Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), is a complex, long-term illness characterized by extreme fatigue that worsens with physical or mental activity and is not relieved by rest.
Ranked by community outcomes, then evidence grade, Health Voice mentions, and recency.
Why it may help Chronic Fatigue Syndrome: Often low; supports energy
Why it may help Chronic Fatigue Syndrome: Vitamin D supplementation may improve fatigue in Chronic Fatigue Syndrome patients by modulating immune function and reducing inflammation.
Why it may help Chronic Fatigue Syndrome: Rhodiola may reduce fatigue and improve mental performance in Chronic Fatigue Syndrome by modulating stress response systems and neurotransmitter activity.
Why it may help Chronic Fatigue Syndrome: Ginseng may improve fatigue and cognitive function in Chronic Fatigue Syndrome by enhancing energy metabolism and reducing oxidative stress.
Why it may help Chronic Fatigue Syndrome: Rhodiola Rosea may reduce fatigue and improve mental performance in Chronic Fatigue Syndrome by modulating stress response systems and neurotransmitter activity.
Why it may help Chronic Fatigue Syndrome: NADH may improve energy levels in Chronic Fatigue Syndrome by enhancing cellular ATP production, which is often impaired in this condition.
Why it may help Chronic Fatigue Syndrome: Panax Ginseng may improve fatigue and cognitive function in Chronic Fatigue Syndrome by enhancing energy metabolism and reducing oxidative stress.
Why it may help Chronic Fatigue Syndrome: Acetyl-L-Carnitine (ALCAR) may improve fatigue in Chronic Fatigue Syndrome by enhancing mitochondrial energy production and reducing oxidative stress.
Licorice root is an herb with a sweet taste, traditionally used for various ailments, but its potential health benefits and safety require further scientific investigation.
Why it may help Chronic Fatigue Syndrome: Supports cellular energy
Why it may help Chronic Fatigue Syndrome: Omega-3 Fish Oil may reduce systemic inflammation and improve mood symptoms associated with Chronic Fatigue Syndrome.
Adrenal steroid hormone precursor that declines with age; supplementation can raise testosterone and estrogen, with the best evidence in older adults with documented low DHEA-S.
Why it may help Chronic Fatigue Syndrome: Improves muscle and sleep
Why it may help Chronic Fatigue Syndrome: Improves fatigue and cognition
Why it may help Chronic Fatigue Syndrome: Supports cognitive symptoms
Why it may help Chronic Fatigue Syndrome: Adaptogen for stress fatigue
Why it may help Chronic Fatigue Syndrome: Adaptogen for vitality
Why it may help Chronic Fatigue Syndrome: Coenzyme Q10 may improve symptoms of Chronic Fatigue Syndrome by enhancing mitochondrial function and cellular energy production, which are often impaired in affected individuals.
Magnesium is an essential mineral vital for numerous bodily functions, including energy production, muscle and nerve function, and bone health.
Why it may help Chronic Fatigue Syndrome: Vitamin B12 (Methylcobalamin) may alleviate fatigue in Chronic Fatigue Syndrome by supporting neurological function and energy metabolism.
Why it may help Chronic Fatigue Syndrome: Omega-3 fatty acids may reduce systemic inflammation and improve mood symptoms associated with Chronic Fatigue Syndrome.
Why it may help Chronic Fatigue Syndrome: Magnesium Malate may reduce muscle pain and fatigue in Chronic Fatigue Syndrome by supporting ATP production and muscle relaxation.
Why it may help Chronic Fatigue Syndrome: Probiotics may alleviate fatigue and other symptoms in Chronic Fatigue Syndrome by modulating gut microbiota, which influences immune and neurological function.
Why it may help Chronic Fatigue Syndrome: N-Acetyl Cysteine (NAC) may help Chronic Fatigue Syndrome by replenishing glutathione, an antioxidant that combats oxidative stress and inflammation, which are implicated in the condition's pathology.
Community outcomes
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How global health authorities view Chronic Fatigue Syndrome.
The National Institute for Health and Care Excellence (NICE) in the UK has updated its guidelines for ME/CFS, emphasizing personalized care, energy management (pacing), and symptom management. They advise against Graded Exercise Therapy (GET) and unsupported Cognitive Behavioral Therapy (CBT) as primary treatments. The Centers for Disease Control and Prevention (CDC) in the US also highlights the importance of symptom management and pacing. While these bodies acknowledge the complexity of ME/CFS, specific natural approaches often lack robust, large-scale clinical trial evidence to be universally endorsed as primary treatments. Many are considered complementary and should be discussed with a healthcare provider.
Indexed studies for Chronic Fatigue Syndrome, grouped by source type and quality.
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Pooled analyses across multiple human trials.
Petrucci-Nelson T, Guilhaumou S, Berrandou TE, Gensemer C, Georges A, Huff M · medRxiv : the preprint server for health sciences · 2025
Hypermobile Ehlers-Danlos syndrome (hEDS) is the most common subtype of EDS, a group of heritable connective tissue disorders. Clinically, hEDS is defined by generalized joint hypermobility and chronic musculoskeletal pain, but its impact extends beyond the musculoskeletal system. Affected individuals frequently experience autonomic, gastrointestinal, immune, and neuropsychiatric involvement, highlighting both the multisystemic nature of the condition and challenges of diagnosis. In contrast to other EDS subtypes with defined genetic causes, the molecular basis of hEDS has remained elusive. We conducted a genome-wide association study (GWAS) of hEDS across three case controls studies, including 1,815 cases and 5,008 ancestry-matched controls. Fixed-effects meta-analysis of 6.2 million variants was complemented with LDAK gene-based association testing, transcriptome-wide association studies, and integrative annotation across multiple tissues and cell types including eQTLs, enhancer mar
Schumann A, Di Giuliano M, Schulz S, de la Cruz F, Kreuder T, Seifert G · Brain communications · 2025
Mental fatigue is a significant psychopathological symptom that has recently gained attention, particularly in chronic fatigue syndrome/myalgic encephalomyelitis and Post-COVID-19 condition. However, fatigue is a clinically relevant symptom across a wide range of mental and neurological disorders. To identify a transdiagnostic functional network associated with fatigue, we conducted an activation likelihood estimation meta-analysis of neuroimaging studies. The primary inclusion criterion was studies involving any medical condition where patients exhibited significantly higher levels of fatigue compared to healthy controls. A systematic literature review across three major scientific databases identified 46 eligible neuroimaging studies, including a total of 2603 individuals. The meta-analysis of these studies revealed a widespread cortical-subcortical network involving frontal, limbic, basal ganglia and parietal structures. Three main clusters were highlighted: a frontal-striatal-limbi
Dehlia A, Guthridge MA · The Journal of infection · 2024
Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria. Clinical studies published between January 2020 and May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool. We identified 13 eligible studies that reported a total of 1973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%-60%) of LC patients satisfied ME/CFS diagnostic criteria, with fatigue, sleep disruption, and muscle/joint pain being th
Structured reviews of the full body of evidence (incl. Cochrane).
Recent research in myalgic encephalomyelitis/chronic fatigue syndrome: an evidence map.
Todhunter-Brown A, Campbell P, Broderick C, Cowie J, Davis B, Fenton C · Health technology assessment (Winchester, England) · 2025
Myalgic encephalomyelitis/chronic fatigue syndrome is a chronic condition, classified by the World Health Organization as a nervous system disease, impacting around 17 million people worldwide. Presentation involves persistent fatigue and postexertional malaise (a worsening of symptoms after minimal exertion) and a wide range of other symptoms. Case definitions have historically varied; postexertional malaise is a core diagnostic criterion in current definitions. In 2022, a James Lind Alliance Priority Setting Partnership established research priorities relating to myalgic encephalomyelitis/chronic fatigue syndrome. We created a map of myalgic encephalomyelitis/chronic fatigue syndrome evidence (2018-23), showing the volume and key characteristics of recent research in this field. We considered diagnostic criteria and how current research maps against the James Lind Alliance Priority Setting Partnership research priorities. Using a predefined protocol, we conducted a comprehensive se
Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review.
Gindri IM, Ferrari G, Pinto LPS, Bicca J, Dos Santos IK, Dallacosta D · American journal of physiology. Endocrinology and metabolism · 2024 · n=489
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NAD+ and NADH are safe and effective when acting as a supplement to humans. This systematic review of randomized clinical trials performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science, and Scopus. Secondary search included the databases (e.g., Clinical trials.gov, Rebec, Google Scholar - advance). Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using version 2 of the Cochrane risk of bias tool for randomized trials. This review includes 10 studies, with a total of 489 part
Reid S, Chalder T, Cleare A, Hotopf M, Wessely S · BMJ clinical evidence · 2011
Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the followin
Controlled human studies with random assignment.
Kodama S, Nakata M, Konishi N, Yoshino M, Fujisawa A, Naganuma M · Nutrients · 2026 · n=56
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency. Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12. Results: Mean sympto
Kodama S, Konishi N, Hirai Y, Fujisawa A, Nakata M, Teramukai S · Nutrition (Burbank, Los Angeles County, Calif.) · 2025 · n=80
Prolonged symptoms have been reported following both COVID-19 infection and vaccination, with some cases leading to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Of 80 patients presenting to our hospital with postvaccination syndrome, 28 met the diagnostic criteria for ME/CFS. We conducted a retrospective study on these 28 patients. We measured serum 25-hydroxyvitamin D levels in 28 patients who developed ME/CFS after COVID-19 vaccination between August 2022 and February 2024. Vitamin D replacement therapy included dietary counseling, sun exposure recommendations, and oral vitamin D supplementation. We evaluated changes in blood vitamin D levels and symptom improvement. At initial visit, 27 of 28 patients diagnosed with ME/CFS had insufficient or deficient serum 25-hydroxyvitamin D levels (16 ± 4 ng/mL, mean ± SD). Following vitamin D replacement therapy, we observed an increase in blood vitamin D levels (28 ± 5 ng/mL) associated with a decrease in ME/CF
Godlewska BR, Sylvester AL, Emir UE, Sharpley AL, Clarke WT, Martens MAG · Nutrients · 2024
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS. Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments. Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004).
Cohort, case-control, and cross-sectional human studies.
Li J, Cao H, Zhu Z, Zhai X, Xing A, Zeng S · Computational biology and chemistry · 2026
Chronic fatigue syndrome (CFS) is a debilitating multisystem disorder with persistent fatigue and functional impairment, yet remains underdiagnosed due to symptom heterogeneity and the lack of objective biomarkers. Developing a lightweight, interpretable diagnostic model requires systematic optimization of the entire analytical pipeline-from control group selection to biomarker identification and model construction. We developed a comprehensive pipeline optimization framework using UK Biobank metabolomic and blood biochemical data (1137 CFS cases; 66,838 controls). Unlike previous studies, our control group included both healthy individuals and patients with CFS-overlapping conditions. We employed stratified bootstrap sampling (1000 iterations) instead of traditional random sampling to ensure balanced covariate distributions between cases and controls. Our systematic approach compared 7 missing value imputation methods, 9 feature selection techniques, and 11 machine learning/deep lear
Missailidis D, Armstrong CW, Anderson D, Allan CY, Sanislav O, Smith PK · Journal of translational medicine · 2026
In recent years, evidence has indicated a metabolic shift towards increased demand for lipids in various lymphoid cell populations from people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We previously screened the mitochondrial function and gene expression of B cell-derived lymphoblastoid cell lines (LCLs) generated from the blood of people with ME/CFS to characterise a model for hypothesis discovery and testing, observing elevated expression of gene products facilitating amino acid and fatty acid degradation for energy. In this follow-up study we have expanded this characterisation by profiling the polar metabolomes and non-polar lipidomes of an all-female cohort of 17 healthy control and 15 ME/CFS LCLs, and we integrated this new data with the previously generated proteomic and transcriptomic data. In the polar metabolome we detected no significantly altered individual features, while integrated multi-omic analysis by MetaboAnalyst indicated 15 dysregulated pa
Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity.
Beentjes SV, Miralles Méharon A, Kaczmarczyk J, Cassar A, Samms GL, Hejazi NS · EMBO molecular medicine · 2025
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common female-biased disease. ME/CFS diagnosis is hindered by the absence of biomarkers that are unaffected by patients' low physical activity level. Our analysis used semi-parametric efficient estimators, an initial Super Learner fit followed by a one-step correction, three mediators, and natural direct and indirect estimands, to decompose the average effect of ME/CFS status on molecular and cellular traits. For this, we used UK Biobank data for up to 1455 ME/CFS cases and 131,303 controls. Hundreds of traits differed significantly between cases and controls, including 116 significant for both female and male cohorts. These were indicative of chronic inflammation, insulin resistance and liver disease. Nine of 14 traits were replicated in the smaller All-of-Us cohort. Results cannot be explained by restricted activity: via an activity mediator, ME/CFS status significantly affected only 1 of 3237 traits. Individuals with p
Public-health agencies: NCCIH, NIH, CDC, NHS.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
CDC · Strength: null
This CDC page provides information on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), including symptoms, diagnosis, and management strategies. It aims to educate healthcare providers and the public.
Chronic fatigue syndrome (CFS/ME)
NHS · Strength: null
The NHS provides information on chronic fatigue syndrome (CFS/ME), covering symptoms, causes, diagnosis, and treatment options available in the UK. It aims to offer accessible health guidance to the public.
Registered ongoing or completed trials (ClinicalTrials.gov).
n=173 · NCT04026425 · COMPLETED · COMPLETED
This study aims to collect and identify key outcome measures or disease parameters in ME/CFS that are altered during elevated symptoms relative to baseline by gathering information before and after symptom provocation using a two-day cardiopulmonary exercise test.
n=54 · NCT02156128 · COMPLETED · COMPLETED
The aim of this study is to examine if repetitive computerized cognitive training improves working memory in patients who are on sick leave due to complex symptom disorders (chronic pain, chronic fatigue, anxiety, depression and or sleep disorders), and whether effects of cognitive control training transfer to other tasks.
n=3 · NCT00977171 · TERMINATED · TERMINATED
A subset of patients suffering from chronic fatigue syndrome exhibit symptoms of neurally mediated hypotension. While the underlying pathophysiology of chronic fatigue syndrome is not precisely understood, a dysfunction of the autonomic nervous system is thought to play a role in this subset of patients. In several small studies, subjects within this subset have noted improvement in their chronic fatigue symptoms when treated for their neurally mediated hypotension. As droxidopa acts on the autonomic nervous system and has been shown to ameliorate symptoms of neurally mediated hypotension, it is hypothesized that droxidopa could aid in the treatment of chronic fatigue symptoms. Neurally mediated hypotension has been associated with patients suffering from chronic fatigue syndrome. Droxidopa meanwhile has been approved in Japan for the treatment of the symptoms of neurogenic orthostatic hypotension. As such, it is hypothesized that regulating the autonomic nervous system in patients with Chronic fatigue syndrome may prove to be clinically beneficial.
Curated cross-source summaries (TRIP Database and similar).
Cochrane Library: Chronic Fatigue Syndrome
Cochrane
The Cochrane Library provides systematic reviews and meta-analyses of healthcare interventions, including those related to chronic fatigue syndrome. It aggregates high-quality evidence to inform clinical decision-making.
TRIP Database: Chronic Fatigue Syndrome
TRIP Database
The TRIP Database is a clinical search engine designed to allow users to quickly and easily find high-quality research evidence to support their practice. Searching for Chronic Fatigue Syndrome provides access to a wide range of evidence-based resources.
Cochrane Reviews on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Cochrane
Cochrane Library offers systematic reviews and meta-analyses on various interventions and aspects related to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, synthesizing evidence for informed decision-making.
Conventional care for Chronic Fatigue Syndrome typically involves symptom management, including pain relievers, sleep aids, and antidepressants, as well as strategies like pacing and cognitive behavioral therapy. A multidisciplinary approach involving various healthcare professionals is often recommended to address the diverse symptoms and impacts of the condition.
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The information provided is for educational purposes only and does not constitute medical advice. Chronic Fatigue Syndrome is a complex condition requiring professional medical diagnosis and management. Always consult with a qualified healthcare provider before making any decisions about your health
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