Evidence browser

Nitric oxide concentrations are normal and unrelated to activity level in chronic fatigue syndrome: a case-control study.

Meeus, Mira, VAN Eupen, Inge, Hondequin, Jasmien et al.·In vivo (Athens, Greece)·2010

This study examined whether a chemical messenger in the blood called nitric oxide (NO) is related to how active people are in ME/CFS. Researchers measured activity levels and blood NO in 30 ME/CFS patients and 29 healthy but inactive people over one week. While ME/CFS patients were indeed much less active than controls, the amount of NO in their blood was normal and had no connection to their activity levels.

E2 ModerateCohortPEM not requiredLongitudinal

Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome.

Perrin, R, Embleton, K, Pentreath, V W et al.·The British journal of radiology·2010

This study used MRI brain scans to look for physical abnormalities in people with ME/CFS compared to healthy people. Eighteen patients with ME/CFS and nine healthy volunteers were scanned twice, one year apart. The researchers found no significant differences between the two groups in brain size, fluid levels, blood flow, or white matter lesions, and these measurements remained stable over the year.

E2 ModerateCohortPEM not requiredLongitudinal

Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome.

Miwa, Kunihisa, Fujita, Masatoshi·Heart and vessels·2010

This study examined whether people with ME/CFS have lower levels of vitamin E, an important antioxidant that protects cells from damage. Researchers found that ME/CFS patients had significantly lower vitamin E levels than healthy controls, and these levels improved when patients went into remission, suggesting that oxidative stress (cellular damage from chemical imbalances) may play a role in ME/CFS.

E2 ModerateCohortPEM unclearCross-Sectional

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome.

Fletcher, Mary A, Rosenthal, Martin, Antoni, Michael et al.·Behavioral and brain functions : BBF·2010

This study measured a stress-related substance called neuropeptide Y (NPY) in the blood of ME/CFS patients and compared it to healthy people and people with Gulf War Illness. The researchers found that ME/CFS patients had significantly higher NPY levels, and these levels correlated with how severe their symptoms were—including stress, depression, fatigue, and cognitive problems. This suggests NPY could be a useful blood test to help identify ME/CFS and track symptom severity.

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study.

Mathew, Sanjay J, Mao, Xiangling, Keegan, Kathryn A et al.·NMR in biomedicine·2009

Researchers used a specialized brain scan to measure a substance called lactate in the fluid surrounding the brain in people with ME/CFS, people with anxiety disorder, and healthy people. They found that people with ME/CFS had about three times more lactate in their brain fluid than the other groups, suggesting their brain cells may not be using energy efficiently.

E2 ModerateCohortPEM unclearCross-Sectional

Vitamin D metabolites as clinical markers in autoimmune and chronic disease.

Blaney, Greg P, Albert, Paul J, Proal, Amy D·Annals of the New York Academy of Sciences·2009

This study measured two types of vitamin D in the blood of patients with autoimmune and chronic diseases, including ME/CFS. The researchers found that a specific form of vitamin D (1,25-D) at high levels was associated with these conditions, but the commonly-tested form of vitamin D (25-D) was not. This suggests doctors may need to test for the right type of vitamin D to properly assess autoimmune disease.

Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue: no evidence of a biomarker.

Byrnes, Andrea, Jacks, Andreas, Dahlman-Wright, Karin et al.·PloS one·2009

Researchers compared blood cells from 44 people with ME/CFS to their identical twins who do not have the illness, looking for genetic differences that might explain the disease. Despite careful testing using advanced technology, they found no differences in how genes were expressed between the two groups. This suggests that if previous studies claimed to find biomarkers (biological signs) of ME/CFS in blood, those findings may have been due to errors in how the studies were conducted rather than real biological differences.

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome.

Natelson, Benjamin H, Intriligator, Roxann, Cherniack, Neil S et al.·Dynamic medicine : DM·2007

This study compared how ME/CFS patients and healthy volunteers responded to standing up for 8 minutes. Researchers measured blood pressure, heart rate, breathing rate, and carbon dioxide levels in the blood. ME/CFS patients were more likely than healthy people to have abnormal responses, particularly low carbon dioxide levels (hypocapnia), which was linked to feeling more ill and short of breath.

Spectroscopic diagnosis of chronic fatigue syndrome by visible and near-infrared spectroscopy in serum samples.

Sakudo, Akikazu, Kuratsune, Hirohiko, Kobayashi, Takanori et al.·Biochemical and biophysical research communications·2006

Researchers used a special light-based scanning technique to analyze blood samples from ME/CFS patients and healthy people. The scans could correctly identify which samples came from ME/CFS patients about 93% of the time. This suggests that a simple blood test using this technology might one day help doctors diagnose ME/CFS objectively, rather than relying only on symptoms and other tests.

E2 ModerateCohortPEM not requiredObservational

Salivary cortisol as a predictor of postoperative fatigue.

Rubin, G James, Hotopf, Matthew, Papadopoulos, Andrew et al.·Psychosomatic medicine·2005

This study tested whether low cortisol (a stress hormone) causes or predicts chronic fatigue by following 161 patients before and after surgery. The researchers measured cortisol levels and fatigue at multiple time points, but found that low cortisol before or after surgery did not predict who would develop fatigue. This suggests that if low cortisol is connected to chronic fatigue, it develops after symptoms begin rather than causing them.

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.

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.

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.

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.

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.

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.

[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.