Evidence browser

The emerging role of autoimmunity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs).

Morris, Gerwyn, Berk, Michael, Galecki, Piotr et al.·Molecular neurobiology·2014

This study explores how ME/CFS may involve the immune system attacking the body's own tissues (autoimmunity). Researchers found that up to 60% of ME/CFS patients show signs of autoimmune responses, likely triggered by a combination of stress on cells, viral infections, and problems with how the body produces energy. The study identifies several pathways that could lead to these harmful immune reactions and discusses potential treatments.

NeuroinflammationGut MicrobiomeImmune System

The gut microbiome and the brain.

Galland, Leo·Journal of medicinal food·2014

Your gut bacteria can communicate with your brain in several ways: they produce substances that trigger your immune system, create chemicals that affect your mood and sleep, and send signals directly to your brain through a major nerve called the vagus nerve. When the balance of gut bacteria is disrupted, this communication can go wrong and may contribute to problems like chronic fatigue, brain fog, and mood changes.

E3 PreliminaryMechanismPEM unclearMechanistic

Restraint Induces Sickness Responses Independent of Injection with Epstein-Barr Virus (EBV)-Encoded dUTPase.

Aubrecht, Taryn G, Abi Salloum, Bachir, Ariza, Maria Eugenia et al.·Journal of behavioral and brain science·2014

This study looked at how stress and a virus protein linked to ME/CFS affect sickness symptoms in mice. Researchers gave mice either saline or a protein made by Epstein-Barr virus, then exposed some mice to restraint stress for either 1 or 3 days. Surprisingly, restraint stress alone caused sickness-like symptoms after 3 days, regardless of whether mice received the virus protein, and the virus protein didn't make stress effects worse.

A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome.

Craddock, Travis J A, Fritsch, Paul, Rice, Mark A et al.·PloS one·2014

This study explored how the body's stress-response system (the HPA axis) may become stuck in a dysfunctional state in ME/CFS and Gulf War Illness, interacting with sex hormones and immune function. Using computer models based on known biology, researchers found that men with Gulf War Illness showed a pattern of high cortisol and low testosterone, while women with ME/CFS showed low cortisol and high estradiol—suggesting the body gets trapped in alternate 'stuck' settings. These findings suggest that treatments might work by helping the body escape these abnormal states.

E3 PreliminaryReviewPEM not requiredReview-Narrative

The developmental basis of epigenetic regulation of HTR2A and psychiatric outcomes.

Paquette, Alison G, Marsit, Carmen J·Journal of cellular biochemistry·2014

This article examines how a gene called HTR2A, which helps control serotonin (a brain chemical), can be chemically modified in ways that affect brain development and mental health. Researchers found that these modifications can happen before birth—even in the placenta—and may influence how our brains develop, potentially affecting conditions like depression, anxiety, and other mental health disorders. The article suggests these changes might also be linked to chronic fatigue syndrome, though more research is needed to understand how and why.

E3 PreliminaryMechanismPEM not requiredObservational

Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome.

Loebel, Madlen, Strohschein, Kristin, Giannini, Carolin et al.·PloS one·2014

This study looked at how the immune system responds to Epstein-Barr virus (EBV), a common virus that causes mono, in people with ME/CFS compared to healthy controls. Researchers found that ME/CFS patients have a weaker immune response to EBV, particularly in their B cells and T cells—the immune cells that normally fight off this virus. The findings suggest that ME/CFS patients may have difficulty controlling EBV reactivation in their bodies.

Main neuroendocrine features, diagnosis and therapeutic possibilities in the chronic fatigue syndrome, an underdiagnosed entity.

Amihăesei, Ioana Cristina, Cojocaru, Elena·Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi·2014

ME/CFS is a serious illness marked by extreme tiredness that doesn't improve with rest, along with problems concentrating, pain, and worsening symptoms after activity. Diagnosis requires at least six months of severe fatigue plus four or more other specific symptoms. Current treatments focus on behavioral approaches and pacing rather than medications, though only about 5% of people fully recover, and more than half become unable to work.

Post-Exertional Malaise

NeuroinflammationImmune System

The glutathione system: a new drug target in neuroimmune disorders.

Morris, Gerwyn, Anderson, George, Dean, Olivia et al.·Molecular neurobiology·2014

This review examines glutathione (GSH), a naturally occurring substance in our cells that protects against damage and helps our immune system work properly. When glutathione levels drop, cells become more stressed and inflamed, which may contribute to ME/CFS and other conditions affecting the brain and immune system. The authors suggest several potential treatments—including supplements like N-acetyl cysteine and natural compounds like curcumin—that might help restore glutathione levels.

[Effect of manual acupuncture stimulation of "Baihui" (GV 20), etc. on serum IFN-gamma and IL-4 contents in rats with chronic fatigue syndrome].

Wang, Chao, Xie, Wen-juan, Liu, Mi et al.·Zhen ci yan jiu = Acupuncture research·2014

Researchers tested whether acupuncture could help rats with fatigue by measuring immune system markers called IFN-gamma and IL-4. Rats that received acupuncture showed improved balance in these immune markers compared to untreated rats with fatigue, suggesting acupuncture may help restore immune function in chronic fatigue syndrome.

E3 PreliminaryBehavioralPEM unclearCross-Sectional

Couples' experiences of interacting with outside others in chronic fatigue syndrome: a qualitative study.

Brooks, Joanna, King, Nigel, Wearden, Alison·Chronic illness·2014

This study looked at how ME/CFS affects not just patients, but also their spouses or partners who live with them. Researchers interviewed two couples to understand their experiences, focusing on how they interact with doctors and people outside their home. The key finding was that both patients and their partners struggle with how others—whether healthcare providers or friends—understand and respond to ME/CFS, and these outside interactions significantly affect how couples cope together.

E3 PreliminaryCohortPEM not requiredCase-Control

Valacyclovir treatment of chronic fatigue in adolescents.

Henderson, Theodore A·Advances in mind-body medicine·2014

This study looked at 15 young people who were referred for treatment-resistant depression but were found to have ME/CFS instead. When treated with an antiviral medication called valacyclovir, 93% of them improved significantly, with fatigue scores dropping substantially. The study suggests that some cases of depression in teenagers may actually be undiagnosed ME/CFS caused by chronic viral infections.

E3 PreliminaryMechanismPEM requiredObservational

Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment.

Keller, Betsy A, Pryor, John Luke, Giloteaux, Ludovic·Journal of translational medicine·2014

This study tested whether people with ME/CFS can perform the same on an exercise test when it's repeated the next day, similar to how healthy people typically do. The researchers found that ME/CFS patients performed significantly worse on the second test—using about 14% less oxygen and doing about 12% less work—even though they were trying their hardest both times. This suggests that doing one exercise test may give doctors an unrealistic picture of what ME/CFS patients can actually do.

Post-Exertional Malaise

NeuroinflammationImmune System

Induction of interleukin-1β by activated microglia is a prerequisite for immunologically induced fatigue.

Ifuku, Masataka, Hossain, Shamim M, Noda, Mami et al.·The European journal of neuroscience·2014

This study used rats to understand how an immune trigger (a synthetic viral mimic) causes prolonged fatigue. Researchers found that when this trigger activates immune cells in the brain called microglia, they release a chemical messenger called IL-1β that affects how the brain handles serotonin, leading to reduced activity and fatigue-like behavior.

E3 PreliminaryCohortPEM not requiredCross-Sectional

Diagnosis and management of chronic fatigue syndrome/myalgic encephalitis in black and minority ethnic people: a qualitative study.

Bayliss, Kerin, Riste, Lisa, Fisher, Louise et al.·Primary health care research & development·2014

This study looked at why people from Black and minority ethnic backgrounds are diagnosed with ME/CFS less often than White British people, even though they may have the condition more frequently. Researchers interviewed 35 healthcare workers and stakeholders in northwest England and found many barriers, including lack of awareness about ME/CFS, language difficulties, cultural differences in how symptoms are discussed, and unfair stereotypes about laziness. The study recommends better training for doctors and culturally sensitive patient information to help improve diagnosis rates.

Review: Vitamin D3 deficiency results in dysfunctions of immunity with severe fatigue and depression in a variety of diseases.

Höck, Anna Dorothea·In vivo (Athens, Greece)·2014

This review explains how vitamin D3 deficiency may contribute to severe fatigue and depression in conditions like ME/CFS. Vitamin D3 helps regulate the immune system, and without enough of it, the body's natural defenses become unbalanced, allowing infections and inflammation to persist. The authors suggest that vitamin D3 supplements might help prevent or improve these chronic conditions.

E3 PreliminaryCohortPEM not requiredCross-Sectional

Evaluating Interactive Fatigue Management Workshops for Occupational Health Professionals in the United Kingdom.

Ali, Sheila, Chalder, Trudie, Madan, Ira·Safety and health at work·2014

This study tested whether one-day training workshops could help occupational health professionals (doctors and nurses who work with employers) better understand and manage fatigue and chronic fatigue syndrome (CFS). After the training, these professionals knew more about fatigue and felt more confident diagnosing and treating it in working people, with improvements that lasted at least 4 months.

A Study of the Protective Effect of Triticum aestivum L. in an Experimental Animal Model of Chronic Fatigue Syndrome.

Borah, Mukundam, Sarma, Phulen, Das, Swarnamoni·Pharmacognosy research·2014

Researchers tested whether wheat leaf extract could help mice recover from exhaustion caused by repeated stress. The stressed mice that received the extract showed improved activity levels and reduced anxiety compared to untreated stressed mice, and their brain chemistry improved. This suggests the extract's antioxidant properties may help protect against some effects of chronic fatigue.

Isoflavones inhibit poly(I:C)-induced serum, brain, and skin inflammatory mediators - relevance to chronic fatigue syndrome.

Vasiadi, Magdalini, Newman, Jennifer, Theoharides, Theoharis C·Journal of neuroinflammation·2014

This study tested whether isoflavones (plant compounds found in soy) could reduce inflammation and fatigue-like symptoms in mice exposed to immune triggers and stress. Mice given a high-isoflavone diet showed less activity loss and lower inflammation markers in their blood, brain, and skin compared to mice on regular diet. The findings suggest isoflavones might help reduce some ME/CFS symptoms by calming the body's immune response.

E3 PreliminaryBehavioralPEM unclear

[Moxibustion at Yongquan (KI 1) for sleep disorders of chronic fatigue syndrome].

Chen, Xiao-Qin, Gang, Zhi-Xiu, Xu, Zhi-Peng·Zhongguo zhen jiu = Chinese acupuncture & moxibustion·2013

This study explored whether moxibustion—a traditional Chinese medicine technique involving burning herbs near the skin—might help improve sleep problems in people with ME/CFS. The treatment focused on a specific acupuncture point on the sole of the foot called Yongquan (KI 1). While the study suggests this approach may have helped some patients sleep better, the research quality is limited and more rigorous testing is needed.

Sleep

E3 PreliminaryCohortPEM not requiredCase-Control

α-1 antitrypsin and chronic fatigue syndrome: a case study from pathophysiology to clinical practice.

Alegre, José, Camprubí, Sandra, García-Quintana, Ana·Pain management·2013

Researchers tested whether a protein called alpha-1 antitrypsin (AAT), which naturally reduces inflammation in the body, could help a woman with ME/CFS. She received weekly intravenous infusions for 8 weeks. After treatment, she showed improvements in how much physical work she could do, her memory, and thinking skills, and her inflammatory markers normalized. She was eventually able to return to part-time work.