Evidence browser

NeuroinflammationEnergy Metabolism

Kynurenine metabolites and ratios differ between Chronic Fatigue Syndrome, Fibromyalgia, and healthy controls.

Groven, Nina, Reitan, Solveig Klæbo, Fors, Egil Andreas et al.·Psychoneuroendocrinology·2021

This study examined a specific metabolic pathway in the blood called the kynurenine pathway, which affects how the brain functions. Researchers compared blood samples from people with ME/CFS, people with fibromyalgia, and healthy people to see if the chemical breakdown products in this pathway differed. They found that the balance of certain chemicals was different in people with these conditions, and these differences may relate to fatigue and pain symptoms.

E2 ModerateCohortPEM unclearObservational

Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms.

Nkiliza, Aurore, Parks, Megan, Cseresznye, Adam et al.·Journal of translational medicine·2021

This study analyzed fatty substances in the blood of ME/CFS patients and healthy controls to see if they differ in ways that might explain symptoms. Researchers found that men and women with ME/CFS had different patterns of these blood fats compared to healthy people. Importantly, certain blood fats were connected to the severity of fatigue, headaches, and thinking difficulties, suggesting that problems with how the body processes fats may play a role in ME/CFS symptoms.

BiomarkersEnergy MetabolismImmune System

E2 ModerateCohortPEM unclearCase-Control

Changes in DNA methylation profiles of myalgic encephalomyelitis/chronic fatigue syndrome patients reflect systemic dysfunctions.

Helliwell, A M, Sweetman, E C, Stockwell, P A et al.·Clinical epigenetics·2020

This study looked at chemical tags on DNA called methylation patterns in people with ME/CFS compared to healthy people. These tags can turn genes on or off without changing the DNA itself. Researchers found that people with ME/CFS have different methylation patterns, particularly in genes related to energy production, immune function, and brain chemistry, which may help explain why they experience the symptoms they do.

Energy MetabolismImmune System

Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Not Due to Anti-mitochondrial Antibodies.

Nilsson, Isabell, Palmer, Jeremy, Apostolou, Eirini et al.·Frontiers in medicine·2020

Researchers tested whether ME/CFS patients have immune system antibodies that attack their mitochondria (the energy-producing parts of cells), similar to what happens in a different disease called primary biliary cholangitis. They found that ME/CFS patients almost never have these specific antibodies, while patients with the other disease have them consistently. This suggests that the energy problems seen in ME/CFS are caused by something other than the immune system attacking mitochondria.

Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids.

Germain, Arnaud, Barupal, Dinesh K, Levine, Susan M et al.·Metabolites·2020

Researchers studied the chemicals in blood samples from 26 ME/CFS patients and 26 healthy controls to understand what might be different in ME/CFS. They found that ME/CFS patients have lower levels of certain fats (especially acyl cholines) and hormones (including some involved in stress response and reproduction) compared to healthy people. These chemical differences might help explain why ME/CFS causes such widespread symptoms affecting many body systems.

Energy MetabolismImmune System

Deep phenotyping of myalgic encephalomyelitis/chronic fatigue syndrome in Japanese population.

Kitami, Toshimori, Fukuda, Sanae, Kato, Tamotsu et al.·Scientific reports·2020

Researchers studied 48 ME/CFS patients and 52 healthy people in Japan to find biological markers of the disease. They tested blood samples, gut bacteria, immune cells, and sleep patterns, identifying 26 potential markers that differ between patients and healthy people. Three markers stood out as most important: certain types of white blood cells, gut bacteria composition, and fat-like molecules in the blood, which were especially linked to sleep problems in ME/CFS patients.

Energy MetabolismImmune System

Multi-omics examination of Q fever fatigue syndrome identifies similarities with chronic fatigue syndrome.

Raijmakers, Ruud P H, Roerink, Megan E, Jansen, Anne F M et al.·Journal of translational medicine·2020

This study compared people with Q fever fatigue syndrome (a prolonged tiredness that develops after a Q fever infection) to people with ME/CFS and healthy controls. Researchers examined three types of biological markers: gut bacteria, blood chemicals, and inflammatory proteins. They found that people with Q fever fatigue syndrome have very similar patterns to ME/CFS patients, suggesting these two conditions may share similar underlying biological mechanisms.

E2 ModerateCohortPEM requiredCross-Sectional

Elevated blood lactate in resting conditions correlate with post-exertional malaise severity in patients with Myalgic encephalomyelitis/Chronic fatigue syndrome.

Ghali, Alaa, Lacout, Carole, Ghali, Maria et al.·Scientific reports·2019

This study looked at lactate levels (a substance produced by muscles) in the blood of ME/CFS patients who were at rest. Researchers found that about 45% of patients had higher-than-normal lactate levels even when not exercising. Importantly, patients with elevated resting lactate tended to experience more severe post-exertional malaise (the symptom flare-ups that follow physical activity).

Energy MetabolismPost-Exertional Malaise

E2 ModerateCohortPEM unclearObservational

MtDNA population variation in Myalgic encephalomyelitis/Chronic fatigue syndrome in two populations: a study of mildly deleterious variants.

Venter, Marianne, Tomas, Cara, Pienaar, Ilse S et al.·Scientific reports·2019

This study looked at mitochondrial DNA (the genetic material in the energy-producing parts of our cells) in people with ME/CFS to see if differences in this DNA might help explain the condition. Researchers compared DNA samples from ME/CFS patients in the UK and South Africa to look for variations. Interestingly, they found that ME/CFS patients were less likely to have certain common genetic variations that most people carry, but they did not find any confirmed disease-causing mutations.

Metabolic features of Gulf War illness.

Naviaux, Robert K, Naviaux, Jane C, Li, Kefeng et al.·PloS one·2019

Researchers studied blood samples from Gulf War veterans with chronic illness and compared them to healthy controls. They found that veterans with Gulf War illness had abnormal levels of certain fats in their blood, particularly a type called ceramides and sphingomyelins. Interestingly, while Gulf War illness and ME/CFS share some similar symptom patterns, the chemical changes in the blood are largely opposite between the two conditions.

Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function.

Wang, Taiwu, Yu, Lei, Xu, Cong et al.·PloS one·2018

Researchers studied the bacteria living in the mouths of ME/CFS patients and compared them to healthy people. They found that ME/CFS patients have a different balance of oral bacteria, with some types being more common and others less common. These bacterial differences appear to affect how the body processes energy and amino acids, which could be relevant to understanding ME/CFS.

Low omega-3 index and polyunsaturated fatty acid status in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Castro-Marrero, Jesús, Zaragozá, Maria Cleofé, Domingo, Joan Carles et al.·Prostaglandins, leukotrienes, and essential fatty acids·2018

This study measured omega-3 fatty acid levels in the blood of 31 ME/CFS patients and found that nearly all of them (92.6%) had unusually low levels. Omega-3 fatty acids are important for heart health and reducing inflammation in the body. The researchers suggest that increasing omega-3 levels in ME/CFS patients might be worth testing as a potential treatment.

E2 ModerateCohortPEM not requiredCase-Control

Higher Prevalence of "Low T3 Syndrome" in Patients With Chronic Fatigue Syndrome: A Case-Control Study.

Ruiz-Núñez, Begoña, Tarasse, Rabab, Vogelaar, Emar F et al.·Frontiers in endocrinology·2018

This study compared thyroid hormone levels in 98 ME/CFS patients with 99 healthy controls and found that ME/CFS patients were more than twice as likely to have low levels of an active thyroid hormone called T3. The patients also showed signs of chronic low-grade inflammation and had more reverse T3 (an inactive form), which may explain why their bodies aren't producing or using thyroid hormones efficiently.

Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome.

Schoeman, Elizna M, Van Der Westhuizen, Francois H, Erasmus, Elardus et al.·BMC medical genetics·2017

This study examined the DNA inside the energy-producing parts of cells (mitochondria) in 93 ME/CFS patients from the UK and South Africa. The researchers looked for specific mutations that are known to cause mitochondrial disease. They found that these known harmful mutations were not present in the ME/CFS patients studied, suggesting that ME/CFS is not caused by these well-established mitochondrial mutations.

Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism.

Germain, Arnaud, Ruppert, David, Levine, Susan M et al.·Molecular bioSystems·2017

This study examined the chemicals in the blood of 17 ME/CFS patients and compared them to 15 healthy people. Researchers found 74 different chemicals at abnormal levels in ME/CFS patients, with 35 showing significant differences. Many of these chemicals are important for producing energy in the body, which could help explain why ME/CFS patients feel so exhausted.

Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Nagy-Szakal, Dorottya, Williams, Brent L, Mishra, Nischay et al.·Microbiome·2017

This study looked at the bacteria living in the gut of 50 ME/CFS patients and 50 healthy people to see if differences in gut bacteria might explain some ME/CFS symptoms. The researchers found that ME/CFS patients have unusual patterns of gut bacteria, and these patterns are different depending on whether the patient also has irritable bowel syndrome (IBS). Importantly, the type and balance of gut bacteria were linked to how severe patients' fatigue, pain, and other symptoms were.

E2 ModerateMechanismPEM unclearMechanistic

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.

E2 ModerateCohortPEM not requiredCase-Control

Genetic evaluation of AMPD1, CPT2, and PGYM metabolic enzymes in patients with chronic fatigue syndrome.

Maltese, P E, Venturini, L, Poplavskaya, E et al.·Genetics and molecular research : GMR·2016

This study looked at three genes that help muscles produce energy during physical activity. The researchers compared these genes in 17 patients with ME/CFS and 50 healthy people to see if differences in these genes might explain why ME/CFS patients experience severe fatigue after exertion. The study found no significant genetic differences between the two groups, suggesting these particular genes are not responsible for causing ME/CFS.

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.

Yamano, Emi, Sugimoto, Masahiro, Hirayama, Akiyoshi et al.·Scientific reports·2016

Researchers analyzed blood samples from ME/CFS patients and healthy people to look for chemical markers that could help diagnose the disease. They found that certain metabolites—molecules involved in energy production and waste removal—were abnormal in ME/CFS patients. Two specific chemical ratios in the blood showed promise as potential diagnostic tools, correctly identifying CFS patients about 75-80% of the time.

E2 ModerateCohortPEM unclearCase-Control

Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome.

Billing-Ross, Paul, Germain, Arnaud, Ye, Kaixiong et al.·Journal of translational medicine·2016

This study examined whether differences in mitochondrial DNA (the genetic instructions inside the energy-producing parts of our cells) are linked to ME/CFS symptoms. Researchers compared DNA from 193 ME/CFS patients and 196 healthy people and found that while certain mitochondrial DNA patterns were associated with specific symptoms like neurological problems, pain, and digestive issues, they were not linked to whether someone actually develops ME/CFS. This suggests mitochondrial DNA variations may influence how severe certain symptoms are, rather than causing the disease itself.