Authors: Saïd Majdi, Thomas Manaugh

Chronic Fatigue

What is chronic fatigue syndrome?

Chronic Fatigue Syndrome (CFS) is a disorder characterized by unexplained fatigue that is not relieved by rest and affects daily activities. A person with CFS feels tired, weak, and often feverish and may also experience pain throughout the body, headaches, and sleep problems. There is no single test to diagnose chronic fatigue syndrome, and there is no cure. Doctors diagnose CFS by ruling out other conditions with similar symptoms. The diagnosis requires months, sometimes years, of symptoms that began suddenly and have not improved with treatment.

A consensus statement established by the United States Institute of Medicine (IOM) in 2015 states that CFS is a real condition, even though the exact causes of the condition are not fully understood. Since the 1980s, various studies have linked CFS to a variety of infectious agents, but there is not enough evidence of an infectious cause to support a formal diagnosis.

CFS is a multisystem condition that is estimated to affect up to 2.5 million people in the U.S. alone. Although some patients may experience a gradual onset of symptoms, others may develop CFS suddenly following a flu-like illness, minor trauma, or other illness. CFS patients often experience profound fatigue, cognitive dysfunction and pain in addition to symptoms related to other systems, such as gastrointestinal, pulmonary, and cardiovascular.

CFS is a complex syndrome characterized by severe fatigue that is not improved by bed rest, and that is made worse by physical or mental activity. The word syndrome is used to describe the collection of symptoms. It is also called myalgic encephalomyelitis (ME).

What causes chronic fatigue syndrome?

There are several theories that explain the cause of CFS, and they vary based on the reason a person is tired in the first place. CFS is usually caused by another illness or infection, which is why it is also called post-infectious, or post-viral, fatigue syndrome. However, the fatigue that follows a cold or other viral infection usually goes away within a few weeks. In CFS, the fatigue can last months or years. One theory is that it is caused by the immune system. Studies suggest that people with CFS have a different immune system from that of people who do not have CFS.

Who is at risk for chronic fatigue syndrome?

Although there is still much to learn about this debilitating disease, there are several contributing factors that are thought to play a role. Age, for example, is a factor. Approximately 75% of those diagnosed with CFS are between the ages of 18 and 55. A person’s genetic background is also a factor. Family members of those with CFS have a higher risk of developing the disease.

How is chronic fatigue syndrome diagnosed?

While a definitive diagnosis of CFS can only be made by a healthcare provider, there are some symptoms that are common in people with this condition. The CDC lists these:

  • A new onset of fatigue that lasts a minimum of six months and is not the result of ongoing exertion.
  • A new onset of significant impairment in short-term memory or concentration.
  • Post-exertional malaise lasting more than 24 hours.
  • Unrefreshing sleep.

Patients also have chronic fatigue syndrome if they have experienced extreme and prolonged exhaustion for at least six months and they have had four or more of the following symptoms:

  • Difficulty concentrating.
  • Sore throat.
  • Tender lymph nodes (glands) in your neck or armpits.
  • Muscle pain.
  • Multi-joint pain without redness or swelling.
  • Feeling dizzy or lightheaded.
  • Headaches of a new type, pattern, or severity. 

What are the treatments for chronic fatigue syndrome?

While CFS is a challenging condition to treat, it is possible to improve symptoms and regain a more fulfilling life.

There are three commonly used treatment options for CFS. While none of the treatments are FDA-approved, many patients find them to be helpful. The three therapies are:

Cognitive-behavioral therapy (CBT). This treatment teaches patients how to deal with the symptoms of CFS, including how to identify sources of stress and change unhealthy behaviors. It can help patients build up their energy and strength, as well as help them deal with depression or other mental health conditions.

Graded exercise therapy (GET). This type of therapy involves slowly increasing activity levels. It is thought that limiting activity can worsen CFS. GET is most often used for treating CFS patients who have increased symptoms on days they don’t exercise.

Complementary or alternative medicine (CAM). CAM is a broad term that encompasses all treatments that fall outside conventional medicine. Some forms of CAM can be helpful in managing the symptoms of CFS, although there is no one specific treatment that works for everyone. CAM treatments may help reduce chronic pain by increasing the body’s natural pain-relieving chemicals and decreasing inflammation. Some CAM treatments that may help manage chronic pain include meditation, yoga, tai chi, chiropractic massage, and acupuncture.

Patients with CFS can develop sensitivity to certain medications, including herbs and supplements. Before starting any treatment, patients are recommended to consult with their doctor.

Is there a connection between CFS and the long-term effects of COVID-19?

Some people infected in 2003 with SARS-CoV-1 continued to report chronic fatigue, musculoskeletal pain, and unrefreshing sleep up to 3 years following the infection. A recent study is reporting similar symptoms among survivors of COVID-19; however, the persistence of these symptoms after COVID-19 is not expected necessarily to result in CFS.

Tens of thousands of COVID long-haulers — those who survived COVID-19 and are experiencing lingering symptoms — are reported to have joined online support groups on social media and special interest websites, where they discuss their symptoms and what to do about them.

Lawmakers proposed a bill called the “Understanding COVID-19 Subsets and ME/CFS Act.” The proposal includes federal funding for research projects looking into the long-term effects of the coronavirus. 

Can the operation of a circuit-breaker mechanism account for ME/CFS?

Those people who have ever had a bad case of the flu have probably experienced a taste — for a day or two – of what chronic fatigue sufferers experience for many days in a row. Both kinds of sufferers may experience fatigue, headaches, body aches, weakness, and a felt loss of energy to do anything but go to bed and sleep.

The mechanism that produces chronic fatigue could be similar to the mechanism that operates to keep flu sufferers inactive and in bed. In both cases, the symptoms force preservation of energy by keeping the sufferers inactive. We speculate that a circuit-breaker mechanism operates in the body to preserve energy. That is needed and useful if one is to survive the flu.

The mechanism that operates in the case of flu does not completely rob the body of energy; it simply makes energy less available to the patient than would normally be the case. In an emergency (e.g., a fire), a flu patient would be quite able to summon enough energy to escape the fire. 

Similarly, a sufferer of CFS would also be able to escape a fire. That would not be evidence that the chronic fatigue sufferer had been malingering. Instead, it would be evidence that the CFS sufferer, like the flu sufferer, (a) had been experiencing the effects from activation of a circuit-breaker mechanism that forced a reduction in energy expenditure, and (b) had been able to tap energy resources that were present but had been made unavailable except when under an extreme life-threatening emergency.

What we are proposing here is a mechanism similar to one described by David Sinclair in his 2019 book, Lifespan: Why We Age  — and Why We Don’t Have to. Sinclair describes a basic survival circuit that evolved during an early stage in the evolution of life on planet Earth. The appearance of that survival circuit conferred such a powerful advantage that life forms with the circuit survived while other life forms became extinct. Here is how Sinclair described the evolution of the circuit (page 6):

[T]his early evolutionary step looks, at first, to be rather simple. It is a circuit. A gene circuit. The circuit begins with gene A, a caretaker that stops cells from reproducing when times are tough. This is key, because on early planet Earth, most times are tough. The circuit also has a gene B, which encodes for a “silencing” protein. This silencing protein shuts gene A off when times are good, so the cell can make copies of itself when, and only when, it and its offspring will likely survive.

The genes themselves aren’t novel. All life in the lake has these two genes. But what makes M. superstes unique is that the gene B silencer has mutated to give it a second function: it helps repair DNA. When the cell’s DNA breaks, the silencing protein encoded by gene B moves from gene A to help with DNA repair, which turns on gene A. This temporarily stops all sex and reproduction until the DNA repair is complete.

Sinclair hypothesizes that the above-described gene circuit that serves to control cellular reproduction and preserve DNA integrity is a previously unknown basic life-survival mechanism. It is hypothesized to have evolved to protect against degradation or death because of insults from unpredictable environmental stresses, especially during the vulnerable time when an organism engages in reproduction by cell division. Sinclair points out that cells that are not paused in reproduction during cell repair would almost surely lose genetic material. Stated simply, when genetic repairs are needed, Gene A shuts down reproduction while the protein produced by Gene B is engaged temporarily in DNA repair.

We hypothesize that a somewhat similar protective mechanism is overactive in patients with ME/CFS and similar diseases (e.g., fibromyalgia and multiple sclerosis). A protective “circuit-breaker” mechanism shuts down energy expenditure to avoid conditions of dangerously low energy. Having such a circuit is needed for the protection it offers, but it could become overly sensitive, leading to unwanted and unneeded disability — disability due to experiencing chronic fatigue.

The operation of a circuit-breaker mechanism has also been hypothesized by Jacob Teitelbaum, a practitioner who wrote a popular book (2001) about treating CFS and fibromyalgia (FMS). On his website (2021), he includes the following hypothesis about the origins of CFS and FMS:

CFS/FMS acts as a “circuit breaker,” with the hypothalamus decreasing its function to protect the individual in the face of what is perceived to be an overwhelming stress (just like blowing a fuse/circuit breaker in a house). This center controls sleep, hormones, temperature, and blood flow/blood pressure/sweating/gut function. When you don’t sleep deeply, your immune system also stops working properly. In addition, if your muscles do not have enough energy, they will get stuck in the shortened position, triggering muscle pain (think rigor mortis). When this muscle pain becomes chronic, it can trigger the numerous other types of pain seen in fibromyalgia.

Your “energy crisis” can be caused by any of a number of infections, stresses or injuries.

Some of you had your illness caused by an infection. In this situation, you can often give the time that your illness began almost to the day. This is also the case in those of you who had an injury (sometimes very mild) that was enough to disrupt your sleep or autonomic function, and trigger this process. In others, the illness had a more gradual onset. This may have been associated with hormonal deficiencies (e.g., low thyroid, estrogen, testosterone, cortisone, etc.) despite normal blood tests. In others, it may be associated with chronic stress, antibiotic use with secondary yeast overgrowth, and/or nutritional deficiencies. Indeed, we have found dozens of common causes and factors that contribute to these syndromes.

During an interview on a CBS television affiliate (WRGB, 2020), Teitelbaum made the following comments that linked Covid-19 symptoms of lingering fatigue symptoms to CFS:

Post-viral fatigue represents a human “energy crisis,” where the virus causes a circuit breaker in the brain called the hypothalamus to malfunction… It’s like when you plug in too many space heaters and you trip a circuit breaker. This pushes people over the cliff.” The hypothalamus controls sleep and hormonal function, and when it trips, it results in a combination of insomnia despite exhaustion, along with chronic pain, he says. “From there, it can then trigger an almost dizzying array of other symptoms.”


Sinclair, D. (2019). Lifespan: Why We Age  — and Why We Don’t Have to. New York, Atria Books.

Teitelbaum, J. (2001). From fatigued to fantastic!: a proven program to regain vibrant health, based on a new scientific study showing effective treatment for chronic fatigue. New York, Avery.

Teitelbaum, J. (2021). Overview of CFS and Fibromyalgia. Retrieved at

WRGB Staff (2020). Fighting post-viral fatigue. Retrieved at,you%20trip%20a%20circuit%20breaker.