For decades, people suffering from myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), have battled more than just an illness. They’ve fought to be believed.
Now, for the first time, a major scientific study has revealed what patients have known all along: their illness is written in their blood.
Published in the journal EMBO Molecular Medicine, this landmark research by scientists at the University of Edinburgh presents the most comprehensive biological investigation into ME/CFS to date. Their findings point to profound, measurable differences in blood biomarkers between those with the illness and healthy individuals—differences so consistent and significant, researchers say they may one day form the basis for a diagnostic blood test.
“For so long, people with ME/CFS have been told it’s all in their head,” said Professor Chris Ponting of the MRC Human Genetics Unit at the University of Edinburgh’s Institute of Genetics and Cancer. “It’s not. We see people’s ME/CFS in their blood.”
A Debilitating Mystery, Long Ignored
ME/CFS is a complex, debilitating condition with no known cause, no approved diagnostic test, and no cure. Its hallmark symptom—post-exertional malaise—is a cruel paradox: even mild physical or mental exertion can lead to an overwhelming, delayed crash in energy, cognition, and physical functioning that may last days, weeks, or longer.
Alongside this, patients often suffer from severe fatigue unrelieved by rest, persistent pain, digestive disorders, brain fog, and sleep disruption. For some, the condition is disabling, leaving them confined to their homes—or even their beds—for years.
Despite its seriousness, ME/CFS has long existed in the margins of medical understanding. Many patients have been dismissed, misdiagnosed, or told their symptoms are psychological. But the new study, drawing on the immense dataset of the UK Biobank, offers powerful, physical evidence that the illness leaves its mark on the body in measurable ways.
Cracking the Code of ME/CFS
The team behind the study analyzed blood samples from 1,455 people diagnosed with ME/CFS, comparing them with more than 131,000 healthy individuals. Drawing on over 3,000 individual biomarkers and applying sophisticated machine learning and statistical models, researchers accounted for age, sex, and levels of physical activity—ensuring that the results pointed to ME/CFS itself, not secondary effects.
What they found was a biological fingerprint.
Across hundreds of biomarkers, ME/CFS patients differed strikingly from the control group. The most consistent changes involved markers linked to chronic inflammation, insulin resistance, and liver function. Crucially, these results were not swayed by how active or inactive the individuals were—a critical point, as critics have sometimes argued that the illness merely reflects deconditioning from inactivity.
“These blood differences are not just a result of patients doing less,” explained Dr. Sjoerd Beentjes of the School of Mathematics, a co-author on the study. “Our analysis shows strong evidence that ME/CFS affects blood traits through mechanisms unrelated to reduced physical activity.”
And in a field where diagnosis remains largely subjective—relying on symptoms, patient history, and the exclusion of other diseases—this objective evidence represents a potential turning point.
A Step Toward Diagnosis—and Recognition
One of the most striking findings involved people reporting post-exertional malaise, the illness’s defining symptom. Among them, the biomarker differences were even more pronounced, suggesting this trait may be at the very core of ME/CFS biology.
The study identified 116 statistically significant blood markers that appeared in both male and female patients—a vital discovery, as ME/CFS can manifest differently depending on sex, and too often, women’s medical conditions have been under-researched or under-recognized. This consistency across sexes bolsters the credibility of the findings.
The study’s results were so robust, they were independently replicated using data from the United States—demonstrating that the biomarker changes observed are not confined to a single population.
The Science of Collaboration
Part of what made this study so powerful was the range of expertise brought to the table. The University of Edinburgh’s Institute of Genetics and Cancer teamed up with specialists in mathematics and informatics, bringing together a fusion of genetic analysis, machine learning, and statistical modeling.
“This work has been an exciting cross-disciplinary and collaborative effort,” said Dr. Ava Khamseh of the School of Informatics. “We used everything from biomedical science to AI-driven data modeling to answer a challenge-led question for ME/CFS research.”
It’s a reminder that cracking medical mysteries often takes more than one kind of scientist—it takes a village of disciplines, speaking a common language of data.
Hope for the Future
For patients, the implications of this research are enormous. Not only does it provide biological proof of a long-dismissed disease, but it opens the door to earlier diagnosis, more targeted research, and, eventually, real treatment strategies.
The hope now is to refine these findings into a reliable blood test—a tool that could finally lift the burden of uncertainty for millions of people worldwide living with ME/CFS. Though such a test is not yet available, this study lays the groundwork.
Importantly, the research also shifts the narrative around ME/CFS. It reframes the illness from an enigma to a solvable biological puzzle. It validates the lived experience of patients. And it challenges the outdated notion that ME/CFS is merely psychosomatic or the result of inactivity.
“We See It in the Blood”
The phrase echoes again: We see people’s ME/CFS in their blood.
It’s more than a scientific observation—it’s a long-awaited affirmation. For patients who have spent years in medical limbo, misdiagnosed or disbelieved, it’s the beginning of recognition. It’s the beginning of science catching up to the truth they’ve known all along.
There is still much to learn. What causes ME/CFS remains a mystery. Whether these blood changes are a result of the illness or part of its origins is still unknown. And how this information can lead to treatments is a question researchers are only starting to explore.
But for the first time, science is seeing clearly. And in that clarity, there is hope.
Reference: Sjoerd Viktor Beentjes et al, Replicated blood-based biomarkers for myalgic encephalomyelitis not explicable by inactivity, EMBO Molecular Medicine (2025). DOI: 10.1038/s44321-025-00258-8
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