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Is the Two Day Exercise Test Ready for the Big Time?

The results I described above are quite foreign and illogical to those who are accustomed to predictable physiological responses to physical activity stress- so skeptics abound, particularly when they know nothing about ME/CFS. Dr. Betsy Keller

Study Results


Is the two-day exercise test ready for the big time?

Is the two-day exercise test ready for the big time?  Has it been validated sufficiently to be employed in a big study like the CDC’s multi-center study?  Some believe not and, indeed, the results are fairly sparse – 71 patients and 102 controls in three studies.

The results are not completely consistent either; some chronic fatigue syndrome studies have found significantly reduced VO2 max and others have found significantly reduced energy out at ventilatory threshold.

The  fact that all three studies found significantly reduced energy output on the second exercise test, however, is encouraging; thus far all studies validate ME/CFS patients claim that their ability to exercise – their exercise capacity – is reduced. This is the only test that’s been able to do that.

Those results prompted ME/CFS advocates to request that the CDC employ the 2-day test-retest exercise protocol in their 2014 multi-center study. That request was denied.

Disability Exams

Anecdotal evidence from disability exams provides more support for the idea that exercise capacity is impaired in ME/CFS. Anecdotal evidence can be important in a poorly funded disorder but it will never be able to compete with evidence from rigorously designed studies.

The disability evidence of diminished exercise capacity probably extend to several hundred patients. We know that many people with ME/CFS apply for disability, but ‘many people’ is not everybody; people applying for disability present a specific slice of the chronic fatigue syndrome population. They’re probably sicker, for instance, and thus are probably more likely to ‘fail’ an exercise test than someone not applying for disability.

Still, they provide another data source that helps us understand the effects of the 2-day exercise test in ME/CFS.

Besides the Workwell researchers, Dr. Betsy Keller is the only exercise physiologist (I know of) who regularly puts ME/CFS patients seeking disability through two-day exercise tests. A professor in the Department of Exercise and Sport Science at Ithaca College in New York, Dr. Keller received her M.S and Ph.D in exercise science.

Staci Stevens suggested I contact Dr. Keller to find out what was popping up in her disability exams,  and last June I contacted her. Here’s what she had to say.

Dr. Betsy Keller Talks on Exercise Testing in Chronic Fatigue Syndrome (ME/CFS)

“I thought our metabolic cart went out of calibration because the results were so unusual.” Dr. Betsy Keller

Dr. Betsy Keller

Dr. Keller on the East Coast and Workwell on the West Coast use 2-day exercise testing t prove disability in ME/CFS

So far as we know there are two people who are using two-day exercise tests to gather evidence for disability for people with ME/CFS.  What lead to you begin doing this?

I’ve been testing patients with ME/CFS at the Ithaca College Wellness Clinic since 2003.  I presently test patients who contact me because they need documentation of their disability. I provide a report of the findings that patients can submit if they wish. I think our findings parallel those of Staci and her group quite consistently.

The first patient I tested was a local woman who was not able to get to Staci’s lab. Like Staci, I thought our metabolic cart went out of calibration because the results were so unusual. A quick recalibration confirmed that the equipment worked as it should, but the physiological response to physical activity in this person was highly unusual.

A two-test CPET protocol is necessary if one wants to document a PEM-related decrease in physical function. Dr. Betsy Keller

You said the results were so unusual that you actually recalibrated your equipment to ensure it was working properly. What kind of results are you getting?

While I cannot predict exactly how those with ME/CFS will respond to the cardiopulmonary exercise tests (CPET), I do know that the response is likely to be abnormal in one of several ways. Most often, ME/CFS patients are unable to reproduce maximum oxygen consumption (VO2max) achieved on test 1 during test 2. I


Highly unusual test results caused Dr. Keller to recalibrate her instruments to see if something was off….

It is well documented that healthy subjects are able to reproduce VO2max within 6-7% variation or less, whereas ME/CFS patients usually exhibit a drop in VO2max presumably due to metabolic anomalies that follow test 1, which we call post-exertional malaise (PEM).

We don’t know why this occurs; but for one with ME/CFS, it certainly helps to validate claims of fatigue, brain fog, pain, etc., when this VO2max decrement occurs.

The gas exchange measurements made during the CPET also provide a metric of the functional decrement experienced by the ME/CFS patient after post-exertional malaise has occurred, which is why a two-test CPET protocol is necessary if one wants to document a PEM-related decrease in physical function.

Other abnormal responses sometimes include a decrease in anaerobic threshold (AT) from test 1 to test 2, which means that, when fatigued, a person with CFS will have an even lower threshold for physical activity. Additionally in some cases, because the nervous system does not communicate appropriately with the cardiovascular system in ME/CFS (autonomic dysregulation), differences in the hemodynamic response (heart rate, blood pressure) to exercise can occur from test 1 to test 2 as well.

In healthy subjects, these variables are quite stable from test 1 to test 2.

Much of the research on exercise and cardio/pulmonary/metabolic responses has been done by those who typically study low-function diseases (heart, lung, muscle), or exercise by healthy people. The results I described above are quite foreign and illogical to those who are accustomed to predictable physiological responses to physical activity stress- so skeptics abound, particularly when they know nothing about ME/CFS.

Do you have a paper in the works, and if so could you give an general idea of its content? Do you have a publication date?  

I do have a manuscript in preparation related to exercise testing in ME/CFS.

ExerciseTiredHow have your colleagues responded to your unusual results? Is any else interested?

There are a few others in my area who do (or have done) research on ME/CFS/FM, but as a field, sports medicine/exercise science has been slow to recognize the impact of ME/CFS.

(In some ways the opposite is true as well. ME/CFS researchers often use exercise challenges to provoke abnormalities in their given field; ie immunologists will look immune abnormalities, pain researchers look for pain factors, etc. but two-day exercise testing that explores ME/CFS patients ability to produce energy is rare. Uncovering the metabolic abnormalities that prevent people with ME/CFS from exercising, for instance, did not make OMI-MERIT’s top ten project list.

The ‘agenda’ in ME/CFS  research is set by the researchers working in the disorder, and, to date, exercise physiologists are rare in a field dominated by immunologists, neurologists, etc.  

In fact, outside of heart and lung disease exercise testing is rare is disease (but is common in Sports Medicine. The American Heart Association asserts exercise testing  is underutilized even in heart disease. Dr. Snell has remarked how difficult it is to find the right journal to publish in. )

So far as you know is this pattern unique to chronic fatigue syndrome? 

Not sure- there are a couple of patient groups who can’t reproduce VO2max, but have a definitive and objectively diagnosed disease, whereas those with ME/CFS do not since there is no objective indicator of the illness.

Would you be willing to hazard a guess as to what’s going on? 

No – blood flow appears to be compromised (and oxygenation), but I think that’s a symptom not a cause.

Do you believe the same issue is occurring in overtraining syndrome? 

I’m guessing you’ve discussed this with Staci, as have I. Such a study about overtraining has yet to happen. We see overtrained athletes recover and return to competition; we see far less of that with ME/CFS.

I hope that future publications from the Workwell Foundation and from our lab will provide additional convincing evidence that the two-test CPET protocol can document physiologic dysfunction and post-exertional malaise in ME/CFS patients.

Validating Disability Using Exercise Testing

 I STRONGLY recommend that anyone who needs to provide documented evidence of the extent of their CFS fatigue or existence of PEM make their way to Ithaca for Dr. Keller’s two-day exercise tolerance test…. It provided terrific evidence for my disability appeal, plus I have never had any other doctor so generous with her time in explaining my test results as Dr. Keller was. She’s a PhD physiologist, not an MD, which might explain some of her willingness to devote time to me, but she’s also simply a very caring as well as very intelligent person. Her entire staff demonstrated a real concern for her patients. Phoenix Rising Forums

Find more on exercise based research and treatment options at our Exercise Resource Center here

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