E3 PreliminaryCommentaryPEM requiredEditorial

mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS.

Bar-Tana, Jacob·Journal of translational medicine·2025

This study proposes that ME/CFS, Long COVID, and similar post-infection illnesses may all be caused by the same underlying problem: excessive activity of a cellular control system called mTORC1. The authors suggest that if this overactive system is the shared driver of these conditions, it could explain why patients experience fatigue, worsening after exercise, pain, heart rate changes, and brain fog—and it might point toward new treatments.

Energy MetabolismPost-Exertional Malaise

E3 PreliminaryMechanismPEM requiredMechanistic

Exertional Exhaustion (Post-Exertional Malaise, PEM) Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics-Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Baraniuk, James N·International journal of molecular sciences·2025

This study examined fluid from around the brain and spinal cord in ME/CFS patients and healthy controls, measuring chemical substances before and after exercise. Researchers found that ME/CFS patients have abnormal levels of certain chemicals related to energy production and brain function, especially after exercise. The study suggests that exercise may trigger harmful changes in brain chemistry in ME/CFS patients that don't happen in healthy people, which could explain post-exertional malaise (the worsening of symptoms after activity).

Post-Exertional Malaise

E3 PreliminaryReviewPEM requiredReview-Narrative

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

Rahman, A F M Towheedur, Benko, Anna, Bulbule, Sarojini et al.·Biomolecules·2025

This review article examines a molecule called tetrahydrobiopterin (BH4) and its possible role in ME/CFS, particularly in patients who experience orthostatic intolerance (dizziness or fainting when standing up). The researchers found that BH4 metabolism—the way the body processes this molecule—is not working properly in ME/CFS patients with these symptoms. By understanding how BH4 goes wrong, scientists hope to explain why ME/CFS patients have problems with blood flow to the brain.

BiomarkersPost-Exertional Malaise

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Stress-Induced Changes in Immune Signatures in ME/CFS Patients Determined by Transcriptome Analysis.

Gamer, Jackson, Van Booven, Derek, Zarnowski, Oskar et al.·Methods in molecular biology (Clifton, N.J.)·2025

Researchers studied how the immune system of ME/CFS patients responds to exercise by examining blood cells before, during, and after a physical challenge. They compared these responses in ME/CFS patients to healthy people using advanced genetic testing. This study is part of ongoing efforts to understand what makes ME/CFS different at a biological level and why exercise can make symptoms worse.

Immune SystemPost-Exertional Malaise

E3 PreliminaryGuidelinePEM requiredGuideline

Multidisciplinary collaborative guidance on the assessment and treatment of patients with Long COVID: A compendium statement.

Cheng, Abby L, Herman, Eric, Abramoff, Benjamin et al.·PM & R : the journal of injury, function, and rehabilitation·2025

This is a comprehensive clinical guide created by over 40 Long COVID treatment centers to help doctors evaluate and care for Long COVID patients. The guide covers how to assess symptoms, manage common problems like fatigue and brain fog, and help patients return to work or daily activities. It emphasizes that Long COVID is real, takes it seriously, and recommends treatments based on what doctors currently know while acknowledging many unknowns remain.

Post-Exertional Malaise

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 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

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

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 PreliminaryPEM unclear

Perspectives of Rehabilitation Professionals on Long COVID Interventions to Facilitate Return-to-Work.

MacKinnon, Cassandra, Castro-Barquero, Cassandra, Kontis, Alexandra et al.·Canadian journal of occupational therapy. Revue canadienne d'ergotherapie·2025

This study asked rehabilitation professionals in Quebec about their experiences helping people with long COVID return to work. The professionals emphasized that education, gradually increasing activity, and self-management are the most helpful approaches, but they noted that returning to work is very difficult without workplace accommodations and proper support for managing post-exertional malaise (when symptoms worsen after activity).

Post-Exertional Malaise

E3 PreliminaryCohortPEM requiredObservational

Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.

Gattoni, Chiara, Abbasi, Asghar, Ferguson, Carrie et al.·Respiratory physiology & neurobiology·2025

This study tested whether Long COVID patients experience a measurable drop in exercise capacity after 24 hours, which would suggest their bodies aren't recovering properly from exercise. Researchers had 15 Long COVID patients do exercise tests on two consecutive days and found no significant difference in performance between day 1 and day 2. Surprisingly, this was true even though 80% of patients reported post-exertional malaise (PEM) symptoms over the previous six months.

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 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

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 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 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

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Creatine and post-viral fatigue syndrome: an update.

Mitochondrial Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Measuring Biomarkers of Oxidative Stress in ME/CFS Patients.

Gulf War Illness Induced Sex-Specific Transcriptional Differences Under Stressful Conditions.

mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS.

Exertional Exhaustion (Post-Exertional Malaise, PEM) Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics-Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

Stress-Induced Changes in Immune Signatures in ME/CFS Patients Determined by Transcriptome Analysis.

Multidisciplinary collaborative guidance on the assessment and treatment of patients with Long COVID: A compendium statement.

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

Repeated Cardiopulmonary Exercise Testing of ME/CFS Patients.

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

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

Perspectives of Rehabilitation Professionals on Long COVID Interventions to Facilitate Return-to-Work.

Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis.

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

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

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

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

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

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