ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

121–140 of 746 studies

Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose-response, crossover study.

Boruch, Alexander E, Barhorst, Ellen E, Rayne, Tessa J et al.·Brain, behavior, and immunity·2024

This study tested whether exercise of different intensities causes post-exertional malaise (PEM)—a worsening of symptoms after physical activity—in veterans with Gulf War Illness, a condition similar to ME/CFS. Forty participants did light, moderate, or vigorous cycling for 20 minutes, or simply rested, while researchers measured their symptoms, pain sensitivity, thinking ability, and blood markers before and after. The study found that exercise did not cause greater symptom worsening or other problems than rest, even at higher intensities.

Post-Exertional Malaise

E1 ReplicatedTrialPEM requiredRCT

Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition - a randomized controlled trial.

Barz, Andreas, Berger, Joshua, Speicher, Marco et al.·Scientific reports·2024

This study tested whether a personalized exercise program that adjusts based on daily fatigue levels helps people with post-COVID condition. Over 10 weeks, 118 participants did exercise at commercial fitness facilities while a qualified trainer adjusted the intensity based on how they felt that day. The program significantly improved fatigue, quality of life, and physical strength without making symptoms worse.

Post-Exertional Malaise

E1 ReplicatedTrialPEM requiredRCT

Videoconference-delivered group Cognitive Behavioral Stress Management for ME/CFS patients who present with severe PEM: A randomized controlled trial.

May, Marcella, Milrad, Sara F, Perdomo, Dolores M et al.·Fatigue : biomedicine, health & behavior·2024

This study tested whether a stress management program delivered by video could help ME/CFS patients who experience severe post-exertional malaise (PEM)—the worsening of symptoms after activity. Patients either received 10 weeks of cognitive behavioral stress management training or health information. For patients with severe PEM, the stress management program led to meaningful improvements in symptom frequency, symptom intensity, and fatigue-related problems, suggesting that managing stress may help reduce PEM severity.

Post-Exertional Malaise

E1 ReplicatedTrialPEM unclearRCT

The effects of 3-month supplementation with synbiotic on patient-reported outcomes, exercise tolerance, and brain and muscle metabolism in adult patients with post-COVID-19 chronic fatigue syndrome (STOP-FATIGUE): a randomized Placebo-controlled clinical trial.

Ranisavljev, Marijana, Stajer, Valdemar, Todorovic, Nikola et al.·European journal of nutrition·2024

This study tested whether a special mixture of beneficial gut bacteria (probiotics) plus fiber and zinc could help people with post-COVID chronic fatigue syndrome (ME/CFS). Over three months, 26 patients took either the synbiotic mixture or a placebo, and researchers measured their fatigue, exercise recovery, and brain/muscle chemistry. The synbiotic group experienced better recovery after exercise and showed improvements in brain chemistry compared to the placebo group, though both groups felt less general fatigue.

Post-Exertional Malaise

E1 ReplicatedTrialPEM unclearRCT

Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance.

Rodriguez, Lucie, Pou, Christian, Lakshmikanth, Tadepally et al.·Oxford open immunology·2023

Researchers tested whether gently stimulating nerve endings inside the nose could help ME/CFS patients feel better. After 8 weeks of treatment, patients showed about a 30% improvement in their overall symptoms. Blood tests showed that ME patients have signs of ongoing immune activation, and those who improved had changes in their immune cells and less inflammation.

Immune SystemPost-Exertional Malaise

E1 ReplicatedTrialPEM requiredRCT

Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.

Joseph, Phillip, Pari, Rosa, Miller, Sarah et al.·Chest·2022

This study tested whether a medication called pyridostigmine could help people with ME/CFS exercise better by improving blood flow and heart function. Researchers gave 45 ME/CFS patients either pyridostigmine or a placebo, then measured their exercise capacity twice using specialized heart and lung tests. The group taking pyridostigmine showed improved oxygen uptake and better heart function during exercise, while the placebo group actually got worse, suggesting the medication may help counteract some of the body's dysfunctional responses to exercise in ME/CFS.

Post-Exertional Malaise

E1 ReplicatedTrialPEM not requiredRCT

A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study.

Kan, Juntao, Cheng, Junrui, Hu, Chun et al.·Frontiers in nutrition·2021

Researchers tested whether a supplement containing two plant extracts (cistanche and ginkgo) could help adults with ME/CFS. Over 60 days, people taking the supplement reported improvements in fatigue, memory, sleep quality, and ability to exercise compared to those taking a placebo. The treatment also lowered certain chemicals in the blood (ammonia and lactic acid) that may be linked to fatigue.

Post-Exertional Malaise

E1 ReplicatedTrialPEM requiredRCT

Cognitive-behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a feasibility study.

Malik, Sadaf, Asprusten, Tarjei Tørre, Pedersen, Maria et al.·BMJ paediatrics open·2020

This study tested whether combining two types of therapy—cognitive-behavioral therapy (which helps change thought patterns and behaviors) and music therapy—could help adolescents recover from prolonged fatigue that started after an Epstein-Barr virus infection. Over 15 months, researchers compared 21 young people who received the combined therapy with 22 who received standard care. The therapy was safe and well-tolerated, and there were hints that it might help with symptom recovery, though the study was too small to prove effectiveness.

Post-Exertional Malaise

E1 ReplicatedCohortPEM requiredObservational

Cardiopulmonary exercise testing and post-exertional malaise in ME/CFS: A retrospective analysis

Staci R. Stevens, Christopher R. Snell, Jared N. Stevens et al.·Journal of Translational Medicine·2018·n=51

ME/CFS patients underwent two consecutive days of cardiopulmonary exercise testing (CPET). On the second day, patients showed significantly reduced VO2 max and anaerobic threshold compared to the first day — and compared to healthy and disease controls who recovered normally. This objective impairment matches the subjective PEM experience.

DiagnosticsPost-Exertional Malaise

E1 ReplicatedTrialPEM requiredObservational

Telephone-administered versus live group cognitive behavioral stress management for adults with CFS.

Hall, Daniel L, Lattie, Emily G, Milrad, Sara F et al.·Journal of psychosomatic research·2017

This study tested whether teaching stress management skills over the telephone worked as well as learning them in a live group setting for people with ME/CFS. Both formats helped reduce stress, but only the in-person group also improved physical symptoms like post-exertional malaise, chills, fever, and sleep quality. This suggests that meeting face-to-face may have extra benefits beyond just learning the techniques themselves.

Post-Exertional Malaise

E1 ReplicatedTrialPEM requiredRCT

Fatigue Exacerbation by Interval or Continuous Exercise in Chronic Fatigue Syndrome.

Sandler, Carolina X, Lloyd, Andrew R, Barry, Benjamin K·Medicine and science in sports and exercise·2016

This study compared how people with ME/CFS feel after two types of exercise: high-intensity interval training (short bursts of harder exercise) and steady, continuous moderate exercise. Both types of exercise caused fatigue to worsen slightly afterward, but there was no meaningful difference between them. The findings suggest that high-intensity exercise might be safe to study further as part of graded exercise therapy programs.

Post-Exertional Malaise

E1 ReplicatedTrialPEM not requiredRCT

Provision of social support to individuals with chronic fatigue syndrome.

Jason, Leonard A, Roesner, Nicole, Porter, Nicole et al.·Journal of clinical psychology·2010

This study tested whether having a student volunteer visit weekly to help with household tasks and errands could improve symptoms in people with ME/CFS. Participants were randomly assigned to receive either 4 months of buddy support or no intervention. People who received the buddy help reported significantly less fatigue and more energy than those who didn't, though there were no differences in physical functioning or stress levels.

Post-Exertional Malaise

E1 ReplicatedTrialPEM not requiredRCT

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Malaguarnera, Michele, Gargante, Maria Pia, Cristaldi, Erika et al.·Archives of gerontology and geriatrics·2008

Researchers tested whether a supplement called acetyl L-carnitine (ALC) could help reduce fatigue in older adults (over 70 years old) who met criteria for chronic fatigue syndrome. After treatment, patients showed meaningful improvements in physical tiredness, mental fatigue, sleep problems, and thinking ability. The supplement appeared to be safe and well-tolerated.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden.

Polli, Andrea, Hendrix, Jolien, Wyns, Arne et al.·Journal of translational medicine·2026

Researchers compared blood cell DNA methylation (a chemical tag that regulates gene activity) in 71 people with ME/CFS, 44 with fibromyalgia, and 73 healthy controls. They found two distinct methylation patterns: one associated mainly with post-exertional malaise and cognitive symptoms in ME/CFS, and another associated with broader pain and sleep symptoms in both patient groups. This is one study in early-stage research; the findings have not yet been replicated in independent groups, and it remains unclear whether these methylation patterns could be used clinically to diagnose or monitor these conditions.

NeuroinflammationPain and SensitizationBiomarkersSleep

E2 ModerateCohortPEM unclearLongitudinal

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Jones, Ansley E, Khan, Zain, McGroder, Claire F et al.·Critical care explorations·2026

This study followed people who were hospitalized with severe COVID-19 for 3 years after they left the hospital. About one-quarter of them continued to experience long COVID symptoms like fatigue, brain fog, and difficulty with physical activity. Surprisingly, when researchers measured inflammation and blood vessel markers in their blood, these markers were not elevated and did not explain why some people had ongoing symptoms.

BiomarkersImmune SystemPost-Exertional Malaise

E2 ModerateCohortPEM not requiredLongitudinal

Long COVID longitudinal symptoms burden clusters within a national community-based cohort.

Shen, Yanhan, Shahn, Zach, Robertson, McKaylee M et al.·BMC infectious diseases·2026

This study followed over 500 people with long COVID for up to a year, tracking their symptoms over time. Researchers identified three groups based on symptom burden: one with persistent severe symptoms (including fatigue, brain fog, post-exertional malaise, and pain), one with moderate symptoms that improved, and one with minimal symptoms. The findings are preliminary and based on self-reported data, so the stability and generalisability of these groups to other long COVID populations remain to be confirmed.

Pain and SensitizationSleepAutonomic Nervous SystemCognitive Impairment

E2 ModerateCohortPEM unclearObservational

Wearable Heart Rate Variability Monitoring, Autonomic Dysfunction and Post-exertional Malaise in Long COVID: An Observational Study.

Ruijgt, Twan M, Slaghekke, Anouk, Ellens, Anneke et al.·Sports medicine (Auckland, N.Z.)·2026

This observational study measured heart rate variability (a marker of nerve system balance) in 121 long COVID patients and 21 healthy controls using wearable devices over multiple days. Researchers observed that long COVID patients had lower heart rate variability during daily activities and sleep, and their heart rate variability remained reduced for 24 hours after exercise, particularly at intensities above their aerobic threshold. The findings suggest wearables may help patients recognise when they are overexerting, though the study does not yet establish whether this monitoring prevents post-exertional malaise.

BiomarkersAutonomic Nervous SystemDiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM requiredObservational

Handgrip strength in children, adolescents, and young adults with suspected myalgic encephalomyelitis/chronic fatigue syndrome.

Mihatsch, Lorenz, Schartner, Lisa, de Luna, Julia Lange et al.·Journal of translational medicine·2026

Researchers tested whether handgrip strength could help identify ME/CFS in young people (ages 10–25). They asked 147 patients referred for ME/CFS assessment and 83 healthy controls to squeeze a hand-strength device twice, an hour apart. Young people with ME/CFS had weaker grip strength than healthy controls, and grip strength was loosely associated with physical functioning; however, grip strength alone could not reliably tell apart ME/CFS patients from other young people with chronic fatigue. The study shows that repeated handgrip testing is feasible and may help track how patients are doing over time, but early findings suggest it works better as a way to measure general weakness rather than as a standalone diagnostic test.

BiomarkersDiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.

Tomaskovic, Aleksandar, Weber, Vincent, Ochmann, David T et al.·Sports medicine - open·2026

A cross-sectional study of 92 severely ill post-COVID patients found that those meeting ME/CFS criteria had lower measured aerobic capacity (oxygen uptake and power output) on exercise testing compared to post-COVID patients without ME/CFS. Two-thirds of all patients showed objective signs of work disability on testing, and these measurements correlated with patients' own reports of disability and their employment status. The relevance of these findings specifically to ME/CFS requires caution, as the study enrolled primarily post-COVID patients, and the overlap between these conditions remains incompletely understood.

Severe MEDiagnosticsLong COVID OverlapPost-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.

Souma, Bernard, Elremaly, Wesam, Akoume, Marie-Yvonne et al.·International journal of molecular sciences·2026

Researchers compared blood levels of two proteins—irisin and thrombospondin-1 (TSP-1)—in 92 ME/CFS patients and 44 healthy controls, measuring them before and after a physical stress test. They observed that ME/CFS patients had lower baseline irisin levels and a weaker response to the stress challenge, while those with more severe symptoms showed elevated levels of both proteins. The study proposes that TSP-1 may interfere with irisin's normal signaling, potentially contributing to energy problems in ME/CFS, but these findings are preliminary and require validation in larger studies.

BiomarkersEnergy MetabolismPost-Exertional Malaise

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Evidence browser

Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose-response, crossover study.

Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition - a randomized controlled trial.

Videoconference-delivered group Cognitive Behavioral Stress Management for ME/CFS patients who present with severe PEM: A randomized controlled trial.

The effects of 3-month supplementation with synbiotic on patient-reported outcomes, exercise tolerance, and brain and muscle metabolism in adult patients with post-COVID-19 chronic fatigue syndrome (STOP-FATIGUE): a randomized Placebo-controlled clinical trial.

Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance.

Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.

A Botanical Product Containing Cistanche and Ginkgo Extracts Potentially Improves Chronic Fatigue Syndrome Symptoms in Adults: A Randomized, Double-Blind, and Placebo-Controlled Study.

Cognitive-behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a feasibility study.

Cardiopulmonary exercise testing and post-exertional malaise in ME/CFS: A retrospective analysis

Telephone-administered versus live group cognitive behavioral stress management for adults with CFS.

Fatigue Exacerbation by Interval or Continuous Exercise in Chronic Fatigue Syndrome.

Provision of social support to individuals with chronic fatigue syndrome.

Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue.

Epigenome-wide profiling identifies distinct DNA methylation architecture underlying ME/CFS and fibromyalgia symptom burden.

Post-Acute Sequelae of COVID-19 Persist Over 3 Years in Acute Lung Injury/Acute Respiratory Distress Syndrome Survivors But Are Not Associated With Persistent Thromboinflammation or Endothelial Dysfunction.

Long COVID longitudinal symptoms burden clusters within a national community-based cohort.

Wearable Heart Rate Variability Monitoring, Autonomic Dysfunction and Post-exertional Malaise in Long COVID: An Observational Study.

Handgrip strength in children, adolescents, and young adults with suspected myalgic encephalomyelitis/chronic fatigue syndrome.

Cardiopulmonary Exercise Testing Reveals Functional Limitations and Work Disability in Severe Post-COVID-19 and ME/CFS Patients.

Irisin Signaling Resistance in Myalgic Encephalomyelitis: A Proposed Mechanistic Framework for Post-Exertional Malaise Involving the TSP-1-HSP90α-αvβ5 Axis.

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