Evidence browser

BiomarkersEnergy Metabolism

Metabolic features of Gulf War illness.

Naviaux, Robert K, Naviaux, Jane C, Li, Kefeng et al.·PloS one·2019

Researchers studied blood samples from Gulf War veterans with chronic illness and compared them to healthy controls. They found that veterans with Gulf War illness had abnormal levels of certain fats in their blood, particularly a type called ceramides and sphingomyelins. Interestingly, while Gulf War illness and ME/CFS share some similar symptom patterns, the chemical changes in the blood are largely opposite between the two conditions.

E2 ModerateCohortPEM not requiredObservational

Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome.

Nguyen, Chinh Bkrong, Kumar, Surendra, Zucknick, Manuela et al.·Brain, behavior, and immunity·2019

This study looked at blood samples from teenagers with ME/CFS to understand how their immune systems and stress-response chemicals differ from healthy teenagers. Researchers found two distinct subgroups of ME/CFS patients based on immune activity and a stress hormone called norepinephrine. Patients with lower norepinephrine levels had more severe fatigue, while those with higher levels showed different patterns of immune dysfunction.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCase-Control

Open Trial of Vitamin B12 Nasal Drops in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Comparison of Responders and Non-Responders.

van Campen, C Linda Mc, Riepma, Klaas, Visser, Frans C·Frontiers in pharmacology·2019

This study tested whether vitamin B12 nasal drops could help people with ME/CFS. Fifty-one patients used the nasal drops for 3 months, and about two-thirds reported feeling better. Those who improved showed increases in their activity levels, better fatigue scores, and significantly higher vitamin B12 levels in their blood. The nasal drops appear to be a practical alternative to vitamin B12 injections for some patients.

Immunosignature Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Günther, Oliver P, Gardy, Jennifer L, Stafford, Phillip et al.·Molecular neurobiology·2019

Researchers used a specialized test to examine antibodies (immune proteins) in the blood of people with ME/CFS and healthy controls. They found a pattern of 256 specific protein signatures in ME/CFS patients' blood that was different from healthy people. This suggests the immune system may be reacting to past infections in a way that could help doctors diagnose ME/CFS in the future.

E2 ModerateCohortPEM not requiredObservational

Unexplained exertional intolerance associated with impaired systemic oxygen extraction.

Melamed, Kathryn H, Santos, Mário, Oliveira, Rudolf K F et al.·European journal of applied physiology·2019

This study examined 313 patients with unexplained exercise intolerance using specialized heart and lung testing. Researchers found that about 12.5% of these patients have trouble exercising because their muscles cannot extract and use oxygen properly from the bloodstream, rather than having heart or lung problems. In these patients, the blood remained less acidic during exercise and had higher oxygen levels than expected, suggesting the muscles simply weren't using the available oxygen efficiently.

Post-Exertional Malaise

General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity.

Irwin, John B, Baldwin, A L, Stenberg, Virgil I·Journal of inflammation research·2019

This study tested whether people with various chronic inflammatory conditions, including ME/CFS, could safely manage their own low-dose hydrocortisone treatment by adjusting it based on symptom flares. Over 2,000 participants achieved an average 76% improvement in symptoms while taking about 12 mg of hydrocortisone daily, and no serious side effects were reported.

Interventions

E2 ModerateBehavioralPEM not requiredCross-Sectional

Cognitive and behavioral coping in people with Chronic fatigue syndrome: An exploratory study searching for intervention targets for depressive symptoms.

Kraaij, Vivian, Bik, Janneke, Garnefski, Nadia·Journal of health psychology·2019

This study looked at how 30 people with ME/CFS cope with depression by using different thinking and behavior strategies. The researchers found that the way people think about and reframe their problems has a bigger impact on depression than what they do. Focusing on positive aspects, looking at problems in a different light, and avoiding catastrophizing (imagining the worst) seemed to help the most.

Cognitive Impairment

Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients.

Blomberg, Jonas, Rizwan, Muhammad, Böhlin-Wiener, Agnes et al.·Frontiers in immunology·2019

This study looked for evidence that common viruses called herpesviruses might be reactivated or causing problems in ME/CFS patients. Researchers tested blood samples from ME/CFS patients and healthy people to measure immune responses (antibodies) against several herpesviruses. While the overall antibody levels were similar between the two groups, the study found subtle differences in how ME/CFS patients' immune systems reacted to a few specific herpesvirus proteins.

E2 ModerateBehavioralPEM not requiredCase-Control

Cognitive and behavioural responses to symptoms in adolescents with chronic fatigue syndrome: A case-control study nested within a cohort.

Loades, Maria Elizabeth, Rimes, Katharine, Lievesley, Kate et al.·Clinical child psychology and psychiatry·2019

This study looked at how adolescents with ME/CFS think about and respond to their symptoms, compared to teenagers with asthma. Researchers found that young people with ME/CFS tend to have unhelpful thought patterns—like believing symptoms cause permanent damage—and unhelpful behaviors like pushing through activity or avoiding it completely. These unhelpful patterns were linked to more fatigue and disability over a 3-month follow-up period.

Cognitive Impairment

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome.

Sweetman, Eiren, Ryan, Margaret, Edgar, Christina et al.·International journal of immunopathology and pharmacology·2019

Researchers studied blood immune cells from 10 ME/CFS patients and 10 healthy people to understand what's different at the genetic level. They found that several genes related to inflammation were more active in ME/CFS patients, and genes related to energy production and circadian rhythms (your body's internal clock) showed abnormal patterns. These findings suggest ME/CFS involves multiple biological systems working incorrectly at the same time.

E2 ModerateCohortPEM not requiredCross-Sectional

Evidence for similarity in symptoms and mechanism: The extra-pulmonary symptoms of severe asthma and the polysymptomatic presentation of fibromyalgia.

Hyland, Michael E, Lanario, Joseph W, Wei, Yinghui et al.·Immunity, inflammation and disease·2019

This study found that people with severe asthma report many symptoms beyond breathing problems—such as fatigue, pain, and digestive issues—that are very similar to symptoms seen in fibromyalgia and chronic fatigue syndrome. The researchers compared symptom patterns between asthma patients and people with various functional disorders, finding that asthma and fibromyalgia symptoms were 75% similar in type and pattern. This suggests these conditions may share common underlying mechanisms related to how the body's systems interact.

E2 ModerateCohortPEM requiredObservational

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome.

Lien, Katarina, Johansen, Bjørn, Veierød, Marit B et al.·Physiological reports·2019

This study looked at how the bodies of ME/CFS patients handle repeated exercise tests done 24 hours apart. Researchers measured how much oxygen patients used and tracked a substance called lactate in their blood during exercise. They found that ME/CFS patients performed worse on the second test and had higher lactate levels, opposite to what happened in healthy people, whose bodies actually recovered better the second time.

Post-Exertional Malaise

E2 ModerateDiagnosticPEM not requiredLongitudinal

A Validated Scale for Assessing the Severity of Acute Infectious Mononucleosis.

Katz, Ben Z, Reuter, Caroline, Lupovitch, Yair et al.·The Journal of pediatrics·2019

Researchers created a simple scoring system to measure how severe a case of infectious mononucleosis (mono) is when someone first gets sick. They found that students with higher severity scores were more likely to need hospitalization or steroid treatment, and importantly, those with higher scores were also more likely to develop ME/CFS within 6 months after their mono infection.

E2 ModerateCohortPEM unclear

MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants.

Venter, Marianne, Tomas, Cara, Pienaar, Ilse S et al.·Scientific reports·2019

This study looked at mitochondrial DNA (the genetic material in the energy-producing parts of our cells) in people with ME/CFS to see if differences in this DNA might help explain the condition. Researchers compared DNA samples from ME/CFS patients in the UK and South Africa to look for variations. Interestingly, they found that ME/CFS patients were less likely to have certain common genetic variations that most people carry, but they did not find any confirmed disease-causing mutations.

Energy Metabolism

Autonomic dysfunction in myalgic encephalomyelitis and chronic fatigue syndrome: comparing self-report and objective measures.

Kemp, Jane, Sunnquist, Madison, Jason, Leonard A et al.·Clinical autonomic research : official journal of the Clinical Autonomic Research Society·2019

This study looked at whether ME/CFS patients experience problems with their autonomic nervous system—the part that controls heart rate, blood pressure, and other automatic body functions. The researchers compared what patients reported about their symptoms with objective medical tests to see if these matched up, helping doctors understand this aspect of ME/CFS better.

Autonomic Nervous System

E2 ModerateCohortPEM requiredCross-Sectional

Deconstructing post-exertional malaise: An exploratory factor analysis.

McManimen, Stephanie L, Sunnquist, Madison L, Jason, Leonard A·Journal of health psychology·2019

This study looked at post-exertional malaise (PEM)—the worsening of symptoms that happens after physical activity in ME/CFS—to understand whether it is one unified experience or two different types. The researchers found that PEM actually consists of two separate experiences: a whole-body fatigue and a muscle-specific fatigue. This suggests that PEM is more complex than previously thought and may need to be understood as having distinct components.

Post-Exertional Malaise

E2 ModerateCohortPEM not requiredCross-Sectional

Artificial intelligence based discovery of the association between depression and chronic fatigue syndrome.

Zhang, Feilong, Wu, Chuanhong, Jia, Caixia et al.·Journal of affective disorders·2019

This study looked at whether depression and chronic fatigue syndrome (CFS) share common biological markers in the blood and urine. Researchers used advanced chemical testing and artificial intelligence to analyze samples from 295 people and found that depression and CFS have some overlapping chemical signatures, though they also have distinct differences. The findings suggest these two conditions may be more closely related than previously thought.

Biomarkers

E2 ModerateCohortPEM not requiredCross-Sectional

Physical activity patterns among children and adolescents with mild-to-moderate chronic fatigue syndrome/myalgic encephalomyelitis.

Solomon-Moore, Emma, Jago, Russell, Beasant, Lucy et al.·BMJ paediatrics open·2019

This study looked at how much physical activity children and teenagers with mild-to-moderate ME/CFS actually do each day using movement trackers. Most young people with ME/CFS were doing much less activity than health guidelines recommend, but the researchers found three different activity groups: some were more active, some did light activity, and some were mostly inactive. Interestingly, those doing some light activity felt they could function better and had less fatigue, though those doing more activity sometimes reported more anxiety.

Clinical symptoms and markers of disease mechanisms in adolescent chronic fatigue following Epstein-Barr virus infection: An exploratory cross-sectional study.

Kristiansen, Miriam Skjerven, Stabursvik, Julie, O'Leary, Elise Catriona et al.·Brain, behavior, and immunity·2019

This study looked at adolescents who had Epstein-Barr virus (EBV) infection and tracked whether they developed chronic fatigue 6 months later. Researchers found that those with ongoing fatigue had more symptoms overall, but blood tests and heart-monitoring showed only small differences compared to those who recovered—mainly slightly higher inflammation markers and changes in nervous system activity. The study suggests that post-EBV fatigue in teenagers involves subtle changes in the body's stress and immune systems, even though the virus itself had cleared.