Chronic Fatigue

Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials.

Park JW, Park BJ, Lee JS, Lee EJ, Ahn YC, Son CG · Journal of translational medicine · 2024 · n=88

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients. We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively. Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigu

Meta-analysis of natural killer cell cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome.

Baraniuk JN, Eaton-Fitch N, Marshall-Gradisnik S · Frontiers in immunology · 2024

Reduced natural killer (NK) cell cytotoxicity is the most consistent immune finding in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Meta-analysis of the published literature determined the effect size of the decrement in ME/CFS. Databases were screened for papers comparing NK cell cytotoxicity in ME/CFS and healthy controls. A total of 28 papers and 55 effector:target cell ratio (E:T) data points were collected. Cytotoxicity in ME/CFS was significantly reduced to about half of healthy control levels, with an overall Hedges' g of 0.96 (0.75-1.18). Heterogeneity was high but was explained by the range of E:T ratios, different methods, and potential outliers. The outcomes confirm reproducible NK cell dysfunction in ME/CFS and will guide studies using the NK cell model system for pathomechanistic investigations. https://www.crd.york.ac.uk/prospero/, identifier CRD42024542140.

Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial.

Cash A, Kaufman DL · Journal of translational medicine · 2022

There is no approved pharmaceutical intervention for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Fatigue in these patients can last for decades. Long COVID may continue to ME/CFS, and currently, it is estimated that up to 20 million Americans have significant symptoms after COVID, and the most common symptom is fatigue. Anhydrous Enol-Oxaloacetate, (AEO) a nutritional supplement, has been anecdotally reported to relieve physical and mental fatigue and is dimished in ME/CFS patients. Here, we examine the use of higher dosage AEO as a medical food to relieve pathological fatigue. ME/CFS and Long-COVID patients were enrolled in an open label dose escalating "Proof of Concept" non-randomized controlled clinical trial with 500 mg AEO capsules. Control was provided by a historical ME/CFS fatigue trial and supporting meta-analysis study, which showed average improvement with oral placebo using the Chalder Scale of 5.9% improvement from baseline. At baseline, 73.7% of t

Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Kim DY, Youn J, Kang N, Cho SI, Ha IH · Journal of translational medicine · 2026 · n=790

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined. We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted. The patient exhibited a significant re

Systematic Review of Mind-Body Interventions to Treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Khanpour Ardestani S, Karkhaneh M, Stein E, Punja S, Junqueira DR, Kuzmyn T · Medicina (Kaunas, Lithuania) · 2021

Background and Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic condition distinguished by disabling fatigue associated with post-exertional malaise, as well as changes to sleep, autonomic functioning, and cognition. Mind-body interventions (MBIs) utilize the ongoing interaction between the mind and body to improve health and wellbeing. Purpose: To systematically review studies using MBIs for the treatment of ME/CFS symptoms. Materials and Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL were searched (inception to September 2020). Interventional studies on adults diagnosed with ME/CFS, using one of the MBIs in comparison with any placebo, standard of care treatment or waitlist control, and measuring outcomes relevant to the signs and symptoms of ME/CFS and quality of life were assessed for inclusion. Characteristics and findings of the included studies were summarized using a descriptive approach. Results: 12 out of 382 retrieved ref

Systematic review of randomized controlled trials for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

Kim DY, Lee JS, Park SY, Kim SJ, Son CG · Journal of translational medicine · 2020 · n=6316

Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date. RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes. Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukud

Appraisal of Clinical Practice Guideline: National Institute for Health and Care Excellence (NICE) clinical practice guideline for myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management.

F Tyson S · Journal of physiotherapy · 2024

2021

EULAR evidence-based recommendations for the management of fibromyalgia syndrome.

Carville SF, Arendt-Nielsen L, Bliddal H, Blotman F, Branco JC, Buskila D · Annals of the rheumatic diseases · 2008

To develop evidence-based recommendations for the management of fibromyalgia syndrome. A multidisciplinary task force was formed representing 11 European countries. The design of the study, including search strategy, participants, interventions, outcome measures, data collection and analytical method, was defined at the outset. A systematic review was undertaken with the keywords "fibromyalgia", "treatment or management" and "trial". Studies were excluded if they did not utilise the American College of Rheumatology classification criteria, were not clinical trials, or included patients with chronic fatigue syndrome or myalgic encephalomyelitis. Primary outcome measures were change in pain assessed by visual analogue scale and fibromyalgia impact questionnaire. The quality of the studies was categorised based on randomisation, blinding and allocation concealment. Only the highest quality studies were used to base recommendations on. When there was insufficient evidence from the literat

"The effect of acupressure on fatigue in individuals with chronic fatigue syndrome".

Kurç D, Şakul AAS, Atilgan E · Explore (New York, N.Y.) · 2025 · n=39

Patients with Chronic Fatigue Syndrome (CFS) often experience fatigue that greatly affects their quality of life. We aimed to investigate the effectiveness of acupressure in alleviating CFS symptoms in office workers. We conducted a randomized controlled trial with 39 participants (28 women, 11 men; average age 29.54 ± 1.27). Participants were divided into treatment and control groups. The acupressure group received 10 sessions over 4 weeks, targeting specific acupoints (Li4, HT7, L9, P6, Gb20, Anmian, Du20, Yin-Tang, Sp6). Each point was stimulated for 30-90 s until numbness was felt; otherwise, stimulation lasted 90 s, totaling approximately 30 min per session. The control group did not receive any treatment. We assessed fatigue using the Fatigue Severity Scale (FSS), quality of life using the Short Form-36 (SF-36), and depressive symptoms using the Beck Depression Scale (BDS) before and after treatment. Data were analyzed using SPSS 22.0. We observed a significant reduction i

Effectiveness of the SYNCHRONIZE + Brief Intervention in Improving Mediterranean Diet Adherence, Nutritional Quality and Intake Pattern in Persons with Fibromyalgia and Chronic Fatigue Syndrome.

Carrasco-Querol N, Cabricano-Canga L, Bueno Hernández N, Martín-Borràs C, Gonçalves AQ, Vila-Martí A · Nutrients · 2024 · n=158

Multidisciplinary lifestyle interventions are being researched to treat fibromyalgia. However, the impact of nutrition as a key treatment component is little studied. This study aimed to evaluate the effectiveness of the SYNCHRONIZE + lifestyle multidisciplinary intervention in improving adherence to the Mediterranean diet, nutrition quality and dietary intake pattern in persons with fibromyalgia and chronic fatigue syndrome. A pragmatic randomized clinical trial was conducted in primary care. Data were collected using the 17-item energy-restricted Mediterranean Adherence Screener (er-MEDAS), the food frequency questionnaire (sFFQ) and the 24 h recall questionnaire (24 HR), in addition to chrono-nutritional, anthropometric, and body composition data, at baseline and 3-, 6-, and 12- month follow-up visits, and statistically analyzed. A total of 158 participants were evaluated. Results showed the effectiveness of the intervention in improving adherence to the Mediterranean diet. The ad

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 M, Stajer V, Todorovic N, Ostojic J, Cvejic JH, Steinert RE · European journal of nutrition · 2024

Considering the observed gastrointestinal issues linked to post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), beneficially modulating the gut microbiota could offer a safe, cost-effective nutritional strategy. This trial aimed to evaluate the effects of medium-term synbiotic supplementation on patient-reported outcomes, exercise tolerance, and tissue metabolism in patients with post-COVID-19 ME/CFS. Between September 2022 and December 2023, we investigated the impact of 3-month supplementation with a synbiotic mixture including L. rhamnosus DSM 32550, Humiome® L. plantarum DSM 34532, B. lactis DSM 32269, B. longum DSM 32946, fructooligosaccharides and zinc, on predetermined primary and secondary outcome measures in twenty six post-COVID-19 ME/CFS patients utilizing a parallel-group, randomized, placebo-controlled, double-blind design. Both the synbiotic and placebo intake resulted in a significant reduction in general fatigue after 3 months compared

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): diagnosis and management.

Fan J, Jiao J, Chang HQ, Zhong DL, Liu XB, Li J · Journal of translational medicine · 2025

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has garnered substantial scientific and clinical interest, due to its rising global prevalence and significant pathophysiological overlap with post-acute COVID-19 syndrome (PACS). This review systematically elucidates the prevailing diagnostic criteria, summarizes recent advances in understanding the potential pathophysiological mechanisms, and evaluates pharmacological and non-pharmacological interventions, and symptom-based assessment and management strategies. A comprehensive literature search was conducted across PubMed, Web of Science, Embase, and the Cochrane Library for articles published from inception to August 2025. Current diagnostic frameworks for ME/CFS rely primarily on clinical symptomatology and lack definitive biomarkers. Immune dysregulation, oxidative stress, mitochondrial dysfunction, and neuroinflammation are central to its pathology. Pharmacological management includes immunomodulatory treatments, antio

Defining a High-Quality Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cohort in UK Biobank.

Samms GL, Ponting CP · NIHR open research · 2025

Progress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) research is being slowed by the relatively small-scale studies being performed whose results are often not replicated. Progress could be accelerated by analyses of large population-scale projects, such as UK Biobank (UKB), which provide extensive phenotype and genotype data linked to both ME/CFS cases and controls. Here, we analysed the overlap and discordance among four UKB-defined ME/CFS cohorts, and additional questionnaire data when available. A total of 5,354 UKB individuals were linked to at least one piece of evidence of MECFS, a higher proportion (1.1%) than most prevalence estimates. Only a third (36%; n=1,922) had 2 or more pieces of evidence for MECFS, in part due to data missingness. For the same UKB participant, ME/CFS status defined by ICD-10 (International Classification of Diseases, Tenth Revision) code G93.3 (Post-viral fatigue syndrome) was most likely to be supported by another data type (72%);

MicroRNA Profiling of Blood Extracellular Vesicles in ME/CFS.

Ljungström M, Nathanson L, Oltra E · Methods in molecular biology (Clifton, N.J.) · 2025

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating neuroimmune disease affecting many organs and systems which, in the absence of validated biomarkers, remains diagnosed by clinical criteria. Extracellular vesicles (EV) in blood come from practically all cells in our body and therefore may carry the disease-specific biomarkers needed for the diagnosis of ME. This chapter presents the methodology used on a single pilot study performed to evaluate this possibility to describe a workflow for EV isolation and the analysis of the miRNAs within, which could serve to interrogate additional cohorts of ME/CFS. Among the diverse nature of EV contents miRNAs may constitute a prominent regulatory layer in the development and progress of complex diseases such as ME/CFS, and therefore their study should be further pursued.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

CDC

This CDC page provides information on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) for patients and healthcare professionals, covering symptoms, diagnosis, and management strategies.

Chronic Fatigue Syndrome

MedlinePlus

MedlinePlus, a service of the National Library of Medicine (NLM), offers a detailed overview of Chronic Fatigue Syndrome. It includes information on causes, symptoms, diagnosis, treatment, and links to research and clinical trials.

The Effect of Foot Deformities on Physical Activity, Fatigue Level and Quality of Life in Elderly COPD Patients

n=77 · NCT04627935 · UNKNOWN · UNKNOWN

The aim of this study is to investigate the effects of changes in foot structure on physical activity level, fatigue and quality of life in COPD patients.

A Double Blind Randomized Trial of Low-dose Naltrexone for Post-COVID Fatigue Syndrome

n=160 · NCT05430152 · COMPLETED · COMPLETED

This study aims to determine if low-dose naltrexone (LDN) reduces fatigue, improves related symptoms, and reduces inflammatory markers in peripheral blood in cases with Post-COVID-19 Fatigue Syndrome (PCFS) from COVID-19 (i.e. confirmed SARS-CoV-2 case). LDN refers to naltrexone given in doses of 1-4.5 mg. Overall, studies have found that LDN is safe and well-tolerated. It may help to reduce pain and inflammation and improve well-being and immune function.The trial will be conducted by the Complex Chronic Diseases Program (CCDP) at BC Women's Hospital and will demonstrate whether LDN could benefit a large number of people with PCFS.

Characteristics and Predictors of Early and Late Cardiovascular Complications of Covid-19 Patients - the PoLoCOV-Study (Polish LONG-COVID Cardiovascular Study)

n=1900 · NCT05018052 · UNKNOWN · UNKNOWN

Coronavirus disease 2019 (COVID-19) is a serious respiratory disease that results from infection with a newly discovered coronavirus (SARS-COV-2). Unfortunately, COVID-19 is not only a short-term infection. Patients (pts) recovering from SARS-COV2 infection complain of persisting symptoms including: fatigue, diffuse myalgia and weakness, which may lead to chronic fatigue syndrome and as well as many other complications. The vast majority of COVID-19 patients remaining in isolation/quarantine, due to the mild course of the disease, do not require hospitalization. In this group of patients, the course of COVID-19 is very different - from asymptomatic patients to very severe and long lasting symptoms also with a decrease in saturation. There are many studies describing the course and complications of patients hospitalized due to COVID-19. There is little published data on how non-hospitalized patients get sick and what are the early and late complications of SARS-CoV-2 infection. In addition, many patients remain ill even many months after COVID-19, entering what is known as LONG-COVID. Therefore, the STOP-COVID Registry was established. The purpose of the Registry is to assess the course of COVID-19 infection, early and late cardiovascular complications of COVID-19 in patients with and without hospitalization. In addition, the purpose of the STOP-COVID Registry is to assess the incidence of LONG-COVID with all other complications and to identify predictive factors.

Chronic Fatigue Syndrome (CFS)

TRIP Database

TRIP Database is a clinical search engine designed to allow users to quickly and easily find high-quality research evidence to support their clinical practice. Searching for 'Chronic Fatigue Syndrome' yields a wide array of relevant evidence.

Reviews on Chronic Fatigue Syndrome

Cochrane

Cochrane provides a collection of systematic reviews on interventions and aspects related to Chronic Fatigue Syndrome, offering high-quality evidence to inform healthcare decisions.