Evidence browser

Chronic fatigue syndrome induced by environmental toxic exposure: Effects of polyhexamethyleneguanidine phosphate exposure on mitochondrial function and neural health.

Yang, Hyo-Seon, Lee, Jin-Seok, Kang, Mi-Hyun et al.·Environmental research·2026

This study found that exposure to humidifier disinfectants—cleaning chemicals used in humidifiers—may trigger ME/CFS by damaging the energy-producing structures (mitochondria) inside our cells and disrupting communication in the brain. Researchers compared patients with ME/CFS who had been exposed to these chemicals to laboratory mice exposed to the same chemicals, and both showed similar problems with mitochondrial function and brain health. The findings suggest that environmental toxins could be a trigger for ME/CFS in some people.

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 not requiredEditorial

Post infectious fatigue and circadian rhythm disruption in long-COVID and other infections: a need for further research.

Livieratos, Achilleas, Lockley, Steven W, Tsiodras, Sotirios·EClinicalMedicine·2025

This article discusses how infections like COVID-19 can disrupt the body's internal 24-hour clock, leading to persistent fatigue and sleep problems. The authors explain that viral infections may damage the genes and cellular machinery that control our daily rhythms, trigger inflammation in the brain, and harm energy-producing structures in our cells. Understanding these mechanisms could help doctors develop better treatments for Long COVID and chronic fatigue syndrome.

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

NeuroinflammationEnergy MetabolismImmune System

The Gut-Brain-Immune Axis in Environmental Sensitivity Illnesses: Microbiome-Centered Narrative Review of Fibromyalgia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Multiple Chemical Sensitivity.

Watai, Kentaro, Taniguchi, Masami, Azuma, Kenichi·International journal of molecular sciences·2025

This review examines how changes in gut bacteria may contribute to ME/CFS, fibromyalgia, and multiple chemical sensitivity—three conditions that share similar symptoms like fatigue, pain, and sensitivity to environmental triggers. The researchers found that people with these conditions tend to have fewer helpful bacteria and more harmful bacteria in their gut, which may affect how their immune system and brain work. The review suggests that treatments targeting the microbiome—such as probiotics or other interventions—might help, though more research is needed to confirm this.

E3 PreliminaryReviewPEM not requiredReview-Narrative

From Fork to Brain: The Role of AGE-RAGE Signaling and the Western Diet in Neurodegenerative Disease.

Pomroy, Haylie J, Mote, Arjun, Mathew, Simeon et al.·NeuroSci·2025

This review examines how certain compounds called AGEs (advanced glycation end products) form in food and in our bodies, and how they may contribute to brain damage and disease. AGEs are created when food is cooked at high temperatures or processed, and when they build up in the body, they can trigger inflammation and harm cells. The authors suggest that limiting AGEs in the diet might help prevent or slow down brain diseases, though more research is needed to confirm this.

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

NeuroinflammationImmune System

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.

PKM2 accelerated the progression of chronic fatigue syndrome via promoting the H4K12la/ NF-κB induced neuroinflammation and mitochondrial damage.

Sun, Meng, Zhang, Xinwen, Feng, Xinli et al.·Scientific reports·2025

This study in mice explored how a protein called PKM2 may contribute to ME/CFS by increasing inflammation in the brain and damaging energy-producing structures inside cells (mitochondria). Researchers found that when PKM2 levels increased, cognitive problems worsened and brain cells showed more damage, while reducing PKM2 improved these outcomes. The mechanism involves lactate buildup and activation of inflammatory pathways in the brain.

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.

Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice.

Wakatsuki, Koji, Kiryu-Seo, Sumiko, Yasui, Masaya et al.·Journal of neuroinflammation·2024

Researchers used mice exposed to repeated cold stress to study how chronic pain develops, similar to fibromyalgia. They found that sensory nerve cells (proprioceptors) become overactive and trigger immune cells in the nervous system called microglia to become inflamed. When they reduced microglial activity with a drug, the pain improved, suggesting that this immune activation along nerve pathways may be a key driver of long-lasting pain.

NeuroinflammationImmune System

Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation.

Theoharides, Theoharis C, Twahir, Assma, Kempuraj, Duraisamy·Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology·2024

This study examines mast cells, which are immune cells found throughout the body, and how they may be involved in conditions like ME/CFS that affect the nervous system and cause abnormal heart rate and blood pressure responses. Mast cells sit near nerve endings and important organs, where they can release chemicals that affect how the body regulates basic functions like temperature and blood pressure. The researchers suggest that controlling mast cell activation might help treat these conditions, though currently there are no proven treatments.

NeuroinflammationImmune System

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome.

Qu, Yuan-Yuan, Feng, Chu-Wen, Sun, Zhong-Ren et al.·Zhen ci yan jiu = Acupuncture research·2024

Researchers tested whether electroacupuncture—a traditional needle-based treatment—could help rats with experimentally-induced fatigue syndrome. The treated rats showed improved physical endurance, better memory, and reduced anxiety compared to untreated sick rats. The researchers also found that treatment reduced inflammatory markers in the brain and blood that were elevated in sick rats.

The molecular fingerprint of neuroinflammation in COVID-19: A comprehensive discussion on molecular mechanisms of neuroinflammation due to SARS-COV2 antigens.

Zayeri, Zeinab Deris, Torabizadeh, Mehdi, Kargar, Masoud et al.·Behavioural brain research·2024

This study explains how COVID-19 can damage the brain and nervous system, causing inflammation and injury. The researchers found that about half of people recovering from COVID-19 develop ME/CFS symptoms, and brain scans show reduced activity in key areas that control memory, movement, and mood. The study focuses on the biological mechanisms—essentially how viruses trigger harmful immune responses in the brain that can lead to long-term neurological problems.

NeuroinflammationImmune SystemPost-Exertional Malaise

A Narrative Review on Gut Microbiome Disturbances and Microbial Preparations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for Long COVID.

Jurek, Joanna Michalina, Castro-Marrero, Jesus·Nutrients·2024

This review examines how changes in gut bacteria may contribute to ME/CFS and long COVID symptoms, and whether taking probiotics or similar microbial preparations might help. The authors looked at existing research to understand the connection between gut health and the brain-immune system, and whether restoring healthy gut bacteria could reduce fatigue, inflammation, and other symptoms in these conditions.

Conceptual foundations of acetylcarnitine supplementation in neuropsychiatric long COVID syndrome: a narrative review.

Helbing, Dario Lucas, Dommaschk, Eva-Maria, Danyeli, Lena Vera et al.·European archives of psychiatry and clinical neuroscience·2024

This review examines whether a natural supplement called acetylcarnitine might help treat long COVID symptoms like fatigue, brain fog, and depression. Acetylcarnitine is a substance your body normally makes that helps cells produce energy. The authors looked at research showing this supplement has helped some people with similar illnesses like ME/CFS and depression, and they propose studying whether it could help long COVID patients too.

NeuroinflammationPost-Exertional Malaise

Current update on the neurological manifestations of long COVID: more questions than answers.

Stefanou, Maria-Ioanna, Panagiotopoulos, Evangelos, Palaiodimou, Lina et al.·EXCLI journal·2024

This review examines the nerve and brain-related symptoms that can persist after COVID-19 infection, which doctors call long COVID. About one-third of COVID-19 survivors experience lasting neurological problems such as fatigue, brain fog, sleep issues, and problems with smell or taste that can last at least 12 months. The authors discuss what we currently know about why these symptoms happen and what treatments might help.

Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers-Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation.

Ramírez-Paesano, Carlos, Rodiera Clarens, Claudia, Sharp Segovia, Allan et al.·Orphanet journal of rare diseases·2023

Some people with Ehlers-Danlos syndrome (a connective tissue disorder) develop neck instability that causes severe pain and fatigue similar to ME/CFS. This review examines how doctors can better manage pain during and after neck surgery in these patients by using less opioid medication and combining multiple pain-relief strategies instead, because opioids often don't work well and can actually make pain worse in these cases.

[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

Zhong, Xiao-Ling, Tong, Bo-Ying, Yang, Yi-Han et al.·Zhen ci yan jiu = Acupuncture research·2023

This study tested whether a non-invasive electrical stimulation treatment applied to specific acupuncture points could help rats with chronic fatigue improve their memory and learning. Researchers found that the treatment reduced fatigue symptoms and improved memory performance in fatigued rats, possibly by protecting brain cells in the memory center of the brain.