Evidence browser

Novel characterization of endogenous transient receptor potential melastatin 3 ion channels from Gulf War Illness participants.

Marshall-Gradisnik, Sonya, Martini Sasso, Etianne, Eaton-Fitch, Natalie et al.·PloS one·2024

This study looked at a specific protein channel (TRPM3) in immune cells called natural killer cells from Gulf War veterans with GWI and compared them to healthy people. The researchers found that TRPM3 doesn't work properly in the Gulf War veterans' cells, whereas it functions normally in healthy people. This finding is important because the same problem with TRPM3 has been seen in ME/CFS patients, suggesting these two illnesses might share a common biological issue.

Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone.

Löhn, Matthias, Wirth, Klaus Josef·Journal of translational medicine·2024

This study explores how a specific ion channel called TRPM3, which helps control pain signals and immune cell function, may not work properly in ME/CFS patients. The researchers found that immune cells called natural killer cells have reduced function due to TRPM3 problems, and a medication called low-dose naltrexone (LDN) may help restore this function in laboratory tests. This could explain why some ME/CFS patients report feeling better with LDN treatment.

E3 PreliminaryCommentaryPEM unclear

False Alarm: XMRV, Cancer, and Chronic Fatigue Syndrome.

Coffin, John M, Kearney, Mary F·Annual review of virology·2024

In 2009, scientists found a virus called XMRV in some people with ME/CFS, which created excitement that they might have discovered a cause of the illness. However, when researchers around the world tried to confirm this finding, they repeatedly could not—and eventually realized the virus had contaminated the laboratory samples with mouse virus rather than coming from patients. This article tells the story of how this discovery was made, why it turned out to be false, and what we learned from this experience.

E3 PreliminaryMechanismPEM not requiredMechanistic

Current understanding of nociplastic pain.

Yoo, Yeong-Min, Kim, Kyung-Hoon·The Korean journal of pain·2024

This article explains 'nociplastic pain'—a type of chronic pain that occurs when the nervous system becomes overly sensitive to pain signals, even when there is no obvious tissue damage or nerve injury. People with ME/CFS, fibromyalgia, and similar conditions often experience this kind of pain. The article describes how doctors can recognize nociplastic pain and groups it with other conditions that share this same underlying mechanism of nervous system sensitivity.

Pain and Sensitization

Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway.

Zheng, Yuan, Ren, Xueyang, Qi, Xiaodan et al.·Journal of ethnopharmacology·2024

This study tested a traditional Chinese herbal medicine called Baoyuan Decoction (BYD) to see if it could reduce fatigue in zebrafish models. The researchers found that BYD contains 114 active compounds and appeared to reduce fatigue, inflammation, and oxidative stress by activating specific cellular pathways related to energy metabolism and the body's internal clock.

Investigation into the restoration of TRPM3 ion channel activity in post-COVID-19 condition: a potential pharmacotherapeutic target.

Sasso, Etianne Martini, Muraki, Katsuhiko, Eaton-Fitch, Natalie et al.·Frontiers in immunology·2024

This study looked at a tiny channel (called TRPM3) that sits on immune cells called NK cells, which help fight infections. Researchers found that both ME/CFS and post-COVID patients have a broken version of this channel. Importantly, they discovered that a drug called naltrexone (NTX) could fix this broken channel in lab-grown cells from post-COVID patients, suggesting it might help real patients feel better.

E3 PreliminaryDiagnosticPEM requiredMethods-Paper

Immunometabolic changes and potential biomarkers in CFS peripheral immune cells revealed by single-cell RNA sequencing.

Sun, Yujing, Zhang, Zhenhua, Qiao, Qincheng et al.·Journal of translational medicine·2024

Researchers used advanced cell analysis to examine immune cells from the blood of 4 ME/CFS patients and 4 healthy people. They found that ME/CFS patients have an unusual mix of immune cells, with too many T cells but too few natural killer cells and other immune cells that normally fight infections. Some of their immune cells also show signs of overactivity while others seem weakened, and the researchers identified a potential blood test marker that could help diagnose ME/CFS.

BiomarkersImmune System

Assessing Functional Capacity in Myalgic Encephalopathy/Chronic Fatigue Syndrome: A Patient-Informed Questionnaire.

Sommerfelt, Kristian, Schei, Trude, Seton, Katharine A et al.·Journal of clinical medicine·2024

Researchers created a new questionnaire called FUNCAP to measure how much people with ME/CFS can actually do in their daily lives. The tool has two versions: a longer one with 55 questions (for doctors and disability assessments) and a shorter one with 27 questions (for regular check-ups). After testing it with thousands of patients from Norway and around the world, they found it works reliably and accurately captures the impact of ME/CFS on real-life activities.

Post-Exertional Malaise

E3 PreliminaryPEM unclear

A suffering body, hidden away from others: The experience of being long-term bedridden with severe myalgic encephalomyelitis/chronic fatigue syndrome in childhood and adolescence.

Krabbe, Silje Helen, Bjorbækmo, Wenche Schrøder, Mengshoel, Anne Marit et al.·Nursing inquiry·2024

This study explored how young women experienced being severely ill with ME/CFS during their teenage years, looking back from a point where they had recovered or improved. Researchers interviewed 13 women aged 16-29 about their memories of being bedridden and isolated. The study found that patients often felt caught between wanting company and needing to be alone, experienced their bodies as fragile and unstable, endured long periods of darkness and isolation, and eventually had to make sense of these painful memories as they recovered.

Severe ME

E3 PreliminaryMechanismPEM unclearCross-Sectional

Dysregulation of the Kynurenine Pathway, Cytokine Expression Pattern, and Proteomics Profile Link to Symptomology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Kavyani, Bahar, Ahn, Seong Beom, Missailidis, Daniel et al.·Molecular neurobiology·2024

This study found that ME/CFS patients have imbalances in a particular chemical pathway in their body (the kynurenine pathway) that appears connected to inflammation and symptom severity. The researchers discovered that higher levels of one early chemical in this pathway correlated with worse symptoms, while lower levels of later chemicals in the pathway might affect how cells produce energy. Interestingly, they also found that five of the most significantly changed proteins in ME/CFS patients are involved in gut health, suggesting the gut microbiome may play an important role in the disease.

BiomarkersGut MicrobiomeEnergy MetabolismImmune System

Exploring the shared mechanism of fatigue between systemic lupus erythematosus and myalgic encephalomyelitis/chronic fatigue syndrome: monocytic dysregulation and drug repurposing.

Zheng, Daisi, Li, Xiaolong, Wang, Peicheng et al.·Frontiers in immunology·2024

Researchers discovered that ME/CFS and lupus (SLE) may share similar immune problems, particularly involving immune cells called monocytes that become overactive and produce excess inflammation. By studying genes and immune cells from both diseases, they identified five key inflammatory proteins that appear important in fatigue, and they predict that certain existing drugs—particularly N-acetyl-L-cysteine and camptothecin—might help reduce this inflammation.

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.

E3 PreliminaryCommentaryPEM requiredEditorial

Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla.

Godlewska, Beata R, Sylvester, Amy L, Emir, Uzay E et al.·Nutrients·2024

Researchers gave 11 people with ME/CFS a creatine supplement (a natural substance that helps cells produce energy) for 6 weeks. Brain scans showed the supplement increased creatine levels in key brain regions, and participants reported feeling less fatigued, had faster reaction times on thinking tests, and showed stronger hand grip strength. The supplement was well tolerated with no side effects reported.

Cognitive Impairment

Attenuating post-exertional malaise in Myalgic encephalomyelitis/chronic fatigue syndrome and long-COVID: Is blood lactate monitoring the answer?

Faghy, Professor Mark A, Ashton, Dr Ruth Em, McNelis, Mr Robin et al.·Current problems in cardiology·2024

This editorial discusses whether measuring blood lactate levels could help manage post-exertional malaise (PEM)—the debilitating fatigue that occurs after physical activity in ME/CFS and long-COVID patients. The authors suggest that blood lactate monitoring might help identify safe exercise limits and prevent PEM crashes. However, this is an opinion piece rather than a research study with new data.

BiomarkersPost-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

E3 PreliminaryCohortPEM unclearCase-Control

Longitudinal cytokine and multi-modal health data of an extremely severe ME/CFS patient with HSD reveals insights into immunopathology, and disease severity.

Jahanbani, Fereshteh, Sing, Justin Cyril, Maynard, Rajan Douglas et al.·Frontiers in immunology·2024

This study tracked one very severely ill ME/CFS patient over time, measuring immune system markers and detailed health information. Researchers found that the patient's immune system was shifted toward a Th2-type response (typically seen in allergies), with unusually high levels of certain immune chemicals. The study also introduced new smartphone apps to help patients and doctors track symptoms and treatment responses in real time.

E3 PreliminaryMechanismPEM not requiredLongitudinal

The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability.

Tankisi, Hatice, Versace, Viviana, Kuppuswamy, Annapoorna et al.·Clinical neurophysiology practice·2024

This review article explains how doctors and researchers can better understand fatigue and 'fatigability'—the reduced ability to sustain physical or mental effort. The authors describe different types of tests that can measure these problems objectively by looking at how the brain, nerves, and muscles work, rather than relying only on what patients report. These specialized tests may help identify the actual cause of fatigue in different conditions, including long COVID and ME/CFS.

Time-dependent complexity characterisation of activity patterns in patients with Chronic Fatigue Syndrome.

Rabaey, Paloma, Decat, Peter, Heytens, Stefan et al.·BioPsychoSocial medicine·2024

Researchers tracked the physical activity patterns of 7 ME/CFS patients over 3 weeks to see if the complexity of how they move changes over time and relates to how well they're functioning. They found that each patient's activity complexity varied significantly from week to week, and these changes didn't consistently match whether patients reported feeling better or worse. This suggests that measuring activity patterns alone may not be a reliable way to track how ME/CFS patients are doing.

Autonomic Nervous System

Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.

Ruiz-Pablos, Manuel, Paiva, Bruno, Zabaleta, Aintzane·Frontiers in immunology·2024

This review proposes that ME/CFS, long COVID, and post-vaccine syndrome may share a common cause: an immune system problem that damages the pituitary gland (a small gland that controls many hormones). The researchers suggest that in genetically susceptible people, a weak initial response to viruses can lead to an overactive immune response that mistakenly attacks the body's own pituitary gland, lowering levels of crucial hormones like cortisol. They propose that treatments like antivirals, steroids, and antioxidants might help by reducing inflammation and restoring hormone balance.

E3 PreliminaryCohortPEM unclearCase-Control

Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report.

Burgard, Harald·International medical case reports journal·2024

This case report describes one woman with ME/CFS for over 15 years who underwent a blood-cleaning treatment called double-filtration apheresis eight times over two years. After treatment, she experienced significant improvement in her fatigue, thinking problems, and other symptoms, with benefits that lasted over time. While this is promising, it is based on just one patient's experience and needs much larger studies to confirm whether this treatment works for others with ME/CFS.