Evidence browser

Metabolic reprogramming in diabetes and other endocrine and metabolic disorders: exploring the Warburg effect, ketones, and SGLT2 inhibitors.

Carrera-Bastos, Pedro, Muskiet, Marcel H A, Mata-Ordoñez, Fernando et al.·Reviews in endocrine & metabolic disorders·2026

This review examines a cellular energy pattern called the Warburg effect, which causes cells to shift from their normal energy-making processes to a different system that prioritizes cell growth over efficient energy production. The authors suggest this pattern occurs not just in cancer, but also in conditions like ME/CFS, diabetes, and other chronic diseases. They explore whether treatments like fasting, special diets, ketone supplements, and certain diabetes medications might help by reversing this metabolic shift.

Energy MetabolismInterventions

Recent Perspectives on the Physiological and Therapeutic Benefits of Placental Extracts in Chronic Noninfectious Diseases and Aging.

Xinliang, Zhang, Dudnik, Elena N, Gavrikov, Leonid K et al.·Current medicinal chemistry·2026

This systematic review examined studies on placental extracts—cell-free preparations derived from human or animal placenta—as potential treatments for various chronic diseases including metabolic disorders and liver disease. The review reports that these extracts were associated with improvements in liver function, muscle preservation, and metabolic markers in the studies reviewed; one study also mentioned chronic fatigue syndrome among the conditions examined. However, the authors note that large-scale, rigorously designed trials are needed to confirm whether these treatments actually work, and the quality of evidence underlying these associations remains unclear.

NeuroinflammationEnergy MetabolismImmune SystemCognitive Impairment

Pathophysiological mechanisms of post-exertional malaise: an integrative analysis based on the metabolism-immune-neuro interaction model.

Jin, Hongjiao, An, Yi, Huang, Jingwei et al.·Frontiers in immunology·2026

This systematic review proposes a framework for understanding post-exertional malaise (PEM)—the worsening of symptoms after mild activity—by examining how energy production, immune activation, and brain inflammation may be associated with each other in people with Long COVID and chronic fatigue conditions. The authors suggest that in vulnerable individuals, exercise may trigger an abnormal cascade involving damaged mitochondria (cellular energy factories), inflammatory molecules, and changes in how the brain perceives fatigue and pain. However, this is a theoretical model based on existing literature; individual mechanisms have not been directly tested in a single study.

E0 ConsensusReviewPEM requiredReview-Narrative

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.

NeuroinflammationEnergy MetabolismImmune SystemPost-Exertional Malaise

Energy MetabolismImmune System

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.

NeuroinflammationEnergy Metabolism

Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.

Hazrati, Ebrahim, Eftekhar, Seyed Parsa, Mosaed, Reza et al.·Molecular pain·2024

This review examined how a specific pathway in the body that breaks down the amino acid tryptophan might contribute to chronic pain, including in ME/CFS patients. The review looked at research across various pain conditions and depression, finding that certain chemicals produced along this pathway can either protect or damage nerve cells. The authors suggest that targeting this pathway could lead to new, non-opioid treatments for chronic pain.

E0 ConsensusReviewPEM requiredSystematic-Review

Comparison of serum acylcarnitine levels in patients with myalgic encephalomyelitis/chronic fatigue syndrome and healthy controls: a systematic review and meta-analysis.

Jinushi, Ryuhei, Masuda, Sakue, Tanisaka, Yuki et al.·Journal of translational medicine·2023

This review combined results from seven studies comparing a chemical in the blood called acylcarnitine between people with ME/CFS and healthy people. Researchers found that people with ME/CFS have significantly lower levels of this chemical. These lower levels might one day help doctors diagnose ME/CFS, though more research is needed before it can be used as a reliable test.

BiomarkersEnergy Metabolism

BiomarkersEnergy Metabolism

Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome.

Monzón-Nomdedeu, María B, Morten, Karl J, Oltra, Elisa·World journal of stem cells·2021

This review examines whether special laboratory cells called induced pluripotent stem cells (iPSCs) could be used as 'sensors' to detect ME/CFS and fibromyalgia. The researchers found that patients with these conditions have unusual chemicals in their blood and body fluids that differ from healthy people. They propose that iPSCs could be grown in patient samples to detect these abnormal chemicals, potentially helping diagnose these diseases and predict how patients might respond to future treatments.

A systematic review of nutraceutical interventions for mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome.

Maksoud, Rebekah, Balinas, Cassandra, Holden, Sean et al.·Journal of translational medicine·2021

This review looked at whether special supplements that target the energy-producing parts of cells (mitochondria) might help ME/CFS patients feel less fatigued. The researchers searched for published studies testing these supplements in ME/CFS patients and found 9 studies. About two-thirds of these studies showed some improvement in fatigue, but the overall evidence isn't strong enough yet to say these supplements definitely work.

Diagnostic and Pharmacological Potency of Creatine in Post-Viral Fatigue Syndrome.

Ostojic, Sergej M·Nutrients·2021

This review examines how creatine—a natural substance in the body that helps muscles produce energy—may be abnormal in people with post-viral fatigue syndrome (PVFS, which includes ME/CFS and long COVID). The authors looked at whether creatine supplements or related compounds might help reduce fatigue and improve function in these conditions. While some studies suggest creatine could be helpful, the review shows we still need more research to know if it actually works.

Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases.

Testai, Lara, Martelli, Alma, Flori, Lorenzo et al.·Nutrients·2021

This review examines how Coenzyme Q10 (CoQ10), a natural substance found in cells that helps produce energy, might help with various conditions including chronic fatigue syndrome. CoQ10 also has anti-inflammatory and antioxidant properties that may protect cells from damage. The researchers looked at studies on CoQ10's effects on migraine, neurological diseases, cancer, and muscle disorders to see if supplementation could improve patient health and quality of life.

Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities.

Morris, Gerwyn, Puri, Basant K, Walker, Adam J et al.·Pharmacological research·2019

This review examines what goes wrong in the bodies of ME/CFS patients and looks at treatments that might help. Researchers found that ME/CFS involves several biological problems, including inflammation, increased cellular stress, gut problems, and energy production issues. The review highlights five promising supplements—coenzyme Q10, melatonin, curcumin, molecular hydrogen, and N-acetylcysteine—that target these problems, though much more testing is needed.

E0 ConsensusReviewPEM requiredReview-Narrative

[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.

BiomarkersEnergy MetabolismImmune SystemPost-Exertional Malaise

Energy MetabolismImmune System

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.

Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review.

Wallis, Amy, Ball, Michelle, McKechnie, Sandra et al.·Journal of translational medicine·2017

This study compared symptoms reported in cases of D-lactic acidosis (a rare condition where a specific type of acid builds up in the body) with symptoms of ME/CFS. Researchers found that many neurological symptoms—like brain fog, movement problems, and nerve-related issues—appeared in both conditions. Both groups also had gut bacteria imbalances and stomach problems. The authors suggest that ME/CFS might involve similar gut-related processes as D-lactic acidosis, but stress that we need more research to understand if this connection is real.

Chronic fatigue syndrome: a personalized integrative medicine approach.

Brown, Benjamin I·Alternative therapies in health and medicine·2014

This review examines how treating ME/CFS with a personalized, whole-body approach might help more patients than current standard treatments. Rather than using a one-size-fits-all method, doctors could tailor treatment plans based on each patient's individual factors—such as diet, nutritional deficiencies, stress, gut health, and immune system problems. The authors suggest this personalized approach could lead to better outcomes and help identify which patients would benefit most from specific treatments.

Pesticides and human chronic diseases: evidences, mechanisms, and perspectives.

Mostafalou, Sara, Abdollahi, Mohammad·Toxicology and applied pharmacology·2013

This review examined whether pesticide exposure is connected to various chronic illnesses, including ME/CFS. Researchers looked at evidence showing that pesticides may damage cells and disrupt the body's normal functions through several pathways, such as causing oxidative stress, harming mitochondria (the cell's energy centers), and interfering with protein disposal systems. The review suggests pesticides could contribute to many diseases, but more specific research is needed to prove direct causation in individual conditions.

E1 ReplicatedTrialPEM unclearRCT

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.

E1 ReplicatedTrialPEM not requiredRCT

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.