Evidence browser

BiomarkersPost-Exertional Malaise

Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms.

Kennedy, Gwen, Spence, Vance A, McLaren, Margaret et al.·Free radical biology & medicine·2005

This study measured harmful molecules called free radicals in the blood of ME/CFS patients and compared them to healthy people. Researchers found that ME/CFS patients had higher levels of these damaging molecules, and in patients without heart disease risk factors, the amount of free radicals correlated with how severe their symptoms were, particularly fatigue after exertion and joint pain.

E2 ModerateCohortPEM not requiredObservational

Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome.

Vernon, Suzanne D, Reeves, William C·Journal of autoimmune diseases·2005

Researchers tested blood samples from people with ME/CFS and healthy controls to look for autoantibodies—proteins the immune system makes that can attack the body's own cells. They found that some people with ME/CFS had higher levels of antibodies against two specific targets: a brain protein called MAP2 and a component of DNA. However, most common autoantibodies were not elevated in ME/CFS patients.

E2 ModerateCohortPEM not requiredObservational

Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome.

Murphy, B E Pearson, Abbott, F V, Allison, C M et al.·Psychoneuroendocrinology·2004

Researchers measured hormone breakdown products in the blood of women with ME/CFS and compared them to healthy women. They found that women with ME/CFS had significantly higher levels of a specific progesterone metabolite called isopregnanolone—more than twice as high as controls. This suggests that abnormal hormone metabolism may be involved in ME/CFS, and that depression alone cannot explain these chemical differences.

Diagnostic evaluation of 2', 5'-oligoadenylate synthetase activities and antibodies against Epstein-Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan.

Ikuta, Kazufumi, Yamada, Takeshi, Shimomura, Tokio et al.·Microbes and infection·2003

This study tested whether certain viral infections and immune system markers are linked to ME/CFS. Researchers measured a protein called 2-5AS in blood cells from ME/CFS patients in Japan and compared it to healthy people. They found that ME/CFS patients had higher levels of this immune marker than healthy controls, and some patients showed signs of past infections with Epstein-Barr virus or another bacteria.

Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway activity in patients with chronic fatigue syndrome.

Snell, Christopher R, Vanness, J Mark, Strayer, David R et al.·In vivo (Athens, Greece)·2002

This study looked at whether exercise test results could predict high levels of RNase L, an enzyme that may be involved in ME/CFS. Researchers asked 73 patients to exercise until they were exhausted, and found that those with elevated RNase L had lower exercise capacity than those with normal levels. The findings suggest that simple exercise tests might help doctors identify which ME/CFS patients have this particular biological abnormality.

Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome.

Vernon, Suzanne D, Unger, Elizabeth R, Dimulescu, Irina M et al.·Disease markers·2002

Researchers examined blood cells from people with ME/CFS and healthy volunteers to see if they could find differences in how genes are turned on or off. They found that blood cells from ME/CFS patients showed different gene activity patterns compared to healthy people, and some of these differences involved immune system genes. This suggests that ME/CFS involves problems with how the immune system is functioning.

E2 ModerateCohortPEM unclearCross-Sectional

Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for hypersomnia and cognitive disorders.

Nishikai, M, Tomomatsu, S, Hankins, R W et al.·Rheumatology (Oxford, England)·2001

Researchers tested blood samples from ME/CFS and fibromyalgia patients to look for specific antibodies (immune proteins) that might be unique to these conditions. They found that about 13% of ME/CFS patients and 16% of fibromyalgia patients had antibodies against a protein called 68/48 kDa. Importantly, patients with these antibodies were more likely to experience severe sleep problems, memory issues, and trouble concentrating.

Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome.

Richards, R S, Roberts, T K, McGregor, N R et al.·Redox report : communications in free radical research·2000

Researchers compared blood samples from 33 people with ME/CFS and 27 healthy people, looking for signs of oxidative stress—a type of cellular damage caused by unstable molecules called free radicals. They found that people with ME/CFS had higher levels of certain markers of this damage, particularly a substance called methaemoglobin. The levels of these damage markers were strongly linked to how severe patients' symptoms were, including fatigue, pain, sleep problems, and cognitive difficulties.

E2 ModerateCohortPEM unclearCase-Control

A 37 kDa 2-5A binding protein as a potential biochemical marker for chronic fatigue syndrome.

De Meirleir, K, Bisbal, C, Campine, I et al.·The American journal of medicine·2000

Researchers found a specific protein (37 kDa) in the blood cells of 88% of ME/CFS patients, compared to only 28% of control subjects. This protein was present in much higher amounts in ME/CFS patients, suggesting it could potentially be used as a blood test to help identify the condition.

[31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration of normal energy metabolites compared with metabolic muscle diseases].

Block, W, Träber, F, Kuhl, C K et al.·RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin·1998

Researchers used a special MRI scanner to measure how muscles use energy during exercise by looking at chemical changes in the calf. They found that healthy people used two different types of energy pathways during exercise, while people with ME/CFS showed unusual resting energy levels but normal recovery after exercise—unlike patients with genetic metabolic disorders, whose muscles recovered very slowly.

BiomarkersEnergy Metabolism

Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases.

Kuratsune, H, Yamaguti, K, Lindh, G et al.·International journal of molecular medicine·1998

Researchers measured a substance called acylcarnitine in the blood of people with ME/CFS and compared it to healthy people and those with other diseases. They found that people with ME/CFS had significantly lower levels of this substance, and this same pattern appeared in both Japanese and Swedish patients. Importantly, this low level was only seen in ME/CFS and one other condition (chronic hepatitis C), not in other common diseases like diabetes or high blood pressure.

E2 ModerateCohortPEM unclearObservational

Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue.

Moorkens, G, Manuel y Keenoy, B, Vertommen, J et al.·Magnesium research·1997

This study tested whether people with chronic fatigue have low magnesium levels. Researchers gave 97 patients a special magnesium test and found that 44 had magnesium deficiency. After magnesium supplements, their bodies retained less magnesium, suggesting the treatment may have helped. However, the researchers did not find a clear link between low magnesium and chronic fatigue syndrome itself.

BiomarkersEnergy Metabolism

Preliminary determination of a molecular basis of chronic fatigue syndrome.

McGregor, N R, Dunstan, R H, Zerbes, M et al.·Biochemical and molecular medicine·1996

Researchers tested the urine of 20 ME/CFS patients and 45 healthy controls to look for chemical differences. They found that ME/CFS patients had different levels of several substances in their urine, particularly one called CFSUM1 and beta-alanine, which were higher in patients with more severe symptoms. These findings suggest ME/CFS may have measurable biological markers that could help identify the condition.

Clinical laboratory test findings in patients with chronic fatigue syndrome.

Bates, D W, Buchwald, D, Lee, J et al.·Archives of internal medicine·1995

Researchers compared blood test results from 579 ME/CFS patients with results from 147 healthy people. They found that ME/CFS patients were much more likely to have certain abnormal results, particularly immune-related changes like unusual white blood cells and immune complexes. However, no single test was abnormal enough in all patients to serve as a reliable diagnostic tool on its own.

Use of dynamic tests of muscle function and histomorphometry of quadriceps muscle biopsies in the investigation of patients with chronic alcohol misuse and chronic fatigue syndrome.

Wassif, W S, Sherman, D, Salisbury, J R et al.·Annals of clinical biochemistry·1994

Researchers tested muscle function and examined muscle samples from people with ME/CFS and people with chronic alcohol problems to see if their muscle problems were similar or different. They found that while some people initially thought to have ME/CFS actually had other conditions (like a rare enzyme deficiency or inflammation), the muscle changes in alcohol misuse were quite distinct and recognizable through muscle biopsies.

Investigation of retroviral involvement in chronic fatigue syndrome.

Folks, T M, Heneine, W, Khan, A et al.·Ciba Foundation symposium·1993

Researchers tested whether certain viruses called retroviruses might be a biological marker that could help diagnose ME/CFS. They looked for five different retroviruses in people with ME/CFS and compared them to healthy controls. None of these viruses were found in either group, meaning they cannot be used to identify who has ME/CFS.

E2 ModerateCohortPEM not requiredObservational

[Chronic fatigue syndrome--cases in the Kanebo Memorial Hospital].

Ogawa, R, Toyama, S, Matsumoto, H·Nihon rinsho. Japanese journal of clinical medicine·1992

This study looked at 134 ME/CFS patients seen at one hospital in Japan and found that many had immune system abnormalities, including weakened natural killer cells and reactions to common substances like dust and pollen. Researchers also discovered some patients had low levels of certain fatty acids in their blood. When treated with a traditional Chinese herbal medicine called Ren-Shen-Yang-Rong-Tang, about 73% of patients were able to return to work or school.

E2 ModerateCohortPEM unclearObservational

Nondiscocytic erythrocytes in myalgic encephalomyelitis.

Simpson, L O·The New Zealand medical journal·1989

Researchers looked at red blood cells from 102 people with ME/CFS using a powerful microscope and compared them to healthy people and those with multiple sclerosis. They found that people with ME/CFS had fewer normal-shaped red blood cells and more cup-shaped red blood cells than the other groups. This suggests ME/CFS may have a physical cause that could potentially be detected through a blood test.

E3 PreliminaryMechanismPEM unclearMechanistic

Indistinguishable mitochondrial phenotypes after exposure of healthy myoblasts to myalgic encephalomyelitis/chronic fatigue syndrome or control serum.

Ryback, Audrey A, Hillier, Charles B, Loureiro, Camila M et al.·PloS one·2026

Researchers wanted to test whether something in the blood of people with ME/CFS could damage the energy-producing parts of cells (mitochondria) when added to healthy cells in the lab. They tested blood from 67 people with ME/CFS and 53 healthy people on cultured muscle cells and measured how well the cells could use oxygen. Unlike a previous smaller study, they found no difference between the ME/CFS blood and healthy blood samples.

BiomarkersEnergy Metabolism

E3 PreliminaryMechanismPEM requiredMechanistic

Deficient TRPM3-linked mitochondrial Ca2+ influx in natural killer cells associated with myalgic encephalomyelitis/chronic fatigue syndrome.

Magawa, Chandi Tabeth, Eaton-Fitch, Natalie, Muraki, Katsuhiko et al.·BMC immunology·2026

Researchers compared immune cells called natural killer cells from people with ME/CFS and healthy controls, focusing on how calcium moves in and out of these cells. They observed that calcium entry into cells was reduced in ME/CFS, but calcium accumulation in the energy-producing part of the cell (mitochondria) was higher. This is a preliminary finding from a small study that may help explain some immune dysfunction in ME/CFS, but much more research is needed before drawing conclusions about what this means for patients.