By David Tuller, DrPH
A recent study investigated a question no one seems to have been asking. That can be a good thing—if it’s a question that’s worth investigating. But that’s not the case here.
The study, published in the journal Brain, Behavior, and Immunity and led by researchers at the University of Wisconsin, was called “Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose–response, crossover study.” The title itself indicates a conceptual problem built into the study. I mean, has anyone seriously argued or raised concerns that exercise “causes” PEM among GWI patients even if they do not report having PEM as part of their GWI in the first place?
Post-exertional malaise or a related construct is a required characteristic of ME or ME/CFS, however defined (excluding pre-2000 definitions like the 1991 Oxford criteria and 1994 Fukuda criteria). In contrast, PEM is not required in GWI but is one of many possible complaints that can combine to generate a diagnosis. Like Long Covid, GWI is an umbrella term and it covers a wide range of presntations for those suffering after military service from what is categorized as a chronic, multi-system illness (CMI). Case definitions for GWI require the presence of various symptoms spread across multiple domains but with no specific symptoms universally mandated, and certainly not PEM.
So the study title is hard to understand. You might want to investigate the impact of exercise in GWI patients in general, or you might want to investigate differential effects of exercise in GWI patients with and without PEM. But you don’t need to investigate whether exercise causes PEM in GWI patients who have already reported that they don’t experience PEM. Am I missing something here?
The study included 40 participants with GWI diagnoses. As described in the paper, it was “a dose–response study that evaluated acute effects of light-, moderate-, and vigorous-intensity cycling on three types of psychometric outcomes previously shown to be exacerbated by exercise in CMIs.” The investigators mentioned ME/CFS and Long Covid as other CMIs. As far as I can tell, they did not point out that only in the former is PEM a required symptom.
Here’s the rationale given for the research: “Studies [of CMI patients] which investigate and document the effect of different aerobic exercise intensities on PEM are needed to better inform exercise prescription and ensure risk minimization for these individuals.” And the main hypothesis was that “higher intensity exercise” would elicit greater levels of PEM
One corollary of this rationale and hypothesis is, or should be, that you can’t study anything about the effects of different aerobic exercise intensities on PEM in patients who don’t experience PEM in the first place. It’s like studying whether standing on the edge of a cliff leads to vertigo in people who don’t experience vertigo while standing on the edge of a cliff. It doesn’t make a lot of sense. The investigators do not seem to grasp this basic notion.
The key data point is in Table 3, which lists “baseline symptoms reported during study visit 1.” In other words, this reflects what participants reported as part of their GWI at the start of the study. Almost all—36 out of 40, or 90%–reported fatigue. Not surprising. But looking down the list, only 6 out of the 40, or 15%, met criteria for PEM as measured with the DePaul Symptom Questionnaire.
In other words, the great majority of this cohort of GWI patients—85%–did not report experiencing PEM. It is therefore hard to understand why the investigators would have expected any kind of exercise challenge to trigger PEM in these patients.
Some participants did report a worsening of symptoms, but those effects got washed out in the averages. “Undesirable effects such as symptom exacerbation were observed for some participants, but the group-level risk of PEM from light-, moderate-, or vigorous-intensity exercise was no greater than seated rest,” the paper noted. Of course, that’s exactly what you’d expect with a study sample in which only 15% reported having PEM as part of their GWI.
Beyond that—and there’s not really much point in going “beyond that,” since the study has essentially invalidated its own premise–the main findings were based on symptom reports taken within one hour after the exercise challenge. It is well-known that PEM frequently manifests as a delayed response. So even if the study were kosher in other regards—which it is not–it wouldn’t be possible to make reliable statements regarding PEM from data that would inevitably miss many or most cases of PEM.
And despite all these caveats, a leading light of the Norwegian branch of the CBT/GET ideological brigades, Professor Vergard Wyller, is nonetheless touting the study as proof of something or other in a commentary in the same journal called “Post-exertional malaise – A functional brain aberration?” Since he takes the findings at face value, he makes some absurd points. For example: “The lack of associations between exercise intensity and PEM experience suggest that sensory input cannot be the sole driver of the symptom.”
No, the lack of associations suggests nothing of the kind. It can be explained by this salient detail–the vast majority of the 40 study participants did not experience PEM as part of their GWI. The fact that exercise did not trigger PEM in this cohort says nothing about the impact of exercise in cohorts of GWI patients who do suffer from PEM. This is such an obvious and elemental point that even to have to express it strikes me as a ridiculous state of affairs.
And more from Professor Wyller: “The study…adds to an increasing body of evidence confirming that physical activity is not harmful in conditions characterised by PEM.”
No, it does nothing of the kind. The word “characterised” is doing a lot of work in that sentence. A case of GWI might be “characterised” by PEM; however, GWI is very frequently not “characterised” by PEM. Excessive physical activity leads to PEM in patients susceptible to PEM. That means all patients accurately diagnosed with ME or ME/CFS. And it means patients with GWI who happen to experience PEM–which was not the case for 85% of the participants in the study under review.
In his comment, Professor Wyller is responding to a straw-person argument. Since the rest of his blathering rests on such fundamental misstatements, it doesn’t warrant further scrutiny.
Exercise would have caused severe difficulties for all of the GW veterans I assessed and worked with. Veterans ill with GWI meet criteria for CCC ME/CFS. PEM is part of their symptom profile.
I’d say that there needs to be much better education on what good science looks like.
To be a little bit charitable to this study, it seems to be an open research question in the literature as to what extent Gulf War Illness patients have post exertional malaise. (With the possible implication: does it have different symptoms to CFS, and do these two classes of patients respond to treatment differently?) So I can see the rationale for doing the study.
I cant access the wyller article from where I’m currently accessing the Internet, but I will note that it is idiotic to conclude anything about PEM from a group of patients that you have just established dont have it.