CFS: illness severity, sedentary lifestyle, blood volume & evidence of diminished car


Senior Member
I don't have the full text for this but happened to come across a second abstract which gives a little extra information:

Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function.

Hurwitz BE, Coryell VT, Parker M, Martin P, Laperriere A, Klimas NG, Sfakianakis GN, Bilsker MS.

Clin Sci (Lond). 2009 Oct 19;118(2):125-35.

Behavioral Medicine Research Center, University of Miami, Miami, FL 33136, USA.


The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle.

Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume).

The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32).

Controls were matched to CFS participants using age, gender, ethnicity and body mass.

Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups.

Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups.

Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal levels), the mean+/-S.D. percentage deficit in TBV, PV and RBCV were -15.4+/-4.0, -13.2+/-5.0 and -19.1+/-6.3% respectively.

Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels.

Analyses indicated that the TBV deficit explained 91-94% of the group differences in cardiac volume indices.

Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index.

Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition.

Further study is needed to address the extent to which the cardiac and blood volume alterations in CFS have physiological and clinical significance.

PMID: 19469714 [PubMed - indexed for MEDLINE]

Abstract 1049


Virginia T. Coryell, M.S., Barry E. Hurwitz, Ph.D., Meela Parker,
CCT, RDCS, Pedro Martin, M.D., Psychology, Arthur LaPerriere,
Ph.D., Psychiatry & Behavioral Sciences, University of Miami, Coral
Gables, FL, Nancy G. Klimas, M.D., George N. Sfakianakis, M.D.,
Martin S. Bilsker, M.D., Medicine, University of Miami, Miami, FL

This study evaluated cardiac structure and function in Chronic Fatigue
Syndrome (CFS) and non-CFS subjects, while controlling for CFS
illness severity and sedentary lifestyle.

In addition, we examined
whether differences in total blood volume (TBV) could account for
differences in cardiac outcomes. Study groups were: severe CFS
(n=30), non-severe CFS (n=26), sedentary control (n=30) and nonsedentary
control (n=30).

Severe illness in CFS subjects was defined as
>=7 of 10 CFS symptoms, self-rated as moderate or severe, that
persisted for >=6 mos.

Sedentary and non-sedentary physical activity
status were defined, respectively, as a reported energy expenditure of
<=1500 and >=2200 kcals/wk.

Measures were obtained from selfreport
of medical history, fatigue and physical activity, as well as
echocardiography and dual tag blood volume testing.

Among potential covariates, group differences emerged for age and education, and hence
were controlled in analyses.

The analyses showed that the severe CFS
group relative to the non-CFS groups evidenced diminished cardiac
index (CI) due to diminished stroke index (SI; ps<.05) and not to heart
rate differences.

The diminished SI in the severe CFS group was due to
lower end diastolic volume (EDV) and contractility (VCFc; ps<.05),
with no group differences in end systolic volume.

Follow-up analyses showed that the percent difference from ideal TBV was lower in the
severe CFS group than the non-severe and sedentary-control groups
(adjusted meanSE: -6.0%1.3 vs. -1.6%1.3 vs. 6.4%1.8; p<.001).

When these TBV differences were controlled, the group differences in
CI, SI, EDV and VCFc were no longer significant.

Notably, the cardiac measures in CFS subjects did not correlate significantly with reported

Therefore, the findings suggest that although a cardiac function
deficit is more probable in severely-affected CFS persons, it is not
linked to sedentary lifestyle or perceived fatigue, but is largely
accounted for by a deficit in blood volume.


Senior Member
I don't claim to fully understand this paper (although I understand the acronyms a little better than I thought I might) so here are some observations and extracts for what they are worth:

CFS group assignment by illness severity
The present study examined outcomes as a function
of illness severity (severe and non-severe) as defined
previously [25]. In brief, to be classified as severely ill
CFS subjects had to report that they had seven or more of
ten CFS symptoms (symptoms included post-exertional
fatigue, unrefreshing sleep, general weakness, memory
or concentration impairments, muscle aches/pain, joint
pain, headache, fever chills, sore throat and tender lymph
nodes), and at least seven of these symptoms had to persist
for 6 months and be rated as moderate or severe either
currently or in the past [11,25].

The sedentary control group seems well-matched with the CFS groups:
The respective mean+/-S.D. physical activity level expended by the sedentary and non-sedentary control subjects was 550.9+/−460.9 and 3878.2+/−2089.7 kcal/week. As can be seen in Table 1, the observed aerobic capacity and the difference from the predicted aerobic capacity did not differ significantly among all three of the sedentary groups. For these groups, the adjusted mean+/−
S.D. aerobic capacity was well below the predicted value (−27.3+− 16.4%), indicating substantial deconditioning.


Senior Member
Discussion section:

I was going to try to summarise it but the table wasn't coming out correctly and only have so much time/energy. So thought I'd post the discussion section.

In terms of practical relevance, search for "anaemi" - it's interesting [abstract doesn't really explain it (at least if you're like me and not "in the know" i.e. don't have much knowledge of biology or medicine)]


The major findings of the present study were that, relative
to healthy non-CFS subjects, patients with CFS and
more substantially those classified with severe CFS had
(i) lower CI, which replicated previous reports [11,15],
due to a decrement in SI of approx. 10.2%; (ii) a cardiac
contractility deficit of approx. 25.1%; and (iii) a TBV
deficit of approx. 15.4%. When cardiac contractility was
controlled, the lack of a significant correction in cardiac
volume measurements (CI, SI and EDV) indicated that
these CFS functional differences were unlikely to be
related to contractility. Similarly, the finding that the
sedentary control subjects did not have a decrement
in cardiac volume level suggests that the lower cardiac
volume level in the CFS subjects was not likely to be
due to deconditioning. This conclusion is supported
by the observation that the CFS groups had a similar
aerobic capacity deficit compared with the sedentary
control group. Moreover, the aerobic capacity deficit did
not correlate significantly with the decrement in cardiac
volume in these subjects. Notably, the observed group
differences for indices of cardiac volume were nullified
by analytically controlling for prevailing TBV deficits;
the TBV deficit accounted for 9194% of the group
differences in cardiac volume. Therefore it is probable
that the decrement in cardiac volume in CFS subjects is
secondary to a hypovolaemic condition, rather than due
to a primary cardiac functional abnormality. However,
without the demonstration that blood volume treatment
provides a resolution of the cardiac abnormalities, such a
conclusion cannot be made with certainty.

The decrement in cardiac volume level in CFS
subjects was of a relatively moderate magnitude
and CI levels remained within nominal ranges for
these patients. Nevertheless, a functional deficit in
the observed magnitude may have physiological
relevance under conditions of physical and mental
challenge. There are numerous studies indicating that,
during head-up tilting, CFS patients relative to their
non-CFS counterparts have haemodynamic dysfunction,
often reflected by excessive tachycardia and susceptibility
to hypotensive collapse, as well as pre-syncopal and
syncopal events [26]. However, it should be noted
that in the present study the decrement in cardiac
volume level did not manifest differences in aerobic
capacity in CFS subjects relative to non-CFS sedentary
controls. A previous study reported that, compared
with healthy controls, a small cohort of CFS patients
had heightened vasomotor sensitivity to sympathetic
stimulation, requiring an approx. 10-fold less
noradrenaline infusion to induce a 50% peripheral
venoconstriction increase [9]. Hence, in subjects with
CFS, altered adrenoceptor, post-receptor vascular or
other mechanisms may be acting to compensate for
prevailing cardiac functional limitations.

Although no group differences in cardiac mass were
observed, the CFS and sedentary control groups had
a smaller LV chamber size than the non-sedentary
control group; this finding appears to support the
previous suggestion of small heart syndrome in CFS [15].
That the present finding arose in the sedentary groups
suggests a common aetiology. The established linkage
between deconditioning and cardiac atrophy, including
myocardial wall thinning, supports this possibility
[36,37]. However, this interpretation may not be valid
because poorer aerobic capacity was not significantly
associated with a smaller LV chamber size in these
study participants. In contrast, the cardiac wall thickness
findings did indicate CFS status differences; cardiac wall
thicknesses were greater in the CFS compared with the
control groups. Although resting BP was not elevated
in the CFS subjects, there was a trend towards greater
SVR in the severe CFS subjects, which may have played a
role in stimulating the observed cardiac wall thickening.
Alternatively, given that CFS onset is often linked with
recent infection and CFS patients tend to have an elevated
prevalence of bacterial and/or viral infections [38,39],
one possible source of the wall thickness differences
may be infection.HHV-6 (human herpesvirus-6), PVB19
(human parvovirus B19) and combined PVB19/HHV-6
are frequently found in cardiac biopsies from patients
with viral myocarditis [40,41]. In addition, some evidence
suggests that these viruses may trigger and perpetuate
fatigue syndromes in non-CFS and CFS patients [39,42].
However, we are not aware of any reported cases of viral
myocarditis in CFS patients.

The present findings of RBCV deficit in CFS are
comparable with a previous study of severely affected
CFS patients [22]. However, the present results extend
this deficit to non-severely affected CFS subjects. In
addition, the CFS subjects in the present study had a
deficit in PBV as well. Notably, approx. two-thirds of the
severe CFS group had a below-normal TBV, a prevalence
that was 2-fold greater than the non-severe CFS subjects
(see Table 4). In addition, the magnitude of TBV deficit
was quite substantial, extending up to 6 S.D. below
normal in some subjects. Although a number of fluid
volume regulation factors could induce an independent
PV decrement, it is common for a primary reduction
in RBCV to result in a corresponding PV decline [43].
An RBCV deficiency suggests the presence of an
associated anaemic condition; however, CDC (Centers
for Disease Control and Prevention) diagnostic criteria
dictate that the presence of anaemia is exclusionary for a
CFS diagnosis [12]. The CFS cohort in the present study
did not have blood chemistry abnormalities that would
warrant such a diagnosis. Thus the elevated prevalence
of low RBCV suggests that the CFS subjects may
have an anaemia type that goes undetected by standard
haematological evaluations. Normochromic normocytic
anaemia is one such condition that is defined by a
low RBCV, despite the presence of normal levels of
haematocrit, haemoglobin and serum ferritin, and red
blood cell count, size and shape [44]. This anaemia
type is common in chronic systemic disorders, such as
heart disease, renal failure, endocrine insufficiency,
hepatic disease, gastrointestinal malabsorption, rheumatological
conditions, chronic infections and cancer,
disorders that are exclusionary for a CFS diagnosis [20].
Thus CFS may be another chronic condition that results
in hypoproliferative anaemia. Current research suggests
that normochromic normocytic anaemia may arise from
a chronic inflammatory process that interferes with renal
erythropoietin production or signalling and by inhibiting
bone marrow red blood cell production [46]. Although a
chronic inflammatory condition accompanying CFS has
been hypothesized [47,48], such findings are inconsistent
and not yet confirmed [49].

The primary limitation of the present study was its
cross-sectional nature, wherein a determination of causal
relationships is not possible. However, no previous studies
of men and women with CFS have evaluated, using
state-of-the-art methods, cardiac structure and function
in the context of blood volume,while controlling for CFS
illness severity and sedentary lifestyle. Notably, subjects
were rigorously classified according to current international
CFS criteria, and were carefully evaluated and
excluded for confounding variables such as medication
use, and co-morbid systemic and psychiatric conditions.
Hence subjects were not deliberately recruited with
prevailing autonomic and cardiovascular symptoms.
Indeed, the prevalence of such symptoms in the CFS
cohort at study entry was comparable with that reported
by other CFS studies [2,7,50,51]. Despite stringent
matching procedures, which successfully controlled for
numerous factors, the CFS cohort was older and more
educated than the control subjects, necessitating statistical
correction. The classification of illness severity was a
study strength and, as expected, yielded a group of
severely affected subjectsmanifesting a greater prevalence
of CFS-related symptoms than their non-severe CFS
counterparts. In addition, another strengthwas the design
control for sedentary lifestyle. It was presumed that
the CFS study participants were sedentary and that the
sedentary control group would provide an appropriate
comparison. However, self-reported physical activity
levels were not ascertained in the CFS subjects. A related
study limitation was that the duration of a sedentary
lifestyle was not known for the sedentary control
subjects. Thus it remains possible that those with CFS
may have been physically inactive for a longer duration
and consequently the observed CFS status differences
may be due to some related process. Despite these
shortcomings, the lack of a difference in aerobic capacity
between the CFS groups and the sedentary control group
suggests that they were well-matched on this factor.

In conclusion, the present findings suggest that the
observed decrement in CFS cardiac volume level may be
a consequence of a co-morbid hypovolaemic condition,
secondary to normochromic normocytic anaemia. Given
these findings, it may be prudent in the clinical setting
to perform a direct examination of blood volume status
in CFS patients and consider treatment for those with
abnormal levels. A blood volume deficit may impact
adversely on oxygen delivery and nutrient supply,
impair haemodynamic regulation, and contribute to the
exacerbation of fatigue and other CFS symptomatology
[52,53]. Future research should consider the pathoaetiological
basis of hypovolaemia in CFS, and the
extent to which this condition may impact physiological
function and other aspects of clinical significance.


Senior Member
Hi, all.

For what it's worth, in my hypothesis ( see ) the low blood volume in CFS is due to what is usually diagnosed as a "mild" case of diabetes insipidus (not the same as diabetes mellitus). This is caused by low secretion of antidiuretic hormone by the hypothalamus/pituitary, which I have suggested is due to glutathione depletion in these organs. The longterm solution to this, as well as the many other aspects of CFS, is to lift the partial methylation cycle block, which will allow glutathione to come back up to normal.

There is a test panel for this called the methylation pathways panel, which I have posted about several times, and there is a non-prescription treatment to correct the root issue, which has helped most of the people who have tried it, though only a small number have experienced complete recovery from CFS with this treatment alone. In most cases of CFS, there appear to be other issues in addition to this core issue that must be specifically dealt with. These include heavy metal toxicity, gut problems, and in some cases mold illness or Lyme disease and coinfections.

Best regards,



Senior Member
Sydney Australia
Paul Cheney documented all this and explained why it is happening in his 2006 and 2009 lectures.

It is the bodys defense against the illness. Cheney shows ~80% of us have a PFO, a opening
between the heart chambers. What is more he explains why. The body is cutting off the oxygen
supply to limit the damage of the illness. It explains all the POTS and a long list of symptoms.

The question should be why are 9 people taking money to research something all ready explained
and only getting 40% of the solution.


Senior Member
Paul Cheney documented all this and explained why it is happening in his 2006 and 2009 lectures.

It is the bodys defense against the illness. Cheney shows ~80% of us have a PFO, a opening
between the heart chambers. What is more he explains why. The body is cutting off the oxygen
supply to limit the damage of the illness. It explains all the POTS and a long list of symptoms.

The question should be why are 9 people taking money to research something all ready explained
and only getting 40% of the solution.
Lots of people say things in lectures - they tend to not be taken seriously until they get published in peer-reviewed journals. Paul Cheney could have helped the cause more in my opinion if he had published more.

The money used for this study was from government grants.
This study was supported by the National Heart, Lung
and Blood Institute of the National Institutes of Health
[research grant number HL65668; training grant number
HL07426], and from the National Institute of Mental
Health of theNational Institutes ofHealth [training grant
number MH18917].