Evidence browser

Energy MetabolismImmune System

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.

Proal, Amy, Marshall, Trevor·Frontiers in pediatrics·2018

This review explores the idea that ME/CFS may be caused by persistent infections (like Epstein-Barr virus) that disrupt the body's microbial communities and normal cell functions. These infections can interfere with how cells work, how genes are expressed, and how the immune system responds, potentially leading to the chronic symptoms patients experience. The authors suggest that treating ME/CFS might involve helping the immune system fight these persistent infections.

Chronic fatigue and immune deficiency syndrome (CFIDS), cellular metabolism, and ionizing radiation: a review of contemporary scientific literature and suggested directions for future research.

Rusin, Andrej, Seymour, Colin, Mothersill, Carmel·International journal of radiation biology·2018

This study looked at whether ME/CFS and radiation sickness might share similar problems in how cells produce energy. Researchers found evidence that both conditions may involve damage to mitochondria (the "power plants" of cells) and disrupted energy production. They suggest specific biological pathways worth studying to better understand ME/CFS and possibly develop new treatments.

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Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS.

Brown, Audrey E, Dibnah, Beth, Fisher, Emily et al.·Bioscience reports·2018

This study looked at muscle cells from ME/CFS patients to understand why their muscles struggle to use energy properly. Researchers tested two drugs (metformin and compound 991) that can activate AMPK, a protein that helps cells use glucose for energy. Both drugs successfully improved how the muscle cells used glucose, suggesting that the problem in ME/CFS muscles is not AMPK itself, but something that happens before AMPK gets activated.

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[Comparison of differential metabolites in urine of the middle school students with chronic fatigue syndrome before and after exercise].

Chi, Ai-Ping, Wang, Zi-Nan, Shi, Bing et al.·Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology·2018

This study looked at chemicals in the urine of teenagers with ME/CFS before and after exercise to understand how their bodies process energy differently. Researchers found that people with ME/CFS had abnormal levels of several metabolites (chemical byproducts), and these changes got worse after exercise, suggesting their bodies struggle to recover from physical activity.

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Therapeutic Effect and Metabolic Mechanism of A Selenium-Polysaccharide from Ziyang Green Tea on Chronic Fatigue Syndrome.

Shao, Changzhuan, Song, Jing, Zhao, Shanguang et al.·Polymers·2018

Researchers tested whether a compound called selenium-polysaccharide (Se-TP) from a Chinese green tea called Ziyang could help rats with fatigue similar to ME/CFS. They found that the treatment improved certain markers in the rats' blood and urine, suggesting it may work by affecting how the body makes and uses steroid hormones and processes amino acids.

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure.

Lacourt, Tamara E, Vichaya, Elisabeth G, Chiu, Gabriel S et al.·Frontiers in behavioral neuroscience·2018

This study explores why people with ME/CFS experience persistent fatigue by examining how inflammation in the body may damage cells' ability to produce energy. The researchers propose that chronic inflammation forces cells to switch to a less efficient energy-production method, while at the same time the body may be spending energy at rates it cannot sustain, creating an energy crisis. Sleep problems and disrupted body rhythms may also play a role in this imbalance.

Energy MetabolismImmune System

Dehydroepiandrosterone Research: Past, Current, and Future.

Klinge, Carolyn M, Clark, Barbara J, Prough, Russell A·Vitamins and hormones·2018

This is a historical review of dehydroepiandrosterone (DHEA), a hormone that naturally decreases with age. Scientists have studied whether DHEA might help with various health conditions including chronic fatigue syndrome, but the evidence in humans is limited. While some benefits have been found in postmenopausal women and certain autoimmune disorders, most human studies show only weak connections between DHEA levels and disease outcomes.

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Tenuous link between chronic fatigue syndrome and pyruvate dehydrogenase deficiency.

Bliksrud, Yngve Thomas·Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke·2017

This study examined whether a specific metabolic enzyme problem called pyruvate dehydrogenase deficiency might be connected to ME/CFS. The researchers found only a weak or unclear link between this enzyme deficiency and ME/CFS symptoms, suggesting it is not a major cause of the illness for most patients.

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.

Tomas, Cara, Brown, Audrey, Strassheim, Victoria et al.·PloS one·2017

This study examined how cells in ME/CFS patients produce energy differently than in healthy people. Researchers tested immune cells from patients and found that when these cells are under stress, they cannot ramp up their energy production as much as healthy cells can. This suggests that ME/CFS patients' cells may struggle to meet energy demands, especially during periods of physical or mental exertion.

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Detection of Urine Metabolites in a Rat Model of Chronic Fatigue Syndrome before and after Exercise.

Shao, Changzhuan, Ren, Yiming, Wang, Zinan et al.·BioMed research international·2017

Researchers used rats exposed to stress and exercise to model ME/CFS and then measured chemicals in their urine before and after exercise. They found abnormalities in how the rats' bodies produce energy and process hormones, particularly in molecules called sphingosine and a hormone precursor called 21-hydroxypregnenolone. These findings suggest that ME/CFS may involve disrupted energy metabolism and problems with the body's stress-response system.

Energy MetabolismImmune SystemPost-Exertional Malaise

Elevated Energy Production in Chronic Fatigue Syndrome Patients.

Lawson, Nick, Hsieh, Chung-Han, March, Dana et al.·Journal of nature and science·2016

This study examined how cells in ME/CFS patients produce energy. Surprisingly, researchers found that patients' blood cells actually produced MORE energy (ATP) than healthy controls, but much of this energy came from sources other than mitochondria (the cell's power plants). The study suggests that ME/CFS fatigue may not be caused by a lack of energy, but rather by an abnormal way the body is producing energy.

Clinical Uses of Membrane Lipid Replacement Supplements in Restoring Membrane Function and Reducing Fatigue in Chronic Diseases and Cancer.

Nicolson, Garth L, Rosenblatt, Steven, de Mattos, Gonzalo Ferreira et al.·Discoveries (Craiova, Romania)·2016

This study examines oral supplements containing special fats (lipids) and antioxidants designed to repair damaged cell membranes, which the authors suggest accumulate in aging and chronic diseases like ME/CFS. The researchers reviewed evidence suggesting these supplements may help reduce fatigue and restore energy-producing mitochondria in cells. The authors propose this approach could benefit people with various conditions including chronic fatigue syndrome, fibromyalgia, and other chronic illnesses.

NeuroinflammationEnergy MetabolismImmune System

The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.

Morris, Gerwyn, Walder, Ken, Puri, Basant K et al.·Molecular neurobiology·2016

This review explains how harmful molecules called oxidative and nitrosative stress damage specific fatty structures in cells that are important for cell communication and brain function. These damaged structures may contribute to ME/CFS, along with other conditions affecting the brain and immune system. The authors suggest that omega-3 fatty acid supplements might help restore these damaged cellular structures.

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Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome.

Fluge, Øystein, Mella, Olav, Bruland, Ove et al.·JCI insight·2016

This study found that people with ME/CFS have abnormal patterns of amino acids (building blocks of protein) in their blood, suggesting their bodies struggle to produce energy efficiently through normal metabolic pathways. The research identified a specific problem with an enzyme called pyruvate dehydrogenase that helps convert fuel into cellular energy, and showed that cells from ME/CFS patients produce excess lactate (a byproduct of incomplete energy metabolism) when stressed. These findings help explain why ME/CFS patients experience exhaustion after exertion and poor recovery.

Metabolic mechanism of a polysaccharide from Schisandra chinensis to relieve chronic fatigue syndrome.

Chi, Aiping, Zhang, Yang, Kang, Yijiang et al.·International journal of biological macromolecules·2016

Researchers tested whether a natural substance extracted from Schisandra chinensis (a traditional Chinese fruit) could help reduce fatigue in rats with a condition similar to ME/CFS. They found that the substance, called SCP, helped improve the rats' activity and behavior. The improvement appeared to work by fixing problems in how the rats' bodies were processing energy and certain amino acids.

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The Many Neuroprogressive Actions of Tryptophan Catabolites (TRYCATs) that may be Associated with the Pathophysiology of Neuro-Immune Disorders.

Morris, Gerwyn, Carvalho, André F, Anderson, George et al.·Current pharmaceutical design·2016

When the body has chronic inflammation and immune activation, it breaks down an amino acid called tryptophan differently than usual, creating byproducts called TRYCATs. Some of these byproducts can damage nerve cells and mitochondria (the energy factories in cells), while others may protect the brain but at the cost of causing brain fog and emotional problems. This review examines how this abnormal tryptophan breakdown might contribute to ME/CFS and other neurological conditions.

NeuroinflammationEnergy MetabolismImmune System

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In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome.

Lengert, Nicor, Drossel, Barbara·Biophysical chemistry·2015

This study used computer models to understand why people with ME/CFS struggle with exercise. The researchers simulated what happens in muscle cells during and after physical activity, focusing on mitochondria—the parts of cells that produce energy. Their model showed that when mitochondrial function is reduced, muscles can't make enough energy (ATP), which causes them to accumulate toxic substances like lactate and acid, and can lead to cell death. Importantly, repeated exercise made this problem much worse in their simulations.

Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome.

Brown, Audrey E, Jones, David E, Walker, Mark et al.·PloS one·2015

Researchers grew muscle cells from ME/CFS patients and healthy people in the lab and stimulated them electrically to mimic exercise. They found that muscle cells from ME/CFS patients didn't respond normally to this simulated exercise: they failed to activate a key energy-sensing protein (AMPK) and didn't increase glucose uptake like healthy cells did. This suggests the problem may be rooted in how the muscle cells themselves are built or programmed, not just from being inactive.

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Yang/Qi invigoration: an herbal therapy for chronic fatigue syndrome with yang deficiency?

Leong, Pou Kuan, Wong, Hoi Shan, Chen, Jihang et al.·Evidence-based complementary and alternative medicine : eCAM·2015

This study explores whether certain Chinese herbal medicines might help ME/CFS by improving how cells produce energy. The researchers suggest that traditional concepts of 'Yang' and 'Qi' deficiency in Chinese medicine may relate to mitochondrial problems (the energy-producing parts of cells) seen in ME/CFS. They propose that specific herbs like Cistanches and Schisandrae might boost mitochondrial function and help patients with fatigue.

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Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies.

Samsel, Anthony, Seneff, Stephanie·Surgical neurology international·2015

This paper explores whether glyphosate (a common herbicide in Roundup) might deplete the body of manganese, an essential mineral needed for brain health, nerve protection, and gut bacteria balance. The authors suggest that low manganese levels could contribute to various neurological conditions and gut problems, and they propose a mechanism connecting herbicide exposure to these health issues.