The Netherlands and the U.K. have been the epicenter of biopsychosocial research (CBT/GET) into chronic fatigue syndrome (ME/CFS) for the past 20 years or so, but that is changing. In 2018, the Dutch Health Council asserted that “Scientific research on ME/CFS is needed to serve patients better”, and that the Minister of Health, Welfare and Sport should commission “a long-term, substantial research programme on ME/CFS“.

The Dutch Surprise: Federal Report Calls for More ME/CFS Research – Less CBT/GET


The Netherlands recently committed to spend 28 million euros (almost $33 million) on chronic fatigue syndrome (ME/CFS) research over the next ten years. It’s not a huge amount of money, but Dutch researchers have shown the ability to make a lot out of a little.

Back in 2014, RC Vermeulen was among the first to conclude that oxygen delivery to the muscles was impaired. Last year, Visser et al. used new technology to show that virtually everyone with ME/CFS exhibits a reduction in blood flows to the brain when they stand.

Low Brain Blood Flows and Orthostatic Intolerance Ubiquitous in Chronic Fatigue Syndrome (ME/CFS)

Now a Dutch team, led by E.G. Klaver-Krol and M.J. Zwarts and including Vermeulen, may have identified a key difference in the muscles between ME/CFS and fibromyalgia (FM).

Klaver-Kroll and Zwarts have been studying muscles issues in fibromyalgia and other disorders for years. In 2019, they found increased muscle membrane reactivity in FM and in 2012, muscle conduction issues in FM. Zwarts assessed muscle fatigue in post-cancer fatigue in 2015 (and didn’t find any).

With their FM findings under their belt, Klaver-Kroll, Zwarts and Vermeulen turned to chronic fatigue syndrome, and compared it to FM.

The Study

The study, “Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load“, used a non-invasive technique called surface electromyography to assess the electrical activity (muscle fiber conduction velocity) as small amounts of force were applied to the biceps muscle.  If I have it right muscle fiber conduction velocity refers to the speed with which electrical activity results when force is applied to the muscle fiber. People with ME/CFS or fibromyalgia and healthy controls were included.

The authors reported that the pain in both ME/CFS and FM “particularly involves the muscles”. That was music to my ears as exertion typically produces muscle burning sensations and feelings of tight, contracted muscles that are impossible to ignore.


“Negligible” levels of force were all that was required to produce a dramatic uptick in muscle membrane activity in FM.

A great deal of evidence suggests that something in the muscles in off in FM. The 2019 FM study “Fibromyalgia: Increased reactivity of the muscle membrane and a role of central regulation” produced a finding that seemed to astonish the researchers. They found that the largest increase in muscle membrane activity occurred when a “near negligible force” was applied to them.

That seemed to imply that the muscles were in a state of near activation, and just needed the slightest push to prod them into action.

That could be the result of two things: the muscle cells were being activated more quickly, or the membranes around the muscle cells were in a constant state of excitation. Since there was no evidence of increased muscle recruitment, the authors concluded that overly excited muscle membranes were the key.

Despite the fact that the muscle membranes were apparently itching to jump into action, the authors found no evidence of increased muscle activity overall. That suggested that the motor neurons in the central nervous system were feeding the muscles a steady stream of signals that was leaving them on high alert – but not quite pushing them into action.

Muscle studies are rarer in chronic fatigue syndrome (ME/CFS), but while the disease is more known for fatigue, muscle pain is common. This study’s unique feature was that it assessed muscle membrane functioning in both ME/CFS and FM. I’m fairly sure that nothing like this has been done before.

The Gist

  • Surface electromyography assesses how quickly the muscles respond to force.
  • Past studies indicate that the muscles in people with fibromyalgia respond very rapidly to “near negligible” amounts of force.
  • The rapid response is believed to be due to something that’s akin to central sensitization: the muscles cells are being bombarded with signals from the central nervous system keeping them on high alert and causing them to respond immediately to even the smallest hint of activity.
  • This study found that people with chronic fatigue syndrome exhibit increased muscle hyperactivity as well – but in a different way.
  • Their muscles demonstrate unusually high levels of activation but at a higher level of force.
  • Since aerobic muscle fibers are recruited first and anaerobic muscle fibers are recruited next, the authors believes the delayed jump in muscle activation seen in ME/CFS reflects their muscles hitting an anaerobic wall.
  • This jives with exercise and other studies suggesting that the aerobic energy production pathways are damaged in ME/CFS. The jump in muscle activity seen in ME/CFS reflects muscle cells desperately trying to produce more energy.
  • The authors suggested that while there may be overlaps, the primary muscle problems in fibromyalgia are due to central nervous system issues while those in ME/CFS are primarily due to problems with energy production.


The membranes surrounding the muscle cells were more excitable in both ME/CFS and FM patients compared to the healthy controls, but there the similarities ended.

As in prior studies, the muscle fiber conduction velocity (MCFV) rose abnormally high when the slightest forces were imposed on the muscles of FM patients.

The muscle conduction velocity rose “sharply” in ME/CFS as well – but only when higher levels of force were applied. . The authors noted that these levels were “far above” those of the healthy controls. The people with ME/CFS, then, didn’t exhibit the excitable response at very low levels of force that the FM patients did. Their muscles were more excitable than the healthy controls but only when a particular level of force was reached.

Different kinds of motor neurons are associated with different kinds of muscle cells. During exercise, the slow motor units linked to aerobic muscle fibers are activated first and then the motor units regulating anaerobic muscle fibers are activated next. The authors proposed that the hyperactivated motor neurons in ME/CFS were associated with the activation of thicker, more anaerobic muscle fibers.

Then they pointed a finger at the early entry into anaerobic energy production that various exercise studies have found in ME/CFS: the people with ME/CFS were  quickly blasting through their aerobic capacities and running into an anaerobic wall.

Next came a key question: could the amplified motor conduction times seen in ME/CFS have been due to muscle disuse or deconditioning? The answer to that couldn’t have been clearer. Deconditioning would have produced the opposite result – reduced muscle fiber conduction, not the increased muscle fiber conduction they found.

Similar Symptoms – Different Causes?


The studies from this Dutch group suggest that FM and ME/CFS are both similar and different. Dramatically increased levels of muscle activation are seen in both.

In fibromyalgia, abnormally high muscle conduction velocities occur at very low force levels. This appears to result from a constant stream of signals from the central nervous system that’s leaving the muscle membranes in a constant state of near activation.

The authors suggested that a process similar to central sensitization was underway in FM patients’ muscles. Either the muscles were being fed too many signals to activate or the inhibition system designed to keep them in check was not working.  Either way, the central nervous system was throwing the muscle activation system out of whack.

Evidence of a kind of hyper-excited muscles in FM goes way back. A 1989 study, “Evidence of neuromuscular hyperexcitability features in patients with primary fibromyalgia”, found that the muscles in FM tend to stay in an activated state long after a task has finished. It also found evidence of twitchy muscles which failed to relax or calm down between contractions.

Mental exertion was all it took to activate the trapezius muscle in FM in one study.

Cause of Upper Body Pain in Fibromyalgia (and ME/CFS?) Identified? Plus: ‘Trapezius Myalgia’ – Another Sister Disorder Identified?

Other studies suggest problems with inflammation, reduced energy production, reduced blood flows and high levels of oxidative stress may be present in FM patients’ muscles.

Fibromyalgia Study Points to Inflammation, Damage and Low Energy Production in Muscles

It’s surprising, given how rich the research on muscle problems in FM is, that this aspect of the disease is not better known.

Chronic Fatigue Syndrome (ME/CFS)

The results jive with those from Workwell’s two-day exercise studies which indicate that people with ME/CFS hit the wall after blowing through their limited aerobic energy production capacity.

In ME/CFS, the abnormally high muscle conduction velocities seen in FM occur only after more force is applied to the muscle. While the authors stated that central nervous system activation may be involved in ME/CFS, they more pinned the blame on a breakdown in aerobic energy production and a subsequent quick entry into anaerobic energy production.

For years, two-day exercise studies have documented that people with ME/CFS are quickly blowing through a broken aerobic energy production – and finding themselves fatigued and in pain as their anaerobic energy tries (and fails) to keep up.

Some exercise studies do suggest that problems with energy production are present in FM, but it’s pretty clear that people with FM can generally tolerate more exercise than people with ME/CFS. This is the first study I’ve seen that might explain why. In FM, the central nervous system appears to be the chief culprit. In ME/CFS, a broken aerobic energy production systems is.

Here’s to more biological Dutch research!


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