Saturday, September 13, 2008

POTS vs. deconditioning

POTS versus deconditioning: the same or different?

Journal: Clin Auton Res. 2008 Aug 12. [Epub ahead of print]

Authors: Joyner MJ, Masuki S.

Affiliation: Dept. of Anesthesiology, Mayo Clinic, 200 First Street
SW, Rochester, MN, 55905, USA,

NLM Citation: PMID: 18704621

The 2007 Streeten Lecture focused on the idea that physical
deconditioning plays a key role in the symptomology and
pathophysiology of POTS. Parallels were drawn between the
physiological responses to orthostatic stress seen in POTS patients
and the physiological responses seen in "normal" humans after
prolonged periods of bedrest, deconditioning, or space flight.
Additionally, the idea that endurance exercise training might
ameliorate some of these symptoms was also advanced. Finally,
potential parallels between POTS, chronic fatigue syndrome, and
fibromyalgia were also drawn and the potential role of exercise
training as a "therapeutic intervention" in all three conditions was raised.

The conceptual model for the lecture was that after some "initiating
event" chronic deconditioning plays a significant role in the
pathophysiology of these conditions, and these physiological changes
in conjunction with "somatic hypervigilence" explain many of the
complaints that this diverse group of patients have. Additionally,
the idea that systematic endurance exercise training might be helpful
was advanced, and data supportive of this idea was reviewed.

The main conclusion is that the medical community must retain their empathy for patients with unusual conditions but at the same time
send a firm but empowering message about physical activity. As
always, we must also ask what do the ideas about physical activity
and inactivity and the conditions mentioned above not explain?

* * *

The one thing that doctors do not like to hear is when I contradict their assumptions about deconditioning.  When I first got sick, I was exercising on a daily basis.  Suddenly, I couldn't make it the 10 feet from the bed to the bathroom without needing a half-hour nap on the bathroom floor before crawling back to bed. It is categorically IMPOSSIBLE to decondition that far, that fast.

Similarly, when I entered the current relapse, I had been walking 4 miles a day (2 miles to work, 2 miles home), and within just a couple of weeks just the 4 blocks from the bus stop to my desk exhausted me so much that I had to rest for an hour before starting to work.  Again, any doctor worth his salt will tell you that that's not "deconditioning", that's indicative of some sort of severe illness that's sapping the patient's energy.

However, since it doesn't match up to the prejudices about CFS patients being too lazy to exercise, I've been told by doctors to "stop lying" about my prior exercise habits; they profess to know better than my friends and I what I had been doing just before getting sick.  Other patients were marathoners and Olympic athletes before being struck down; unlike me having to say "take my word for it", they have medals and videotape proving that they were previously able to do what they say they did.

A little more empathy and a lot less accusation would be nice for any of us with an invisible chronic illness.

Any doctor who can't express empathy with a patient who's so seriously ill that they are unable to work probably needs to re-evaluate his career choice.  Perhaps lab work where there are no patients hoping for a kind word would be more appropriate.

Oxygenation during exercise

Prefrontal cortex oxygenation during incremental exercise in chronic
fatigue syndrome.

Journal: Clin Physiol Funct Imaging. 2008 Jul 29. [Epub ahead of print]

Authors: J. Patrick Neary [1], Andy D. W. Roberts [2], Nina Leavins
[2], Michael F. Harrison [1], James C. Croll [2] and James R.  Sexsmith [2]

[1] Faculty of Kinesiology & Health Studies, University of Regina,
Regina, SK, Canada and

[2] Faculty of Kinesiology, University of New Brunswick, Fredericton NB, Canada

Correspondence to J. Patrick Neary, PhD, Faculty of Kinesiology &
Health Studies, University of Regina, Regina, SK, Canada S4S 0A2

Affiliation: Faculty of Kinesiology & Health Studies, University of
Regina, Regina, SK, Canada.

NLM Citation: PMID: 18671793

This study examined the effects of maximal incremental exercise on
cerebral oxygenation in chronic fatigue syndrome (CFS) subjects.
Furthermore, we tested the hypothesis that CFS subjects have a
reduced oxygen delivery to the brain during exercise.

Six female CFS and eight control (CON) subjects (similar in height,
weight, body mass index and physical activity level) performed an
incremental cycle ergometer test to exhaustion, while changes in
cerebral oxy-haemoglobin (HbO(2)), deoxy-haemoglobin (HHb), total
blood volume (tHb = HbO(2) + HHb) and O(2) saturation [tissue
oxygenation index (TOI), %)] was monitored in the left prefrontal
lobe using a near-infrared spectrophotometer. Heart rate (HR) and
rating of perceived exertion (RPE) were recorded at each workload
throughout the test.

Predicted VO(2peak) in CFS (1331 +/- 377 ml) subjects was
significantly (P </= 0.05) lower than the CON group (1990 +/- 332
ml), and CFS subjects achieved volitional exhaustion significantly
faster (CFS: 351 +/- 224 s; CON: 715 +/- 176 s) at a lower power
output (CFS: 100 +/- 39 W; CON: 163 +/- 34 W). CFS subjects also
exhibited a significantly lower maximum HR (CFS: 154 +/- 13 bpm; CON:
186 +/- 11 bpm) and consistently reported a higher RPE at the same
absolute workload when compared with CON subjects. Prefrontal cortex
HbO(2), HHb and tHb were significantly lower at maximal exercise in
CFS versus CON, as was TOI during exercise and recovery. The CFS
subjects exhibited significant exercise intolerance and reduced
prefrontal oxygenation and tHb response when compared with CON subjects.

These data suggest that the altered cerebral oxygenation and blood volume may contribute to the reduced exercise load in CFS, and supports the contention that CFS, in part, is mediated centrally.

Medication and CFS

Medication and ME/CFS?
Margaret Williams

Mitochdondria are the powerhouses of the cells.
They are responsible for generating energy as
adenosine triphosphate (ATP) and are involved in the
apoptosis signalling pathway (apoptosis being
programmed cell death).

There is a significant literature suggestive of
mitochondrial defects (both structural and functional)
in ME/CFS from 1984 to date and it is accepted by
informed ME/CFS clinicians and researchers that
there is actual biopsy evidence of mitochondrial
damage in ME/CFS
, for example:

      *    Behan WM et al, Acta Neuropathol
      1991:83(1):61-65 ("Mitochondrial
      degeneration was obvious in 40 of the
      biopsies, with swelling, vacuolation, myelin
      figures and secondary lysosomes.  The
      pleomorphism of the mitochondria in the
      patients' muscle biopsies was in clear
      contrast to the findings in the normal
      control biopsies.  Diffuse or focal atrophy
      of type II fibres has been reported, and
      this does indicate muscle damage and not
      just muscle disuse")

      *    Pizzigallo E et al, JCFS 1996:2
      (2/3):76-77 ("We performed histochemical
      and quantitative analysis of enzymatic
      activities and studies of mitochondrial DNA
      deletions. All specimens showed
      hypotrophy, fibres fragmentation, red
      ragged fibres, and fatty and fibrous
      degeneration.  Electron microscopy
      confirmed these alterations, showing
      degenerative changes, and allowed us to
      detect poly/pleomorphism and cristae
      thickening of the mitochondria.  The
      histochemical and quantitative
      determination of the enzymatic activity
      showed important reduction, in particular
      of the cytochrome-oxydase and
      citrate-synthetase. The 'commondeletion'
      of 4977 bp of the mitochondrial DNA was
      increased as high as 3,000 times the
      normal values in three patients.  Our
      results agree with those of Behan et al
      1991 and Gow et al 1994.  The alterations
      are compatible with a myopathy of
      probable mitochochondrial origin (which)
      could explain the drop in functional
      capability of the muscle")

      *    Cheney P, Orlando Workshop,
      International Congress of Bioenergetic
      Medicine 1999, audio tape #2 ("The most
      important thing about exercise is not to
      have them do aerobic exercise.  If you have
      a defect in the mitochondrial function and
      you push the mitochondria by exercise, you
      kill the DNA"
).  Cheney's findings were
      supported by Benjamin Natelson, Professor
      of Neurology at New Jersey Medical School
      – in his 1999 lecture at the Fatigue 2000
      Conference in London, Natelson discussed
      his work on muscle metabolism using NMR
      testing the muscle of patients with ME/CFS
      after exercise, in which his team
      demonstrated a problem with mitochondrial
; this Conference was reported in
      the ME Association Newsletter
      Perspectives, Summer 1999:18

      *    Klimas NG et al, Curr Rheumatol Rep
      2007:9(6):482-487 ("Gene microarray data
      have led to better understanding of
      pathogenesis. Research has evaluated
      genetic signatures (and) described biologic
      subgroups.  Genomic studies demonstrate
      abnormalities of mitochondrial function").

      *    Nestadt P:
      ("These results show that a significant
      proportion of patients diagnosed with
      (ME)CFS have elevated ventricular lactate
      levels, suggesting anaerobic energy
      conversion in the brain and / or
      mitochondrial dysfunction").  (Elevated
      blood lactate levels after mild exercise are
      considered to be a sign of mitochondrial

      *    Bell DS:  

      ("I agree that ME/CFS is a mitochondrial
      disease (but) ME/CFS is a mitochondrial
      disease like no other
. There are lots of
      studies that implicate mitochondrial
      problems:  Dr Hirohiko Kuratsune and
      carnitine; Dr Suzanne Vernon and
      genomics; Dr Kenny DeMeirlier (Brussels);
      Dr Martin Pall (New York); Dr Paul Cheney
      and many others").
      That there is evidence of disrupted
      apoptosis in ME/CFS cannot be disputed

      (Increased neutrophil apoptosis in Chronic
      Fatigue Syndrome.  Kennedy G et al.  J Clin
      Pathol 2004:57(8):891-893)

Attention is therefore drawn to a paper by Neustadt
and Pieczenik which reviews the evidence that
medications have now emerged as a major cause of
mitochondrial damage (Medication-induced
mitochondrial damage and disease.  Mol Nutr Food
Res 2008:52:780-788).

In addition to medication-induced systemic
dysfunction, systems most affected are listed as
being the muscles, brain, nerves, kidneys, heart,
liver, eyes and pancreas.

Acquired conditions in which mitochondrial
dysfunction has been implicated include (ME)/chronic
fatigue syndrome and fibromyalgia.

The mechanisms of mitochondrial-induced injury and
the damage caused by medication-induced
production of free radicals are explained in detail by
the authors.

Medications documented to induce mitochrondial
damage include analgesics; anti-inflammatories;
anaesthetics; angina medications; antibiotics;
antidepressants; anxiolytics; barbiturates;
cholesterol-lowering medications (statins);
chemotherapy; and the mood-stabiliser lithium,
amongst others, including  medications for
Parkinson's Disease, diabetes, cancer and HIV/AIDS.

It is a matter of record that psychiatrist Professor
Simon Wessely advises the prescription of lithium for
patients with ME/CFS:  "There is no doubt that at
least half of CFS patients have a disorder of mood.
The management of affective disorders is an
essential part of the treatment of CFS/ME.
Numerous trials attest to the efficacy of tricyclic
antidepressants in the treatment of fatigue states.
Patients who fail to respond should be treated
along similar lines to those proposed for
treatment-resistant depression. Adding a second
antidepressant agent, especially lithium, may be
beneficial" (The chronic fatigue syndrome – myalgic
encephalomyelitis or postviral fatigue. S Wessely PK
Thomas.  In: Recent Advances in Clinical Neurology
(ed): Christopher Kennard.  Churchill Livingstone
1990: pp 85-131).

In addition to lithium, specific medications listed
that are known to induce mitochondrial damage
include aspirin; acetaminophen (paracetamol /
Tylenol); fenoprofen (Nalfon); indomethacin (Indocin,
Indocid); naproxen (Naprosyn); lidocaine;
amiodarone (Cordarone); tetracycline; amtitriptyline;
citalopram (Cipramil); fluoxetine (Prozac);
chlorpromazine (Largactil); diazepam (Valium);
galantamine (Reminyl) and the statins, amongst

The authors state that damage to mitochondria may
explain the side effects of many medications:
"Recently it has become known that iatrogenic
mitochondrial (damage) explains many adverse
reactions from medicines".

It was in 1994 at the Dublin International Meeting on
ME/CFS (held under the auspices of the World
Federation of Neurology) that Charles Poser,
Professor of Neurology at Harvard, confirmed that
adverse reactions to medication is virtually
"pathognomonic" of ME/CFS, and that a paradoxical
or inappropriate reaction to medications is one of the
most important criteria in ME/CFS.

As Neustadt and Pieczenik state that mitochondrial
dysfunction has been implicated in fibromyalgia (FM)
as well as in (ME)CFS, and as FM has been
recognised as an additional burden of suffering in
many patients with ME/CFS (Buchwald D et al.
Rheum Dis Clin N Am 1996:22:2:219-243), it is of
interest that a 2007 paper estimated the prevalence
and number of FM patients in ten countries, looking
specifically at FM patients' AAT (alpha-1 antitrypsin)
phenotypic distribution worldwide. Those countries
were Canada, the USA, Denmark, Finland, Germany,
Italy, the Netherlands, Spain, Sweden and Pakistan.
The authors noted that during the last few years,
clinical, epidemiological and pathological evidence
suggests that alpha-1 antitrypsin (AAT) deficiency
may play a role in the development of FM.  Studies
on AAT gene frequencies and FM were retrieved from
all ten countries.  Results showed that a severe
deficiency Z allele was found in all these countries,
with very high frequencies in Denmark and Sweden;
high frequencies in Italy and Spain; intermediate
frequencies in Germany, the Netherlands, Canada
and the USA, and a low frequency in Pakistan.  The
authors conclude that AAT phentotype
characterisation should be recommended in all FM
patients, and that the possible efficacy of AAT
replacement therapy in severely deficient FM patients
warrants further study.

This is evidence that argues robustly against the
Wessely School belief that, together with "CFS/ME",
FM is a single somatoform disorder (S Wessely et al.
Lancet 1999:354:936-939).

It also adds to the existing evidence that
demonstrates the lack of scientific rigour accepted by
the Medical Research Council (MRC) in permitting the
Wessely School investigators (who are in charge of
the PACE trials on cognitive behaviour therapy and
graded exercise therapy in "CFS/ME") intentionally to
include people with FM in those trials. Including
different patient populations from the outset will
inevitably skew the results, and under the WHO
taxonomic principles, FM is classified separately from
ME/CFS at ICD-10 M79, whereas ME/CFS is classified
at G93.3.

Of further concern is the fact --- confirmed by the
then Minister of State Dr Stephen Ladyman in July
2004 at the All Party Parliamentary Group of
Fibromyalgia (now disbanded) ---that doctors were
offered financial inducements to persuade those who
do not have ME/CFS (but who have FM) to take part
in the MRC trials.

In a separate paper by Professor Julia Newton et al
comparing mitochondrial function in patients with
primary biliary cirrhosis (PBC), patients with primary
sclerosing cholangitis, patients with ME/CFS and
normal controls (Pilot Study of Peripheral Muscle
Function in Primary Biliary Cirrhosis: Potential
Implications for Fatigue Pathogenesis. Hollingsworth
KG, Newton JL et al. Clin Gastroenterol Hepatol; in
press, September 2008) the authors state that PBC
is characterised in 95% of patients by autoantibody
responses directed against the mitochondrial antigen
pyruvate dehydrogenase complex (PDC). To define
mitochondrial function in peripheral muscle during
exercise, (31)P magnetic resonance spectroscopy was

Whilst the paper is chiefly concerned with
mitochondrial dysfunction in patients with primary
biliary cirrhosis (and the results clearly indicate
mitochondrial dysfunction in patients with PBC, who
showed excess muscle acidosis at higher levels of
exercise), the authors state about ME/CFS patients:
"Interestingly, prolonged time to maximum proton
efflux was also seen in the (ME)CFS control group,
indicating that there are aspects of muscle pH
handling that are abnormal in this important clinical

Professor Newton is Lead Clinician in the
internationally renowned Cardiovascular
Investigations Unit at the University of Newcastle,
UK, which is the largest autonomic function testing
laboratory in Europe; her work focuses on the role of
the autonomic nervous system in the development of
fatigue, specifically in primary biliary cirrhosis, but
also in the pathogenesis of fatigue in ME/CFS. In her
Conference pack for the ME Research UK
International Research Conference held at the
University of Cambridge on 6th May 2008, Professor
Newton said: "Recent results from a series of MR
scans have shown impaired proton removal from
muscle during exercise in patients with ME/CFS
compared to matched controls.  This has led us to
hypothesise that fatigue arises due to impaired pH
run off from muscle during exercise which is
influenced by the degree of autonomic dysfunction".

Despite the irrefutable evidence of mitochondrial
dysfunction and damage in patients with ME/CFS, the
NICE Guideline on "CFS/ME" proscribes mitochondrial
testing and recommends only behavioural
modification in the form of cognitive behavioural
therapy, together with incremental aerobic exercise,
and refers to "perceived exertion" (52 page
version, page 30). It claims that it "offers the best
practice advice on the care of people with
CFS/ME" (52 page version, page 6) and that its
advice is "evidence-based". It is notable that the
alleged evidence-base upon which the Guideline
Development Group relied specifically states: "If
patients complained of increased fatigue, they were
advised to continue at the same level of exercise"
(Fulcher and White, BMJ 1997:314:1647-1652). Given
the evidence of mitochondrial damage, such advice
cannot conceivably qualify as "best practice advice".

CFS as Energy Metabolism Dysregulation

Medical Hypotheses  

Treating Chronic Fatigue states as a disease of the regulation of energy metabolism William Bains(*) Delta G Ltd, 37 The Moor, Melbourn, Royston, Herts SG8 6ED, UK * Corresponding author. Tel. +790 4931369. E-mail address:


Chronic Fatigue Syndrome is a physiological state in which the patient feels high levels of fatigue without an obvious organic cause, which affects around 1 in 400 people in the developed world. A wide range of causes have been suggested, including immune or hormonal dysfunction, viral or bacterial infection, and psychological somatization. It is likely that several causes are needed to trigger the disease, and that the triggers are different from the mechanisms that maintain fatigue over months or years. Many treatments have been tested for CFS, with very limited success - a programme of combined CBT and graded exercise shows the most effect. I suggest that patients with CFS have a reduced ability to increase mitochondrial energy production when exertion requires it, with fewer mitochondria that are each more efficient, and hence nearer to their maximum energy output, than normal. A range of indirect evidence suggests that the renin-angiotensin system stimulates mitochondrial responsiveness and reduces mitochondrial efficiency: chronic under-stimulation of this system could contribute to CFS aetiology. If correct, this means that CFS can be successfully treated with RAS agonists (eg angiotensin mimetics), or adrenergic agonists. It also suggests that there will be a positive link between the use of adrenergic- and RAS-blocking drugs and CFS incidence, and a negative link between adrenergic agonist use and CFS.


Chronic Fatigue Syndrome is a physiological state in which the patient feels high levels of fatigue without an obvious organic cause. Abnormal fatigue is known to be a pathological feature of many diseases. In a set of syndromes together called Chronic Fatigue Syndromes (CFS) fatigue is a defining symptom, and does not have an obvious organic cause, such as physical exertion or the metabolic effects of another disease process [1,2]. Clinical diagnosis emphasises the presence of symptoms of fatigue and the absence of obvious causes [3-5]. For reasons of social acceptability, CFS is often called Myalgic Encephalomyelitis (ME) in the non-technical literature [2].

'Fatigue' in this context is not the same as 'weakness'. CFS patients usually have normal muscle strength [6-8] (although a few studies find loss of muscle power in CFS patients, possibly an effect of 'deconditioning', ie being 'out of shape' from prolonged lack of muscle use [9,10]), so CFS is caused neither by a failure of muscle power or a failure of motivation. It is also not caused by failure of the cardiovascular system to support muscle physiology [10] (although see [11] who finds some cardiovascular deconditioning). The chronic fatigue found in chronic heart failure patients is also metabolic rather than due to haemodynamic effects[12,13]. Rather, CFS is an inability to apply that power to sustained effort. This is usually taken to meanphysical effort, but mental effort seems to be similarly impaired, independent of any depressive or other psychiatric disease [14].

CFS can be severely disabling [15]. The disease can last for years, while some patients recover on their own, others show resistance to recovery over a decade or more [16]. This variability of outcome, as well as the variability of symptoms and different diagnostic criteria, make comparison between studies and therapeutic approaches very hard [17].

Typical prevalence estimates suggest around 1/400 people are suffering from CFS at any one time [2,18 ­25]. Some studies have found lifetime risk of suffering prolonged, inexplicable fatigue as high as 33% [26].

CFS causes and treatments

Most studies show that no single factor is necessary and sufficient to trigger CFS, and that a combination of triggering factors applies, such as allergy and psychological factors [27], heavy exercise and viral infection [28] or other muscle damage [29,30], or CNS and immunological factors [31]. Consequently, there has been little progress in finding a cure.

Several meta-studies of the trials literature show that graded exercise programmes and Cognitive Behavioural Therapy (CBT) are the only approaches which shows a consistently good track record of benefit in clinical trials [17,32,33]. There is no effective pharmacological treatment for CFS [33,34], although this is not for lack of searches - Whiting et al analysed found 350 trials, and in a meta-analysis of 44 of them found 31 different interventions [17,32]. A major issue is that the trigger for CFS is believed to be different from the mechanisms that sustain the disease [1,35], so searches for, and treatments of, triggering factors may say little to how to treat or cure the disease once it is established.

Suggested etiologies for CFS generally fall in the category of psychological/psychiatric [1,36], immunological/viral, or hormonal [37]. The disease is at least partly psychological [1,26], and it is often comorbid with psychiatric disease, especially depres- sion [1,38-41]. But antidepressants are generally considered ineffective against all but the psychological sequelae of CFS [37,42,43], and a large trial using treatments to enhance cognition [14] was not successful [44]. Association with immune and allergic disease and immune activation parameters [27,45] or abnormal immune regulation [46] has suggested immunological treatment, but these have not generally shown any objective value [47,48]. Anti-viral agents do not seem to help [2,49], and the symptomatic similarities to adrenal insufficiency are not supported by any more than mild impairment of the hypothalamic-adrenal axis [50-53], although these are the only consistent hormonal changes in CFS [52,54]. A wide range of other etiologies have been suggested for CFS (eg. [55-58]).

In part, the variability in trial outcome may be because 'CFS' is not one disease [2,4,59], or if a single disease (as Ciccone and Natelsson argue on epidemiological grounds [60]) that is has distinct sub-types [2]. So it is likely that, even if a treatment does work well for one sub-group of patients, it will not work as well for others.

Metabolism in CFS There are no obvious metabolic 'problems' that could cause CFS, but a common finding is a reduced level of oxidative metabolism [61] and increase in lactate production [9,10], which these workers attribute to deconditioning - loss of muscle tone and power from prolonged lack of use. (Lactate elevation could also be related to the reduction in post-exercise delivery of oxygen to tissues observed by McCully and Natelson [62], although this reduction does not in itself seem to alter muscle metabolism [63]). Mitochondrial abnormalities and degeneration are frequently [64] although not always [10] found.

RAS, alarm response and CFS

A common (although not obvious) theme running through CFS is the involvement of the body's 'fight or flight' systems, and particularly the neurotransmitters and hormones of the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). Several indirect lines of evidence suggests that low RAS activation is related causally linked to CFS triggering or maintenance.

* Serum Angiotensin converting enzyme (ACE) is recognised as a marker for CFS [65]. * Gulf war veterans with the Tissue ACE gene I allele (high level expression) are less likely to be found to develop CFS as part of the 'Gulf War Syndrome' spectrum of disorders than veterans who carry the D allele. DD veterans are 8 times as likely to suffer chronic fatigue as the whole population [66]. * Chronic heart failure is often accompanied by CFS-like fatigue (which is not designated CFS because of the co-morbidity with heart failure). Haemodynamic parameters do not explain this. The principle difference between the two patient sets is the extensive dosing of heart failure patients with AT-II inhibitors, beta blockers and ACE inhibitors, usually in combination [12]. * Vasopressin levels have been reported to be lower in CFS patients, suggesting relative inactivity of all blood pressure control systems [67]. Oxygen delivery to muscles post exercise has been found to be reduced in CFS, which has been attributed to reduced autonomic control of vasodilation in CFS [62].

RAS, SNS and mitochondria

A mechanism for the effect of the RAS on fatigue is through mitochondrial efficiency and energy reserve. Several pieces of evidence suggest that RAS and SNS activation reduce the efficiency of mitochondrial energy production, and increase mitochondrial number. * Beta-3 agonist induce UCP-1, through mechanism involving rB protein, in fat (turning white to brown fat) [68,69] and muscle [70]. Beta adrenorecetopr knockouts depress brown fat formation [71]. The same pathways stimulate mitochondrial biogenesis via CaMK and PGC-1 [72]. * AT-II antagonists increase the duration and energy of sperm swimming. Sperm are almost totally dependent on mitochondrial metabolism of externally supplied sugars for their energy. AT-II antagonists increase this power generation, ie increase the efficiency with which the sperm generate energy. [73,74]. * RAS blockade is associated with increased abilityto build muscle mass.There are several pieces of evidence of this type, from cachexic patients, training athletes and high altitude moutaineers [75-77]. This may seem a contrary piece of evidence. However, any body builder knows that muscle mass is best increased through intense anaerobic exercise, not through aerobic exercise. If RAS blockade reduces the ability of mitochondria to upregulate their energy generation, then a given level of activity would exhaust the aerobic energy generation capacity of low-RAS individuals before it exhausted the aerobic capacity of high-RAS individuals.

Consistent with this hypothesis (but with many others as well) is that CFS symptoms are increasingly being shown to be associated with, and possibly caused by, increased oxidative stress [78], which would be expected of long-term loss of adequate mitochondrial function as other systems took up the task of balancing muscle redox balance [79,80].

RAS, SNS and mitochondrial responsiveness in CFS

Why should the same hormonal system increase mitochondrial number yet decrease mitochondrial efficiency? I hypothesise that this is due to an inverse correlation between mitochondrial efficiency and the ability of mitochondria to increase energy output on demand, and that this links the same systems to CFS.

For rapid response to shock or stress (such as caused by psychological shock, such as activates the SNS, or haemodynamic shock such as activates the RAS), mitochondrial energy production must be capable of being upregulated in seconds. One of the more common ways of enabling metabolic pathways to respond rapidly to changes in control, and to provide greater response than feedback inhibition and substrate activation mechanisms can allow, is to use substrate cycles at key points in the metabolic pathway concerned [81]. Such a cycle in mitochondria would have the effect of making the mitochondria 'inefficient', ie causing it to oxidise substrate to H2O and CO2 without generating maximal energy. Uncoupling proteins allow precisely this to happen: other mechanisms can also be imagined to achieve this in oxidative phosphorylation.

The physiological benefit of such cycles is that the body can respond rapidly to increased energy demand. The downside is that you need more mitochondria at rest (because each is less efficient), and some resting energy is 'wasted', ie dissipated as heat.

The paradoxical effects of RAS and the SNS can therefore be seen as the cell's response to chronic stimulation from hormonal systems that alert the body to the need for immediate, substantial energy demand, through increasing mitochondrial number and mitochondrial responsiveness. Blockade of these systems signals a reduction in stress demand and hence the need for fewer, more efficient and less potentially responsive mitochondria. This relates to muscle mass because mitochondrial cycling is not something that can be switched on and off on a matter of minutes - protein synthesis, and creation of new mitochondria take hours or days. If a patient has their RAS chronically blocked, genetically or pharmacologically, then the number of mitochondria will fall and their ability to rapidly increase energy output will fall. When such muscle is exercised, it will rapidly reach its limit of oxidative phosphorylation and move into a glycolytic metabolism, typical of sprint rather than marathon training regimes. This will result in more muscle build-up, as it does in more conventional training. For patients sufferingsevere muscle wasting (cachexia), even everyday tasks would become sprint training tasks, resulting in muscle build-up (or slowing of muscle decline).

Hypothesis: chronic lack of ras/sns stimulation maintains CFS

My hypotheses is that the failure of CFS patients to maintain power output in physical or mental activities is due to an inability of their metabolism to deliver increased energy in response to increased demand. This is a key component of the maintenance of CFS. Any event that causes the patient to reduce their exertion to a low level might trigger the state: the likelihood that it did so would be influenced by other physiological and genetic factors. Once the capacity to increase energy production on demand has been reduced, any exercise will be 'felt' to be like heavy exertion, and will rapidly cause the muscle to become hypoxic, generating lactic acid, and sometimes causing muscle damage more normally associated with over-exercise. Depending on other physiological and psychological factors, this may be sufficient to deter the individual from exercising, maintaining a vicious cycle. This is illustrated in Figure 1.

This means that treating the initial, triggering causes of CFS - viral infection, injury, inflammation, depression ­ are very unlikely to be cure the disease: this is found to be the case. The only two approaches likely to be effective are i. increasing physical activity: this is the only therapeutic approach presently shown to have an effect ii. increasing mitochondrial mass and responsiveness

I propose to treat CFS through the second of the two options above. The pharmacology for doing this could include use of stimulants of the renin-angiotensin system, or sympatheticomimetic agents, especially beta adrenergic agonists such as salbutamol, thiotropium or ephedrine. In practice, because of the redundancy of biological circuitry and the need to avoid unwanted pharmacological effects, combinations of low doses of these compounds are likely to be the best approach.

I note that this is unlikely to be a 'universal cure'. In some groups of patients other factors than cell-level power generation may be a dominant maintaining factor, and in particular in some defects in neuromuscular transmission or inappropriate psychological attitudes are strongly suspected to be important in the disease [59]. However it is plausible to suggest that this approach will be of some use to a lot, maybe a majority of patients, and as it is very easy to administer and should have a rapid effect, if proven successful it could be used as a 'first line' treatment, with more costly and time-consuming psychological and exercise approaches being brought in subsequently.

Predictions and tests

Testable predictions flow from this hypotheses. Most obviously, it suggests that a suitable combination of RAS and adrenergic agonists will be an effective treatment for CFS. However proving this is a long-term prospect. In the more immediate term, the following experimental tests are available. * In any cycling system, as flux through the pathway is increased, back flux through the cycle becomes less a factor in the overall flux (although it never reaches 0). One would expect that the 'efficiency' of mitochondria in cells that were being energetically exercised would be higher thanthe same cells under resting conditions. This could be tested with cultured muscle cells. * Tissue (specifically muscle) in chronically-RAS- stimulated or RAS-blocked animals would be expected to have more or less mitochondria per unit mass than average, respectively, and less or more efficient mitochondria respectively. * Other agents associated with the 'fight or flight' response might be expected to have similar effects: The effect of a-adrenergic agonists would be interesting in this regard, as the a-adrenergic system does not activate RAS: in this respect I note that Naschitz et al [82] report that Midodrine, an a-adrenergic agonist, was effective in one case of CFS. * Other agents associated with tissue growth, and with muscle bulk, such as growth hormone or IGF, would however not be expected to have these effects. * Other agents associated with the clinical control of blood pressure, but acting other than through the RAS, such as the thiazide diuretics, would not have these effects.

The measurement of mitochondrial number can be done by electron microscopy. Mitochondrial mass may be estimated from assay of any one of several mitochondrion-specific enzymes, or measuring relative amount of mitochondrial DNA [83,84]. 'Efficiency' can be measured by three approaches - measuring the net amount of oxygen and glucose consumed by resting cells (assuming that drug treatment has not altered the cells' energy requirements), measuring intracellular ATP pools compared to oxygen and glucose consumtion, and measuring mitochondrial membrane potential. This last is most direct, and can be achieved by using dyes such as rhodamine 123 [85] or JC-1 [86].

In addition, there is a clear epidemiological prediction of the logic above, that patients treated with RAS or SNS antagonists will be more prone to develop long-term, disabling fatigue than patients treated for the same diseases with other classes of drugs. The obvious comparison is in cardiovascular disease, where the sequelae of the use of ACE inhibitors, AT-II antagonists, and beta-blockers can be compared to those arising from use of diuretics, Ca2+ blockers, cardiotonics, or nitrates. Conversely, patients treated with adrenergic agonists might be expected to have a lower than normal level of fatigue syndromes. Asthmatics are an interesting case here, being treated with inhaled beta adrenergic agonists that act primarily topically but which do have a low level of systemic penetration [87-89]. Very extensive academic databases of cardiovascular medicine treatments and outcomes have been compiled over the last two decades. These databases could be tested by suitable 'data mining' of these patient and clinical trial databases for these predicted outcomes.


I am very grateful to Dr Aubrey de Grey (Cambridge), and Johanna Busch, David Hampton, Charles Conrad Uy and Ponarul Palanisamy (Cambridge M. Phil in Bioscience Enterprise programme) for their comments and contributions.


Energy Metabolism REFERENCES

Figure caption    Figure 1 Cartoon of the mechanism of the proposed hypothesis(A wide range of insults can result in a patient reducing activity over a substantial period of time (weeks or months). This leads to reduced RAS and sympathetic activity, and hence to an decrease in mitochondrial number and increase in efficiency which leads to an inability to sustain high power output levels, and hence exertional pain on even mild exercise).


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Fibro Conference Today in SLC,5150,700258150,00.html

Fibromyalgia conference in Salt Lake on Saturday

By Lois M. Collins

Deseret News

Published: Friday, Sept. 12, 2008 12:19 a.m. MDT

Understanding of fibromyalgia - and even its recognition as a legitimate
illness - has come a long way in the past few years. But the most important
advance is Food and Drug Administration approval of two drugs to modulate
the nerve pain or central nervous pain that marks the illness.

That's according to Dr. Lucinda Bateman, a Salt Lake City doctor who was
treating the condition long before many of her colleagues had stopped
debating whether it's real. She's one of the featured speakers at a half-day
education conference Saturday presented by the Organization for Fatigue and
Fibromyalgia Education and Research.

The FDA approved Lyrica, an anti-seizure drug, and Cymbalta, an
antidepressant, which both modulate the pain associated with fibromyalgia. A
"poor, orphan sister disease," chronic fatigue syndrome, has been less
lucky, she said, because its research has yielded less information, although
high-tech genomic studies are expected to change that.

The two conditions often co-exist.

The film, "Living With Fibromyalgia" has a free screening at 10 a.m.
Saturday at the Broadway Theater, 111 E. 300 South, in conjunction with the
conference, which will be held at the Radisson Hotel, 215 W. South Temple,
beginning at 12:30 p.m. Cost is $15.

You can register online at or call 801-328-8080. Later,
Daneen Akers, who wrote, directed and produced the film with Stephen Eyre,
will discuss it during the conference.

Bateman said Kathleen Light, a researcher at the University of Utah, will talk about her team's research, which has found what may be novel markers for pain and fatigue. It is possible to document the increase in those blood markers when patients with fibromyalgia and chronic fatigue syndrome exercise.

"It's a wonderful demonstration of how patients with these illnesses have to limit their activity or get sick," she said.

Dr. N. Lee Smith of Lifetree Pain Clinic will update diagnosis and treatment
information and Bateman will do the same for chronic fatigue syndrome.

As many as 8 percent of people may have fibromyalgia nationally, the number
being highest among middle-aged women. Bateman said at least 10 percent in
that category of middle-aged women are believed to suffer fibromyalgia,
which varies greatly in severity from one case to another. Estimates are
less sure for chronic fatigue syndrome, and sometimes when people meet the
criteria, a different explainable or reversible problem is found. Bateman
points out that the American health system struggles with complex disorders.


(People can comment online; Dr Bateman has replied to a person who had said:
"THERE IS NO SUCH THING! Too often this is a catch-all term for a missed diagnosis OR more often, a psychotic disorder."

* * *

I will agree that too often CFS/fibro are used as a catch-all for a missed diagnosis, but that does not mean that all patients with these diseases are misdiagnosed (or psycho).  Some CFS patients were initially misdiagnosed with "atypical MS", which certainly is not understood to mean that MS is a catch-all!  It simply means that the doctor had insufficient information or knowledge to differentiate.

This is why it's important to get your diagnosis confirmed by a CFS or fibro specialist.  Some of the things misdiagnosed as CFS/fibro are things that can be treated.  Why suffer for years thinking you can't be helped when there are things that can be done for some of the lookalike illnesses?

And although there are still plenty of people out there -- some of whom comment in this blog -- who think that these are purely psychotic disorders, there are thousands upon thousands of research studies identifying abnormal physiological symptoms and systems, such as the blood markers to be discussed at this conference.  You can decide for yourself who's truly psychotic: the patients who have numerous demonstrable biochemical abnormalities, or the doctors who insist there's nothing wrong with them!

Thursday, September 11, 2008

Staying Updated on CFS Research

Here's how to stay updated on the latest CFS research sent to pubmed via their email service-    

1. Go to and register(free)-   

2. Type 'chronic fatigue syndrome' into the search box. When the results come up, click on the blue 'save search' link next to the search box. A box will pop up asking 'Would you like to receive e-mail updates of new search results?' -Click yes.  

3. It will then ask 'how often', with options for once a month, once weekly, or daily. Leave 'send email even when there are no new results' unchecked.  

4. If 'daily' is chosen, new results are sent anywhere from 3-5 times per week, on average.  

Please post this anywhere you think people would want to stay updated on the latest CFS research!

Opportunity Knocks for CFS

A Force to Be Reckoned With Or Not?  

Part I By Cort Johnson

(For the website version

“In recent years there has been, in my opinion, an apathy that has crept in and pervaded some parts of the support community. Perhaps it has been due to ill health, perhaps the patient community is giving up, discouraged by a perceived lack of progress  but whatever the reason, people need to remember that nearly everything good that has come to patients with [M.E.] CFS has come via the support community.” 
                                                                        Dr. David Bell

Opportunities Knock.
Two powerful opportunities to make a difference in this disease have appeared

       *The IACFS/ME is attempting to hire an Executive Director -  their first full-time paid staffer –.

       *The CFIDS Association of America began a million dollar research initiative that would quadruple their research effort. 

Both organizations have taken bold strides recently. 

Dynamic Leadership
Under Dr. Nancy Klimas’s leadership, the International Association of CFS/ME
(IACFS/ME), has created the first Pediatric Definition of ME/CFS
and is working on producing a new journal and creating treatment guidelines for
ME/CFS. The last, a consensus document produced by top ME/CFS physicians, presents a tremendous opportunity for both physician and patient education. If you’re
looking for an alternative to the CDC’s health tips for ME/CFS here it is. 

A Bold Move With the hiring of Dr. Suzanne Vernon and the announcement of their million dollar research initiative the CFIDS Association of America made a bold thrust to
quadruple their research funding, build an active research network, and advocate more effectively in the halls of government. All these are vitally needed at a time when federal research funding for ME/CFS is reaching new lows.
Small Organizations -
Big Plans. Both groups are small given the needs of the ME/CFS
community; the IACFS/ME is entirely volunteer run by already overworked
physicians and researchers. The CFIDS Association of America advocates on the
federal level, runs a media campaign, provides physician education programs, publishes
an informative monthly e-link newsletter, does outreach to local support
groups, publishes the Chronicle, maintains its large website and funds research
all on a staff of fourteen.  

These projects have the potential to give ME/CFS patients stronger, more effective voices. 

But will they respond?

A Force to Be Reckoned With? Or More of the Same?

With 200,000 diagnosed ME/CFS patients in the U.S.
we have the ability to build powerful, influential organizations. We have the
numbers, for instance, to tell the federal government that spending peanuts on
a disease that affects 4 million American’s is not acceptable! But we’re not.

Cattle Cars or A Run For It? . 

Over dinner at the International Symposium on Viruses in CFS
two prominent, longtime physicians lambasted the inactivity of ME/CFS
patients. One went so far as to state they were basically allowing themselves
to be locked into cattle cars without protesting (!) He said that at least he
would try and make a run for it. 

Strong words yes but with only 2-4% of diagnosed ME/CFS
patients actually contributing to their national organizations they resonate.
By not supporting these organizations fully chronic fatigue syndrome (ME/CFS)
patients have left their fates up to a national medical agenda that has no room
for chronic fatigue syndrome. They’ve ceded their power to government officials
who have time and time again demonstrated they have no interest in ME/CFS.
Whatever anyone’s justification for not supporting these organizations the
result is the same - a loss of power – and an enfeeblement in an environment
which is hostile to our interests.  

We desperately need to build these organizations into powerful
partners that can make a difference at the highest levels. Sick patients
working by themselves can’t do that but they can provide the resources
professional organizations need to make a difference.  Let’s start with these projects – let’s make a run for it. 

To contribute to the IACFS/ME capital funds campaign. 
To join the IACFS/ME

To contribute to the CFIDS Association of America‘s Research

To become a member of the CAA 

Even better become a member of the Chairman’s Circle and get
on the monthly payment plan

  Cort Johnson 


Cheney to Speak October 26 near DC

Paul Cheney, MD, PhD, will be speaking from noon to 4 pm on Sunday,
October 26th at the Fairfax Board Auditorium of the Government Center in
Fairfax, VA (just outside Washington, DC, east of Dulles Airport).

The title of his presentation and a summary of topics to be covered will
be made available as soon as possible. His three-hour presentation to
the International IFM conference in May of this year received a
five-minute standing ovation, and he has made several conceptual and
treatment breakthroughs since then, so the October patient seminar
should be an exciting, groundbreaking event.

This event is being co-sponsored by the Northern Virginia CFS/ME, FMS,
OI Support Group and the CFS/FM Support Group of Dallas - Fort Worth.

A 2-disc DVD master will be produced by a firm in Washington, and orders
will be taken, duplicated and mailed out by a DVD fulfillment company in
New York. DVDs will be available in both NTSC and PAL formats, making
them compatible with DVD players around the world. No pre-orders will be
taken. Ordering information will be posted once it is available.

Carol Sieverling
CFS/FM Support Group of DFW

Elly Brosius
N. VA CFS/ME, FMS, OI Support Group

Overview of Conference on Viruses in CFS

Welcome to a special edition of Phoenix Rising. In this
edition we cover the first conference ever devoted specifically to viruses in chronic
fatigue syndrome (ME/ CFS ): the Symposium on
Viruses in CFS . The Symposium took place
directly after the International HHV-6 Conference in Baltimore ,
Md. in May of this year. It featured a
who-who's lineup of speakers in CFS research
including Dr. Montoya, Dr. Kerr, Dr. Klimas, Dr. Vernon, Dr. Lloyd, Dr.
Peterson, Dr. Chia, Dr. De Meirleir and others.

ME/ CFS patients also turned out in force. By
the time the 'Symposium' was underway the room was as full as it ever was
during the three day HHV-6 'Conference'. Dr. Vollmer-Conna marvelled at all the
patients present stating she'd never seen anything like it at a scientific

The infectious side of the research community may be the most innovative and
creative of all. During the conference we got introduced to intriguing
questions such as

Is a difficult to detect central nervous infection responsible for the mood
disorders in ME/ CFS ?

Could an endogenous retrovirus residing in ME/ CFS
patients DNA somehow have sprung to life?

Could a smoldering infection in the heart be causing the fatigue in ME/ CFS ?

Is there a distinct neuro-immune fatigue subset in this disease?

Are we close to finding an immune biomarker for this disease?

Has the Dubbo team figured out what happens as people come down with ME/ CFS during an infection?

How well do antiviral drugs work and what kinds of drugs are in the pipeline?

Are entire networks of cells acting strangely in ME/ CFS ?

The overview of the conference comes in two parts.

Part I ConHHV6PtI.html  

Part II ConHHV6PtII.html

Zombiefication of CFS

More Zombiefication of ME/CFS?

Margaret Williams           

Not only is NICE facing a judicial review of its Guideline on "CFS/ME", it
has also come under fire from other quarters, with calls for it to be
abolished after "a series of 'barbaric' and 'crazy' decisions"  ("Call to
abolish NICE over 'crazy' decisions"; Daily Telegraph, 14th August 2008).
The article quoted Jonathan Waxman, Professor of Oncology at Imperial
College, London: "Professor Jonathan Waxman said NICE was bureaucratic,
unaccountable and run by economists, not doctors".  The article also said:
"There were concerns that some of its processes were not transparent" and it
quoted Professor Waxman verbatim: "NICE should be abolished. It is an
unaccountable body that has made some barbaric decisions and is preventing
patients getting the care they need".

Four days earlier, in an article entitled "NICE distinctions may save money
but they don't save lives" (Sunday Telegraph, 10th August 2008), Professor
Karol Sikora said: "A conspiracy theorist would think that the conclusion was given to NICE by the Government and that data was found to justify the outcome.  Current policy-making is reminiscent of the line in one of the Indiana Jones movies where the heroine asks Indiana at a point of crisis: 'What shall we do next?'   He responds: 'I don't know.  I'm making this up as we go' ".

The ME/CFS community is well aware that evidence continues to mount showing
that in the production of its Guideline on "CFS/ME", the conclusion may
indeed have been given to NICE and that "data was found to justify the

It cannot be denied that powerful forces are at work to deny the validity of

It is irrefutable that certain UK psychiatrists, all deeply involved with the medical insurance industry, have worked unceasingly to deny the nature of ME/CFS. The three key players are Professor Simon Wessely, Professor
Peter White and Professor Michael Sharpe, but there are others with undue
influence such as Dr William Hamilton, a member of the NICE Guideline
Development Group, who for the past 15 years has been Chief Medical Officer
of a medical insurance company (Exeter Friendly Society) and who drew up
that company's policy to exclude ME/CFS from benefit cover as long as it
remains categorised as a "behavioural" problem.

Following publication of the Chief Medical Officer's Working Group Report on
"CFS/ME" in January 2002, the medical insurance company was alarmed and set
about tightening control of such claims with heightened self-preservation.
The following quotations come from an article by Peter Pallot:

"Official recognition has not brought clarity for insurers.  Insurers see
the devil in the long-term nature of CFS.  Take for instance a 30-year-old
City high flier who succumbed aged 30 when earning £75,000 a year. (He)
might be in line to get two-thirds salary -- £50,000. Over 35 years, if the
condition never resolved, the insurer would be paying out £1.75 million".
"Renaming the condition CFS and discarding earlier labels, including myalgic
encephalomyelitis (ME), was helpful".
" 'Syndrome' implies a range of causes and symptoms, rather than a specific
reaction to an organism".

"Sun Life Financial of Canada managing director Paul Davies thinks the
condition could account for as much as ten per cent of claims by value".

"Norwich Union's Louise Zucchi says this accounts for a considerable part of
the gamut of mental illnesses which make up a third of all claims".

"Friends Provident technical claims manager Andy Parkinson says: 'Mental
health and chronic fatigue claims comprise round about a quarter of all the
claims we have".

James Vallender, benefits operations manager of the largest company, UNUM,
said: " 'We experienced a big rise in the 1990s but in the last 18 months or
so it's got quieter.  In 2000, cases accounted for 1.5 per cent of the
caseload but increased last year to two per cent'.  According to Vallender,
some claims that formerly might have been classified as chronic fatigue are
today examined more thoroughly.  To this end, it is becoming standard
practice for insurers to pay for medical interventions such as cognitive
behaviour therapy in CFS cases".

"Norwich Union uses neurologists (and) psychiatrists.  Zucchi recalls: 'We
had our first claims 12 years ago and they have continued to grow.  We send
trained people to their homes.  We have put more and more emphasis on home
visits and rehabilitation over the past five or six years' ".

"A typical rehabilitation programme could be designed to entail exercise in
a gym (and) this might be paid for by the insurer".

"Sun Life Financial of Canada has co-opted the German occupational health
company PRISMA Health to help.  At the insurer's Basingstoke offices, Davies
says insurers need just such a specialist company. The company's exposure to
chronic fatigue claims has pushed it into a very proactive approach. Davies
explains: 'We are probably a little more expensive but we have put a lot
greater effort into getting people back to work.  We've been looking at
cases that have been on the books a couple of years. The crux is that if you
did not apply rigorous medical attention and rehab programmes you really
would have very long- term claims.  We get PRISMA to talk to the family and
also the partner and PRISMA will work out a programme to get that person's
life back".

"PRISMA's assessment costs 'a significant sum' says Davies.  The group
insurer could spend £50,000 on one rehabilitation".

"Until recently, the role of IP (income protection) providers stopped at
paying claims.  Now they are initiating intervention in a way that seems to
help all parties".

The article can be accessed at

This confirms what the ME/CFS community has known for many years, namely, the influence of the medical insurance industry on the management of people with ME/CFS, which is reflected in the NICE Guideline. It would seem to be proof that medicine has been commandeered by industry and that the only outcome measure regarded as important is company profits.

As one comment on an ME internet group so aptly noted, it is an unmitigated
disaster "when the basic definition of the disease is wrong, when the
guidelines for treatment are not grounded in credible evidence or in science
at all, and the guidelines misinform health professionals so badly.  We need
another word for what we mean by 'multidisciplinary', because we mean
relevant immunology, cardiology, neurology (and) endocrinology, and the
psychosocial school don't" (16th August 2008; ).

Of course they don't - the paymaster of the psychosocial school is the
medical insurance industry, which for the most part excludes "mental"
disorders from eligibility for income protection payments.

On the fees known to be charged by these psychiatrists for reports for the
insurers on "CFS/ME" patients advising against the payment of insurance
benefit, it has been calculated that each psychiatrist could easily earn an
additional £4,000 per week on top of their NHS and academic remuneration.

Many ME/CFS patients have to fight - in future, likely to be every three months -- for the right to exist on £84.50 per week.


God Grant Me The Courage to Change the Things I Can...

If you don’t like something, change it. If you can’t change it, change your attitude. Don’t complain.

                                                 Maya Angelou

I don’t like the way people with CFS are treated by the medical establishment and disability programs, and I’m doing what I can to change that.

Part of that work for change is writing this blog, bringing to light the research that proves CFS is a valid physical illness, which cannot be cured by taking anti-depressants or thinking happy thoughts. The two medications which seem to have the best results are both anti-viral medications – that’s a far cry from the assertion that CFS is all in our heads.

Another part of that work for change is helping Dr. John with his mission to flood the media with letters to the editor when they publish false or misleading information about CFS.

If it improves with anti-depressants, it’s not CFS. If it improves with exercise, it’s not CFS. Plain old garden variety fatigue is not CFS.

CFS is a post-infectious neurological condition. There’s nothing psychiatric about it. Dr. Jay Goldstein describes "limbic system encephalopathy causing autonomic dysfunction and subtle neuroendocrine derangements" and Dr. Katrina Berne cites "abnormalities of the immune system, circulatory system, central nervous system, and hypothalamic_pituitary_adrenal axis." Doctors who don’t recognize these basic facts about the condition have no business treating it. It’s my personal opinion that these doctors need to be brought up on ethics charges for misrepresenting their qualifications to treat you, when, in fact, they should be referring you to someone who does know how to treat CFS. Just because the doctor may not be familiar with your medical condition does not mean it isn’t real.– Devin Starlanyl, M.D. There again, any doctor who says that to a patient deserves to be smacked upside the head by the Ethics Committee for speaking outside his area of expertise. Untold damage has been done to CFS patients by ignorant doctors who recommend things that are, in fact, dangerous for CFS patients, and it’s time that the doctors pay the price for their ignorance instead of the innocent victim patients being the only ones who suffer.

Dr. Elizabeth Dowsett, who’s been studying CFS since it was known as ME, observes "There is ample evidence that M.E. is primarily a neurological illness. It is classified as such under the WHO international classification of diseases (ICD 10, 1992) although non-neurological complications affecting the liver, cardiac and skeletal, muscle, endocrine and lymphoid tissues are also recognized. Apart from secondary infection, the commonest causes of relapse in this illness are physical or mental over-exertion." However, she notes that researchers "should first be directed to papers published before 1988, the time at which all specialized experience about poliomyelitis and associated infections seem to have vanished mysteriously!"

What happened in 1988 to cause that mysterious disappearance? The CDC, by executive fiat, abolished the name Myalgic Encephalomyelitis and re-named it CFS, then proceeded to define the ME component out of existence! Those of us who have the ME version of CFS (instead of the fictional psychiatric version created to replace it) find ourselves, like the Man Without A Country, as patients without a disease. We don’t fit the current definition of CFS, but it’s impossible to get an ME diagnosis in the US, because that disease has been wiped off the books. Gone with the Wind. As Dr. Dowsett observes, like it never existed at all. The goal appears to have been to have all the older doctors who remember ME die off and take their knowledge with them, leaving only the new research showing that patients who have psychiatric illnesses misdiagnosed as CFS for the purposes of that research, have purely psychiatric problems.

Unfortunately for them, some of our older researchers have kept the ME name in circulation and taught it to the patient-activists. If you google CFS, you’ll also get websites that refer to it as myalgic encephalomyelitis, or draw those connections to poliomyelitis. (For the newer readers of this blog, it was noted that polio and ME traveled in side-by-side epidemics and that those who got ME were later immune to polio, leading to the conclusion that they were related viruses. Those of us born after the mid-1950s got the polio vaccine, but that protects against only the 3 most virulent strains of the virus, leaving 69 variants that can still get you. And, you guessed it, the researchers before then did surmise that ME wasa milder variantof the polio virus.)

Dr. Richard Bruno even wrote a book, "Polio Paradox", summarized in an earlier post here, which again popularized the notion that CFS and polio have a lot in common. Too many people who know the truth have been willing to speak out, unafraid, that the CDC’s emperor has no clothes: CFS is scientifically closer to ME, MS, and polio than it is to depression or malingering, no matter what CDC tells you to believe.

Ken Fujioka, M.D. of the respected Scripps Clinic in San Diego says "For a long time, we've known that viruses can get into your DNA and reprogram your body." That knowledge makes sense to doctors for everything else except CFS, which many of them still prefer to denigrate as being lazy or crazy rather than accepting that a large percentage of patients (like me) report their symptoms starting with a virus, and that similar symptoms have been shown to be caused by other viruses.

I sincerely believe that I can change attitudes about CFS by getting the facts out there. I know the truth in my own life is that exercise and anti-depressants make me sicker, which proves the problem is not depression. Even one of my former detractors, when she got as sick as I had been, found herself needing to apologize for disbelieving my reports that it was possible to be that debilitated. Some of the doctors who once laughed at CFS patients got their dose of karma when they got sick themselves.

The scariest CFS Fact out there is ... there’s no vaccine, no treatment, no cure. Today you can be making fun of us, tomorrow you could be one of us. The best health habits in the world have not been enough to protect people from this contagious disease. Using hand sanitizer every two minutes is not going to protect you if someone coughs directly in your face. So don’t pat yourself on the back and gloat that it will never happen to you because you eat right, exercise, and don’t smoke, because I did all those things and got sick anyway.

Wednesday, September 10, 2008

Dr. John's Contribution to Invisible Illness Awareness Week

[A version of this letter was published in the Times of Malta, and the Newcastle Journal, 3 September 2008; the Bristol Evening Post, 9 September 2008]


M.E. (Myalgic Encephalomyelitis) is one of the illnesses included amongst those for consideration during Invisible Illness Week (8 – 14 September 2008) blog here. An amazing 96% of all illness is invisible and an equally incredible percentage of people with M.E. remain hidden, unaccounted for and unrepresented.


Some of the reasons for an illness being invisible are obvious. People, who are too ill to go out, or only on occasions when they feel a little better, remain behind closed doors and, ironically, may contribute to it by staying in to avoid disbelief, ridicule and prejudice from an ignorant population and, sometimes, doctors who prefer to say they must be malingering or attention seeking rather than admit they do not understand it.


No one knows, for sure, how many people have M.E. but it is likely that it is towards to lower end of the Department of Health's estimate of between 2 and 4 people in 1000, which would be about 120,000 people. The range is probably so large because it also includes all illnesses with chronic fatigue as a symptom and that doubles the number to 240,000. This larger total not only "hides" the number of M.E. sufferers within CFS (Chronic Fatigue Syndrome)/ME patients but distorts any conclusions from experiments in which they are used.


If there were only one organisation for people with M.E. and only a half of sufferers joined it, we should expect at least 60,000-70,000. There are several organisations at national and local level but the biggest UK Charity has a membership of 7,500. Allowing for multiple membership of specialist groups for children and the severely affected it is doubtful that the total would be double this. You don't need a calculator to see that this is less that 10% of the M.E. population.


So, where are they? Where is the largest portion of people, by 9:1, with this illness? It's unlikely that they don't know there are organisations to represent them. They are well advertised, mentioned in articles about M.E., GPs know about them, so do many MPs. Perhaps they have been members at one time but are no longer.


It is so important to find these missing people for a number of reasons, not least to know that they are not alone. We can't know how many people are in any distinct group until we define its characteristics (blue eyes, Sagittarians, over six feet tall etc.) and exclude those, which do not fit (all other colour eyes, zodiac signs, under six feet tall etc.) The bigger the sample of people having the most pure definition, the better picture of what we are dealing with will emerge and the more likely we are to find a common physical cause which should, in turn, suggest effective treatment towards cure.


In the meantime, people with M.E. need advice about the best treatments available for symptoms such as pain, or to aid sleep and they need support with practical matters, including benefits and the opportunity to meet other people in the same boat.


ME Free For is amongst those saying that we should make this Invisible Illness Week the one when we take M.E. off the list of invisible illnesses because it no longer remains behind closed doors.


Yours sincerely

Dr John H Greensmith

ME Free For

Neuroendocrinology of CFS and Fibromyalgia;jsessionid=F2EE2FEAA265F50F665EBAB76A7098E3.tomcat1?fromPage=online&aid=91581

Background. Disturbance of the HPA axis may be important in the pathophysiology of chronic fatigue syndrome (CFS) and fibromyalgia. Symptoms may be due to: (1) low circulating cortisol; (2) disturbance of central neurotransmitters; or (3) disturbance of the relationship between cortisol and central neurotransmitter function. Accumulating evidence of the complex relationship between cortisol and 5-HT function, make some form of hypothesis (3) most likely. We review the methodology and results of studies of the HPA and other neuroendocrine axes in CFS.

Method. Medline, Embase and Psychlit were searched using the Cochrane Collaboration strategy. A search was also performed on the King's College CFS database, which includes over 3000 relevant references, and a citation analysis was run on the key paper (Demitrack et al. 1991).

Results. One-third of the studies reporting baseline cortisol found it to be significantly low, usually in one-third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function, and enhanced 5-HT function on neuroendocrine challenge tests. The opioid system, and arginine vasopressin (AVP) may also be abnormal, though the growth hormone (GH) axis appears to be intact, in CFS.

Conclusions. The significance of these changes, remains unclear. We have little understanding of how neuroendocrine changes relate to the experience of symptoms, and it is unclear whether these changes are primary, or secondary to behavioural changes in sleep or exercise. Longitudinal studies of populations at risk for CFS will help to resolve these issues.

Address for correspondence: Dr A. J. Cleare, Section of Neurobiology of Mood Disorders, Academic Department of Psychological Medicine, GKT School of Medicine and Institute of Psychiatry, 103, Denmark Hill, London SE5 8AF.

* * *

Here's more proof for those who insist that because it doesn't show up on the basic first-round blood tests, it must be imaginary.  Hard evidence of neuroendocrine abnormalities that are invisible until these specific tests are done.

Do not let any doctor laugh at you or tell you it's all in your head until you've had thorough neurological and endocrinological tests done.  The first series of blood tests that are given to every patient should be relatively normal, because you don't have lupus, diabetes, etc. that those test for.

Buy Holiday Cards, Fund Research

The National CFIDS Foundation, Inc. is, once again, offering holiday cards
for sale.  The beautiful cards inform people about this devastating illness
(CFIDS/ME) and that the proceeds support research funding.  The  cards are
offered at the same price as they've been offered in the past.

The full-color cards feature a photograph of Quandry Peak in  Colorado.  The
vivid picture was taken by longterm patient, Diane Rose who  turned to
photography after she was unable to continue her high tech  career.

The card can be viewed on our website (see "fundraising shop" under the
research tab) at .  The
cards are  sent out in packages of 10 along with envelopes.  They can be
ordered via  regular (snail) mail as well as online.

For better health,

Gail Kansky
President, National CFIDS Foundation, Inc.
103 Aletha Rd.
Needham, MA 02492-3931

Living with Invisible Illness

I had hoped to make at least one blog post every day this week in honor of Invisible Illness Awareness Week, but guess what -- I have an invisible illness and couldn't manage that!
On Tuesday, I needed to take a payment to my insurance agent, and as long as I was out decided to pop into two stores at the mall and treat myself to lunch.  I wasn't in either store more than 10-15 minutes; I don't do long shopping expeditions any more.  I was out less than 3 hours (most of it sitting on the bus, in the insurance office, or at lunch) and because I have an invisible illness, I collapsed into bed when I came home and accomplished nothing the rest of the day.
Ah, who am I kidding?  I barely made it home.  I over-estimated my stamina by about a block and a half, and after getting off the bus, really had to tough it out to get home instead of collapsing on the street corner a few hundred yards away.  It took 5-10 minutes to walk that last block (a healthy person should be able to do it in a little over 1 minute).
Those are the times that I wish the detractors could see me -- not when I'm well enough to be out and about, but when I'm exhausted from being out and struggling to get home.  That's when it becomes apparent that I have a disabling invisible illness.