ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

121–140 of 729 studies

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 not requiredRCT

Impact of combined plant extracts on long COVID: An exploratory randomized controlled trial.

Lukkunaprasit, Thitiya, Satapornpong, Patompong, Kulchanawichien, Pongsiri et al.·Complementary therapies in medicine·2024

Researchers tested whether a supplement made from five plant extracts could help people with long COVID feel better. Over 7 days, people taking the supplement reported feeling less fatigued and had fewer severe symptoms like post-exertional malaise (worsening after activity) compared to those taking a placebo. The supplement was generally safe, though the study was small and longer research is needed to confirm these results.

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 not requiredObservational

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.

Ghali, Alaa, Lavigne, Christian, Ghali, Maria et al.·Journal of clinical medicine·2026

A French hospital study observed that post-COVID patients infected in 2020–2021 reported post-exertional malaise (PEM) more often than those infected later, and that PEM was associated with higher fatigue levels. By analogy, this may be relevant to ME/CFS patients, though the study examined post-COVID populations and the reasons for these differences remain uncertain—they could reflect changes in the virus, vaccination, immunity, or other unmeasured factors.

Long COVID OverlapPost-Exertional Malaise

E2 ModerateCohortPEM unclearCase-Control

Interpreting hand grip strength in hospital employees with post-COVID syndrome compared to non-infected controls: a case-control study.

Tack, Matthias, Gruber, Rosalie, Betting, Leia et al.·Scientific reports·2026

This small study compared hand grip strength in 19 hospital workers with post-COVID syndrome (including 7 who met ME/CFS criteria) to 23 healthy controls. Researchers found that grip strength tended to be lower in the post-COVID group, particularly when tested a second time after a 60-minute break, which might suggest difficulty recovering after repeated effort. However, these are preliminary findings from a small group, and the authors note that grip strength alone is not reliable enough to diagnose post-COVID syndrome.

DiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome.

Mancini, Donna M, Cook, Dane B, Brunjes, Danielle L et al.·Frontiers in physiology·2026

Researchers asked whether doing two exercise tests on consecutive days could reliably detect post-exertional malaise (PEM) in ME/CFS patients. They found that oxygen consumption and other key exercise measures did not change between Day 1 and Day 2 in either ME/CFS patients or healthy controls. However, ME/CFS patients reported much greater fatigue during exercise and had lower maximum heart rates. One study's findings do not establish whether this two-day test method is truly useful for measuring PEM in clinical practice.

DiagnosticsPost-Exertional Malaise

E2 ModerateCohortPEM requiredObservational

[The Role of ME/CFS Phenotype in Outpatient Post-COVID Rehabilitation].

Kaiserseder, Moritz, Prüfer, Ferdinand, Untersmayer-Elsenhuber, Eva et al.·Pneumologie (Stuttgart, Germany)·2026

This study looked at 216 people recovering from COVID-19 in rehabilitation programs to see how many had ME/CFS—a condition with severe fatigue and worsening after physical activity. The researchers found that about 7% of these patients met the criteria for ME/CFS. These patients were typically younger, mostly women, and experienced much more severe fatigue that didn't improve with rehabilitation compared to other COVID-19 patients.

Post-Exertional Malaise

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 requiredObservational

Assessment and Incidence Determination of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following a SARS-CoV-2 Infection in a Prospective Cohort of Hospital Employees.

Tack, Matthias, Gruber, Rosalie, Betting, Leia et al.·Medicina (Kaunas, Lithuania)·2026

This study followed hospital workers who got COVID-19 to see how many developed long-lasting fatigue and ME/CFS. About 12% still had fatigue months later, and 3% met the criteria for ME/CFS. Researchers found that people with these conditions often had signs of viral reactivation, immune system changes, and blood clotting abnormalities.

Post-Exertional Malaise

E2 ModerateCohortPEM unclearCross-Sectional

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Aregawi, Lillian, Walitt, Brian, Sullivan, Patti et al.·Brain communications·2026

Researchers measured levels of norepinephrine (a brain chemical) in cerebrospinal fluid from people with ME/CFS, Long COVID, and Parkinson's disease, comparing them to healthy volunteers. They observed that norepinephrine pathway activity was lower in all three patient groups, and in Long COVID patients with post-exertional malaise, this reduction was particularly pronounced. This is one study in a small sample, and it remains unclear whether these findings fully explain fatigue and brain fog or apply directly to ME/CFS.

BiomarkersCognitive ImpairmentLong COVID OverlapPost-Exertional Malaise

E2 ModerateCohortPEM requiredCross-Sectional

Impact of post-exertional malaise frequency and fatigue in Long COVID patients on health-related quality of life.

Thölking, Theresa, Müller, Frank, Riester, Tim et al.·Health and quality of life outcomes·2026

This study surveyed German adults with Long COVID and post-exertional malaise (PEM) to understand how the frequency and severity of PEM relates to quality of life. Researchers found that people reporting more frequent and more severe PEM were associated with lower quality-of-life scores, even after accounting for age, sex, and employment status. These are preliminary findings from a single survey and do not establish that PEM causes poor quality of life, but rather that the two observations occurred together in this group.

Post-Exertional Malaise

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

Impact of combined plant extracts on long COVID: An exploratory randomized controlled 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.

Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases.

Interpreting hand grip strength in hospital employees with post-COVID syndrome compared to non-infected controls: a case-control study.

Cardiopulmonary exercise test results do not change over two sequential days in patients with chronic fatigue syndrome.

[The Role of ME/CFS Phenotype in Outpatient Post-COVID Rehabilitation].

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.

Assessment and Incidence Determination of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Following a SARS-CoV-2 Infection in a Prospective Cohort of Hospital Employees.

Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.

Impact of post-exertional malaise frequency and fatigue in Long COVID patients on health-related quality of life.

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