What Causes Chronic Fatigue Syndrome?

by Karen Lee Richards Patient Advocate

By Karen Lee Richards, ChronicPainConnection Lead Expert

Currently, the cause of chronic fatigue syndrome (also called myalgic encephalopathy or ME/CFS) remains a mystery. While it frequently occurs following a cold, flu or viral infection, it can also begin during a time of severe physical or emotional stress. In some cases, however, it will develop gradually and have no clear starting point. Although research over the past two decades has revealed a number of very real, physical abnormalities, it has yet to yield a definitive cause for chronic fatigue syndrome.

Over the years, a number of theories have been proposed and studied. Some possible causes that have been looked at include:

  • Virus infection (for example, Epstein-Barr or human herpesvirus6)

  • Hormonal changes in the hypothalamus, pituitary or adrenal glands

  • Allergies

  • Mild, chronic low blood pressure

  • Low blood sugar (hypoglycemia)

  • Iron deficiency anemia

A number of studies have found immune system irregularities in chronic fatigue syndrome patients. A particularly promising area of immune system research is delving into the theory that ME/CFS patients have an overactive immune system. Imbalances in T-cells (white blood cells that act as infection fighters) have been reported in several studies. Abnormal T-cells cause the immune system to become persistently overactive and produce an excess of cytokines, an inflammatory substance that can damage the cells, producing fatigue, muscles aches and other ME/CFS symptoms. Two cytokines in particular, interleukin-6 and interleukin-1, are elevated in chronic fatigue syndrome patients. Although the cause of the overproduction is unknown, researchers agree that cytokine over-production plays an important role in ME/CFS and might eventually be used as a marker to identify the illness.

Many experts believe that chronic fatigue syndrome develops from a convergence of two or more factors. They theorize that one or more of these factors may interact with certain neurological or genetic abnormalities, triggering ME/CFS. Those factors may include:

  • Genetic factors

  • Brain abnormalities

  • A hyper-reactive immune system

  • Viral or other infectious agents

  • Psychiatric or emotional conditions

More info on the Causes of Chronic Fatigue Syndrome


"About CFIDS," The CFIDS Association of America, Inc., 2004

"Chronic Fatigue Syndrome," MayoClinic.com, 2005.

Last Updated: July 31, 2007

Karen Lee Richards
Meet Our Writer
Karen Lee Richards

Karen is the co-founder of the National Fibromyalgia Association. She writes for HealthCentral as a patient expert for Pain Management.