Is ME/CFS a Real Disease? The TRPM3 Study and What Came Next

Originally published 2017-02-28.

Yes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a real, physical illness. Major health bodies, including the US National Academy of Medicine (formerly the Institute of Medicine) and the UK's National Institute for Health and Care Excellence (NICE), describe it as a serious, chronic, multi-system disease. For years, though, many patients were told their symptoms were "all in the head". A small Australian study published in early 2017, which found faulty calcium channels called TRPM3 in immune cells of ME/CFS patients, was greeted at the time as proof that the old myth was wrong.

That study was an early piece of a much bigger puzzle. Here is what it actually found, what its limits were, and how the science and medical guidance have moved since.

What ME/CFS is

ME/CFS is a long-term illness whose core feature is post-exertional malaise (PEM): a worsening of symptoms after physical, mental or even emotional effort that is out of proportion to the effort. The crash often starts 12 to 48 hours later and can last days, weeks or longer. Alongside PEM, people typically have profound fatigue that rest does not relieve, unrefreshing sleep, problems with memory and concentration ("brain fog"), and often dizziness when standing, pain or sensitivity to light and noise.

Severity varies a lot. Some people can work part-time; others are housebound or bedbound for years. Women are diagnosed roughly 1.5 to four times as often as men.

Estimates of how common it is depend on the diagnostic criteria used. A US Centers for Disease Control and Prevention (CDC) survey from 2021–2022 found that about 1.3% of American adults, roughly 3.3 million people, reported a diagnosis, far more than the "up to 1 million" figure often quoted in older articles. Global estimates range from under 0.2% to about 0.9% depending on the definition; higher figures sometimes repeated online, such as 2.6%, come from looser criteria and are not widely accepted.

Why it was dismissed for so long

There is still no single blood test or scan that confirms ME/CFS. Routine tests usually come back normal, and diagnosis rests on symptoms and on ruling out other conditions. For decades that gap allowed the illness to be treated as psychological, and the name "chronic fatigue syndrome" did not help, because it made a disabling multi-system disease sound like ordinary tiredness.

A turning point came in 2015, when the US Institute of Medicine reviewed the evidence and called ME/CFS a "serious, chronic, complex, systemic disease". It proposed new diagnostic criteria built around PEM, which the CDC adopted. Its suggested new name, systemic exertion intolerance disease, never caught on.

The 2017 Griffith University TRPM3 study

The study that made headlines came from Griffith University's National Centre for Neuroimmunology and Emerging Diseases on Australia's Gold Coast. Its authors were T. Nguyen and colleagues, including Sonya Marshall-Gradisnik and Don Staines, and published in Clinical and Experimental Immunology (online in late 2016, in print in February 2017).

What the team measured

TRPM3 (transient receptor potential melastatin 3) is an ion channel, a gate in the cell membrane that lets calcium into the cell. Calcium acts as a signal that switches on many cell functions. The team had earlier reported that people with ME/CFS more often carried small genetic variations in the TRPM3 gene.

In this study they looked at natural killer (NK) cells, immune cells that destroy infected or abnormal cells, in blood from 15 patients and 25 healthy controls. One subtype of NK cell from the patients had significantly less TRPM3 on its surface, and calcium signalling in these cells behaved differently when the channel was stimulated.

Why it mattered and why caution was needed

The finding was important because it pointed to a measurable biological difference, and to a possible target for future tests and drugs. Queensland's science minister at the time said it confirmed ME/CFS was a real illness rather than a psychological issue.

But the paper itself described the work as a preliminary pilot. Its limits included:

• A very small sample of 15 patients for a condition that varies a great deal between people.
• An age mismatch: patients were on average almost 10 years older than the controls.
• Laboratory measurements only, using isolated cells under specific stimulants, not tests of how the whole body works.
• Untested mechanisms: ideas such as faulty TRPM3 channels driving every symptom were hypotheses, not results.

Some popular coverage went further than the evidence, claiming the receptor sits on every cell in the body and explains every symptom. TRPM3 is indeed found in many tissues, including the brain, but the link to all of ME/CFS's symptoms remains unproven. The Griffith group has continued to research TRPM3, and its findings still need replication by independent teams.

The exercise therapy controversy

Back in 2017, Staines also argued that prescribing exercise could harm patients. That was a controversial position then. The leading treatments in the UK were graded exercise therapy (GET), which gradually increases activity, and cognitive behavioural therapy (CBT), based largely on the 2011 PACE trial, which reported that both were moderately effective.

PACE came under sustained criticism. Its authors had changed their definition of "recovery" during the trial, and about 13% of participants already met one recovery threshold at the start. A reanalysis using the original protocol found no significant difference in recovery between treatment groups and controls. Patient surveys repeatedly reported that GET made people worse, which is consistent with PEM.

On 29 October 2021, NICE published new guidance for England and Wales that removed GET as a treatment. It advises clinicians: Do not advise people with ME/CFS to undertake exercise that is not part of a programme overseen by an ME/CFS specialist team. CBT is now offered only as support for living with the illness, not as a cure.

What research has found since

Research has accelerated, partly because of COVID-19. Between 15% and 50% of people with long COVID, depending on the study, meet the criteria for ME/CFS, and that overlap has brought far more funding and attention.

In August 2025, the UK's DecodeME project, the largest genetic study of ME/CFS so far, reported early results from the DNA of more than 15,000 people with the condition. It found eight regions of the genome that differed significantly from the general population, involving genes linked to the immune and nervous systems, including at least two related to how the body responds to infection. Lead investigator Chris Ponting called it a wakeup call. The researchers stressed that the findings were not yet peer-reviewed, covered only people of European ancestry, and were not ready to guide diagnosis or treatment.

Taken together, these findings support what the 2017 study suggested: ME/CFS has a biological basis involving the immune system. They also show the picture is more complex than any single faulty receptor.

Living with ME/CFS: practical points

• Get a proper assessment. Many conditions, including thyroid disease, anaemia and sleep disorders, can cause similar symptoms. If you have long-lasting exhaustion that worsens after effort, talk to a doctor, ideally one familiar with ME/CFS.
• Learn about pacing. Current guidance focuses on helping people find their own energy limits, which they can work out with their healthcare team, rather than pushing through.
• Be wary of "miracle cures". There is no proven cure yet. Treatment focuses on managing symptoms such as sleep problems, pain and dizziness.
• Believe people who have it. For friends, family and employers, the biggest help is often taking the illness seriously.

Myths and facts

Myth: it is just tiredness or depression. Fact: it is recognised as a multi-system disease. Depression can occur alongside it, as with any chronic illness, but it does not explain PEM.

Myth: exercise will cure it. Fact: UK guidance no longer recommends graded exercise, because exertion can trigger relapses.

Myth: one study proved the cause. Fact: the 2017 TRPM3 study was an early, small step. Genetic studies such as DecodeME suggest many biological factors are involved.

Sources: Nguyen et al., Clinical and Experimental Immunology (2017); Wikipedia: Myalgic encephalomyelitis/chronic fatigue syndrome; Patient Safety Learning hub (BBC News): NICE guidance scraps exercise therapy (October 2021); University of Edinburgh: DecodeME genetic findings (August 2025). Originally reported by ScienceAlert.

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