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Chronic Fatigue Syndrome

Causes and Risk Factors

No reliable single cause or group of causes has been conclusively demonstrated for CFS. However, several studies have revealed various factors that correlate with CFS incidence.


CFS affects all population groups, although it is more common in women. While early studies suggested that CFS mostly affects young, Caucasian, professional women, more recent research reveals it is more common among people of early or middle adulthood, and community studies have reported that it is somewhat more common in people of African, Hispanic, or Native American descent compared to those of European or Asian ancestry (Afari 2003; Dinos 2009).

CFS often occurs concurrently with other conditions that cause similar symptoms. Studies have reported that US Centers for Disease Control and Prevention (CDC) CFS criteria (see Diagnosis section) have been met by 88% of people with multiple chemical sensitivity (Ziem 1999), 20-70% of people with fibromyalgia (Afari 2003), and 15.7% of veterans in the US VA Gulf War Registry (Kipen 1999). Given the similarities between CFS and fibromyalgia, and their high degree of concurrence, studies on fibromyalgia are often viewed as potentially relevant to CFS, and integrative practitioners frequently apply similar approaches to the two conditions.

Viral Infections

Viral infection may cause prolonged fatigue during active infection, and some studies suggest that viruses such as human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) may play a role in the development of CFS (Morelli 2011; Bansal 2012; Klimas 2007; Montoya 2013). However, the exact mechanisms by which viral infection may trigger CFS are poorly understood. Some scientists have suggested that post-viral alterations in the host’s immune system may underlie CFS, but this theory is debated (Moss-Morris 2013; Hickie 2006). Chronic viral infections may alter white blood cell activity (such as triggering abnormalities in T cell function and decreasing activity of natural killer cells) and damage mitochondrial function (Klimas 2007; Bansal 2012).

Allergies and Food Sensitivities

Some evidence suggests that allergies may play a role in CFS (Bellanti 2005; Straus 1988); however, understanding the link between the two is complicated by the fact that not all CFS patients have allergies (Jones 2011). Similar to viral infections, it has been proposed that allergies may trigger immune abnormalities that lead to CFS (UMMC 2013). One study found that drug allergies were more frequently reported by people with CFS than healthy controls (Ferré Ybarz 2005). Additionally, certain measures of allergic reactions (ie, eosinophil activation) were increased in patients with CFS (Conti 1996).

Food sensitivities have also been considered as a potential cause or cofactor in CFS (Lind 2013; Trabal 2012; Berstad 2012). In one study, it was reported that 54% of a sample of CFS patients tried dietary modifications; of those, 73% reported reduced fatigue (Logan 2001). In an Australian study, 90% of CFS patients who eliminated wheat, milk, benzoates, nitrites, nitrates, and food colorings reported that the severity of their symptoms improved (Logan 2001; Emms 2001).


Many individuals with CFS show signs of excessive inflammation and increased levels of the pro-inflammatory factors interleukin-1, leptin, and tumor necrosis factor-alpha (TNF-α) (Bansal 2012; Maes 2012; Stringer 2013). A 2014 brain imaging study found that individuals with CFS had significantly more neuroinflammation in many areas of the brain compared to healthy controls (Nakatomi 2014). Evidence from an animal model suggests that induction of an activated, pro-inflammatory state in the resident immune cells of the central nervous system, microglial cells, may be involved in the heightened pain sensitivity observed in CFS (Yasui 2014). Animal models also demonstrated that fatigue arises when a stimulus induces activation of microglial cells and/or there is an increase in inflammatory chemicals within the brain (Harrington 2012).

Mitochondrial Dysfunction

Mitochondria are organelles within cells that are responsible for most of the cell’s supply of energy in the form of a chemical called adenosine triphosphate (ATP), which is used throughout the body (Myhill 2009). Research suggests dysfunction of mitochondria and mitochondrial enzymes may be associated with chronic fatigue and fibromyalgia. The proinflammatory cellular milieu seen in many individuals with CFS can impair mitochondrial functions and may reduce production of ATP in cells. An electron microscopy study of muscle biopsies from 50 CFS subjects reported that 80% had mitochondrial degeneration (Behan 1991).

Orthostatic Hypotension

Orthostatic hypotension is a syndrome comprised of low blood pressure, weakness, or faintness after moving from a lying or sitting position to a standing position (Lanier 2011). One study reported that 96% of subjects with CFS experienced orthostatic hypotension. Many of these subjects were on low-salt diets. Following treatment with a balanced diet and adequate amounts of liquid and salt, chronic fatigue was completely resolved in 39% of subjects. Some of these patients were also treated with the corticosteroid fludrocortisone (Florinef) to help increase blood pressure (Bou-Holaigah 1995). Studies in Australia and the UK, respectively, reported that 11% and 13% of those who met the CDC or Canadian CFS diagnostic criteria also met criteria for postural orthostatic hypotension (Reynolds 2014; Lewis 2013). Some researchers have suggested that measuring blood pressure at various postures may be a useful diagnostic tool for CFS (Frith 2012).​