ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

3901–3920 of 6,162 studies

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 PreliminaryReviewPEM unclearReview-Narrative

Mucosal Viruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Missing Piece of the Puzzle?

Perera, Krishani Dinali, Cameron, Paige, Sarwar, Tayyibah et al.·International journal of molecular sciences·2025

Many people with ME/CFS report that their illness started after a viral infection, but scientists haven't found clear evidence of viruses in their blood. This review suggests researchers have been looking in the wrong places—focusing on blood instead of mucosal tissues (like the throat and gut lining) where viruses naturally enter the body and may hide. The authors propose that viruses could be persisting in these mucosal sites and occasionally reactivating, potentially triggering the ongoing inflammation and symptoms that characterize ME/CFS.

Immune System

E3 PreliminaryMechanismPEM unclearObservational

Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Schlömer, Ella, Stein, Elisa, Kedor, Claudia et al.·Frontiers in neuroscience·2025

This small study tested whether a medication called pyridostigmine could help ME/CFS patients recover hand grip strength after exertion. Twenty patients with ME/CFS showed significant muscle weakness and fatigue. When given pyridostigmine, their hand strength improved by about 2.6 kg after one hour, compared to a loss of 4.65 kg without the medication. The medication also appeared to help with blood pressure responses when standing up.

Autonomic Nervous System

E3 PreliminaryReviewPEM not requiredReview-Narrative

A Direct Relationship Between 'Blood Stasis' and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment.

Kell, Douglas B, Pretorius, Etheresia, Zhao, Huihui·Pharmaceuticals (Basel, Switzerland)·2025

This study proposes that tiny blood clots called fibrinaloid microclots may be the physical basis behind a traditional Chinese medicine concept called 'blood stasis,' which describes sluggish blood flow. The authors suggest that these microclots block small blood vessels and reduce oxygen delivery to tissues, and that certain Chinese herbal remedies—particularly a formula called Xue Fu Zhu Yu—may help by reducing microclot formation. If correct, this could open new treatment avenues for ME/CFS, long COVID, and other chronic inflammatory conditions.

E3 PreliminaryReviewPEM unclearReview-Narrative

Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.

Fronticelli Baldelli, Giovanni, Buonsenso, Danilo·Children (Basel, Switzerland)·2025

This review proposes that a protein called mTOR may be the key link between infections and the long-lasting symptoms seen in ME/CFS and similar post-infection illnesses. The authors suggest that when mTOR stays overactive after an infection, it can damage the barrier that protects the brain, allow immune cells to enter brain tissue, and cause ongoing inflammation that affects how the brain works. They outline a step-by-step pathway explaining how this might happen and suggest that targeting mTOR could be a new treatment approach.

NeuroinflammationImmune System

E3 PreliminaryReviewPEM unclearReview-Narrative

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.

Yong, Shin Jie, Kenny, Tiff-Annie, Halim, Alice et al.·Reviews in medical virology·2025

This review describes a condition called post-COVID-19 vaccination syndrome (PCVS), where some people develop long-lasting symptoms similar to long COVID after receiving a vaccine. Symptoms typically start within days to weeks after vaccination and can last for months or years, including fatigue, brain fog, and nerve tingling. The study examines what might cause PCVS and discusses possible treatments, though researchers emphasize that much remains unknown about this condition.

Immune SystemPost-Exertional Malaise

E3 PreliminaryReviewPEM not requiredReview-Narrative

Myopraktikk (NO): A Narrative Review and Conceptual Hypothesis on Intrafasciomembranal Fluid Pressure, Biotensegrity, and Immediate Remote Myofascial Responses.

Hopen, Stig Runar, Mjøen, Tor Arne·Cureus·2025

This article proposes a new theory about muscle pain and stiffness called Myopraktikk, which focuses on fluid pressure building up in the spaces around muscles. The authors suggest that when fluid pressure increases in these areas, it can cause muscles to feel tight, knotted, and painful—similar to what happens in conditions like ME/CFS and fibromyalgia. According to their hypothesis, releasing this pressure through manual treatment may help reduce symptoms in both the treated area and elsewhere in the body.

Pain and Sensitization

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 PreliminaryReviewPEM not requiredReview-Narrative

Cerebral Blood Flow in Orthostatic Intolerance.

Khan, Muhammad Shahzeb, Miller, Amanda J, Ejaz, Arooba et al.·Journal of the American Heart Association·2025

When you stand up, your body normally adjusts blood flow to keep your brain supplied with oxygen. Some people have problems with this adjustment, causing dizziness, fatigue, or fainting—a condition called orthostatic intolerance. This review explains that many ME/CFS and long COVID patients have reduced blood flow to the brain when standing, even though their heart rate and blood pressure look normal on standard tests. The authors review different tools doctors can use to actually measure brain blood flow, rather than just relying on heart rate and blood pressure readings.

Autonomic Nervous System

E3 PreliminaryReviewPEM not requiredReview-Narrative

Management of Fibromyalgia: Novel Nutraceutical Therapies Beyond Traditional Pharmaceuticals.

Antonelli, Antonella, Bianchi, Marzia, Fear, Elizabeth Jane et al.·Nutrients·2025

This review examines how natural plant-based compounds, particularly polyphenols, might help manage fibromyalgia pain without the side effects of traditional medications. Fibromyalgia and ME/CFS are related conditions that involve abnormal pain signaling in the nervous system, persistent fatigue, and sleep problems. The authors suggest that natural products could be safer alternatives to current drugs like antidepressants and anticonvulsants, which can cause dependence and tolerance over time.

Neuroinflammation

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Using the Ratio of Phosphorylated to Non-phosphorylated Forms of Stress Kinase PKR as a Potential Diagnostic Test for ME/CFS.

Sweetman, Eiren, Tate, Warren P·Methods in molecular biology (Clifton, N.J.)·2025

Researchers developed a new blood test that measures a specific immune protein called PKR in white blood cells to help diagnose ME/CFS. The test looks at whether PKR is in an active or inactive form—people with ME/CFS appear to have different patterns of active PKR compared to healthy people. If this method works well in larger studies, it could provide doctors with a simple, quick way to diagnose ME/CFS instead of waiting months while ruling out other illnesses.

Immune System

E3 PreliminaryMechanismPEM unclearObservational

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

Fluge, Øystein, Rekeland, Ingrid Gurvin, Sørland, Kari et al.·Frontiers in medicine·2025

Researchers tested a drug called daratumumab that targets specific immune cells (plasma cells) in 10 ME/CFS patients to see if removing these cells could improve symptoms. Six patients experienced significant improvement in fatigue, physical function, and daily activity levels after treatment, while four showed no major changes. The drug was well-tolerated with no serious side effects, and improvements were sustained over 8-24 months of follow-up.

Immune System

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Real-Time Measurement of Mitochondrial Function and Glycolysis in Lymphoblastoid Cell Lines.

Katsaros, Tina, Missailidis, Daniel, Annesley, Sarah J·Methods in molecular biology (Clifton, N.J.)·2025

This study describes a new method to measure how cells make energy in people with ME/CFS. Researchers use a special machine to track two main energy-production pathways in cells: one that happens quickly (glycolysis) and one that happens in the cell's energy factories called mitochondria. By measuring how much oxygen cells use and the acids they produce, scientists can see if these energy pathways are working differently in ME/CFS patients compared to healthy people.

Energy Metabolism

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Multifaceted evolution focused on maximal exploitation of domain knowledge for the consensus inference of Gene Regulatory Networks.

Segura-Ortiz, Adrián, Giménez-Orenga, Karen, García-Nieto, José et al.·Computers in biology and medicine·2025

Researchers created a new computer tool called BIO-INSIGHT that helps scientists better understand which genes control other genes by analyzing genetic data from patients. They tested this tool on data from people with fibromyalgia, ME/CFS, and both conditions together, and found it could identify different gene patterns specific to each illness. This could help doctors find better ways to diagnose and treat these conditions in the future.

Biomarkers

E3 PreliminaryMechanismPEM not requiredMechanistic

Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study.

Chuwen, Feng, Chaoran, L I, Yan, Yang et al.·Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan·2025

This study tested whether moxibustion—a traditional Chinese medicine technique involving gentle heat applied to a specific acupuncture point on the leg—could help rats with chronic fatigue syndrome. Researchers found that moxibustion improved the rats' activity levels, memory, and reduced damage to a brain region involved in learning and emotion. The treatment appeared to work by restoring balance to specific proteins in the brain that were abnormal in the fatigued rats.

E3 PreliminaryMechanismPEM unclearMechanistic

A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study.

Hung, Li-Yuan, Wu, Chan-Shuo, Chang, Chia-Jung et al.·Frontiers in human neuroscience·2025

Researchers used advanced computer analysis to examine genetic information from people with severe ME/CFS, looking for patterns in how genes work together. They found that ME/CFS involves multiple body systems working incorrectly, particularly the immune and nervous systems, and discovered connections to viral infections like EBV and COVID-19. The study also found clues about why more women than men develop ME/CFS, relating to how estrogen affects the body.

Immune System

E3 PreliminaryMechanismPEM unclearCross-Sectional

Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients.

Shahbaz, Shima, Rezaeifar, Maryam, Syed, Hussein et al.·Brain, behavior, and immunity·2025

Researchers studied blood samples from Long COVID patients with ME/CFS-like symptoms and compared them to healthy controls. They found that certain genes related to immune function and brain health were turned on in the patients, while others were turned off. The study also discovered unusual activation of smell-related genes and changes in immune cell types, suggesting the body remains in a state of ongoing inflammation and stress.

NeuroinflammationBiomarkersImmune System

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Deep Immunophenotyping in ME/CFS Using Spectral Flow Cytometry.

Gibson, Anton, Chometon, Thaize Q, Damani, Tanvi et al.·Methods in molecular biology (Clifton, N.J.)·2025

Researchers developed a new laboratory technique to examine immune cells in the blood of ME/CFS patients in much greater detail than previously possible. Using advanced flow cytometry, they simultaneously measured over 40 different markers on individual immune cells, allowing them to create a detailed map of immune system abnormalities in ME/CFS. This technique is like upgrading from a simple photograph to a high-resolution image, revealing much more about how immune cells are behaving.

Immune System

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

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Evidence Atlas

Evidence browser

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

Mucosal Viruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Missing Piece of the Puzzle?

Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

A Direct Relationship Between 'Blood Stasis' and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment.

Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.

Post-COVID-19 Vaccination (or Long Vax) Syndrome: Putative Manifestation, Pathophysiology, and Therapeutic Options.

Myopraktikk (NO): A Narrative Review and Conceptual Hypothesis on Intrafasciomembranal Fluid Pressure, Biotensegrity, and Immediate Remote Myofascial Responses.

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

Cerebral Blood Flow in Orthostatic Intolerance.

Management of Fibromyalgia: Novel Nutraceutical Therapies Beyond Traditional Pharmaceuticals.

Using the Ratio of Phosphorylated to Non-phosphorylated Forms of Stress Kinase PKR as a Potential Diagnostic Test for ME/CFS.

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome-a clinical pilot study.

Real-Time Measurement of Mitochondrial Function and Glycolysis in Lymphoblastoid Cell Lines.

Multifaceted evolution focused on maximal exploitation of domain knowledge for the consensus inference of Gene Regulatory Networks.

Identifying potential biomarkers in the hippocampus of chronic fatigue syndrome rats treated with moxibustion at Zusanli (ST36): a proteomics study.

A network medicine approach to investigating ME/CFS pathogenesis in severely ill patients: a pilot study.

Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients.

Deep Immunophenotyping in ME/CFS Using Spectral Flow Cytometry.

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.

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