ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

961–980 of 6,187 studies

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

Lloyd, A R, Hickie, I, Brockman, A et al.·The American journal of medicine·1993

This study tested whether two treatments—an immune-boosting extract and cognitive-behavioral therapy (a talk therapy focused on thoughts and behaviors)—could help people with ME/CFS. Ninety patients received either these treatments, a placebo, or combinations of both in a blinded trial. Neither treatment worked better than placebo, suggesting that the improvement some patients experienced may have been due to placebo effect or natural recovery rather than the specific treatments tested.

Interventions

E1 ReplicatedTrialPEM not requiredRCT

Non-pharmacological approaches to treatment.

Sharpe, M·Ciba Foundation symposium·1993

This study looked at whether talking therapies and behavioral changes could help people with ME/CFS feel better. Researchers tested cognitive behavioral therapy (CBT)—a type of counseling that helps people change unhelpful thought patterns and gradually increase activity—in patients with ME/CFS. Early results showed that most patients receiving CBT improved, especially in their ability to do daily tasks.

E1 ReplicatedTrialPEM not requiredRCT

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

Hickie, I, Lloyd, A, Wakefield, D·The Australian and New Zealand journal of psychiatry·1992

This study examined whether depression and immune system problems in ME/CFS patients are connected. Researchers gave 33 patients with ME/CFS either a high-dose immune treatment or placebo and tracked changes in both mood and immune markers. Patients who received the real treatment showed that when their immune systems improved, their depression symptoms also improved together, suggesting these problems may be linked to the same underlying cause rather than one causing the other.

Immune System

E1 ReplicatedTrialPEM unclearRCT

Chronic fatigue syndrome and chronic primary magnesium deficiency (CFS and CPMD).

Durlach, J·Magnesium research·1992

This study explored whether people with chronic fatigue syndrome (ME/CFS) might have low magnesium levels in their bodies. Magnesium is a mineral that helps muscles and nerves work properly. The researcher examined the connection between magnesium deficiency and ME/CFS symptoms to understand if treating low magnesium could help patients feel better.

Energy Metabolism

E1 ReplicatedTrialPEM not requiredRCT

Red blood cell magnesium and chronic fatigue syndrome.

Cox, I M, Campbell, M J, Dowson, D·Lancet (London, England)·1991

This study tested whether people with ME/CFS have lower magnesium levels in their red blood cells and whether magnesium injections could help them feel better. Researchers compared 20 ME/CFS patients to 20 healthy people and found the patients did have lower magnesium. When 15 ME/CFS patients received weekly magnesium injections for 6 weeks, 12 reported feeling better with more energy and less pain, compared to only 3 out of 17 patients who received a placebo injection.

E1 ReplicatedTrialPEM not requiredRCT

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

Peterson, P K, Shepard, J, Macres, M et al.·The American journal of medicine·1990

Researchers tested whether a blood product called intravenous immunoglobulin G (IV IgG) could help people with ME/CFS by giving it to 28 patients every month for 6 months. Although some patients had low levels of this protein at the start, IV IgG did not improve fatigue, daily functioning, or overall health compared to placebo, even though the treatment restored protein levels to normal.

Immune System

E1 ReplicatedTrialPEM not requiredRCT

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

Lloyd, A, Hickie, I, Wakefield, D et al.·The American journal of medicine·1990

This study tested whether a high-dose immune protein treatment (intravenous immunoglobulin) could help people with ME/CFS. Researchers gave 49 patients either the treatment or placebo and measured changes in fatigue, mood, physical function, and immune markers. More people who received the treatment reported significant improvement and returned to work and activities compared to those who received placebo, suggesting immune system problems may play a role in ME/CFS.

Immune System

E1 ReplicatedTrialPEM not requiredRCT

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome.

Kaslow, J E, Rucker, L, Onishi, R·Archives of internal medicine·1989

Researchers tested a liver extract injection containing folic acid and B12 (a treatment some doctors in Southern California were recommending for ME/CFS) against a placebo injection in 15 ME/CFS patients. Both the real treatment and placebo improved patients' symptoms and function, but there was no meaningful difference between the two groups. The strong response to placebo suggests that patients' expectations and other non-chemical factors may play a significant role in how they experience symptom improvement.

Interventions

E1 ReplicatedTrialPEM not requiredRCT

Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial.

Straus, S E, Dale, J K, Tobi, M et al.·The New England journal of medicine·1988

Researchers tested whether acyclovir, an antiviral drug, could help people with ME/CFS who had signs of past Epstein-Barr virus infection. In this carefully controlled study of 27 patients, about half received the real drug and half received a placebo (fake treatment). After 37 days of treatment, similar numbers of people felt better in both groups—suggesting the drug itself wasn't the reason for improvement.

E2 ModerateCohortPEM requiredCross-Sectional

Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.

Inderyas, Maira, Thapaliya, Kiran, Marshall-Gradisnik, Sonya et al.·Journal of translational medicine·2026

This study used advanced brain imaging to compare how the brains of ME/CFS patients, long COVID patients, and healthy people work during a challenging thinking task. Researchers found that patients' brains show different patterns of communication between regions compared to healthy controls, particularly in areas related to motivation, memory, and emotional processing. These brain differences appeared to worsen as fatigue built up during the task.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearLongitudinal

Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.

Palomo, Irene Mena, Cox, Brandon, Williams, Marshall V et al.·Journal of medical virology·2026

This study found that people with ME/CFS have higher levels of immune responses to three common viruses (EBV, HHV-6, and VZV) compared to healthy people. About 72% of ME/CFS patients showed antibodies to multiple viruses at the same time, versus only 31% of healthy controls. The antibody levels were higher in patients with moderate to severe fatigue, suggesting a possible connection between these viral reactivations and symptom severity.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Understanding concussion in myalgic encephalomyelitis/chronic fatigue syndrome: Findings from the 2023 National Health Interview study.

Sirotiak, Zoe, Adamowicz, Jenna L, Thomas, Emily B K·Brain injury·2026

This study found that people with ME/CFS are nearly 5 times more likely to have had a concussion in the past year compared to people without ME/CFS. People with ME/CFS also experienced more falls and dizziness or balance problems. The researchers suggest that doctors should screen patients with ME/CFS more carefully for concussions and take steps to reduce their concussion risk.

Autonomic Nervous System

E2 ModerateBehavioralPEM not requiredObservational

Obesity and inactivity cluster the strongest risk factor for the development of heart failure in a population-based study.

van Essen, Bart J, Dan, Nathalie Ang En, Tharsana, Ganash N et al.·International journal of cardiology·2026

This study found that people with a combination of obesity and physical inactivity have the highest risk of developing heart failure compared to other groups with different health problems. Researchers followed nearly 7,000 people for about 10 years and identified six distinct groups based on their health conditions, discovering that the obesity and inactivity group had almost 4 times higher risk of heart failure than the healthiest group.

E2 ModerateBehavioralPEM not requiredCross-Sectional

Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.

Saini, Urvi, Aggen, Steven H, Oldehinkel, Albertine J et al.·BMC psychiatry·2026

This study looked at how symptoms of depression, anxiety, ME/CFS, fibromyalgia, and irritable bowel syndrome overlap in over 100,000 people. Researchers found that these conditions share common symptoms like fatigue, sleep problems, and difficulty concentrating—which they call 'general malaise'—rather than being completely separate diseases. Understanding these shared symptoms may help explain why people often have multiple conditions at the same time.

Pain and SensitizationCognitive Impairment

E2 ModerateCohortPEM unclearLongitudinal

Validation of the Wood Mental Fatigue Inventory in adolescents with myalgic encephalomyelitis/chronic fatigue syndrome.

Welch, David C, Edwards, Charles C, Broussard, Camille A et al.·Brain, behavior, & immunity - health·2026

This study tested whether a questionnaire called the Wood Mental Fatigue Inventory (WMFI) works well for measuring brain fog and cognitive problems in teenagers with ME/CFS. Researchers compared it to another commonly used teen fatigue scale and found that both questionnaires measured mental fatigue similarly and could track changes over time as teenagers received treatment.

Cognitive Impairment

E2 ModerateCohortPEM unclearCross-Sectional

Chronic Pain Prevalence, Characteristics, and Impact in United States Adults With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Adamowicz, Jenna L, Sirotiak, Zoe, Lendvai, Dora et al.·Pain management nursing : official journal of the American Society of Pain Management Nurses·2026

This study looked at how common chronic pain is in people with ME/CFS and how it affects their lives. Researchers found that about 7 out of 10 people with ME/CFS also experience chronic pain lasting months or longer. People with both ME/CFS and chronic pain reported more depression, anxiety, and difficulty with daily activities compared to people who only have chronic pain.

Pain and Sensitization

E2 ModerateCohortPEM not requiredCross-Sectional

Ocular Symptoms in Long COVID: A Cross-Sectional Study.

Kaleem, Shayaan, Sawano, Mitsuaki, Arun, Adith S et al.·Clinical ophthalmology (Auckland, N.Z.)·2026

This study looked at eye problems in people with long COVID, comparing those who developed new eye symptoms (like blurred vision, dry eyes, or floaters) after infection with those who didn't. About 57% of the 595 participants reported new eye symptoms. People with eye symptoms had worse overall health, more financial struggles, and were more likely to have dysautonomia (problems with blood pressure and heart rate control) and ME/CFS.

Autonomic Nervous System

E2 ModerateCohortPEM unclearCross-Sectional

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

Hoel, August, Hoel, Fredrik, Dyrstad, Sissel Elisabeth et al.·Cell reports. Medicine·2026

Researchers analyzed thousands of proteins in the blood of ME/CFS patients and compared them to healthy people. They found significant differences in protein patterns, including too much of certain immune-related proteins and too little of proteins normally made by muscles. These differences might help explain why ME/CFS causes such severe exhaustion and could eventually lead to new ways to diagnose or treat the condition.

BiomarkersImmune System

E2 ModerateCohortPEM unclearCase-Control

Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.

Gülmez, Dilara, Siwy, Justyna, Kurz, Katharina et al.·Proteomics·2026

Researchers found a simple urine test that can accurately identify people with long COVID (PASC) by measuring tiny protein fragments in the urine. The test correctly identified long COVID patients 96% of the time compared to healthy people and those with ME/CFS. The urine signatures suggest that long COVID involves ongoing inflammation and changes in how the body breaks down and rebuilds connective tissue.

BiomarkersImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Long COVID disability burden in US adults.

Bonuck, Karen, Gao, Qi, Congdon, Seth et al.·Communications medicine·2026

This study measured how much disability Long COVID causes in American adults and compared it to other diseases like Alzheimer's and asthma. The researchers found that Long COVID causes as much disability as these well-known conditions, yet the U.S. government funds research on Long COVID with only 14% of the money it should based on that disability burden. The study also found that diseases affecting mostly women receive about 5 times less research funding per unit of disability than diseases affecting mostly men.

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Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

Non-pharmacological approaches to treatment.

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome.

Chronic fatigue syndrome and chronic primary magnesium deficiency (CFS and CPMD).

Red blood cell magnesium and chronic fatigue syndrome.

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome.

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

Liver extract-folic acid-cyanocobalamin vs placebo for chronic fatigue syndrome.

Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial.

Distinct functional connectivity patterns in myalgic encephalomyelitis and long COVID patients during cognitive fatigue: a 7 Tesla task-fMRI study.

Chronic Reactivation of Persistent Human Herpesviruses EBV, HHV-6 and VZV and Heightened Anti-dUTPase IgG Antibodies Are a Recurrent Hallmark in Post-Infectious ME/CFS and is Associated With Fatigue.

Understanding concussion in myalgic encephalomyelitis/chronic fatigue syndrome: Findings from the 2023 National Health Interview study.

Obesity and inactivity cluster the strongest risk factor for the development of heart failure in a population-based study.

Disentangling comorbidity: symptom dimensions of internalizing and functional disorders in a large general population sample.

Validation of the Wood Mental Fatigue Inventory in adolescents with myalgic encephalomyelitis/chronic fatigue syndrome.

Chronic Pain Prevalence, Characteristics, and Impact in United States Adults With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Ocular Symptoms in Long COVID: A Cross-Sectional Study.

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights.

Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.

Long COVID disability burden in US adults.

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