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Despite a vigorous search, scientists have not yet identified what causes CFS. While a single cause for CFS may yet be identified, another possibility is that CFS has multiple causes. Conditions that have been studied to determine if they cause or trigger the development of CFS include infections, immune disorders, stress, trauma, and toxins.


Various types of infections have been studied to determine if they might cause or trigger CFS:

  • Epstein-Barr virus infection, also known as mononucleosis
  • Human herpesvirus 6 infection, a virus that can cause problems for people with impaired immune systems, such as AIDS patients or organ transplant recipients taking immune-suppressant drugs
  • Enterovirus infection, a type of virus that enters through the gastrointestinal track and can have no symptoms, mild flu-like symptoms, or rarely severe and even deadly symptoms
  • Rubella, a viral infection also known as German measles
  • Candida albicans, a fungus that causes yeast infections
  • Bornaviruses, which cause borna disease, an infectious neurological syndrome
  • Mycoplasma, a cause of atypical pneumonia
  • Ross River virus, which causes Ross River Fever, a mosquito-borne tropical disease
  • Coxiella burnetti, the agent that causes Q fever
  • Human retrovirus infection, such as HIV, the virus that causes AIDS, or xenotropic murine leukemia virus-related virus (XMRV), a gammaretrovirus

Could One Type of Infection Lead to CFS?

Researchers from around the world have studied if a single type of infection might be the cause of CFS, analyzed the data, and not yet found any association between CFS and infection. Researchers are still analyzing samples from CFS patients using the latest molecular methods to search for previously unknown infections (pathogen discovery). To date, these studies suggest that no one infection or pathogen causes CFS and that the illness may be triggered by a variety of illnesses or conditions. In fact, infection with Epstein-Barr virus, Ross River virus, and Coxiella burnetti will lead to a post-infective condition that meets the criteria for CFS in approximately 10-12% of cases. People who had severe symptoms when they became infected were more likely than those with mild symptoms to later develop CFS symptoms. The possibility remains that there may be a variety of different ways in which patients can develop CFS.

Immune System and Allergies

Studies have looked to see if changes in a person's immune system might lead to CFS. The findings have been mixed. Similarities in symptoms from immune responses to infection and CFS lead to hypotheses that CFS may be caused by stress or a viral infection, which may lead to the chronic production of cytokines and then to CFS.

Antibodies against normal parts of the body (auto-antibodies) and immune complexes have been seen in some CFS patients. However, no associated tissue damage typical of autoimmune disease has been described in CFS patients. The opportunistic infections or increased risk for cancer observed in persons with immunodeficiency diseases or in immunosuppressed individuals is also not observed in CFS.

T-cell activation markers have been reported to be different between groups of CFS patients and healthy persons, but not all investigators have consistently observed these differences.

Allergic diseases and secondary illnesses such as sinusitis could be one predisposing factor for CFS, but not all CFS patients have allergies. Many patients do, however, report intolerances for certain substances that may be found in foods or over-the-counter medications, such as alcohol.

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Hypothalamic-Pituitary Adrenal (HPA) Axis

The central nervous system plays an important role in CFS. Physical or emotional stress, which is commonly reported as a pre-onset condition in CFS patients, alters the activity of the hypothalamic-pituitary-adrenal axis, or HPA axis, leading to altered release of corticotrophin-releasing hormone (CRH), cortisol, and other hormones. These hormones can influence the immune system and many other body systems.

Some CFS patients produce lower levels of cortisol than do healthy people. Similar hormonal abnormalities have also been observed among CFS patients and in persons with related disorders like fibromyalgia. Cortisol suppresses inflammation and cellular immune activation, and reduced levels might relax constraints on inflammatory processes and immune cell activation. Even though CFS patients had lower levels of cortisol than healthy individuals, their cortisol levels were still within the acceptable range of what is considered normal. Therefore, doctors cannot use cortisol levels as a way to diagnose CFS.

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Abnormally Low Blood Pressure and Lightheadedness (Neurally Mediated Hypotension)

Disturbances in the autonomic regulation of blood pressure and pulse have been found in CFS patients. This problem with maintaining blood pressure can be diagnosed by using tilt table testing, which involves laying the patient horizontally on a table and then tilting the table upright to 70 degrees for 45 minutes while monitoring blood pressure and heart rate. Persons with neurally mediated hypotension (NMH) or postural orthostatic tachycardia (POTS) will develop lower blood pressure under these conditions, as well as other characteristic symptoms, such as lightheadedness, visual dimming, or a slow response to verbal stimuli. Others may develop an unusually rapid heart rate also associated with the symptoms of the syndrome. Many CFS patients experience lightheadedness or worsened fatigue when they stand for prolonged periods or when in warm places, such as in a hot shower -- all circumstances that are known to trigger NMH or POTS.

NMH and/or POTS share some of the symptoms of CFS. They should be considered in a CFS patients whose symptoms are worsened with changes in position, after eating, following unusual amounts of or inadequate fluid intake, or increases in activity. Not all patients with CFS will have these conditions, however.

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Nutritional Deficiency

There is no published scientific evidence that CFS is caused by a nutritional deficiency. While evidence is currently lacking for nutritional defects in CFS patients, it should also be added that a balanced diet can be favorable to better health in general and would be expected to benefit a person with any chronic illness.