Fatigue can stem from a variety of illnesses and life stressors, but when that exhaustion lasts for months — often following an infection — it may indicate a condition called chronic fatigue syndrome.

Approximately 3.3 million people in the United States currently have the syndrome, with about one in four people confined to their bed at some point during the illness, according to the Centers for Disease Control and Prevention.

Despite its prevalence, experts say it’s a poorly understood condition that physicians frequently miss, with past research suggesting that only about 15% of those affected are diagnosed correctly.

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What is chronic fatigue syndrome?

Formally known as myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS) is a chronic disease that causes fatigue so severe that it impairs the ability to perform daily activities.

The National Academy of Medicine defines the syndrome as having the following three symptoms that last at least six months.

• Severe fatigue that is 1) new and 2) decreases the ability to perform activities that you did normally prior to illness
• “Malaise” that worsens after physical or mental effort that previously was well-tolerated
• Unrestful sleep

People may also experience trouble with thinking and memory (often called “brain fog”) or lightheadedness when standing up. 

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There are no tests to confirm chronic fatigue, so doctors diagnose it by talking to their patients, examining them and excluding other disorders, like hypothyroidism and depression, that often share the same symptoms.

“CFS, fibromyalgia and long COVID are all related conditions with different names,” Dr. Jacob Teitelbaum, author of “From Fatigued to Fantastic” — whose research focuses on chronic fatigue syndrome — told Fox News Digital. “What these illnesses have in common is that they are immune disorders, and immune disorders predominantly affect women.”

Many genes related to immune disorders are on the X chromosome, suggesting a genetic component, the doctor added.

Causes of chronic fatigue

Chronic fatigue syndrome may be triggered by infection or other physiologic stressors, but its causes and symptoms can vary widely from person to person, according to Dr. Julia Oh, a professor in dermatology, molecular genetics and microbiology, and integrative immunobiology at the Duke University School of Medicine in North Carolina.

Teitelbaum compared the condition to a “severe energy crisis” in the body. When energy drops low enough, the “control center” in the brain — the hypothalamus, which regulates sleep, hormones, blood pressure and pulse — may not work as well.

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Although hypothalamic dysfunction can trigger dozens of other symptoms, the hallmark signs are insomnia (despite exhaustion), brain fog and widespread pain, the doctor said.

Anything that causes severe energy depletion can trigger the syndrome, including chronic life stressors, nutritional deficiencies, thyroid and stress hormone imbalances, and sleep problems.

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These triggers are usually associated with a gradual onset of CFS, but sudden onset can be caused by certain infections, with two classic ones being COVID and mononucleosis, past research has shown.

Head and neck trauma and sudden hormonal shifts after pregnancy can also trigger chronic fatigue, Teitelbaum warned.

There aren’t currently any blood tests to uniformly diagnose the syndrome, but Dr. Oh said she is hopeful that will change in the future.

Her research team developed an experimental artificial intelligence-based tool, BioMapAI, that has been shown to identify the condition with high accuracy by analyzing stool, blood and other common lab tests, according to early research published in July in the journal Nature Medicine.

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“Instead of finding one smoking gun for the disease, our AI model uncovered a distinct biological fingerprint that was dysregulated in the patients, which spanned changes in gut bacteria, hyperactive immune cells and disrupted metabolism,” Oh told Fox News Digital.

Treatments and therapies

Given how differently chronic fatigue syndrome can affect people, there is no universally effective therapy, according to Oh.

The CDC recommends that patients with CFS work with their doctors to create a management plan based on the symptoms that most affect quality of life.

There are no tests to confirm chronic fatigue, so doctors diagnose it by evaluating symptoms and excluding other disorders.

Treatments generally include a combination of lifestyle changes, therapies and medications. Patients and their physicians should weigh the potential benefits and risks of any approach.

There are some alternative therapies that have shown to be effective for some. Teitelbaum developed a protocol called SHINE, which focuses on sleep, hormones and hypotension, infections, nutrition and exercise. Some research has shown that this approach can help to improve the quality of life for people with CFS and fibromyalgia.

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Others may find alternative treatments, like physiotherapy (physical therapy) to be helpful.

Those who experience persistent fatigue that hinders their ability to participate in regular activities or impacts their quality of life should speak with a doctor.