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2-Day CPET: A gold standard test for ME fatigue

The absence of reliable diagnostic laboratory tests or biomarkers for ME and CFS presents significant problems for sufferers, treating clinicians, and the research community.

However, 2-day Cardiopulmonary Exercise Testing (CPET) is considered an accepted, reliable test for post-exertional malaise (PEM), one of the cardinal symptoms of ME and CFS.

The two-day CPET regimen known as the Stevens Protocol provides gas exchange and other objective and measurable results “which can’t be faked.”

Furthermore, the 2-day CPET protocol is considered one of the few legally admissible tests for disability assessment for ME and CFS impairment available.

See also on Shoutout About ME:


CPET measures the capacity to produce energy

Cardiopulmonary exercise testing (CPET) uses objective measures to accurately assess an individual’s
capacity to produce energy.

According to Laura Black, MD, of the Hunter Hopkins Center, “With objective measures like evaluation of oxygen consumption, onset of anaerobic threshold and other parameters of cardiovascular response to stress testing, we no longer have to rely solely on subjective symptomatology reported by the patient.

“Instead, we have standardized studies and classified measures of functional capacity that are recognized by The American Medical Association, American College of Cardiology, the New York Heart Association, the American College of Sports Medicine, and others based on cardiopulmonary exercise testing.”

CPET is the gold standard for measuring physical capacity used by athletes wanting to measure the effectiveness of their training programs. It’s also used medically e.g. to diagnose cardiovascular, breathing and muscle disorders.

The principle is to get someone to exercise to exhaustion, using a protocol that starts easy and gets increasingly difficult until the subject can do no more.

The key measures for this study are the Volume of Oxygen consumed (VO2) and the amount of work done, measured in Watts on the exercise bike.

Anaerobic/Ventilatory Threshold
A critical factor is the anaerobic threshold, the point at which the body has to supplement normal aerobic (oxygen-burning) metabolism with much less efficient anaerobic metabolism, creating lactic acid.

This threshold is measured in CPET by finding the point where carbon dioxide (CO2) starts to be produced faster than Oxygen, and is called the Ventilatory Threshold, or VT (strictly, VO2 VT).

VO2 max versus VO2 peak
One challenge of CPET is detecting if the person is using maximal effort, as opposed to trying pretty hard.

VO2 max (also maximal oxygen consumption, maximal oxygen uptake, peak oxygen uptake or maximal aerobic capacity) is the maximum rate of oxygen consumption as measured during incremental exercise.

Snell (2013) showed that CFS patients and subjects all went deep into anaerobic exercise and met at least one other measure of high effort.1

However, as it’s almost impossible to be completely sure, the study reported ‘peak’ measures instead of maximum, e.g. VO2 peak, not VO2 max.

PEM is one of the cardinal symptoms of ME and CFS

Worsening of symptoms following physical exertion in ME and CFS patients is most often the largest obstacle to daily living, gainful employment, exercise, and more.

This exacerbation is considered one of the most common and recognizable aspects of the illness2,3 in the two best ME and CFS case definitions, the International Consensus Criteria (ME) and the Canadian Clinical Case Definition (ME/CFS).

In the video below, Prof Mark VanNess from the Workwell Foundation USA presents evidence of the damaging consequences of aerobic exercise programmes (such as GET) for people with ME.


The Science Behind 2-Day CPET

The science behind 2-day CPET is well established. Studies show that while a majority of sedentary but otherwise healthy subjects recover from a maximal exercise test within 24 hours, in individuals with CFS, fatigue persists at levels close to those reported immediately postexercise for 24 hours and beyond.4,5,6

Among all fatiguing conditions, a limited ability to reproduce metabolic and workload measurements on repeated maximal CPET is thought to be unique to CFS.4,7

Snell (2013),1 found that a 2-day CPET protocol objectively documents post-exertional malaise (PEM), the most commonly recognized symptom in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

In the Snell study, which included 51 me/cfs patients and 10 matched, non-disabled, sedentary individuals, me/cfs patients had a statistically significant performance decrease on Day 2 in workload at ventilatory threshold (VTWL), workload at peak exercise (WLpeak), volume of oxygen consumed at ventilatory threshold (VTO2) and volume of oxygen consumed at peak exercise (VO2peak).

In short, me/cfs patients were unable to reproduce their Day 1 performance on Day 2.

Snell suggested that the statistical classification analysis pointed to a diagnostic biomarker for CFS/ME with a 95.1% accuracy.

In a recent report, Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness, the Institute of Medicine (IOM) included CPET in its list of tools that could be used to assess PEM, stating the 2-day test would “demonstrate marked inability to reproduce maximal or anaerobic threshold measures on the second day.”

Determining Disability

Considered by many to be the gold standard for determining disability, CPET uses objective measures to accurately assess an individual’s capacity for work.

Social Security in the US accepts the two-day CPET as objective proof of disability in ME.

Importantly, it must be noted that a single exercise test is insufficient to reliably demonstrate functional impairment in individuals with me/cfs. A second test is necessary to document the atypical recovery response and protracted fatigue possibly unique to ME and CFS, which can severely limit productivity in the home and workplace.

Availability of 2-Day CPET

In the US, the Workwell Foundation offers one of the few cardiopulmonary exercise testing services specializing in the evaluation of disability impairment for ME and CFS, Fibromyalgia Syndrome (FMS), and other fatiguing conditions.

Their two-day testing regimen (Stevens Protocol) is particularly helpful in documenting post-exertional malaise (PEM) and symptom exacerbation following physical activity. Testing is performed on a stationary bicycle with resistance added incrementally to keep tests approximately 8-12 minutes.

Importantly for patients, their assessments have proven to be a valuable adjunct to any medical and/or legal argument.

PHOTO: A111104_jb_contractors 001 by JBLM PAO

CPET studies demonstrating Post-Exertional Malaise

The following references link to studies using CPET to demonstrate post-exertional malaise in ME/CFS patients.

  • Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterizing chronic fatigue syndrome. Disabil Rehabil. 2011 Jan 6. [PubMed]
  • Keller, B. Micale, F. Exercise Testing to Quantify Effects of Fatigue on Functional Capacity in Patients With CFS. in IACFS/ME Biennial Conference; Translating Evidence Into Practice. 2011. Ottawa, Ontario, Canada.
  • Snell, C., Stevens, S., Davenport. T., Van Ness, M. Discriminative Validity of Metabolic and Workload Measurements to Identify Individuals With Chronic Fatigue Syndrome. Physical Therapy. 27 June 2013 doi: 10.2522/ptj.20110368. [PubMed]
  • VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). 2010 Feb; 19(2):239-44. [PubMed]
  • Vermeulen, R. Kurk, Visser, F. Sluiter, W. Scholte, H. Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med, 2010. 8: p. 93. [PubMed]

Further Reading

  • Carruthers, BM. The New International Consensus Criteria for M.E. – content and context. Invest in ME. [Article]
  • Carruthers, BM., van de Sande, MI., Myalgic Encephalomyelitis – Adult & Paediatric: International Consensus Primer for Medical Practitioners, 2012 [PDF]
  • Ruud CW Vermeulen and Ineke WG Vermeulen van Eck, Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome, J Transl Med. 2014; 12: 20. [PubMed]
  • NAAME Letter to CDC re one-day exercise test, NAAME, July 22, 2013 [PDF]
  • Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J. Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev. 2014;20:94-116. [PubMed]
  • McGrath, S., Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity, Phoenix Rising, July 29, 2013, [Article]
  • The Stevens Protocol – Repeat Exercise Testing at the Pacific Fatigue Lab: Part I by Lannie, Phoenix Rising, November 11, 2010 [Article]


  1. Snell, C., Stevens, S., Davenport. T., Van Ness, M. Discriminative Validity of Metabolic and Workload Measurements to Identify Individuals With Chronic Fatigue Syndrome. Physical Therapy. 27 June 2013 doi: 10.2522/ptj.20110368. [PubMed], [Full Text]
  2. Nijs J, Van Oosterwijck J, Meeus M, et al. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med. Apr 2010;267(4):418-435. [PubMed]
  3. Van Oosterwijck J, Nijs J, Meeus M, et al. Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study. J Intern Med. Sep 2010;268(3):265-278. [PubMed]
  4. VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). Feb 2009;19(2):239-244. [PubMed]
  5. Davenport TE, Stevens SR, Baroni K, Mark Van Ness J, Snell CR. Reliability and validity of Short Form 36 Version 2 to measure health perceptions in a sub-group of individuals with fatigue. Disabil Rehabil. Jun 20 2011. [PubMed]
  6. Davenport TE, Stevens SR, Baroni K, Van Ness M, Snell CR. Diagnostic accuracy of symptoms characterising chronic fatigue syndrome. Disabil Rehabil. 2011;33(19-20):1768-1775. [PubMed]
  7. Davenport TE, Stevens SR, VanNess MJ, Snell CR, Little T. Conceptual model for physical therapist management of chronic fatigue syndrome/myalgic encephalomyelitis. Phys Ther. Apr 2010;90(4):602-614. [PubMed]

Written by Russell Logan

Russell Logan worked as a magazine publisher and editor until forced into early retirement through ill health with ME. He has battled with moderate to severe ME for 25 years. He now lives in Noosaville, Australia.

87 posts


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  1. We need scientists and exercise physiologists to move towards a less invasive test. This test whilst providing evidence of disability does so at huge cost and risk to the patients. Many are too ill to actually do the test. Recovery is slow – weeks to months and recovery is NOT guaranteed. It’s extremely dangerous.

    • I know I would not be able to do the test at all. I would not be able to breathe. Also, if I pushed myself to my limit I might never recover.

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