Townsend Letter 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
of short-term memory or difficulties concentrating
neck or armpit lymph nodes
pain or weakness
painful joints with no swelling or redness
or depressed vision
intolerance to light
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, 1997).
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 the illness.
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 Treatment
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:
steroidal anti-inflammatory drugs (NSAIDs) such as naproxen
(Aleve, Anaprox, Naprosen), ibuprofen (Advil, Bayer Select,
Motrin, Nuprin), and piroxicam (Fdldene)
inhibitors such as celecoxib (Celebrex), and refecoxib (Vioxx)
• A centrally
acting synthetic analgesic named tramadol hydrochloride (Ultram)
For Sleeping Problems:
antidepressants such as doxepin (Adapin, Sinequan), amitriptyline
(Elavil, Etrafon, Limbitrol, Triavil), desipramine (Norpramin),
and nortriptyline (Pamelor)
like diphenhydramine (Benadryl)
hypnotic drug zolpidem (Ambien)
reuptake inhibitors, such as fluoxetine (Prozac), sertraline
(Zoloft), and paroxetine (Paxil)
such as venlafaxine (Effexor), trazodone (Desyrel), bupropion
(Wellbutrin) and nefazodone (Serzone)
agents such as alprazolam (Xanax), lorazepam (Ativan),
and clonazeparn (Klonopin)
such as DHEA and low-dose hydrocortisone
For Central Activation:
wake-promoting agent modofanif (Provigil)
For dysautonomias including neurogenic hypotension, postural
orthostatic tachycardic syndrome, and vasovagal syncope:
Beta-blockers such as atenolol (Tenormin) and propranolol
peripheral alpha agonist miclodrine (ProAmantine)
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
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 psychological stresses.
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 gear.
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
Myalgia is 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.
Additionally, as demonstrated
in vitro, mesenchymal extract has the capacity to increase
mitochondrial metabolism, the primary aerobic source of energy
for cells (Fig. 1).
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 case reports.
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