ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

21–40 of 214 studies

Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome.

Ostojic, Sergej M, Stojanovic, Marko, Drid, Patrik et al.·Nutrients·2016

Researchers tested whether a supplement called guanidinoacetic acid (GAA) could help women with ME/CFS. Twenty-one women took either GAA or a placebo for three months. While GAA increased muscle creatine levels and improved some measures of strength and aerobic power, it did not reduce fatigue or muscle pain—the main symptoms patients care about most.

Energy Metabolism

E1 ReplicatedCohortPEM requiredObservational

Metabolic features of chronic fatigue syndrome

Robert K. Naviaux, Jane C. Naviaux, Kefeng Li et al.·Proceedings of the National Academy of Sciences (PNAS)·2016·n=84

This study analyzed blood metabolites from 84 ME/CFS patients and 45 healthy controls using untargeted metabolomics. Researchers found 80% of the abnormal metabolites were decreased in ME/CFS patients, suggesting a hypometabolic state — the body running in energy conservation mode. The pattern resembled a 'dauer-like' state seen in organisms under stress.

BiomarkersEnergy Metabolism

E1 ReplicatedTrialPEM not requiredRCT

Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?

Castro-Marrero, Jesús, Cordero, Mario D, Segundo, María José et al.·Antioxidants & redox signaling·2015

This 8-week study tested whether taking two supplements—coenzyme Q10 and NADH—could reduce fatigue in people with ME/CFS. Seventy-three Spanish patients received either the supplements or a placebo. The group taking the supplements reported less fatigue and showed improvements in blood markers related to energy production and oxidative stress compared to the placebo group.

Energy Metabolism

E1 ReplicatedTrialPEM not requiredRCT

Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.

Plioplys, A V, Plioplys, S·Neuropsychobiology·1997

This study tested whether two medicines—L-carnitine and amantadine—could help reduce fatigue in ME/CFS patients. Researchers gave 30 patients each medicine for 2 months to compare which worked better. L-carnitine was well-tolerated and showed improvement in most measured symptoms, while amantadine caused side effects that forced half the patients to stop taking it.

Energy Metabolism

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

E2 ModerateCohortPEM unclearObservational

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.

Gile, Brooke, Bulbule, Sarojini, Toriola, Mubaraq A et al.·Journal of translational medicine·2026

A pilot study observed that people with ME/CFS who received low-dose rapamycin reported improvements in fatigue symptoms over 90 days, and blood tests showed changes in purine metabolism and mitochondrial energy markers. However, this was a small observational study without a placebo control group, so it does not yet establish whether rapamycin actually causes these improvements or whether the observed biochemical changes are responsible for symptom relief.

NeuroinflammationBiomarkersEnergy MetabolismInterventions

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

E2 ModerateCohortPEM unclearObservational

Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID.

Moezzi, Atefeh, Elremaly, Wesam, Leveau, Corinne et al.·International journal of molecular sciences·2026

This study observed that Long COVID patients with different versions of a protein called haptoglobin showed different patterns of cognitive problems after physical exertion. Patients carrying certain haptoglobin variants (Hp2) reported worse fatigue and cognitive decline following a challenge test, while those with the Hp1-1 variant showed better cognitive resilience. The findings are preliminary and come from a small group; larger studies are needed to confirm whether haptoglobin type could help identify which Long COVID patients are at higher risk for these cognitive changes.

BiomarkersEnergy MetabolismCognitive ImpairmentLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome.

Donchev, Deyan, Nikolova, Ralitsa, Vaseva, Katya et al.·Biomedicines·2026

Researchers compared gut bacteria in people with ME/CFS, long COVID, and healthy controls using stool samples. They observed that both ME/CFS and long COVID showed similar patterns of bacterial changes—including more of a bacterium called Sutterella and less of others—compared to healthy people, though the two conditions were not identical. The strongest links between bacterial patterns and symptoms were observed in fatigue and physical symptoms, though this is one study and findings require confirmation in larger follow-up research.

BiomarkersGut MicrobiomeEnergy MetabolismLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection.

Yagin, Fatma Hilal, Korkmaz, Yavuz, Colak, Cemil et al.·International journal of molecular sciences·2026

Researchers analysed blood metabolite patterns (small molecules in blood) from 106 people with ME/CFS and 91 healthy controls using machine learning to see whether these patterns could distinguish ME/CFS from health. A computer model called Explainable Boosting Machine achieved 91% accuracy in this one study group. Importantly, the findings remain preliminary—they describe associations observed in this cross-sectional sample and require external validation in new populations before clinical use.

BiomarkersEnergy MetabolismDiagnostics

E2 ModerateCohortPEM unclearCross-Sectional

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Ikeda, Gentaro, Koike-Ieki, Mariko, Inoue, Hiroyuki et al.·Open forum infectious diseases·2026

Researchers analyzed tiny cell particles called extracellular vesicles in blood samples from people with Long COVID, ME/CFS, and healthy controls. They observed that both Long COVID and ME/CFS groups had elevated levels of certain immune cell-derived particles and alterations in mitochondrial (energy-producing) markers within B cells and other immune cells, though the findings were not identical between groups. These preliminary results suggest there may be shared immune and metabolic changes in these conditions, but the meaning of these changes for patient health remains unclear and needs further study.

BiomarkersEnergy MetabolismImmune SystemLong COVID Overlap

E2 ModerateCohortPEM unclearCross-Sectional

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis.

Rostami-Afshari, Bita, Elremaly, Wesam, McGregor, Neil R et al.·International journal of molecular sciences·2025

Researchers found that people with ME have lower levels of a kidney protein called SMPDL3B in their blood and urine compared to healthy people. This protein is important for keeping the kidney's filtering system working properly. The study also identified several metabolic imbalances in ME patients' blood that are linked to kidney problems. These findings suggest that kidney function may be affected in ME, and this protein could potentially be used as a simple blood test to help understand the disease.

BiomarkersEnergy Metabolism

E2 ModerateCohortPEM unclearLongitudinal

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.

Xiong, Ruoyun, Aiken, Elizabeth, Caldwell, Ryan et al.·Nature medicine·2025

Researchers used artificial intelligence to analyze blood, gut bacteria, immune cells, and symptoms from 249 ME/CFS patients tracked over 4 years. The AI model discovered that ME/CFS involves abnormal patterns in gut bacteria products, blood fats, and immune cells that attack infections—particularly special T cells that become overactive. These findings suggest ME/CFS isn't caused by a single problem but by multiple connected systems going wrong together.

BiomarkersGut MicrobiomeEnergy MetabolismImmune System

E2 ModerateCohortPEM not requiredCross-Sectional

Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID.

Al Masoodi, Wasim Talib Mahdi, Radhi, Sami Waheed, Abdalsada, Habiba Khdair et al.·PloS one·2025

This study looked at 90 people, some with Long COVID and some without, to understand why Long COVID patients develop depression, anxiety, and chronic fatigue. Researchers measured several substances in the blood related to inflammation and metabolism. They found that people with Long COVID had higher levels of inflammatory markers and abnormal insulin function, and these changes were linked to their mood and fatigue symptoms.

NeuroinflammationEnergy MetabolismImmune System

E2 ModerateCohortPEM unclearCross-Sectional

Leveraging Explainable Automated Machine Learning (AutoML) and Metabolomics for Robust Diagnosis and Pathophysiological Insights in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Yagin, Fatma Hilal, Colak, Cemil, Al-Hashem, Fahaid et al.·Diagnostics (Basel, Switzerland)·2025

Researchers used advanced computer learning and blood tests to find chemical markers that could help diagnose ME/CFS. They analyzed 888 different chemicals in blood samples from 106 ME/CFS patients and 91 healthy people, and found a pattern of chemical imbalances that correctly identified ME/CFS patients 87% of the time. The key chemical imbalances involved energy production in cells, inflammation, and gut health—areas that have long been suspected in ME/CFS.

Energy Metabolism

E2 ModerateCohortPEM not requiredCase-Control

Alterations in gut microbiota and associated metabolites in patients with chronic fatigue syndrome.

Cheng, Xinxin, Wang, Wenkuan, Xu, Tingting et al.·Scientific reports·2025

This study looked at the bacteria living in the gut of people with ME/CFS compared to healthy people, and found that ME/CFS patients have fewer types of bacteria and lower levels of helpful compounds called short-chain fatty acids (SCFAs) that bacteria produce. The study found that people with ME/CFS who eat more fiber have higher levels of these beneficial compounds, suggesting diet may help restore some of the bacterial imbalances seen in ME/CFS.

Energy Metabolism

E2 ModerateCohortPEM unclearCase-Control

Case-control study on post-COVID-19 conditions reveals severe acute infection and chronic pulmonary disease as potential risk factors.

Ghosh, Pritha, Niesen, Michiel J M, Pawlowski, Colin et al.·iScience·2024

This study looked at nearly 89,000 COVID-19 patients to understand why some develop long COVID (lasting symptoms months after infection) while others recover quickly. Researchers found that people with a history of lung disease, migraines, or fibromyalgia were more likely to develop long COVID, and those who had severe acute COVID infections were also at higher risk. The findings suggest that reducing the severity of the initial COVID infection, especially in vulnerable patients, might help prevent long COVID from developing.

Energy Metabolism

E2 ModerateCohortPEM unclearCross-Sectional

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

Saito, Suguru, Shahbaz, Shima, Luo, Xian et al.·Frontiers in immunology·2024

This study looked at blood samples from people with long COVID who have ME/CFS-like symptoms and compared them to people who recovered from COVID, people with acute COVID, and people who never had COVID. Researchers found that long COVID patients had unusual chemical patterns in their blood, higher levels of inflammation-promoting substances, and lower energy molecules (ATP). They also discovered that two specific chemicals (sarcosine and serine) were reduced in long COVID patients and connected to depression, anxiety, and brain fog.

Energy MetabolismImmune System

E2 ModerateCohortPEM not requiredObservational

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome.

Raij, Tommi, Raij, Kari·Frontiers in endocrinology·2024

This study examined whether a supplement called L-carnitine could help reduce fatigue by increasing serotonin levels in the blood. Researchers tracked 12 people with ME/CFS and 40 people with hypothyroidism who were experiencing fatigue, measuring their serotonin and fatigue levels before and after taking L-carnitine for 7 weeks. They found that L-carnitine increased serotonin levels significantly and fatigue decreased by about half in both groups, suggesting a possible connection between low serotonin and fatigue.

BiomarkersEnergy Metabolism

E2 ModerateCohortPEM unclearLongitudinal

Muscle abnormalities worsen after post-exertional malaise in long COVID.

Appelman, Brent, Charlton, Braeden T, Goulding, Richie P et al.·Nature communications·2024

This study looked at muscle tissue changes in long COVID patients, particularly focusing on post-exertional malaise (PEM)—the worsening of fatigue and pain after activity. Researchers found that muscles in long COVID patients showed structural damage, metabolic problems, and unusual deposits that got worse after activity triggered PEM. These findings help explain why exertion makes symptoms worse in some long COVID patients.

Energy MetabolismPost-Exertional Malaise

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Evidence browser

Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome.

Metabolic features of chronic fatigue syndrome

Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?

Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome.

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

Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study.

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

Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID.

Comparative Gut Microbiome Alterations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID-19 Syndrome.

Metabolomic Classification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome via Explainable Ensemble Learning and Pareto-Guided Feature Selection.

Plasma Extracellular Vesicle Surface Marker Profiling Reveals Immune Cell-Associated Mitochondrial Membrane Potential Alterations in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis.

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.

Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID.

Leveraging Explainable Automated Machine Learning (AutoML) and Metabolomics for Robust Diagnosis and Pathophysiological Insights in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Alterations in gut microbiota and associated metabolites in patients with chronic fatigue syndrome.

Case-control study on post-COVID-19 conditions reveals severe acute infection and chronic pulmonary disease as potential risk factors.

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome.

Muscle abnormalities worsen after post-exertional malaise in long COVID.

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