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Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity

Hooked up for a CPET

Hooked up for a CPET

Simon McGrath reports on Dr Snell’s new study demonstrating that ME/CFS patients have a reduced capacity to exercise when they repeat a maximum exercise test one day on – unlike healthy controls.

One of the biggest problems of getting ME/CFS taken seriously is that often we ‘look’ normal, even though we feel lousy, and most lab tests produce ‘normal’ findings. How do we prove to the world that we are sick?

A defining feature of ME/CFS is Post-Exertional Malaise (PEM) and a couple of studies have clearly demonstrated PEM in patients [see box]. However, PEM is a subjective experience and one that can only be measured by patient self-report, which won’t satisfy everyone.

Dr Chris Snell, Staci Stevens, Dr Todd Davenport, and Dr Mark VanNess’s new study aimed to objectively demonstrate the problem of post-exertional malaise, by using a repeat Cardiopulmonary Exercise Test (CPET). As they formally hypothesized in their paper: “an exacerbation of symptoms following the first test would be reflected in physiological responses to the second”.

The study

The 51 CFS patients were all women, met Fukuda criteria and also reported PEM. Controls, also female, were similar in age and BMI, and were fairly sedentary. In fact, the results of the first CPET revealed that the controls were in the bottom 10% of published population norms and would count as deconditioned. CFS patients were barely different from controls so were also deconditioned, but, crucially, they were ill while controls were healthy, casting doubt on the idea that deconditioning is responsible for CFS.

CPET: Cardiopulmonary Exercise Testing explained

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.

cPETb

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).

CPETaVO2 max versus VO2 peak

One challenge of CPET is detecting if the person is using maximal effort, as opposed to trying pretty hard. Data showed that CFS patients and subjects here all went deep into anaerobic exercise and met at least one other measure of high effort. 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.

Note there are equivalent thresholds for work output, in watts: W max, W peak and W VT

More: Lannie’s blog on PR about her CPET at Pacific Fatigue Labs.

Day 2 results separated patients from controls

Day 2 CFS patient...

A Day 2 CFS patient…

The big differences between the groups emerged on the second maximal CPET test, 24 hours after the first. On average, controls did slightly better on Day 2 (something that has been observed in other studies too) while patients did substantially worse. Interestingly, VO2 peak did not differ significantly between patients and controls, but peak Watts output was significantly lower, as was VTO2 . The biggest difference of all was for Watts output at VT, down for the patient group by over half.

The study found the repeat test could separate CFS patients from controls in this sample with 95% accuracy (3 errors in total). They also used a statistical technique called ‘cross-validation’, which indicated the test would achieve a 90% accuracy in an independent sample (though see issue with convenience sample below).

This ability of a 2-day repeat test to discriminate healthy but sedentary controls from CFS patients is critical. In theory, doctors can manage this easily enough without a CPET test. However, where there is doubt about the reality of symptoms, as can happen with disability insurance claims, an objective test can demonstrate that a patient really is sick. As Workwell Foundation notes, it’s useful in legal or medical disputes; the reduced performance on VT is “impossible to fake”, adds Dr Snell.

“the post-exertional state in CFS is characterized by objectively measurable deficits in submaximal metabolism and workload that would be nearly impossible for patients to fabricate”

In some ways the findings are unexpected, as it was the same group’s earlier finding of a substantial drop in VO2 max on the second test that caused such a buzz amongst patients. And the big drop in output at VT wasn’t seen in a study (albeit a small one) by a separate research group, though a smaller drop was seen for VT, and VO2 max in a study presented at an IACFS conference. I asked Chris Snell if he was surprised by the finding. “No”, came the reply: the initial study was small making the findings less robust, and he said that a much bigger effect on VT than VO2 max has been seen in the clinic too.

Evidence of Post-Exertional Malaise from subjective studies

As well as the objective evidence from this new paper, PEM has been shown by self-report measures too. A 2010 study from Pacific Fatigue Labs found that only 1 of 25 female CFS patients recovered from a maximal exercise test 48 hours later while all 23 sedentary controls did. Another study using a moderate exercise test found that fatigue and pain increased in the 48 hours after exercise in CFS patients – while it returned to normal in that time for both healthy controls and Multiple Sclerosis patients.

Committed to Maximal CPET

Given that it’s hard enough for people with ME/CFS to do one maximal test, let alone two, these results create the temptation to just run the second test as far as the Ventilatory Threshold and forget about VO2 max. But Chris Snell stressed that the Workwell Foundation remains committed to the repeat-maximal approach. First, VT can’t be measured on the fly so they wouldn’t know when to stop the test. And perhaps more importantly, the post-exertional effect appears to differ by patient, with some showing a greater effect on peak measures and others at VT.  Dr Snell suggested that varying post-exertional responses may well reflect different underlying pathologies.

Unique to ME/CFS?

Is this the killer test that uniquely identifies CFS patients? Dr Snell has reported that their clinic has tested patients with numerous illnesses including Multiple Sclerosis and Congestive heart failure, but have only seen the problem in ME/CFS patients. Published studies show normal repeat CPET performance for sarcoidosis, angina, Chronic Airflow Obstruction, Pulmonary Hypertension and heart disease. I’ve seen no studies showing failure to reproduce CPET results in other illnesses, but it’s probably too soon to say if this is unique to ME/CFS, or just very unusual.

What might cause the exercise problems?

The authors suggest that a synergy of small effects across multiple systems could be responsible for the poor exercise performance of the individuals with CFS. Lower oxygen carrying capacity could result from low blood volume, while low oxygen consumption could also result from autonomic dysfunction and reduced ventilation. But research into the causes is needed.

No study is perfect…

  • There were only 10 controls, though as the repeatability of CPET results is firmly established (with 94% reliability between tests), in some ways controls mainly serve to demonstrate that the protocol is working properly.
  • The CFS patients were a convenience sample, rather than, for example, consecutive referrals to a secondary clinic. This, and the fact that patients had agreed to a repeat maximal exercise test, means the results might not generalize to the patient population as a whole.
  • The earlier study by this group, and the other studes from independent groups, didn’t find the dramatic changes with workload at the ventilatory threshold, so further replication would help to confirm the nature of the changes.

These findings, which make visible the hallmark ME/CFS problem of post-exertional malaise, have potentially huge importance. Replication of this study, perhaps with a more representative sample of CFS patients and some sick controls, should in my view be a priority for the research community. Stage two of the huge CDC multi-clinic study could provide the perfect opportunity for this.

Simon McGrath tweets on ME/CFS research:

 

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{ 155 comments… add one }

  • SOC October 21, 2013, 11:06 pm
    alex3619

    Which leads me to a question I have not thought about much, are there stages to PEM, with different symptoms in those stages?

    Good question, Alex, and well worth some research. If only we had the funding. :(

    I've wondered a lot lately about the definition of PEM. It seems that if you've experienced it, it's easy to identify. It's entirely different from fatigue, or exhaustion, or any other symptom in the same class. I've had exhaustion along with PEM/PENE, but it was clearly much more than just exhaustion. I frequently wonder if most of our doctors, and researchers even more so, don't really get it.

    I sometimes think some patients who believe they have PEM, actually have other types of fatiguing symptoms and/or exercise intolerance which, while disabling in their own right, are different from PENE — post-exertional neuro-immune exhaustion.

    Now that I've cleared a number of viruses (for the time being, anyway), my experience of PEM is different — much less flu-like and multisystem collapse, and more mostly exhaustion. Is it just less severe PEM, or do I only get some fatiguing symptoms but not true PEM? Is it that it would just take more now for me to get the whole system collapse thing, or that I wouldn't get there at all, although I would have extreme mental and physical fatigue? Frankly, I'm not going to experiment with testing to destruction unless it's for some valuable scientific research. 😉 I kinda like not being crashed. 😀

    I'd love to see more research on PEM — What is it, exactly? Are there stages to PEM? Are there different flavors of PEM? Do different types of exertion — physical, mental, emotional — cause different types of PEM or is it all the same PEM?

  • alex3619 October 21, 2013, 11:19 pm

    I'd love to see more research on PEM — What is it, exactly? Are there stages to PEM? Are there different flavors of PEM? Do different types of exertion — physical, mental, emotional — cause different types of PEM or is it all the same PEM?

    Quark, strangeness and charm versions of PEM?

    http://en.wikipedia.org/wiki/Quark,_Strangeness_and_Charm

    http://en.wikipedia.org/wiki/Quark

    There are six types of quarks, known as flavors: up, down, strange, charm, bottom, and top.[4] Up and down quarks have the lowest masses of all quarks. The heavier quarks rapidly change into up and down quarks through a process of particle decay: the transformation from a higher mass state to a lower mass state. Because of this, up and down quarks are generally stable and the most common in the universe, whereas strange, charm, top, and bottom quarks can only be produced in high energy collisions (such as those involving cosmic rays and in particle accelerators).

  • Valentijn October 22, 2013, 9:49 am
    alex3619

    Which leads me to a question I have not thought about much, are there stages to PEM, with different symptoms in those stages?

    I started taking Yohimbe, a bark extract, about two weeks ago, and I haven't had any PEM while on it despite exceeding my limitations pretty badly, by flying back home (10+ hours in the airplane, 3-4 hours in airports). My heart rate was elevated for most of the trip, 100-105 on the airplane, and 105-130 after getting off the airplane, which would usually mean a bad crash.

    So I still have my abnormal reaction to exertion shown by raised heart rate and/or dropping oxygen levels, but I don't seem to be crashing afterward. Basically there have been a couple recent papers by the Lights, showing a three-fold increase in ADRA2A expression after exertion in ME patients, but not in well-matched sedentary controls. And ADRA2A is capable of accounting for much of the symptoms of PEM, as well as suppressing norepinephrine production, which can cause orthostatic intolerance.

    So I switched from taking an NRI to taking Yohimbe, which is a very potent antagonist of ADRA2A, and my OI symptoms have remained under control, in addition to thus far avoiding PEM. Gut motility has also improved, to the extent that I've had to cut my daily magnesium dose in half. I've had none of the muscle twitches or cramps that I would usually get from cutting back magnesium.

    So in my very brief experience thus far, it seems possible that the up-regulation of that one gene after exertion can account for all of my PEM symptoms, both physical and cognitive, as well as a few other symptoms. Hence my experience says there's just one stage, with a single trigger – though there's obviously something triggering that abnormal reaction, since gene expression is normal prior to exertion.

    Of course, there's also symptoms immediately following over-exertion (pain, weakness, etc), but I think those are a separate issue from PEM.

  • lansbergen October 22, 2013, 10:22 am
    Valentijn

    Gut motility has also improved, to the extent that I've had to cut my daily magnesium dose in half.

    I tried one magnesium tablet once and it gave me bad diaree. I never did it again. As I treat the step after ADRA2A upregulation with the immuneregulator I use that makes sense to me now.

    Keep digging valentijn

  • MeSci October 22, 2013, 12:05 pm
    alex3619

    The problem with PEM and current science is that it is still a syndrome. We don't understand it. I suspect its a composite symptom cluster with multiple issues, each of which has their own time scale. Some aspects of it are being unravelled though, from mitochondrial and delayed energy production issues, to more immediate muscle lactate responses.

    Given that this involves metabolism, nerve signals, hormonal signals and immunological signals, each with its own time frame, the way to think of PEM might be one to many overlapping curves, each with its own maximum intensity spike\s, and what we experience is the combination of these effects. In terms of waves, this means intensification or nullification based on how the waves superimpose on each other. Three big waves coincide and whammo, you have big symptoms.

    Which leads me to a question I have not thought about much, are there stages to PEM, with different symptoms in those stages?

    A message by beaverfury here yesterday contains a link to a paper that excites me greatly as I believe that it may provide an important clue to how exertion can perpetuate ME autoimmunity, and perhaps also how the gut can be involved in the process of PEM being caused.

    Unable to get the full text of that paper, I did some searching and found this one.

    Put together with this paper that shows how excessive gut permeability could lead to, and perpetuate, autoimmune disease, some good clinical research addressing these issues in combination could perhaps scotch the psychoquacks' nonsense once and for all, and prove how GET can not only exacerbate symptoms on various timescales but also make recovery impossible.

  • MeSci October 22, 2013, 1:32 pm
    Valentijn

    I started taking Yohimbe, a bark extract, about two weeks ago, and I haven't had any PEM while on it despite exceeding my limitations pretty badly, by flying back home (10+ hours in the airplane, 3-4 hours in airports). My heart rate was elevated for most of the trip, 100-105 on the airplane, and 105-130 after getting off the airplane, which would usually mean a bad crash.

    So I still have my abnormal reaction to exertion shown by raised heart rate and/or dropping oxygen levels, but I don't seem to be crashing afterward. Basically there have been a couple recent papers by the Lights, showing a three-fold increase in ADRA2A expression after exertion in ME patients, but not in well-matched sedentary controls. And ADRA2A is capable of accounting for much of the symptoms of PEM, as well as suppressing norepinephrine production, which can cause orthostatic intolerance.

    So I switched from taking an NRI to taking Yohimbe, which is a very potent antagonist of ADRA2A, and my OI symptoms have remained under control, in addition to thus far avoiding PEM. Gut motility has also improved, to the extent that I've had to cut my daily magnesium dose in half. I've had none of the muscle twitches or cramps that I would usually get from cutting back magnesium.

    Anything suggested by the great Valentijn :love: has to be worth looking into. So I did me some searching for info on Yohimbe.

    Looks like it's not for me, unfortunately.

    For example this page says

    Yohimbe bark has traditionally been used in Africa as an aphrodisiac

    No thanks! 😮 I can do without that complication.

    This lot is further cause for concern for me:

    Yohimbe has been associated with high blood pressure, increased heart rate, headache, anxiety, dizziness, nausea, vomiting, tremors, and sleeplessness. Yohimbe can be dangerous if taken in large doses or for long periods of time.

    OK, it only says 'associated', but I already have high blood pressure, and the others are common ME symptoms. It may be that further searches will reveal actual evidence, but it's 'No' to Yohimbe for me.

  • peggy-sue October 22, 2013, 2:20 pm

    My reaction to the mention of Yohombin was an immediate; "eeeeeeeek!"

    (something from the recesses of pharmacology studies and from work)

    I couldn't remember what it was, or what was scary about it, but I remembered it was scary.

    Early on in being ill, I found that mental overdoings could cause physical PEM and vice versa.

    I'm not quite so sure this still happens. Sometimes, if I've been very happy, I will get a payback of being really down.

    Mostly nowadays, PEM is an exacerbation of everything, my "baseline" level of functioning reduces.

    I get that peculiar difficulty with breathing that Alex describes – as if the air hasn't got enough oxygen in it – (I do not know what thin air at altitude feels like, I'm only imagining) and that while I am labouring to breathe, it's still not doing what it it supposed to!

    PEM should be a priority for research.

  • Valentijn October 22, 2013, 3:32 pm
    MeSci

    OK, it only says 'associated', but I already have high blood pressure, and the others are common ME symptoms. It may be that further searches will reveal actual evidence, but it's 'No' to Yohimbe for me.

    It is heavily marketed as a male erection type drug, probably due to improvements in circulation. Many sources go way overboard in trying to make it look effective, to the extent that my bottle of it says "Not for use by females" :rofl:

    Anyhow, I do about 1/4 of the recommended daily maximum on the bottle, split into two doses. So a quite small dose. My heart rate has lowered, not raised, probably due to my pulse pressure rising to a normal level. I haven't experienced any side effects yet.

    But yeah, if you don't have a problem with norepinehprine getting low, then your ADRA2A gene might not be getting overexpressed after exertion, or your body is compensating differently than the hypotensive folks. In which case, Yohimbe might not help, and might cause problems.

    I haven't had any increase in libido, and no signs of growing a penis yet :thumbsup:

  • lansbergen October 22, 2013, 3:39 pm
    Valentijn

    But yeah, if you don't have a problem with norepinehprine getting low, then your ADRA2A gene might not be getting overexpressed after exertion, or your body is compensating differently than the hypotensive folks. In which case, Yohimbe might not help, and might cause problems.

    Or maybe a med prevents the drop.

  • Valentijn October 22, 2013, 3:39 pm
    peggy-sue

    My reaction to the mention of Yohombin was an immediate; "eeeeeeeek!"

    It has been banned from OTC sales in some countries, as well as in Australia. Possibly due to it raising norepinephrine and potentially epinephrine quite a bit, if taken in large doses. But pretty much the only thing it does is down-regulate three closely related genes, one of which is over-expressed in ME patients (and another of which might be involved in fibromyalgia).

    Ideally it probably should be regulated due to the impact it has on the central nervous system, and it can be prescribed by a doctor in some countries. But here in the Netherlands, it's illegal to manufacture or sell it as a supplement, and it's not available in any form as a prescription. So once again, the medical system drops the ball, and we do the best we can with what's available.

    The only other drugs which act as antagonists to ADRA2A are less powerful and far less specific. So probably much more side effects, and issues with tolerance, withdrawal, etc. And it's a nice alternative for people who can't get a doctor to give them any prescription, for whatever reasons.

  • Valentijn October 22, 2013, 3:55 pm

    I finally remembered to check my blood pressure properly: 130/88 with a pulse of 72. That means my pulse pressure is 42, whereas prior to starting Yohimbe it mostly stayed around 35, and my pulse was usually around 85 when rested.

  • lansbergen October 22, 2013, 4:07 pm
    Valentijn

    I finally remembered to check my blood pressure properly: 130/88 with a pulse of 72. That means my pulse pressure is 42, whereas prior to starting Yohimbe it mostly stayed around 35, and my pulse was usually around 85 when rested.

    As the pulse of atletes is lower than of normal people the psych could conclude you are less deconditionded now. :D:D:D

  • Valentijn October 22, 2013, 4:13 pm
    lansbergen

    As the pulse of atletes is lower than of normal people the psych could conclude you are less deconditionded now. :D:D:D

    But … but … drugs can't help me! Only exercise! A psychologist and an extremely egotistical neurologist said so, hence it must be true :rolleyes:

  • MeSci October 22, 2013, 4:45 pm
    Valentijn

    It is heavily marketed as a male erection type drug, probably due to improvements in circulation. Many sources go way overboard in trying to make it look effective, to the extent that my bottle of it says "Not for use by females" :rofl:

    Anyhow, I do about 1/4 of the recommended daily maximum on the bottle, split into two doses. So a quite small dose. My heart rate has lowered, not raised, probably due to my pulse pressure rising to a normal level. I haven't experienced any side effects yet.

    But yeah, if you don't have a problem with norepinehprine getting low, then your ADRA2A gene might not be getting overexpressed after exertion, or your body is compensating differently than the hypotensive folks. In which case, Yohimbe might not help, and might cause problems.

    I haven't had any increase in libido, and no signs of growing a penis yet :thumbsup:

    Trouble is, I don't know what my adrenaline/noradrenaline(aka epinephrine/norepinephrine – how on earth does one pronounce these?!) levels are. I have doubts over whether a UK doctor would be willing to test them. Or do you test them yourself?

    Glad you've managed not to change sex yet! :thumbsup:

  • Valentijn October 22, 2013, 5:26 pm
    MeSci

    Trouble is, I don't know what my adrenaline/noradrenaline(aka epinephrine/norepinephrine – how on earth does one pronounce these?!) levels are. I have doubts over whether a UK doctor would be willing to test them. Or do you test them yourself?

    I got mine tested privately at a local lab which has blood platelet testing as an option, with my US ND signing off on it. They also do international testing, but you'd still have to get blood drawn somewhere. But it's a fairly common test, so I'd be surprised if there aren't private labs in the UK offering it.

    If you have low blood pressure and/or low pulse pressure (difference between systolic and diastolic values), then norepinephrine is a reasonable culprit. But if un-medicated pulse pressure and blood pressure are high or normal, then low epinephrine seems unlikely.

  • MeSci October 22, 2013, 5:34 pm
    Valentijn

    I got mine tested privately at a local lab which has blood platelet testing as an option, with my US ND signing off on it. They also do international testing, but you'd still have to get blood drawn somewhere. But it's a fairly common test, so I'd be surprised if there aren't private labs in the UK offering it.

    If you have low blood pressure and/or low pulse pressure (difference between systolic and diastolic values), then norepinephrine is a reasonable culprit. But if un-medicated pulse pressure and blood pressure are high or normal, then low epinephrine seems unlikely.

    OK, thanks. I can take my own blood samples if no special technique is needed (e.g. if it is particularly important to avoid leakage from blood cells – I don't have the expertise for that). But it sounds as though it's unnecessary in this case.

  • peggy-sue October 22, 2013, 5:53 pm

    Adrenaline is pronounced a-dren-a-lin
    Noradrenaline is pronounced nor-a-dren-a-lin

    the "e" at the end should not be pronounced or alter the sound of the word.

    Epinephrin(e) norepinephrin(e) are pretty much the same..

    e-pin-e-frin

    nor-e-pin-e-frin

    😉 I think…. but as we all know, that can be dodgy in PWME .:p

  • MeSci October 22, 2013, 9:09 pm
    peggy-sue

    Adrenaline is pronounced a-dren-a-lin
    Noradrenaline is pronounced nor-a-dren-a-lin

    the "e" at the end should not be pronounced or alter the sound of the word.

    Epinephrin(e) norepinephrin(e) are pretty much the same..

    e-pin-e-frin

    nor-e-pin-e-frin

    😉 I think…. but as we all know, that can be dodgy in PWME .:p

    But which syllable(s) is/are stressed in the latter two?

    They seem such cumbersome (if perhaps more accurate) words. I can't imagine saying that someone is an epinephrine junkie or that they enjoy epinephrine rushes!

  • SOC October 23, 2013, 4:05 am
    Valentijn

    Anyhow, I do about 1/4 of the recommended daily maximum on the bottle, split into two doses. So a quite small dose. My heart rate has lowered, not raised, probably due to my pulse pressure rising to a normal level. I haven't experienced any side effects yet.

    Do you have a brand suggestion? When I did a brief hunt at my favorite supplements site, all the brands I saw looked a bit dodgy. If I'm going to try something a little risky, I like to stick with brands I'm fairly confident have in the bottle what is claimed to be there.

    Do you mind saying how much is 1/4 of the max dose on your bottle?

    I need to find a doc who will test norepinephrine. Unfortunately, there's not an ND or similar anywhere near here. All "evidence-based medicine" in my neck of the woods. If only that phrase actually meant what it says….

  • Valentijn October 23, 2013, 10:12 am
    SOC

    Do you have a brand suggestion? When I did a brief hunt at my favorites supplements site, all the brands I saw looked a bit dodgy. If I'm going to try something a little risky, I like to stick with brands I'm fairly confident have in the bottle what is claimed to be there.

    I've been using Yohimbe Fuel from Twinlab, and it seems to work quite well.

    I also tried Yohimbe Bark from Gaia Herbs, which my mom thinks is a good brand, and that also seemed to work. But it's an extract with an alcohol base, which might have been causing me some problems until I switched to Twinlab (headache and feeling a bit hung over).

    Do you mind saying how much is 1/4 of the max dose on your bottle?

    Twinlab says 400mg of bark per capsule, twice per day, which they claim is 8mg of Yohimbine (the active part of the yohimbe bark) per capsule. I do 1/4 of a capsule twice per day, so that's about 100mg of bark and 2mg of Yohimbine twice per day. Which gives me a daily total of 200mg of bark and 4mg of Yohimbine.

    A smaller dose might work, but I haven't tried it yet. Basically the 100mg dose isn't causing me any problems, and the stuff is dirt cheap, so I'm not worried saving cash. 4 bottles will last me over a year 😀

    I need to find a doc who will test norepinephrine. Unfortunately, there's not an ND or similar anywhere near here. All "evidence-based medicine" in my neck of the woods. If only that phrase actually meant what it says….

    In the US, it shouldn't be too hard to find a doctor who is somewhat willing to investigate things. It might help to check websites for someone who likes to treat complex and chronic disease . . . autism, IBS, fibromyalgia, etc. Even if you can't find someone who knows much about ME/CFS, you might be able to find a doctor who isn't afraid of a challenge.

  • Valentijn October 23, 2013, 10:16 am
    MeSci

    But which syllable(s) is/are stressed in the latter two?

    They seem such cumbersome (if perhaps more accurate) words. I can't imagine saying that someone is an epinephrine junkie or that they enjoy epinephrine rushes!

    Actually I would say:
    EP-in-EF-rin
    nor-EP-in-EF-rin

    But maybe that's more of an American thing. I'd have trouble putting the emphasis just on a single vowel.

  • peggy-sue October 23, 2013, 1:28 pm

    I would stress the E s. pronounced "eh" as in enjoy.

    I never say epinephrin(e) or norepinephrin(e).

    :confused: I do have a slightly Scottish accent – I also rrr-oll my rrr-s :p

  • Little Bluestem October 24, 2013, 6:56 am
    Valentijn

    . But if un-medicated pulse pressure and blood pressure are high or normal, then low epinephrine seems unlikely.

    In which case yohimbe is unlikely to be helpful?

  • Valentijn October 24, 2013, 1:00 pm
    Little Bluestem

    In which case yohimbe is unlikely to be helpful?

    Maybe unhelpful, maybe with harmful side effects from BP getting too high. If unsure, getting norepinephrine tested might be the way to go.

  • Firestormm February 11, 2014, 7:08 pm

    AfME report following presentation evening in Bristol. 07 February 2014: http://www.actionforme.org.uk/get-informed/news/your-news/exercise-and-me-event-research-findings

    "…After the film, Prof Mark VanNess spoke about the work he and his team are doing at the fatigue laboratory in the Health, Exercise, and Sport Sciences Department, University of the Pacific, California.

    Working with people who have mild to moderate M.E., they are finding objective, rather than self-reported or subjective, evidence for the kind of fatigue that is specific to M.E.

    Using cardiopulmonary exercise testing, Prof VanNess has proven that people with M.E.:

    • experience significant post-exertional malaise, though he prefers to call it post-exertional amplification of symptoms
    • have significantly impaired ability to generate energy from aerobic activity.

    The key is that subjects are tested over two days. People with M.E. and healthy controls, all volunteers, spend 10 minutes on the treadmill on the first day, and then again 24 hours later. Results show that on the second day the metabolic function of people with M.E. has dropped by around 25%, such a marked decrease that, Prof VanNess told us, exercise physiologists protested that the machine must not be calibrated properly.

    As a result of the data he has gathered, Prof VanNess has concluded that therapeutic interventions for people with M.E. should avoid aerobic exercise. Instead, they should be offered analeptic activity, intended to retrain the short-term (anaerobic) energy system to increase range of motion and improve functional strength. Crucially, he said, the ratio of activity to rest should be one to three, and physical therapists should be trained and experienced in this type of physical therapy.

    Prof VanNess and his colleagues wrote an article for the CFIDS Chronicle, which explains these findings in more detail. He has also published numerous papers in peer-reviewed journals on his topic, including:

  • Firestormm February 11, 2014, 8:08 pm

    Conversely, or at least some have interpreted it that way, here is Nancy Klimas (hint: I suggest you watch the trailer and interpret it for yourselves):

    Posted 1 week ago

    Exercise and ME/CFS with Dr Nancy Klimas

    Dr. Nancy Klimas, one of the most respective authorities on chronic fatigue syndrome in the world, emphatically states:

    “It is very important for my patients to know how to approach exercise in a safe way…. if they don’t exercise, they will only get worse."

    Watch Trailer here: http://vimeo.com/ondemand/9757

    With the kind assistance of Dr Klimas and Connie Sol, the physiologist on staff at the Neuroimmune Institute (nova.edu/nim), we have created a series of three videos on VO2 Max exercise testing, the consult and the implementation of the program for sufferers.

    View attachment 6424

    Also included in the video are two bonus segments with Dan Moricoli on how he has employed the system to go from a housebound, virtually bed bound, status to a near normal lifesytle.

    DVDs of the video are available for worldwide delivery for only $19.99. To order a DVD via PayPal go to: paypal.com/cgi-bin/webscr?cmd=_s-xclick&hosted_button_id=M6YMPECUBDV4U.

    The three part series plus a personal view on the program by Dan Moricoli

  • MeSci February 11, 2014, 8:20 pm
    Firestormm

    Dr. Nancy Klimas, one of the most respective authorities on chronic fatigue syndrome in the world, emphatically states:

    “It is very important for my patients to know how to approach exercise in a safe way…. if they don’t exercise, they will only get worse."

    Really? Then how have I improved so much without 'exercise'? And re the previous message, how have I improved in strength (don't know what 'functional strength' means) without exercise?

    I have been active, in my essential daily tasks, as usual, but not 'exercised' because there is no energy to spare after the essentials.

  • Bob February 11, 2014, 8:21 pm
    Firestormm

    Conversely, or at least some have interpreted it that way, here is Nancy Klimas

    Thanks for posting both bits of info, Firestormm.

    Whenever I've seen Nancy Klimas talk about exercise, her emphasis is always on what is 'safe' for patients to do. She uses CPET tests and heart rate to determine what she considers to be safe for individual patients. So perhaps Klimas' exercise prescription is not so different to what VanNess recommends, but I don't know enough about either's recommendations to be able to compare them.

    I don't approve of the suggestion in Klimas' video that exercise is therapeutic, and leads to improvement, for obvious reasons.

    All the power walking and squats etc seen in the video are utterly inappropriate for an ME patient. (I think most of us would expect that level of activity to provoke a post-exertional flare-up.)
    Many of us participate in gentle activity, but if a 'patient' can do power-walking and squats etc, then I question if they actually have ME. (They don't seem to have much disability.)
    In my opinion, the level of exercise that is shown in the video is way out of proportion, in terms of what patients can be expected to do.

    Is it a promotional video for Klimas' clinic?

  • Snowdrop February 11, 2014, 8:27 pm

    The Klimas approach is at least extremely useless for severe illness. If not dangerous even with the safeguards.
    I don't know how the ill patients managed exercise and daily living too.
    I have found brushing my teeth, getting dressed and feeding myself challenging.
    Showing people out power walking seems ridiculous to me.
    It would seem that they really don't have any idea of the symptoms we face and their severity.

  • Firestormm February 11, 2014, 8:40 pm
    Snowdrop

    The Klimas approach is at least extremely useless for severe illness. If not dangerous even with the safeguards.
    I don't know how the ill patients managed exercise and daily living too.
    I have found brushing my teeth, getting dressed and feeding myself challenging.
    Showing people out power walking seems ridiculous to me.
    It would seem that they really don't have any idea of the symptoms we face and their severity.

    Snowdrop, did you see the chap who was talking at the end, I can't remember his name. I actually remember speaking very similarly to him when I was at my worst, but I don't do that any longer, and it isn't through exercise specifically.

    I don't know what it is – but I think slowly building up again, and learning to manage, being able to sweep things aside and rest when I need to etc. all have helped me to improve over time. I think speech is one of more noticeable improvements commented on by others like my family.

    I have worked hard to regain some of my ability to function mentally again I think, through reading, writing (well typing really) and stuff, and I do take walks now, but I don't have any rigidity in my life really, I have routines but they are flexible of necessity.

    I think acceptance has finally paid dividends as well. Learning not to fight but not to surrender to it either. Of course I can't always avoid a crash but I can be more aware of when one is likely, and be prepared for it.

    Actually I am overdue a shower… been waiting for a phone call but better have one now before bed I think. Good luck to you :)

  • Snowdrop February 11, 2014, 9:50 pm

    I really am not wanting to be over critical of someone wanting to help our community.
    But I confess to being really sceptical about this.

    As well as what I said above I forgot (ironically) to mention the cognitive aspect of this illness as it pertains to draining my energy resources. I have been astounded to realise just how much I've been affected. It's taken me a long time to realise that I tire not just from physical effort and even cognitive effort but also from emotional effort. I have become emotionally flat simply because I don't have the energy to produce an emotional response.
    Physical exercise works well for the healthy in maintaining their overall function but I'm not sure about how well it works for us.

    I would like more information. More transparency. How did these two people get to Dr Klimas' clinic if they were so ill/bedbound.
    Then after getting there how did they manage to do anything on the bike never mind coming back the next day.

    And I'm not accusing anyone here but I'd like to know what kind of financial compensation the patients had for doing this advertising of the treatment. I'd also like to know if they were doing other treatments at the same time.

    I'd be very happy if this worked as brilliantly as it seems to do but I have reservations until I know more.
    Perhaps there are some brave souls who will give it a go and report back.

    And regarding my own illness/recovery. I spent a great deal of time resting. Many months. I couldn't consider any other treatment including supplements because I didn't have the energy or even ability to organise my mind to deal with that. I am now a little better cognitively and physically and am able to try simplified methylation. This has made a small improvement.
    One of my cognitive measures involves being able to do a single Sudoku without tiring.

    It seems to me that there are other things going on that are wrong eg the hippocampus low N-acetylaspatate. Does simply exercising solve all these other findings?

  • Firestormm March 4, 2014, 12:17 pm

    Videos from the event at Bristol are now on YouTube (Courtesy of Tate Mitchell via Co-cure). I don't know if this has been posted before:

    Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One

    Prof Mark VanNess from the Workwell Foundation explains how damaging aerobic exercise can be for patients with ME/CFS. Their 2 day testing protocol demonstrates an astonishing post exertional amplification of symptoms in ME patients; a hallmark symptom of ME. This damage to the aerobic energy system means that it is utterly counter productive to try to use aerobic exercise to improve health in these patients.

    The evidence from their research is so unexpected and contrary to accepted views of exercise and graded exercise, both in ME and in other illnesses, that many people actually find it difficult to hear and take on-board what he is saying. Fortunately you can go over what he says repeatedly and follow up the links on the Workwell Foundation website to watch or read other information.

    Interestingly, he reflects on comments made in the film, explaining that these are consistent with their evidence from cardiopulmonary testing. He also explains how patients can try to find a more appropriate way of managing their activities of daily living and exercise, by trying to avoid causing any worsening of symptoms and so allowing their bodies a better chance of healing. He explains about analeptic exercise, which means restorative; not causing relapse!

  • Bob March 4, 2014, 12:53 pm

    Thanku, @Firestormm

    The other videos can be found here:
    http://www.youtube.com/user/VftSFilm

    These are the three videos that have been posted of the Bristol Watershed conference…

    Mark VanNess 'Exercise and ME/CFS' at Bristol Watershed. Part One.
    http://www.youtube.com/watch?v=q_cnva7zyKM

    Nigel Speight: 'Exercise and ME/CFS' at Bristol Watershed. Part Two.
    http://www.youtube.com/watch?v=208JacsB5kM

    Erina Bowman: 'Exercise and ME/CFS' at Bristol Watershed. Part Three.
    http://www.youtube.com/watch?v=iIQpBDgFZNw

  • Valentijn March 4, 2014, 1:55 pm

    The evidence from their research is so unexpected and contrary to accepted views of exercise and graded exercise, both in ME and in other illnesses, that many people actually find it difficult to hear and take on-board what he is saying.

    Except for ME/CFS patients and anyone who's actually listened to them :rolleyes:

  • alex3619 March 4, 2014, 2:16 pm

    In case anyone is unaware of the type of protocol Workwell uses for treatment (not testing) exercise, the VanNess video gives an example. First, exercise does not last for more than thirty seconds at a time. Second, there is at least a threefold break before doing any more, which in this case is about ninety seconds I guess. Third, the exercise is light strength improving calisthenics, without any aerobic component. As he stresses, the aerobic system is broken, it cannot be retrained. Those who have tried have failed.

  • peggy-sue March 4, 2014, 2:17 pm

    Do folk watch all these videos and can they take in what is being said?
    I might be odd, but I detest having to watch videos on youtubey things, I don't bother any more.:(

    You have to spend ages and ages, paying close attention to a load of introductory waffle, then when a point of interest is made – it's gone in a flash and you've missed it.

    I like information in the written form. I can skip the bits I don't need to pay attention to, and spend time on the bits that are important, I can go back to the beginning bit if it does turn out to be relevant…

  • alex3619 March 4, 2014, 2:19 pm

    I saw all three tonight, while the sound does fade for a second here and there if the speaker turns their face from the microphone, the sound was fine otherwise. I found myself pausing the videos on key slides … there is good written info, some of which I was interested in, including Speight on fallacies, my pet topic.

  • Valentijn March 4, 2014, 3:15 pm

    I watched that one too, though like @peggy-sue I really hate videos and audio things :p

    In addition to what @alex3619 mentioned (30 second intervals, anaerobic activities only, 3 times as much rest as activity), he listed 4 stages (starting at 30:45 into the video):
    Stage 1: Stretching and Strengthening
    Stage 2: Stretching with Resistance Training
    Stage 3: Dose-Controlled Interval Training (short, anaerobic)
    Stage 4: Maintenance

    He mentioned that it might take someone a year to progress from one stage to another, and based on the example it looks like it's normal to take months. He also said this activity would have to be compensated for by cutting out other activities.

    An example of the Interval Training –
    Goal: 1×4 reps increased to 2×8 reps
    Activities: Breathing, step-ups, wall push-ups, modified chair dips, toe raises

    Then for maintenance, the patient would maintain that level of activity and add stair intervals. For the example given, the woman wanted to be able to walk downstairs and then upstairs so she could go shopping without crashing, and she could use a heart rate monitor and rest on the landing to help accomplish that.

    All in all I think it was pretty reasonable and realistic, both regarding the activities and the expectations (get down a flight of stairs without becoming extremely ill, versus "recovery"). He was almost derisive about GET, or any other deliberate aerobic activities.

    There's also a nice chart he shows at 13:15, which describes how disabled someone is based on their VO2max results, according to the American Medical Association. Mine's 11.9 mL/kg/min which puts me right in the middle of the "severe" group :p

  • SOC March 4, 2014, 3:40 pm
    alex3619

    In case anyone is unaware of the type of protocol Workwell uses for treatment (not testing) exercise, the VanNess video gives an example. First, exercise does not last for more than thirty seconds at a time. Second, there is at least a threefold break before doing any more, which in this case is about ninety seconds I guess. Third, the exercise is light strength improving calisthenics, without any aerobic component. As he stresses, the aerobic system is broken, it cannot be retrained. Those who have tried have failed.

    This is just what Connie Sol (at Dr Klimas' office) told me about how to exercise. No aerobic, less than 2 mins (for me, based on testing), 5-10 mins supine rest between sets, no more than 3 sets per session. Only stretching and strengthening.

    My problem with it, to be honest, was that it drove me nuts to do 1 min of exercise, rest 5 mins three times. That's about 20 mins for 3 mins of wimpy exercise — besides having to get up and down off the floor. Life was hard enough at the time and I gave up on that particular "annoyance". It might help in the long run, but my personality rebelled. 😳

  • MeSci March 4, 2014, 4:59 pm
    peggy-sue

    Do folk watch all these videos and can they take in what is being said?
    I might be odd, but I detest having to watch videos on youtubey things, I don't bother any more.:(

    You have to spend ages and ages, paying close attention to a load of introductory waffle, then when a point of interest is made – it's gone in a flash and you've missed it.

    I like information in the written form. I can skip the bits I don't need to pay attention to, and spend time on the bits that are important, I can go back to the beginning bit if it does turn out to be relevant…

    I am the same. Videos are so time-consuming, and use a lot of mental energy and visual exertion. I am the same with chatty pages which take too long to get to the point. Straight facts, either in small doses or in something like a blog that I can dip in and out of, are much better for me.

  • SOC March 5, 2014, 12:10 am
    Valentijn

    He also said this activity would have to be compensated for by cutting out other activities.

    Oh yeah, that part got me, too. What am I going to cut out in order to do this wimpy bit of exercise? Taking a shower? Making a meal? I'm not fully caring for myself and my home. I'd rather spend the energy on vacuuming one carpet or making a meal than on 3 minutes of exercise for the sake of exercise. Maybe if I get well enough to do basic care for myself and my house, then I'll be more motivated to add in the exercise appropriate for PWME.

    I see the value of this kind of exercise, just not how to make it work for me where I am in the illness.

  • alex3619 March 5, 2014, 2:27 am

    I don't know that the rest/compensation comment about exercise was in relation to their exercises, I think it was in relation to GET or similar unless I am misremembering. The point of keeping exercise to 30 seconds (NOT the Klimas 3 minutes) is to avoid any exacerbation.

    I do understand the frustration of doing limited exercise for only seconds, and having to wait to do more. I want to be back to heavy exercise, and running, and I want it now! That is the wrong thing to do though. The key feature is to get as much exercise without incurring any oxygen debt. If we start breathing hard then whatever it is is too much. Its the tortoise not the hare.

  • Nielk March 5, 2014, 4:22 am
    alex3619

    I don't know that the rest/compensation comment about exercise was in relation to their exercises, I think it was in relation to GET or similar unless I am misremembering. The point of keeping exercise to 30 seconds (NOT the Klimas 3 minutes) is to avoid any exacerbation.

    I do understand the frustration of doing limited exercise for only seconds, and having to wait to do more. I want to be back to heavy exercise, and running, and I want it now! That is the wrong thing to do though. The key feature is to get as much exercise without incurring any oxygen debt. If we start breathing hard then whatever it is is too much. Its the tortoise not the hare.

    Exactly! Case in point: I walked up a flight of stairs today and ended up in the emergency room! Thank God it was just a scare and I'm okay but my great struggle as I'm sure with all of you is the fact that my capabilities change all the time and fluctuate where one day I can walk up the stairs fine or go for a 10 minute walk and on other days I am much safer staying in bed. This makes it so difficult and it's hard enough to stay in one's envelope, to push that envelope is insanity!

  • Firestormm March 5, 2014, 5:18 am
    Nielk

    Exactly! Case in point: I walked up a flight of stairs today and ended up in the emergency room! Thank God it was just a scare and I'm okay but my great struggle as I'm sure with all of you is the fact that my capabilities change all the time and fluctuate where one day I can walk up the stairs fine or go for a 10 minute walk and on other days I am much safer staying in bed. This makes it so difficult and it's hard enough to stay in one's envelope, to push that envelope is insanity!

    :hug:

    And yet we do do more when we feel able and even when we don't. Especially I would say when it comes to mental exertion – which I tend now to do too much of and to the detriment of physical exertion. We can't live in a bubble and I don't think we would want to – when we have a choice of course. I still think these exercise tests are a reflection of our functional ability, and not (yet) a reflection of any disease process that might be unique to ME i.e. indicative of a biomarker which has been floated about.

    That said I haven't watched the video yet. Hope to do so later today – after my diabetes check :)

  • Valentijn March 5, 2014, 9:29 am
    Firestormm

    I still think these exercise tests are a reflection of our functional ability, and not (yet) a reflection of any disease process that might be unique to ME i.e. indicative of a biomarker which has been floated about.

    A single maximal exercise test is proof of impairment, but not of the cause of the impairment. It could simply reflect deconditioning, though I've only seen deconditioning shown to cause milder reductions than are seen in the "severe" group, and maybe even the "moderate" group.

    The two-day CPET results (severe worsening on the 2nd day) are unique to ME/CFS thus far. However it is possible that that's only because a two-day test has not been used in certain other diseases. But it sounds like it has been used by the same group somewhat in some similar illnesses (MS, RA?) without a similar result.

    An expected exception to this might be in the case of rhabomyolysis or mitochondrial disease, etc. But even in that case, it would likely still be a biomarker for ME/CFS, when combined with the tests which rule out those other diseases.

    And at the very least, the two-day CPET will remain a gold-standard indicator of both disease and disability.

  • Nielk March 5, 2014, 12:42 pm
    Firestormm

    :hug:

    And yet we do do more when we feel able and even when we don't. Especially I would say when it comes to mental exertion – which I tend now to do too much of and to the detriment of physical exertion. We can't live in a bubble and I don't think we would want to – when we have a choice of course. I still think these exercise tests are a reflection of our functional ability, and not (yet) a reflection of any disease process that might be unique to ME i.e. indicative of a biomarker which has been floated about.

    That said I haven't watched the video yet. Hope to do so later today – after my diabetes check :)

    Good luck @Firestormm with the diabetes check.

  • MeSci March 5, 2014, 1:59 pm
    Nielk

    Good luck @Firestormm with the diabetes check.

    and lay off the Mars bars! 😀

  • Firestormm March 5, 2014, 4:58 pm
    Nielk

    Good luck @Firestormm with the diabetes check.

    Sugar was high, so my pee has gone off with my bloods to the laboratory. If there is a diabetes – if – then it might account for me peeing all the time and the incontinence at night: which is what took me to the doctor in the first place on this occasion. You know how I (or maybe you don't) crave sugar after having one of my 'funny turns' at night – well I don't think for a minute it has anything to do with any possible diabetes – but the doctor said a funny thing. Just a throw away comment that struck home: it was that it could be because of the exertions I was making in my sleep-state. Seems obvious I suppose – but I hadn't actually connected this desire for a 'quick hit' of energy with physical and mental exertion before. All good stuff :)

  • peggy-sue March 5, 2014, 5:12 pm

    I am gobsmacked. Your gp took your ME into consideration? Suggested the troubles might be related to ME stuff?
    wow.
    If I wasn't already sitting down, I'd have to.:p

  • Firestormm March 6, 2014, 1:30 pm

    @Nielk Here I am sat with my Mum and we just watched this video which was rather good and comes from Diabetes UK. Not that we think I have diabetes of course – cross that bridge when the results come back.

    My question – should you chose to accept :) – is this: If the glucose can get into our muscles that could it be what is causing me to experience the pain/aches etc.? I am thinking it might be.