Topic

Metabolic Dysfunction

Domain: Metabolism

PEM-relevant research

10 studies in the atlas

Altered energy metabolism and mitochondrial function in ME/CFS patients.

What We Know

Naviaux et al. (2016) found a hypometabolic state in ME/CFS resembling a dauer-like survival response. Metabolomics studies consistently show disrupted amino acid, lipid, and purine pathways.

What We Think

Mitochondrial function assays, NAD+ metabolism research, and seahorse respirometry are actively being applied to ME/CFS cohorts.

What We Don't Know

Causal direction is unknown — metabolic changes may be downstream of other pathology. Sample sizes remain small. Most findings need replication in independent cohorts.

Studies in this Topic

E0 ConsensusPEM ?Moderate confidenceReviewed

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease.

Arron, Hayley E, Marsh, Benjamin D, Kell, Douglas B et al.·Frontiers in immunology·2024

This review examines what we know about ME/CFS by looking at how the disease develops from a combination of genetic factors, infections, and immune problems. The researchers found that ME/CFS appears to result from multiple body systems going wrong at the same time—including the immune system, inflammation, digestive health, and energy production. The study argues that doctors and scientists need to stop looking at ME/CFS as a single problem and instead understand it as a complex condition involving many interconnected issues.

Metabolic DysfunctionImmune Dysregulation

E0 ConsensusPEM ✓Moderate confidenceReviewed

[Myalgic encephalomyelitis or chronic fatigue syndrome].

Brinth, Louise, Nielsen, Henrik, Varming, Kim et al.·Ugeskrift for laeger·2019

ME/CFS is a serious condition that causes extreme tiredness affecting both mind and body, along with pain, sleep problems, difficulty thinking clearly, and a symptom called post-exertional malaise where activity makes symptoms worse. Research has found changes in patients' cells, hormones, immune systems, and how their bodies process energy, which could lead to better ways to diagnose and treat this condition.

Metabolic DysfunctionBiomarkersPost-Exertional MalaiseImmune Dysregulation

E0 ConsensusPEM ?Moderate confidenceReviewed

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease.

Sotzny, Franziska, Blanco, Julià, Capelli, Enrica et al.·Autoimmunity reviews·2018

This review examines evidence that ME/CFS may be caused by the immune system attacking the body (autoimmune disease). Researchers found that people with ME/CFS have unusual immune patterns, including abnormal antibodies and changes in immune cells. Importantly, a treatment that removes certain immune cells (rituximab) helped about half of ME/CFS patients in clinical trials, suggesting an autoimmune mechanism in at least some people.

Metabolic DysfunctionImmune Dysregulation

E0 ConsensusPEM ✓Moderate confidenceMachine draft

Insights into the Complex Biological Network Underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Dudova, Dobrina, Bozhkova, Martina, Petrov, Steliyan et al.·International journal of molecular sciences·2025

This review brings together research showing that ME/CFS involves multiple body systems going wrong at the same time—including problems with the immune system, energy production in cells, hormone balance, and gut health. These problems appear to feed into each other, creating a cycle that keeps the illness going. The findings suggest ME/CFS is not just one thing breaking down, but rather many interconnected systems all struggling together.

Metabolic DysfunctionNeuroinflammationPost-Exertional MalaiseImmune Dysregulation

E1 ReplicatedPEM ✓Moderate confidenceReviewed

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.

Metabolic DysfunctionBiomarkers

E1 ReplicatedPEM ?Moderate confidenceMachine draft

RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Cash, Alan, Vernon, Suzanne D, Rond, Candace et al.·Frontiers in neurology·2024

This study tested whether a supplement called oxaloacetate could help reduce fatigue in ME/CFS patients. Eighty-two people with ME/CFS took either 2,000 mg of oxaloacetate or a placebo daily for three months. The oxaloacetate group experienced a significant 25% reduction in fatigue, while the placebo group only improved by 10%, and the supplement was well tolerated with no safety concerns.

Metabolic Dysfunction

E2 ModeratePEM ?PreliminaryReviewed

Evidence of mitochondrial dysfunction and impaired redox signalling in a subgroup of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Cara Tomas, Jessica Newton, Stuart Watson·The EPMA Journal·2017·n=25

This UK study analyzed mitochondrial function in immune cells from ME/CFS patients using the Seahorse assay. They found reduced ATP production capacity, impaired electron transport chain function, and altered redox signaling in a subgroup of ME/CFS patients compared to healthy controls.

Metabolic Dysfunction

E3 PreliminaryPEM ✓PreliminaryReviewed

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·medRxiv : the preprint server for health sciences·2025

This study found that people with ME/CFS may have an overactive immune system that responds too strongly to germs and infections. The research showed problems with how the body produces energy and manages inflammation, and these problems got worse after exercise in ME/CFS patients but not in healthy people. The findings suggest multiple biological systems are working abnormally in ME/CFS, which could help doctors develop better treatments.

Metabolic DysfunctionPost-Exertional MalaiseImmune Dysregulation

E3 PreliminaryPEM ✓PreliminaryReviewed

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Che, Xiaoyu, Ranjan, Amit, Guo, Cheng et al.·npj metabolic health and disease·2025

This study examined blood samples and immune responses in ME/CFS patients to understand why they experience extreme fatigue and feeling worse after activity. Researchers found that patients' immune systems overreact to germs, their bodies have trouble producing energy efficiently, and they have several chemical imbalances in their blood. These problems got worse after exercise and matched how sick patients felt.

Metabolic DysfunctionPost-Exertional MalaiseImmune Dysregulation

E3 PreliminaryPEM ✓Moderate confidenceMachine draft

Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3rd International Conference of the Charité Fatigue Center.

Fehrer, Annick, Windzio, Lara, Schoening, Simon et al.·Autoimmunity reviews·2026

Nearly 4,000 ME/CFS researchers and experts gathered at an international conference in May 2025 to share the latest discoveries about this serious illness. They discussed how ME/CFS develops, better ways to diagnose it, and new treatments being tested. The conference highlighted that while COVID-19 has brought more attention and funding to ME/CFS research, the disease is still not well understood and needs much more study.

Metabolic DysfunctionPost-Exertional MalaiseImmune Dysregulation