And the Envelope, Please

My exercise test results are in. The numbers were, quite frankly, shocking. Two numbers – VO2max and anaerobic threshold – provide the evidence that I have significant metabolic dysfunction, and I’ll try to explain what they mean. Check out my description of the test itself for background. What I do now that I have the results will be the subject of my next post.

VO2max is a measurement of the maximum amount of oxygen that a person can use during exercise. The more oxygen you can use, the more energy you can produce. VO2 max is considered the best measurement of a person’s physical fitness or functional capacity, and it is affected by factors such as age, gender, training, altitude, etc. A sedentary woman my age has an average of 27.0. My VO2max was 20.7 on day one, and 19.6 on day two. In other words, my maximum ability to use oxygen is 23% lower than what would be expected for a sedentary woman my age.

One interesting thing about my VO2max number is that I was able to reproduce the result on day two. Typically, people can reproduce their VO2max value on a two-day test with about 6-7% of variation. My number was about 5% different. So this is a good thing, but not necessarily typical of CFS patients. One study found that CFS patients had a drop of 20% in their VO2max on the second test day.

Dr. Betsy Keller of Ithaca College, who conducted my exercise test, included functional equivalents in her report to help translate the numbers into information I could actually understand. Looking at just the VO2max number, my capacity equates to slow cycling, but carrying groceries upstairs exceeds my functional capacity. That’s pretty grim.

Anaerobic threshold is where things get really interesting. The anaerobic threshold is the point at which your body is producing most energy through anaerobic metabolism, as opposed to aerobic metabolism which uses oxygen. This means that you will feel increasing fatigue, your workload will drop, and you will have to stop activity within a few minutes. It also takes longer to recover from this kind of activity, requiring rest and more oxygen. (Is this sounding familiar to anyone?)

On day one, my anaerobic threshold occurred at 105 beats per minute. That is not horrible, although it is low. A deconditioned but otherwise healthy person might have a result like that. On day two, however, my anaerobic threshold dropped to 93 beats per minute. That is abnormal, not just because it is low but because it represents such a significant drop from day one. Healthy people, even deconditioned people, are able to reproduce their anaerobic threshold results on day two. That I failed to do so is proof of metabolic dysfunction.

When you put the VO2max result together with the anaerobic threshold result, you can see the metabolic dysfunction another way. Normally, the anaerobic threshold will occur at about 50-75% of a person’s VO2max. But for me, my anaerobic threshold on day one occurred at 30% of VO2max. Anything below 40% is considered an abnormal result and evidence of metabolic dysfunction. On day two, my anaerobic threshold occurred at 17% of VO2max. That is crazy low. In fact, I reached that anaerobic threshold just sitting on the bike before I started pedaling on day two. Just sitting there, I was already maxed out. These are grossly abnormal results.

To equate these numbers to functionality, Dr. Keller said that my day one anaerobic threshold is the equivalent of standing to fold laundry, or putting clothes in the washer, but that walking around to put away laundry would be beyond my capacity. But on day two? The day two result is the equivalent of lying down watching television. So when I am in a crash, I am exceeding my anaerobic threshold by just lying down and watching tv or doing nothing.

So no wonder I feel like shit all the time, yeah?

There were other abnormalities, including blunted heart rate and blood pressure responses, but these two numbers are the key for me. As Dr. Keller points out, most activities of daily living require me to work above my anaerobic threshold. This means my ability to perform those activities is limited, and resulting fatigue prevents me from continuing to perform those activities.

Here’s the killer fact for me, though. On day two, I was at my anaerobic threshold before I even started cycling. Then I proceeded to cycle for 11.5 minutes, and came close to the length and workload I produced on day one. The whole second day was past my anaerobic threshold. I felt and rated day two as more difficult, but I kept going anyway. I draw two conclusions from this. First, I have become accustomed to operating over my anaerobic threshold and have probably developed that as an adaptive coping mechanism. Second, I cannot trust my my own assessment of when I am overdoing it. My sense of how I am feeling is not reliable.

My husband’s reaction to that was “Duh.” It will surprise no one who knows me that the test proves I am a stubborn and determined woman who does not accept her own limitations. But it was a shock to see this reduced to numbers and written in black and white on the page.

A friend pointed out to me that nothing has actually changed. It’s not like I’ve suddenly developed a heart condition. The only thing that has changed is the information I have about the metabolic dysfunction. Knowledge is power, and next time I’ll share what steps I’m taking to apply this knowledge.

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13 Responses to And the Envelope, Please

  1. timv says:


    For me, your post is enlightening and confusing. I think part of the reason it’s confusing because you forgot to use units of measure for your heart rate number? I don’t understand the anaerobic threshold being 17% of VO2max. If I use your anaerobic threshold percentage to calculate a VO2 max heart rate – (93/0.17) I get a VO2max heart rate of 547 beats per minute!! I’m confused…. Maybe if you also stated your VO2 max heart rate then I could understand your numbers. I’d love to be able to use your numbers as an example for communicating CFS to others…. maybe I’m confused.

    • Jennie Spotila says:

      Thanks for asking this question! The VO2max number is actually measured as milliliters of oxygen used per minute per kilogram of body weight (ml/kg/min).

      On day one, I hit my anaerobic threshold heart rate of 105bpm at a VO2 of 6.46ml/kg/min which is 30% (31.2% to be precise) of my VO2max of 20.7ml/kg/min. On day two, I hit the anaerobic threshold heart rate of 93bpm at a VO2 of 3.23ml/kg/min which is 17% (16.4% to be precise) of my VO2max of 19.6ml/kg/min. A healthy person would hit the anaerobic threshold at 50-75% of VO2max. In my case, my heart rate at 50% of my VO2max was about 118bpm, so that is where my anaerobic threshold should be.

      One of the reasons these numbers are confusing to me is that there are formulas behind all of them, as opposed to straight up measurements. The anaerobic threshold is accurately measured by taking periodic blood samples and measuring the level of lactate. The point at which lactate starts to build up in the blood is the anaerobic threshold. In my test, no blood samples were taken, so the anaerobic threshold number came from a calculation (which I do not understand).

      I hope this helps. Please let me know if you have more questions.

  2. Linda says:

    How did you feel on day 3 ?

  3. This makes so much sense. Basically if we over do it big time we’ll still be overdoing it whilst we rest up in the following days. No wonder it can be so difficult to break the cycle of stiff and sore overworked muscles. I guess we shouldn’t get tempted to do too much even as an ocassional treat. Hard though! Or if we do overdo it we have to seriously apply ourselves to quality restfulness fo a long time afterwards!

    Once again thanks for putting yourself though all this so that we could all learn something!

  4. Shar Childers says:

    Jennie, Thanks so much for this post. I have read the research but this is the best explaination in plain english I’ve seen. Although, I have to admit that I still don’t understand all the calculations/percentages. But since I went to the grocery store yesterday I know it’s a waste of time to try to figure it out today. I’ll try sometime when I’m better rested. I think what really struck me was that you could be beyond your threshhold just laying down watching TV. Pretty sure I spent the better part of 3 years in that state! Hope you are finally recovered from the test and I look forward to reading your next post. Just curious, do you have POTS?

    • Jennie Spotila says:

      I have some form of orthostatic intolerance, but it’s not clear whether it’s POTS or NMH. I’ve never had a tilt table or other testing specifically for that.

  5. Anne Ö says:

    I agree with Shar Childers! [“I have read the research but this is the best explaination in plain english I’ve seen.”]

    Jennifer, you are so knowledgeable about this, can I ask two questions?

    – Could you possibly list all the studies relating to this topic? I know there are some from Pacific Fatigue Lab, some from Ithaca and some from Holland (?), but I haven’t seen a full list. Would you have the time, energy and possibility to provide us with one?

    – Do the researchers also include the reaction AFTER the two-day-testing in their studies? That is, do they follow up and report on the many weeks it has taken you to recover?

    Thank you for reporting on this, it is hugely helpful.

    • Jennie Spotila says:

      Anne, I can try to pull together a list of the studies. I’m not sure it would be completely comprehensive, but I will try.

      The only study I am aware of that followed people beyond two days was the Pacific Fatigue Lab study that followed participants for 7 days. I linked to it in an earlier blog post but here is the link again.

  6. John says:

    Anne O, here’s a list I made a while ago of ME/CFS exercise papers. I’m not sure how up to date it is though, I can’t remember if any good studies have come out in the last year or so-

    Neary et al 2008 Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome

    White et al 2005 Immunological Changes After Both Exercise and Activity in Chronic Fatigue Syndrome: A Pilot Study

    This link should have most of the papers from the Pacific Fatigue Lab-


    2. Complement activation in a model of chronic fatigue syndrome. Sorensen B, Streib JE, Strand M, Make B, Giclas PC, Fleshner M, et al. J Allerg Clin Immunol 2003; 112: 397–403.
    “Exercise challenge induced significant increases of the complement split product C4a, but not C3a or C5a, at 6 hours after exercise only in the CFS group (P < .01), regardless of allergy status. Mean symptom scores were significantly increased after exercise through the use of a daily diary (P < .03) and a weekly diary (P < .01) for the CFS group only. Mean scores for the Multidimensional Fatigue Inventory categories “reduced activity” and “mental fatigue” were significantly increased in the CFS group only (P < .04 and P < .02, respectively).”

    3. Chronic Fatigue Syndrome: Exercise Performance Related to Immune Dysfunction. Nijs, Jo; Meeus, Mira; McGregor, Neil R.; Meeusen, Romain; De Schutter, Guy; Van Hoof, Elke; De Meirleir, Kenny Medicine & Science in Sports & Exercise:Volume 37(10)October 2005pp 1647-1654

    Conclusion: These data provide evidence for an association between intracellular immune deregulation and exercise performance in patients with CFS.;jsessionid=JbSX8HTkTz9pksQG6Z2JQp1qQSPQmZyYbfspfMqYzm1byTqwFHVv2852599181811956288091-1

    4. Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. Jammes Y, Steinberg JG, Mambrini O, Bregeon F, Delliaux S Journal of Internal Medicine:Volume 257(3)March 2005p 299-310

    “The response of CFS patients to incremental exercise associates a lengthened and accentuated oxidative stress together with marked alterations of the muscle membrane excitability. These two objective signs of muscle dysfunction are sufficient to explain muscle pain and postexertional malaise reported by our patients.”

    Notes- Further discussion by MERUK-;jsessionid=JbfTvF2Jd3jQVyrVTtTdRqTfwhyvsvTYxhQL9BrQ5k5r1Tnjysrb2852599181811956288091-1

    5. Exercise responsive genes measured in peripheral blood of women with Chronic Fatigue Syndrome and matched control subjects. T Whistler, JF Jones, ER Unger, SD Vernon BMC Physiol, 2005

    "CFS is defined by a post-exertional fatigue that does not subside 24 hours following physical stress. In contrast, exercise in healthy, untrained people induces changes in cellular homeostasis in 1 to 4 hours and a return to basal levels within 24 hours, as measured in muscle. Analysis of peripheral blood gene expression in the healthy control subjects confirmed this observation since the majority of gene expression levels were the same before and 24 hours following exercise challenge. This implied that expression either returned to basal levels or was unchanged as a result of the exercise challenge. And indeed, many of the 21 exercise-induced, differentially expressed genes in control subjects were characterized by gene ontologies(GO) that reflect a diverse set of molecular functions necessary for cell function and viability. (These ontologies overlapped with those identified in the GO comparison analysis given in Figure 2a). Figure 1 clearly illustrates the reciprocal pattern of gene expression in the 21 genes for most of the control subjects. In contrast, 11 of the genes were unchanged in CFS subjects before and after exercise; with 5 being classified in a transport-related ontology. Because this difference in gene expression is so dramatic, it implicates a fundamental perturbation in the biochemical activity of lymphocyte and monocyte peripheral blood fractions from CFS subjects compared with control subjects that does not affect classical immunologic markers (i.e, CD45) that have been shown to be unaffected in CFS patients. Rather, low expression of these genes may have subtle effects on immune function. Immune dysfunction has been inconsistently implicated in CFS pathogenesis.

    It is evident that ion transport and ion channel activity segregate cases from controls and that exercise seems to intensify these differences. Several other conditions have been reported in which fluctuating fatigue occurs that are known to be caused by abnormal ion channels. These conditions include genetically determined channelopathies and acquired conditions such as neuromyotonia, myasthenic syndromes, multiple sclerosis, and polyneuropathies. There are other transmembrane functions associated with differences between controls and CFS patients, including signal transducer activity through receptor binding/activity (Figure 3a). Signal transduction of transmembrane receptors occurs by a number of mechanisms, including structural changes, ion channels, and changes of transmembrane potentials. The G-protein-coupled receptors play an important role in the membrane trafficking machinery. The most obvious exercise-induced changes in CFS cases pertain to gene regulation at the point of chromatin structure; whether these changes reflect the differences seen in the mRNA transcripts relating to membrane trafficking differences between cases and controls has not yet been determined."

    6. Prefrontal cortex oxygenation during incremental exercise in chronic fatigue syndrome. J. Patrick Neary, Andy D. W. Roberts, Nina Leavins, Michael F. Harrison, James C. Croll and James R. Sexsmith Clin Physiol Funct Imaging (2008)

    “In this study, there was a 3-8% decrease in TOI in the CON group, in comparison with only 1-3% decrease in the CFS group during the exercise period (Fig. 4). This equates to a 64-5% difference in the amount of O2 extraction between the two groups.”

    “Research has shown that cerebral blood flow is reduced in subjects with CFS when using transcranial Doppler sonography (Ichise et al., 1992; Yoshiuchi et al., 2006). In particular, Ichise et al. (1992) showed a significant blood-flow reduction in multiple regions of the brain of CFS subjects, including the prefrontal cortex. Some have suggested that this reduction in blood flow is related to an autonomic (cerebral autoregulation) dysregulation also noted in subjects exhibiting neurally medicated syncope under a number of different experimental conditions (Stewart et al., 1998; Yamamoto et al., 2003). Because cerebral autoregulation, metabolic regulation of O2 and CO2-mediated vasodilation are the most important mechanisms to ensure cerebral blood flow (Nybo & Rasmussen, 2007), our results would support the premise that the central nervous system of CFS subjects is somehow altered, and support previous research that suggests a CNS mechanism(s) is implicated in the pathogenesis of CFS (Georgiades et al., 2003; Chaudhuri & Behan, 2004; Siemionow et al., 2004b)”;jsessionid=JbgJvg15mSXPDV7F0gnrX6zB2vT83q24KcGTcRyJvpDR4vHj92hZ2852599181811956288091-1

    Findings from the 2009 IACFS/ME Conference-

    1. A diagnostic test for the identification of metabolic dysfunction was discussed by J.Mark VanNess (Stockton,USA). Two graded exercise tests with cardio-pulmonary analysis were performed within 24 hours of each other. There was a “fatigue effect” of prior physical activity not characteristic of other illnesses. There was reduction of peak oxygen consumption and/or oxygen consumption at anaerobic threshold in CFS patients and in particular those with a high viral load. This provides evidence of metabolic dysfunction.

    2.Patients with fibromyalgia and/or CFS demonstrate sustained increases in gene expression for metabolite sensing receptors and $adrenergic receptors on leucocytes from 0.5 to 48 hours after exercise. This is the time when pain and fatigue worsen, even when muscles are inactive. This study by Alan Light (Utah, USA) suggests a predisposition for these receptors to increase dramatically after exercise, stress and infection. There is potential for the increases in gene expression to provide biomarkers.

    3. Gordon Broderick (Edmonton, Canada) found that subjects with Gulf War Illness (GWI) can be discriminated by demonstrating significantly different neuro-endocrine-immune dynamics in response to exercise. Changes in cytokines, NPY and cortisol are evident both at rest and much more so under challenge, and could separate subjects completely from the control group.

    Note- This study was on Gulf War Illness and not CFS patients, but many similarities exist between GWI and CFS, and it is speculated that GWI and CFS might share some of the same pathologies.

    4. Remodeling of lymphocyte-cytokine networks in GWI under challenge – Gordon Broderick (Edmonton,Canada) – Characteristic immune responses occur spontaneously in these patients after exercise challenge, and resolve once the challenge is removed. Results suggest a potential shift in the regulation of body fat and energy metabolism in GWI and a bias toward Th2 mediated humoral immune response.

    5. Toni Whistler (Atlanta,USA) used gene arrays to look at the mediators of NK cell function. She found that there was decreased functional capacity of NK cells in Gulf War Illness. There was impaired immune function involving Th2 and proinflammatory cytokines, cytokines, cytotoxic NK cells and T cells, and dysregulated mediators of the stress response such as salivary cortisol. These differences were augmented by exercise challenge. Laboratory diagnostic tests maybe developed as a result of this research.
    Note- Another study on Gulf War Illness that shows abnormal response to exercise.


    1. Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls. Thambirajah AA, Sleigh K, Stiver HG, Chow AW Clin Invest Med. 2008 Dec 1;31(6):E319-27

    "Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness. METHODS: HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise. RESULTS: Basal HSP27 was higher among CFS patients than in controls (0.54 +/- 0.13 vs. 0.19 +/- 0.06, mean +/- SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 +/- 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 +/- 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 +/- 0.40 vs. 1.32 +/- 0.46; P < 0.05), and for HSP90 (0.34 +/- 0.09 vs. 0.49 +/- 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 +/- 0.27) and day 7 (1.24 +/- 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 +/- 0.06) (P < 0.05, respectively). CONCLUSION: These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness."

    2. Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis. Bassi N, Amital D, Amital H, Doria A, Shoenfeld Y. Isr Med Assoc J. 2008 Jan;10(1):79-82. Review.

    "Patarka [19] demonstrated higher serum levels of interleukin-4 and interferon-gamma and lower levels of TGFß. Fulle and co-authors [20] showed a dysregulation of the Na+/K+ and Ca2+-ATPase pumps and alterations in ryanodine channels in sarcoplasmic reticulum membranes in CFS patients. Extracellular K+ accumulation can induce a negative feedback signal for sarcolemma excitability [21], and dysregulation of the pump activities can cause increased sarcoplasmic reticulum membrane fluidity [20], leading to the formation of lipid hydroperoxides[22]. All these alterations in muscle excitability can cause post-exercise oxidative stress, explaining muscle pain and post-exertional malaise reported by the patients [23]. The oxidative stress can be generated by a lower maximal aerobic capacity and by a reduced baseline oxygen uptake by tissues that occurs in CFS patients [23]."

    3. Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. Wyller VB, Saul JP, Walløe L, Thaulow E. Eur J Appl Physiol. 2008 Apr;102(6):623-32.

    "The chronic fatigue syndrome (CFS) has been shown to be associated with orthostatic intolerance and cardiovascular dysregulation. We investigated the cardiovascular responses to combined orthostatic stress and isometric exercise in adolescents with CFS. We included a consecutive sample of 15 adolescents 12-18 years old with CFS diagnosed according to a thorough and standardized set of investigations, and a volunteer sample of 56 healthy control subjects of equal sex and age distribution. Heart rate, systolic, mean and diastolic blood pressure, stroke index, and total peripheral resistance index were non-invasively recorded during lower body negative pressure (LBNP) combined with two consecutive periods of handgrip. In addition, we measured baseline plasma catecholamines, and recorded symptoms. At rest, CFS patients had higher heart rate, diastolic blood pressure, plasma norepinephrine (P < 0.01), mean blood pressure and plasma epinephrine (P < 0.05) than controls. During LBNP, CFS patients had a greater increase in heart rate, diastolic blood pressure, mean blood pressure (P < 0.05) and total peripheral resistance index (n.s.) than controls. During handgrip, CFS patients had a smaller increase in heart rate, diastolic blood pressure (P < 0.05), mean blood pressure and total peripheral resistance index (n.s.) than controls. Our results indicate that adolescents with CFS have increased sympathetic activity at rest with exaggerated cardiovascular response to orthostatic stress, but attenuated cardiovascular response when performing isometric exercise during orthostatic stress. This suggests that CFS might be causally related to sympathetic dysfunction."

  7. Anne Ö says:


    Thank you so much for this! If I understand things correctly, when it comes to the abnormalities in the 2-day exercise testing, the Pacific Fatigue Lab has published a few papers, but none in a really major medical journal (?), Betsy Keller has repeated the findings, but not yet published (looking forward to that!) and a Dutch team has repeated the findings and published, see (not sure how major the journal is, J Transl Med). Please comment or correct me if I got any of this wrong!

    The reason I’m looking into this, is that I think the findings are extraordinary and should really help removing the remaining doubts about whether ME/CFS is a real and physical disease. Also this research must be a great starting point for future research to find out what is really going on in our bodies. So I have been surprised at the relatively small attention this research has gotten. I’m guessing what we need is confirmation of the findings in yet other group and some published articles in major journals?

  8. Pingback: Overcoming The Symptoms Of Chronic Fatigue Syndrome

  9. @Anne Ö
    I’d say Journal of Translational Medicine is a pretty decent journal. Impact factor 3.5 and well-known by name. Not BMJ or Lancet by any means, but it’s definitely not obscure.

    We already have hundreds of studies demonstrating very well the physiological origins of CFS/ME, but people just won’t listen. :-/

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