Chronic Fatigue Syndrome: The Invisible Illness Affecting Millions of Americans

Fatigue can stem from various illnesses and life stressors, but when exhaustion persists for months—often following an infection—it may indicate chronic fatigue syndrome (CFS), a condition that remains widely misunderstood and underdiagnosed in the medical community.

Approximately 3.3 million Americans currently suffer from the syndrome, with about one in four patients becoming bedridden at some point during their illness, according to the Centers for Disease Control and Prevention (CDC). Despite its prevalence, experts warn that only about 15% of those affected receive an accurate diagnosis.

“CFS is frequently missed by physicians,” explains Dr. Jacob Teitelbaum, author of “From Fatigued to Fantastic” and a researcher who specializes in the condition. “What many people don’t realize is that CFS, fibromyalgia, and long COVID are all related conditions with different names. They share a common thread as immune disorders, which predominantly affect women.”

The gender disparity may have a genetic basis, as many immune disorder-related genes are located on the X chromosome, according to Teitelbaum.

Formally known as myalgic encephalomyelitis (ME), chronic fatigue syndrome causes debilitating fatigue that significantly impairs a person’s ability to perform daily activities. The National Academy of Medicine defines the syndrome as having three primary symptoms that must persist for at least six months: severe fatigue that is both new and reduces normal activity levels, post-exertional malaise (worsening of symptoms after physical or mental effort), and unrestful sleep.

Many patients also experience cognitive difficulties, commonly referred to as “brain fog,” and orthostatic intolerance—lightheadedness when standing up.

Dr. Julia Oh, a professor at Duke University School of Medicine specializing in immunobiology, notes that CFS may be triggered by infections or other physiological stressors, but its causes and manifestations vary widely among individuals.

Teitelbaum describes the condition as a “severe energy crisis” in the body. “When energy levels drop low enough, the ‘control center’ in the brain—the hypothalamus, which regulates sleep, hormones, blood pressure, and pulse—may not function properly,” he explains. This hypothalamic dysfunction can trigger numerous symptoms beyond the primary ones.

Multiple factors can precipitate this energy depletion, including chronic stress, nutritional deficiencies, hormonal imbalances, and sleep disorders. While these triggers typically lead to a gradual onset of CFS, infections like COVID-19 and mononucleosis can cause a sudden onset, as confirmed by research. Head and neck injuries and hormonal shifts following pregnancy can also serve as triggers.

Currently, there are no definitive laboratory tests to diagnose CFS. Instead, physicians must rely on patient histories, physical examinations, and the exclusion of other conditions with similar symptoms, such as hypothyroidism and depression. This diagnostic challenge contributes to the high rate of underdiagnosis.

However, promising developments are on the horizon. Dr. Oh’s research team has developed an experimental artificial intelligence tool called BioMapAI, which has demonstrated high accuracy in identifying CFS by analyzing biological samples including stool and blood. According to preliminary research published in the journal Nature Medicine in July, this technology could revolutionize diagnosis.

“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 explains.

Given the heterogeneous nature of CFS, treatment approaches must be individualized. The CDC recommends that patients work with healthcare providers to create management plans targeting the symptoms that most significantly impact their quality of life. These typically include combinations of lifestyle modifications, therapeutic interventions, and medications.

Teitelbaum has developed a protocol called SHINE, which focuses on sleep, hormones, infections, nutrition, and exercise. Some studies suggest this approach can improve quality of life for individuals with CFS and fibromyalgia. Physical therapy and other alternative treatments may also provide relief for some patients.

Medical experts emphasize that anyone experiencing persistent fatigue that interferes with daily activities or diminishes quality of life should consult a healthcare provider. With greater awareness and emerging diagnostic tools, there’s hope that more CFS patients will receive proper diagnosis and effective treatment in the future.