Myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS is a debilitating illness that affects millions worldwide yet remains one of medicine’s biggest mysteries. Researchers estimate that 17 to 24 million people worldwide1 live with this condition, but there is still no single test to confirm it. ME/CFS can leave people exhausted, foggy, and in pain for years, yet standard blood tests often look normal, leaving patients struggling with uncertainty and misdiagnosis for years.
However, that may soon change. Scientists have developed a new approach that could finally help provide doctors with a clear answer. If confirmed in larger studies, this discovery could even lead to improved testing for other conditions, such as long COVID.
Key Findings from the New Study on Chronic Fatigue Syndrome
A major study published in the Journal of Translational Medicine examined whether a blood test could provide doctors with an objective way to diagnose ME/CFS. For decades, patients have faced years of uncertainty because diagnoses relied solely on symptoms. Researchers aimed to change that using cutting-edge genomic technology.2
• Researchers used a new method to read DNA folding patterns in blood — Scientists from the University of East Anglia and Oxford Biodynamics analyzed blood samples from 47 people with severe ME/CFS and 61 healthy volunteers using EpiSwitch® 3D Genomics, which examines how DNA folds within immune cells.3
• The test was highly accurate in spotting the illness — The blood test correctly identified ME/CFS patients with 92% sensitivity and 98% specificity. Sensitivity means it seldom misses a case, and specificity means it rarely misclassifies a healthy person. For patients who wait years for answers, this level of precision is a big deal.4
• How the blood test works — The test examines the 3D shape of your DNA inside immune cells. These shapes act like switches, turning genes on or off and controlling key body systems. In ME/CFS, the pattern of these switches changes when the immune system is disrupted. Using EpiSwitch® 3D Genomics, scientists scan over a million folding points and focus on 200 key spots linked to immune and inflammation pathways.5,6
• Immune system signals stand out — The blood test found strong activity in immune and inflammation-related pathways. Among the most affected were interleukin-2 (IL-2), which helps immune cells grow and communicate, and tumor necrosis factor (TNF), which triggers inflammation.
These signals activate key pathways that help regulate immune defense and how the body responds to stress.7 Together, these markers form a distinct biological fingerprint, showing ME/CFS is a condition of chronic immune activation — not just vague symptoms. As the researchers explained:8
“By mapping the top 3D genomic biomarkers to the closest genetic loci captured by their topological control (within 3Kb), it is possible to broaden the biological insights into genes, pathways and protein networks under the influence of 3D genomic regulation.”
• Findings show that ME/CFS is real — Although often called an invisible disability,9 ME/CFS is a genuine physical illness characterized by a specific biological marker in the immune system. A straightforward blood test could revolutionize diagnosis.10
• Experts say more research is needed before doctors can use the test — The study only looked at severe cases and healthy controls, not people with similar conditions like fibromyalgia or autoimmune disorders. That means the test still needs to be validated in larger, more diverse groups.11
• Other scientists are finding similar clues using different methods — Cornell University researchers used machine learning and cell-free RNA analysis to identify hundreds of immune-related changes in ME/CFS patients. Their approach was less accurate (about 77%) but points to the same biological theme: immune dysfunction and exhaustion.12
Shedding Light on an ‘Invisible’ Illness
Often called an “invisible illness,” the disabling symptoms of ME/CFS aren’t necessarily visible, and standard blood tests may appear normal. Yet patients experience profound exhaustion that impairs movement, focus, and strength. Without visible markers, they often face disbelief from others who can’t see their struggles.
• Once mislabeled as “all in the mind” — ME/CFS was first documented during a 1934 outbreak in Los Angeles.13 Because doctors couldn’t find clear biological markers, it was wrongly labeled as hysteria for decades. Today, it’s recognized as a real, multi-system illness involving immune and metabolic dysfunction.14
• As many as 80% of patients may not have an official diagnosis — ME/CFS can strike anyone at any age, ethnicity, or stage of life. Most cases develop after an infection, and roughly 5% to 10% of people who experience viral or bacterial illness fail to recover fully. Known infectious triggers for ME/CFS include:15
◦ Coronaviruses (MERS, SARS, and COVID-19)
◦ Enteroviruses (e.g., Coxsackie B)
◦ Epstein Barr virus (e.g., mono, glandular fever)
◦ Human herpesvirus (cytomegalovirus or herpes zoster)
◦ Human parvovirus B19
◦ Viral or bacterial meningitis
◦ Bacterial pneumonia (Streptococcus pneumoniae)
◦ Q fever (Coxiella burnetii) (bacterial)
◦ Rhinoviruses (the common cold)
• Symptoms go beyond tiredness — Patients with ME/CFS often feel wiped out and energy-depleted, and their symptoms are worsened by physical or mental exertion, with rest often ineffective.16 But this is just the start — it can cause multiple symptoms, many of which mimic other medical conditions:
◦ Muscle pain
◦ Memory problems
◦ Headaches
◦ Joint pain
◦ Difficulty sleeping
◦ Tender lymph nodes
◦ Visible muscle twitching (fasciculations)
◦ Difficulty concentrating
◦ Short attention span
◦ Word-finding problems
◦ Excessive sweating
◦ Palpitations
◦ Fainting
◦ Clumsiness
◦ Enlarged glands
◦ Intermittent flu-like symptoms
◦ Alcohol intolerance
◦ Irritable bowel syndrome-like symptoms
◦ Mood swings
◦ Temperature control
◦ Food intolerance
◦ Gastrointestinal problems
◦ Hypersensitivity to light and noise
• Middle-aged women are hit hardest — Although the illness affects people of all ages, women in their 40s and 50s are four times more likely to develop it. Many lose careers and independence as their energy systems seem to shut down.17
Although the symptoms of ME/CFS are well documented, its underlying cause is still unknown. The condition can cause serious complications, such as depression and anxiety. If you suspect you might have ME/CFS, don’t hesitate to consult a medical professional or health care provider to explore treatment options.18
The Gut-Brain-Immune Connection in Chronic Fatigue Syndrome
Chronic fatigue syndrome may start in the gut. A separate study from Columbia University found that people affected by it often have changes in gut bacteria and signs of an overactive immune system. These changes can weaken the gut lining, let harmful particles into the blood, and cause ongoing inflammation. Over time, this can affect the brain and lower the body’s energy.19
In their Microbiome study, the team correctly diagnosed the condition in nearly 83% of patients using stool and blood samples.20,21 They found that patients had fewer anti-inflammatory bacterial species and more signs of immune activation — evidence of a “leaky gut,” where bacteria and toxins escape into the bloodstream. This chronic immune stimulation can trigger exhaustion, pain, and cognitive dysfunction.
As explained by Maureen Hanson, the Liberty Hyde Bailey Professor in the Department of Molecular Biology and Genetics and the paper’s senior author:
“Our work demonstrates that the gut bacterial microbiome in ME/CFS patients isn’t normal, perhaps leading to gastrointestinal and inflammatory symptoms in victims of the disease … Furthermore, our detection of a biological abnormality provides further evidence against the ridiculous concept that the disease is psychological in origin.”22
Could SSRIs Be Fueling Chronic Fatigue?
Serotonin — also called 5-hydroxytryptamine (5-HT) — is often labeled the “happiness hormone.” For decades, low serotonin was believed to cause depression, which is why selective serotonin reuptake inhibitors (SSRIs) became the go-to treatment.
But here’s the problem: it’s not the magic mood molecule we were told it was. In fact, raising serotonin may do more harm than good. In fact, the old “low serotonin equals depression” theory has been solidly debunked. Instead of fixing the root cause of mood disorders, boosting serotonin might create new problems, including fatigue and metabolic issues.
• SSRIs may push serotonin beyond healthy limits — SSRIs are designed to boost mood by raising serotonin in the brain. But too much serotonin can have the opposite effect — slowing energy production, overstimulating the immune system, and creating symptoms that look a lot like ME/CFS. In his blog, bioenergetic medicine researcher Georgi Dinkov explains:23
“I am actually surprised it took researchers so long to make that connection, considering the well-tested so-called ‘central fatigue hypothesis’ (CFH), which stipulates that most of the perception of fatigue is brain-derived and often is not peripherally biochemically justified.
More specifically, it is the accumulation of serotonin in the brain, which leads one to perceive severe fatigue even if the bioenergetic state of their muscles do not demonstrate signs of fatigue (e.g. lactate buildup, creatine kinase and LDH leakage, ammonia accumulation, etc).
Conversely, lowering serotonin levels in the brain usually leads to abolishing the feelings of fatigue. In fact, there are multiple animal studies demonstrating that tryptophan depletion in the brain (which leads to lower 5-HT levels in the brain) is a reliable mechanism to delay or even abolish feelings of fatigue even in animals whose muscles are biochemically fatigued …
Another fact implicating 5-HT as a causal agent in CFS is the fact that most CFS patients seem to develop the condition as a result of viral infection … [M]ost viral infections require activation of specific 5-HT receptors (by elevated serotonin) in order for the infection to take hold, and blocking these receptors either prevents the infection altogether or can treat an already established one.”
• Fatigue may start in the brain, not the muscles — When a chemical called serotonin builds up too much in the brain, it can send strong “I’m exhausted” signals — even if your muscles are still ready to work. A separate 2024 study in the Journal of Translational Medicine supports this idea, showing that excess serotonin activity in the brain can trigger ME/CFS-like symptoms, suggesting that tiredness often starts in the nervous system, not just in the body.24
• One month of Prozac caused ME/CFS-like symptoms in mice — ME/CFS researcher Jin-Seok Lee, along with his colleagues at Daejeon University, tested whether excess serotonin could drive chronic fatigue syndrome. They treated mice with fluoxetine (Prozac) for four weeks at doses higher than typical for depression. Serotonin levels spiked in the hypothalamus and dorsal raphe nucleus — areas in the brain that regulate sleep and energy.25
Afterward, the mice showed hallmark ME/CFS behaviors: unrefreshing sleep, post-exertional malaise, and orthostatic intolerance. These symptoms were reversed after stopping the drug, and blocking serotonin production improved them. ScienceAlert noted that the team’s work addresses a long-standing gap: “No animal-derived evidence verifying the ‘hyper-serotonergic hypothesis’ has been reported yet,”26 the researchers explain.
“Our findings support the involvement of 5-HTergic hyperactivity in the pathophysiology of ME/CFS. This ME/CFS-mimicking animal model would be useful for understanding ME/CFS biology and its therapeutic approaches,” they concluded.27
For more information on SSRIs and mindful ways to ease anxiety without popping pills, check my article “SSRI Drugs Can Cause Chronic Fatigue Syndrome.”
Are You Chronically Tired?
Being tired all the time is not necessarily evidence that you have ME/CFS. In many instances, you’re just not getting proper rest. From poor breathing at night to diet issues and stress, various factors can drain your energy. Understanding these causes is the first step to fixing fatigue.28
• Poor sleep quality or not enough sleep — Getting less than six to nine hours or having disrupted sleep can leave you exhausted.
• Too little or too much exercise — Both extremes can cause fatigue; aim for balanced activity.
• Excess caffeine — Drinking coffee or soda can harm sleep quality and energy levels.
• Too much alcohol — Alcohol disrupts sleep cycles and breathing, making you feel tired.
• Chronic stress — Ongoing stress drains energy and affects sleep patterns.
For tips on how to clean up your sleep hygiene, check out my article “Top 33 Tips to Optimize Your Sleep Routine.”
Restoring Balance and Rebuilding Energy
While there’s no single cure for chronic fatigue syndrome, addressing its root causes, such as mitochondrial stress, inflammation, and gut imbalance, can help the body heal itself. These foundational steps may support energy production and calm an overactive immune response:
• Support calm and focus with GABA instead of SSRIs — Unlike SSRIs, which flood the brain with serotonin and can trigger fatigue, gamma-aminobutyric acid (GABA) acts as your body’s natural “brake pedal,” calming the nervous system without harmful side effects.
According to Dr. Scott Sherr, director of integrative hyperbaric medicine and health optimization at Hyperbaric Medical Solutions and an expert on neurotransmitter balancers like GABA:
“GABA deficiencies are associated with anxiety, fear, depression, short temper, phobias, impulsiveness, disorganization, addictions … Many have been prescribed an SSRI for some of these symptoms, but … we know that depression is not related to serotonin deficiency.”
Start with 100 milligrams of GABA daily for mild anxiety or sleep issues. For stronger effects, 500 milligrams to 2,000 milligrams (2 grams) per day has been shown to relieve anxiety and insomnia, even in people already taking SSRIs. Combining GABA with L-theanine can also amplify its calming benefits. Avoid high-magnesium GABA blends to prevent laxative effects.
• Cut linoleic acid (LA) to restore energy — Excess LA acts as a mitochondrial toxin, draining cellular energy and worsening fatigue. Eliminate seed oils such as soy, canola, and sunflower, and limit olive or avocado oil to 1 tablespoon daily. Aim for under 5 grams of LA per day, or below 2 grams if possible, to support energy and reduce chronic fatigue symptoms.
• Eat mindfully — Consume fiber-rich foods and incorporate fermented vegetables. Reducing refined sugar can also help seal the gut barrier and stabilize immune function.
• Boost cellular energy — Supplement with ubiquinol (the active form of coenzyme Q10) and D-ribose to support antioxidant defenses and enhance ATP production,29 the body’s primary energy molecule. These compounds help fuel mitochondrial function, which is often impaired in people with chronic fatigue syndrome.
Chronic fatigue syndrome isn’t a failure of will — it’s a failure of energy. And for the first time, science is beginning to understand why. The path to recovery starts with awareness: understanding that this illness is biological, not imagined. From new diagnostic tests that read the body’s molecular signals to nutritional and lifestyle strategies that calm inflammation and restore balance, the future of ME/CFS research is promising.
Frequently Asked Questions (FAQs) About ME/CFS
Q: What exactly is ME/CFS?
A: Myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, is a neurological and immune-based disorder that impairs the body’s ability to produce and manage energy. It affects the brain, immune system, and endocrine system, leading to unrelenting fatigue, pain and cognitive difficulties.
Q: Why is it called an “invisible illness”?
A: Most symptoms — like exhaustion, pain, and brain fog — can’t be seen or measured with standard tests. Patients often seem outwardly healthy while experiencing extreme physical and mental fatigue, making the illness easily misunderstood or dismissed.
Q: Who is most at risk?
A: ME/CFS can affect anyone, but it’s four times more common among women in their 40s and 50s. It often follows a viral or bacterial infection, and about 5% to 10% of people never fully recover from these triggers.
Q: Can antidepressants like SSRIs make fatigue worse?
A: Yes. New research shows that excessive serotonin activity can disrupt mitochondrial energy production and immune balance, sometimes worsening fatigue and brain fog. Supporting the calming GABA pathway may be a safer alternative.
Q: What can help improve energy and reduce symptoms?
A: Core strategies include eliminating seed oils high in linoleic acid, supporting GABA for nervous system calm, healing the gut with fiber and fermented foods, and strengthening mitochondria with nutrients such as coenzyme Q10 and D-ribose.
