for Doctors and Patients, April 2003
A Natural Approach to Chronic Fatigue Syndrome
by Ramon Scruggs, MD
New Hope Health Center, California
Introduction to CFS
Despite an always increasing medical
and technical knowledge, chronic fatigue syndrome
(CFS) remains an elusive pathology. Unfortunately,
there is no simple test for CFS and diagnosis still
relies on clinical evaluation and exclusion of other
possible diseases with overlapping symptoms. In 1994,
in an effort to harmonize clinical evaluation and
research, the Center for Disease Control has defined
Chronic Fatigue Syndrome (CFS) by "the presence of
unexplained persistent fatigue that is not relieved
by rest and that results in a substantial reduction
in occupational, social and personal activities."
Moreover, as criteria for CFS diagnosis, at
least four of the following symptoms must have been
present for a minimum of six consecutive months with
a history of previous wellbeing:
Impairment of short-term memory or difficulties concentrating
Tender neck or armpit lymph nodes
Muscle pain or weakness
Migratory painful joints with no swelling or redness
Lost or depressed vision
Visual intolerance to light
Post-exertional malaise lasting more than 24 hours
In the USA, it is estimated that
200-700 per 100,000 people (0.2% to 0.7%) suffer from
CFS. The syndrome potentially affects people of all
ages (including children) but the onset is most common
in the early thirties (Dowsett, 1990; Shepherd, 1999).
CFS afflicts women twice as much as men (Ho-Yen,
1991). Social background seems to be irrelevant although
upper-class, well educated Caucasians are more likely
to consult for CFS.
No single cause can explain CSF.
It is generally accepted that CFS develops
through exposure to convergent factors such as:
There is a high incidence of abnormalities
in the HPA axis of people suffering from CFS.
The HPA axis is a major component of the body's response
to stress and refers to the hypothalamus, pituitary,
and adrenal glands. The hypothalamus is located
in the brain where it physically interacts and stimulates
the pituitary gland through the release of the corticotrophin-releasing
hormone (CRH). The pituitary gland itself is
considered as the key master of the endocrine system.
Hormones that are produced by the pituitary
control other glands activities at distant sites throughout
the body. As an example, liberation of the adrenocorticotropic
hormone (ACTH) in the blood stream by the pituitary
commands the adrenal to secrete cortisol.
Cortisol is a glucocortical hormone also referred
as the "stress hormone," Its role is to mobilize the
glucose reserves so that the body can respond quickly
to a challenging situation. Both CAH and cortisol
influence the immune system and cortisol additionally
can suppress inflammation.
CFS has been associated with smaller
adrenal glands (Scott, 1999) and mild signs of adrenal
failure as well as reduced levels of related hormones
are seen in almost halt of the people suffering from
CFS (Demitrack, 1998). The CRH and cortisol
levels are generally low, although still in the normal
range, in these patients. The negative feedback
loop of the HPA axis is prolonged, contributing to
maintaining the cortisol level in its lower range
(Gaab, 2002). Moreover, the CRH response to exercise
is reduced (Ottenweller, 2001) and the response to
cortisol inducers is impaired (Scott, 1998).
Lower levels of CRH and cortisol, per se, are known
to result in extreme fatigue, decreased plasma volume,
myalgias, arthralgias, fever, allergic responses,
as welt as mood and sleep disturbances, all common
complaints in CFS.
Several immunological anomalies
have been inconsistently reported in CFS. For
instance, decreased number and activity of natural
killer cells are sometimes seen In CFS (Levine, 1998),
In other cases, the RNAse antiviral pathway is impaired
- opening the door to infections (DeMeirleir, 2000).
Other patients have higher titers of infection-fighting
CD8+ T cells combined with a low count of suppressor
T cells, leading to an exhausting immune overactivity,
(Landay, 1991). But the most striking immunological
trait in CFS remains a shift from cell-mediated (Thl)
to humoral immunity (Th2). The shift to humoral
immunity is marked by an increased productiori of
Th2 type cytokines. More IL-5 is produced that
stimulates antibodies formation. The levels
of IL-6 and IL-8 are raised as well, and these cytokines
are presumed to be involved in myopathic pain and
hyperalgesia respectively, as seen in CFS (Wolfe,
A viral origin has long been suspected
for CSF. Indeed some features of CSF are reminiscent
of those of viral infection. For instance, a
sudden onset of illness and a high level of antibodies
to many virus are commonly seen in patients with CSF
(Manian, 1994). Arguing against an infectious
origin are the facts that most cases of CSF appear
sporadically (US Dept. of Health, 1995), CSF does
not spread through contacts of any kind and no single
pathological agent could be pointed out (Farrar, 1995).
Recent studies are suggestive of
oxidative stress involvement in CFS (Logan, 2001;
Richards, 2000; Fulle, 2000). Oxidative stress
results from the accumulation of free radical species
inside the cell, Free radicals are molecules with
an impaired electron. This makes them very unstable
molecules that react quickly with neighboring molecules
from which they try to steal the missing electron.
Once started, the process may generate a cascade
of oxidation reactions ending in serious damage to
the cell. Free radicals arise spontaneously
during normal metabolic activities so the cell has
evolved antioxidant defenses to handle them.
But the cell defense system may become overwhelmed
by excessive oxidative assaults generated by environmental
factors or in the course of illness. Mitochondrial
dysfunction can further exacerbate this oxidative
stress phenomenon by releasing additional oxidants.
Signs of oxidative stress involvement
in CFS include a high level of oxidative damage to
DNA and lipids, as seen in biopsy samples of patients
with CFS (Fulle, 2000). Reduced oxidative metabolism
(McCully, 1996) and mitochondrial abnormalities in
CFS (Behan, 1991) also support a mitochondrial defect
as a contributor. Moreover, since mitochondria
supply energy to the cell through oxidative phosphorylation,
the lower level of ATP that results from a low mitochondrial
activity may explain the low exercise capacity reported
in patients with CFS (Lane, 1998).
Fatigue is a frequent complaint
in psychological disorders. Conversely, a long
lasting fatigue can generate emotional problems and
be a source of anxiety. In CFS, psychological
distress and depression are commonly seen (Katon,
1993). Whether this is a cause or a consequence
of chronic fatigue can be debated. In any case,
psychological wellbeing should be addressed in the
management of CFS since it may exacerbate and/or perpetuate
Some of the biological and physiological
parameters known to be involved in CFS etiology, such
as hormonal and immunological functions as well as
aerobic capacity, are heritable and a growing number
of studies point toward a genetic influence on chronic
fatigue. For example, in one study, specific
HLA antigens (HLA-D03 and HLA-DR5) were found in association
with CFS (Keller, 1994). Moreover natural
killer cell dysfunction was reported in siblings with
CFS (Levine, 1996). A high incidence of auto-antibodies
against specific phospholipids and gangliosides is
also found in families where CFS runs (Klein, 1995).
Globally these findings are interpreted as
signs of an inherited predisposition to CFS.
A recent twin study estimated the liability of CFS
to be around 19% (Buchwald, 2001). Nevertheless,
the often CFS associated psychological distress showed
no evidence of genetic covariation (Walsh, 2001).
Chronic Fatigue Syndrome
In treating CFS patients, an empathic
approach is crucial. CFS is a long and frustrating
illness with no specific cure. The treatment
is symptomatic and should be tailored to each individual
with increased patient quality of life as a target.
A combination of drugs is generally prescribed
along with promotion of mild but regular physical
activity as well as healthy dietary and sleeping habits,
Behavioral cognitive therapy may help patients to
cope with CFS limitations. Other potentially
useful non-pharmacological therapies include massage,
acupuncture, chiropractic, homeopathy, hypnosis, yoga
and relaxation techniques. Current options for
prescription medication are as follows:
For Muscle Pain:
Non steroidal anti-inflammatory drugs
(NSAIDs) such as naproxen (Aleve, Anaprox, Naprosen),
ibuprofen (Advil, Bayer Select, Motrin, Nuprin), and
Cox-2 inhibitors such as celecoxib (Celebrex), and
A centrally acting synthetic analgesic named tramadol
For Sleeping Problems:
Low-dose antidepressants such as doxepin
(Adapin, Sinequan), amitriptyline (Elavil, Etrafon,
Limbitrol, Triavil), desipramine (Norpramin), and
like diphenhydramine (Benadryl)
hypnotic drug zolpidem (Ambien)
Serotonin reuptake inhibitors, such
as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine
Antidepressants such as venlafaxine (Effexor), trazodone
(Desyrel), bupropion (Wellbutrin) and nefazodone (Serzone)
Anxiolytic agents such as alprazolam (Xanax), lorazepam
and clonazeparn (Klonopin)
Corticosteroids such as DHEA and low-dose hydrocortisone
For Central Activation:
The wake-promoting agent modofanif (Provigil)
Amphetamine-based stimulants (Dexedrine)
For dysautonomias including neurogenic hypotension,
postural orthostatic tachycardic syndrome, and vasovagal
Beta-blockers such as atenolol (Tenormin)
and propranolol (Inderal)
The peripheral alpha agonist miclodrine (ProAmantine)
The corticoid fludrocortisone (Florinef)
Other experimental drug avenues are being explored.
For example, a synthetic nucleic acid (Ampligen)
with anti-viral and immune modifying activities has
shown some positive results. The drug is currently
undergoing phase III clinical trial for CFS and results
are expected by September 2003.
Nutritional supplementation with
Vitamins (B12, C and A), coenzymes (0-10, NADH, adenosine
monophosphate and glutathione), minerals (iron, zinc,
germanium and selenium), essential fatty acids and
some amino acids (1-tryptophan, L carnitine) may be
of value as adjunctive therapies. On the
herbal side, numerous preparations are claiming to
have positive effects on
CFS symptoms. These include astralagus,
b ' orage seed oil, bromelain, cornfrey, echinacea,
garlic, Ginkgo biloba, ginseng, primrose oil, quercetin,
St. John's wort, and Shiitake mushroom extract.
With the exception of primrose oil, for which
there is a documented clinical trial with positive
results (Behan et al 1990), the rationale for the
use of these herbs with CFS is based on in vitro studies.
Another herb, Ruscus aculeatus, has some potential
in treating orthostatic hypotension that would deserve
further evaluation with CFS patients (Redman, 2000).
CF Support, a New Natural
Therapeutic Approach to Chronic Fatigue Syndrome
There is an additional option for
dietary supplementation in CFS patients. The product
is called CF support and is a blend of adrenal and
mesenchymal cell extracts derived from mammalian tissues.
Both extracts are obtained by breaking down cells
of the corresponding tissues to liberate active molecules.
These active biofactors are then selectively picked
up to obtain a liquid extract that provides a natural
rich source of cellular growth factors and other signaling
Adrenal Extract to Support
the Hypothalamus-Pitultary-Adronal Axis
Adrenal extract from the gland of
mammals has a long history of use as a booster for
adrenal functions. Originally administered in
an injectable form along with vitamins, it is currently
more conveniently available for oral administration.
Animal studies have shown that both forms had
comparable activities (Craveri, 1971).
Adrenal extract acts by supplying
small amounts of adrenal hormones and factors that
promote an improved adrenal function. The adrenals
are little triangular-shaped glands located on top
of each kidney. The inner part of the adrenal,
called the medulla, produces epinephrine (adrenaline)
that is directly involved in the "fight or flight"
response to a perceived danger. Epinephrine
raises pulse rate, blood flow and blood sugar. The
outer part of the adrenal, called the cortex, secretes
three major corticosteroids: 17-ketosteroids (DHEA),
mineralocorticoids (aldosterone) and glucocortocoids
(cortisol and corticosterone), These hormones have
diverse functions in the body. Androgen
precursors such as DHEA have anti-inflammatory and
growth-promoting functions and are believed to have
anti-aging properties in both men and women.
Aldosterone controls sodium excretion by the
kidney to maintain blood volume and blood pressure.
Cortisol is the most potent glucocorticoid
produced by the adrenal. It is structurally
derived from cholesterol and acts on specific receptors
throughout the body to influence glucose homeostasis,
fat and protein metabolism, immune function, vascular
tone and bone metabolism. It also has potent
antiinflammatory effects. As mentioned before,
cortisol secretion is controlled through the HPA axis
via ACTH secretion by the pituitary gland. Cortisol
secretion is subjected to circadian variations with
peaks in the early morning and at night. Cortisol
can also be triggered in situations of physical and
In Chronic Fatigue Syndrome, the
adrenal can still produce minimal level of these hormones
but the normal circadian rhythm of cortisol secretion
is disrupted and the adrenal reserve is low (MacHale,
1998). As a consequence, the depleted
adrenal cannot respond adequately to any stressful
situation whether physical or psychological.
Adrenal depletion results in reduced physical and
emotional resistance as well as general exhaustion
and weakness. Supplementing with adrenal extract
may stimulate such a sluggish gland by providing the
little hormonal kick needed to get back in the right
Mesenchymal Extract to Regenerate
Relieve Muscle Pain, and Boost Energy Level
Mesenchymal extract is prepared from
mammal extra-embryonic connective tissue and, like
other gland extracts, also has a long history of use.
Dr. Niehans (a reputed Swiss endocrinologist) used
it in the 30s to rejuvenate
aging calls (Niehans, 1960). Mesenchymal stem
cells are undifferentiated cells that, when triggered
under appropriate conditions, can become almost any
type of cells to help restore damaged or aging tissues
(Caplan, 1994). Mesenchymal extract is obtained by
breaking down mesenchymal stem cells to liberate active
a significant feature of Chronic Fatigue Syndrome.
The diffuse muscle pain seen in CFS is, in fact, quite
reminiscent of that observed in fibromyalgia, a rheumatoid
disease. Recent studies have linked insufficient
plasma levels of growth hormone to both conditions
(Berwaerts, 1998; Bennet, 2002) and administration
of growth hormone to patients with fibromyalgia was
able to reduce pain symptoms (Leal-Cerro, 1999).
Mesenchymal extract being a rich source of growth
factors, is expected to be helpful in reducing the
chronic pain experienced by many CFS sufferers.
as demonstrated in vitro, mesenchymal extract has
the capacity to increase mitochondrial metabolism,
the primary aerobic source of energy for cells (Fig.
sets of experiments revealed that mesenchymal
extract contains a biological activity capable
of inducing aerobic respiration (as measured
through WST- 1 mitochondrial activity) in fibroblast,
while negligibly affecting their proliferation
(as measured through Hoescht DNA count). Such
a biological activity supports the use of mesenchymal
extract as a nutritional supplement in physiological
conditions for which an increase in cellular
metabolic activity may bring benefits. This
is certainly the case with Chronic Fatigue Syndrome.
Muscle weakness is a common symptom
among CFS patients and is believed to be linked to
reduced oxidative metabolism (McCully, 1996) caused
by some mitochondrial defect (Behan, 1991).
As reduced mitochondrial oxidative phosphorylation
directly affects ATP synthesis, there is less energy
available for physical activity. As a metabolic
booster, mesenchymal cell extract may help restore
the body energy level to relieve the fatigue and the
muscle pain of CFS patients. As a result, mesenchymal
cell extract should increase their capacity to exercise,
an important step in the recovery process.
Chronic fatigue syndrome with its wide range of
symptoms and multiorgan involvement, is a challenge
for any health care practitioner faced with its
treatment and a source of frustration and anguish
for the patient who suffers from it.
The etiology of CFS remains largely undefined but
appears to develop through exposure to convergent
factors. There is no single treatment
for Chronic Fatigue Syndrome. A supportive
program of patient management should include empathic
listening, education about the disease, symptom-based
treatment, a mild exercise program and incentives
for better diet and sleeping habits when necessary.
Symptomatic treatment options can be found
in the conventional Western pharmacopoeia but also
in various alternative approaches including diet
supplementation. CF Support is a new diet
supplement that was specially formulated to alleviate
the symptoms of chronic fatigue syndrome.
CF Support is a unique blend of adrenal cell extract
to support the hypothalamus-pituitary-adrenal
axis, and mesenchymal
cell extract to regenerate functional tissues, relieve
muscle pain, and boost energy level. Its
efficacy in alleviating CFS symptoms is supported
by in vitro studies and a growing number of anecdotal
TOWNSEND LETTER for DOCTORS & PATIENTS - APRIL
CF Support is the newest addition to the NatCell
line products of Atrium Biotechnologies.
CF Solution is an extra strength Adrenal version
of CF Support developed by Atrium for
Lloyd Wright of Alternative Medicine Solutions.
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