Evidence browser

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 requiredCase-Control

An unusual presentation of Kikuchi-Fujimoto disease.

Van den Bergh, Magali, Bauer, Frank A, Posteraro, Anthony F et al.·Connecticut medicine·2014

This report describes one patient with a rare condition called Kikuchi-Fujimoto disease (KFD), which causes swollen lymph nodes and fever. What makes this case unusual is that the patient also had fibromyalgia and ME/CFS, and her lymph node swelling was in an atypical location. The patient improved with steroid treatment, though her symptoms returned a few months later and responded well to treatment again.

Prolonged school non-attendance in adolescence: a practical approach.

Hawkrigg, S, Payne, D N·Archives of disease in childhood·2014

This article discusses why some teenagers stop attending school and how doctors can help them return. The authors explain that missing school can lead to serious problems like depression and difficulties with relationships and jobs later in life. They suggest a practical framework for understanding why a student is absent and developing a plan to help them go back to school.

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.

Identification of a novel anti-inflammatory compound, α-cubebenoate from Schisandra chinensis.

Kang, Saeromi, Lee, Kyoung-Pil, Park, Soo-Jin et al.·Journal of ethnopharmacology·2014

Researchers tested a natural compound called α-cubebenoate, found in a traditional plant called Schisandra chinensis, to see if it could reduce inflammation. In laboratory tests with immune cells and in mice, the compound successfully reduced the production of inflammatory molecules that are believed to contribute to fatigue and illness. This suggests the plant compound may have potential as a treatment for conditions involving excessive inflammation.

E3 PreliminaryMechanismPEM unclearMechanistic

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.

Effect of trimethylgallic acid esters against chronic stress-induced anxiety-like behavior and oxidative stress in mice.

Dhingra, Mamta Sachdeva, Dhingra, Sameer, Kumria, Rachna et al.·Pharmacological reports : PR·2014

This study tested whether a new compound derived from gallic acid (a plant antioxidant) could help reverse the harmful effects of chronic stress in mice. Researchers stressed mice by making them swim daily for 15 days, then treated them with the compound and measured changes in anxiety, memory, and harmful molecules in the brain. The treated mice showed improvements in movement, reduced anxiety, better memory, and lower levels of inflammation compared to untreated stressed mice.

Spectrum of mast cell activation disorders.

Petra, Anastasia I, Panagiotidou, Smaro, Stewart, Julia M et al.·Expert review of clinical immunology·2014

Mast cells are immune cells that can become overactive and release chemicals causing symptoms like flushing, itching, dizziness, stomach problems, headaches, and brain fog. This review describes different types of mast cell activation disorders and explains how they can overlap with conditions like ME/CFS and fibromyalgia. The authors suggest these conditions exist on a spectrum and outline how doctors can test for and treat them.

E3 PreliminaryCohortPEM unclearCase-Control

Metals as a common trigger of inflammation resulting in non-specific symptoms: diagnosis and treatment.

Stejskal, Vera·The Israel Medical Association journal : IMAJ·2014

This small study looked at whether metal allergies might trigger or worsen ME/CFS and fibromyalgia symptoms. Researchers tested 5 patients (3 with ME/CFS, 2 with fibromyalgia) who suspected metals were making them sick, and found that most had immune reactions to metals in dental fillings or surgical implants. When these metal sources were removed, patients reported long-term improvement in their symptoms.

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

The effective mechanism of the polysaccharides from Panax ginseng on chronic fatigue syndrome.

Wang, Jia, Sun, Chengxin, Zheng, Yan et al.·Archives of pharmacal research·2014

Researchers tested a compound extracted from ginseng called WGPA-A in mice to see if it could help reduce fatigue. They found that mice given WGPA-A could swim longer before becoming tired, and the treatment reduced signs of cellular damage (oxidative stress) and improved the health of mitochondria—the energy-producing structures inside muscle cells. This suggests ginseng compounds might help fight fatigue by protecting cells from damage.

Energy Metabolism

Modeling Bivariate Longitudinal Hormone Profiles by Hierarchical State Space Models.

Liu, Ziyue, Cappola, Anne R, Crofford, Leslie J et al.·Journal of the American Statistical Association·2014

This study developed a new statistical method to track how stress hormones change over time in people with ME/CFS and fibromyalgia. The researchers found that in patients with these conditions, the two main stress hormones (ACTH and cortisol) don't work together as well as they do in healthy people, suggesting their stress-response system may function differently.

Endocrine Disruption

The saga of XMRV: a virus that infects human cells but is not a human virus.

Arias, Maribel, Fan, Hung·Emerging microbes & infections·2014

In 2006, scientists discovered a virus called XMRV and thought it might cause both prostate cancer and chronic fatigue syndrome (ME/CFS). After years of research and controversy, it became clear that XMRV was not actually infecting humans naturally. Instead, the virus had accidentally been created in a laboratory when human cancer cells were grown inside immunocompromised mice, where two mouse viruses combined to form XMRV. This discovery was important because it showed why initial findings linking XMRV to these diseases were false.

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Effect of compound bushen recipe on chronic fatigue syndrome in C. elegans: an experimental study].

Nie, Li-jin, Cai, Wai-jiao, Zhang, Xin-min et al.·Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine·2014

Researchers tested a traditional Chinese herbal recipe called compound bushen recipe (CBR) in a simple organism (C. elegans) to see if it could help with stress tolerance and lifespan—similar to what happens in chronic fatigue syndrome. The treatment showed promising results: it helped organisms survive better under heat stress, protein damage, and oxidative stress, and improved movement and feeding behaviors without harming reproduction.

Metabolism in chronic fatigue syndrome.

Armstrong, Christopher W, McGregor, Neil R, Butt, Henry L et al.·Advances in clinical chemistry·2014

This review examines how the body produces and uses energy in people with ME/CFS. Research suggests that people with ME/CFS have problems with how their bodies break down food and nutrients for energy, and their cells may not be using their energy factories (mitochondria) efficiently. The review highlights that metabolomics—a technique that measures thousands of molecules in the body at once—could be a powerful tool for understanding what goes wrong in ME/CFS.

Energy Metabolism

E3 PreliminaryBehavioralPEM not requiredLongitudinal

Mechanisms of change underlying the efficacy of cognitive behaviour therapy for chronic fatigue syndrome in a specialist clinic: a mediation analysis.

Stahl, D, Rimes, K A, Chalder, T·Psychological medicine·2014

This study looked at how cognitive behavioral therapy (CBT) works for ME/CFS by following 389 patients over a year. The researchers found that when patients reduced their avoidance behaviors, their fearful beliefs about activity decreased, which in turn helped reduce fatigue and improve their ability to engage socially. This suggests CBT's benefits come partly from changing how people think about and approach activity.

E3 PreliminaryMechanismPEM unclearCross-Sectional

DNA methylation modifications associated with chronic fatigue syndrome.

de Vega, Wilfred C, Vernon, Suzanne D, McGowan, Patrick O·PloS one·2014

This study looked at chemical tags attached to DNA (called methylation) in the blood cells of people with ME/CFS compared to healthy people. The researchers found that people with ME/CFS have differences in these chemical tags on genes related to immune function, energy production, and cell signaling. These differences might help explain why the immune system and energy systems aren't working properly in ME/CFS.

E3 PreliminaryCohortPEM unclearCase-Control

Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the 'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA).

Agmon-Levin, Nancy, Zafrir, Yaron, Kivity, Shaye et al.·Immunologic research·2014

This study looked at 19 people who developed chronic fatigue syndrome (CFS) or fibromyalgia (FM) after receiving the hepatitis B vaccine. Researchers found that most patients experienced multiple symptoms including fatigue, muscle/joint pain, and neurological problems within weeks to months of vaccination. The study suggests that in some cases, these conditions may be triggered by the vaccine's components, particularly in people with genetic predisposition to autoimmune diseases.

E3 PreliminaryCohortPEM not requiredCase-Control

[Effect of acupuncture intervention on learning-memory ability and cerebral superoxide dismutase activity and malonaldehyde concentration in chronic fatigue syndrome rats].

Liu, Chang-zheng, Lei, Bo·Zhen ci yan jiu = Acupuncture research·2013

Researchers tested whether acupuncture could help rats with chronic fatigue syndrome (CFS) learn and remember better. They found that acupuncture improved memory performance in fatigued rats and also increased protective molecules in the brain while reducing harmful ones, suggesting acupuncture may work by protecting brain cells from oxidative damage.

Cognitive Impairment

[A case of lyme disease requiring over 1 year to diagnose at an infectious-disease clinic].

Iwata, Kentaro, Shimada, Tomoe, Kawabata, Hiroki·Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases·2013

This case report describes a 42-year-old woman who had fever and vague symptoms for years but was initially diagnosed with chronic fatigue syndrome. After 14 months, she developed facial paralysis, which prompted testing that revealed she actually had Lyme disease—an infection spread by tick bites. A month of antibiotics improved her symptoms. The report highlights that Lyme disease is rare in Japan but may be underdiagnosed and should be considered in patients with unexplained fevers.

E3 PreliminaryMechanismPEM not requiredObservational

Acute psychosocial stress-mediated changes in the expression and methylation of perforin in chronic fatigue syndrome.

Falkenberg, Virginia R, Whistler, Toni, Murray, Janna R et al.·Genetics & epigenetics·2013

This study looked at how a stressful situation affects a type of immune cell protein called perforin in people with ME/CFS versus healthy people. Researchers gave both groups a stress test and measured changes in perforin levels and a chemical modification (methylation) that controls whether genes are turned on or off. They found that while both groups increased perforin during stress, people with ME/CFS had a lower peak response and differently regulated perforin levels afterward.