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Chronic Fatigue
Chronic fatigue syndrome (CFS) is a complicated condition characterized by profound fatigue that persists for more than six
months. It is often accompanied by cognitive difficulties, muscle and joint pain, depression, poor sleep quality, or other
nonspecific symptoms (Cella 2011; Jones 2011; Ciccone 2010). Between one and eight million people in the United States
are believed to have CFS (Jason 2013; CDC 2012; Dinos 2009).
There is no clear cause of CFS, though numerous factors may contribute (Cairns 2005), including viral infections (Henderson
2014), nutritional deficiencies (Brown 2014), hormonal imbalance (Van Den Eede 2007; Aschbacher 2012), and
immunological disturbances (Brown 2014). Concurrent psychological abnormalities have been observed among individuals
with CFS, but the nature of the relationship remains unclear (Wessely 1996; Yoshiuchi 2007; Hickie 1990).
CFS can be a debilitating condition (Cairns 2005). Many people with CFS have difficulty working, attending school,
exercising, and carrying out daily activities (Ross 2004; Anderson 1997; Taylor 2010). Sadly, conventional physicians often
overlook this condition, and as many as 80% of individuals suffering with CFS may not receive an accurate diagnosis (Ward
1996; Griffith 2008; Nacul 2011). Worse yet, it has been estimated that achieving an accurate diagnosis of CFS may take as
long as five years from the onset of symptoms (Brown 2014).
CFS is a multifactorial condition and requires complex management, which must begin with a rigorous clinical evaluation to
rule out other possible causes of fatigue (Brown 2014; Teitelbaum 2001). Once the diagnosis has been established, an
effective treatment strategy must take into consideration the medical, nutritional, physical, psychological, and social needs of
each patient (Griffith 2008; Brown 2014). Unfortunately, the conventional medical establishment often fails to provide this
kind of comprehensive care for individuals with CFS.
However, emerging research has led to the development of a number of novel treatment strategies that may benefit those
with CFS. For instance, in one study, 15 individuals who met diagnostic criteria for CFS were treated with the antiviral drug
valacyclovir (Valtrex) and 93% of them exhibited a positive response, suggesting that viral infection, and possibly post-viral
alterations in the hosts immune system, may represent a piece of the CFS puzzle (Henderson 2014; Montoya 2013;
Stringer 2013).
In addition, evidence suggests that individuals suffering with CFS may attain some benefit through the use of natural,
integrative interventions including magnesium (Cox 1991), NADH (Santaella 2004; Forsyth 1999), L-carnitine (Plioplys
1997), D-ribose (Teitelbaum 2006), B vitamins (Maric 2014), omega-3 fatty acids (Behan 1990), melatonin (Van Heukelom
2006), and probiotics (Sullivan 2009).
In this protocol you will learn about the complex nature of CFS and several factors that may contribute to its onset. You will
also learn about the treatment approach typically taken by conventional physicians and how a more comprehensive,
integrative approach may be necessary if CFS relief is to be achieved. You will read about several novel and emerging
therapeutic strategies that may ease CFS symptoms, and a number of natural interventions that may benefit those affected
by CFS.

Causes and Risk Factors

No reliable single cause or group of causes has been conclusively demonstrated for CFS. However, several studies have
revealed various factors that correlate with CFS incidence.

Demographics
CFS affects all population groups, although it is more common in women. While early studies suggested that CFS mostly
affects young, Caucasian, professional women, more recent research reveals it is more common among people of early or
middle adulthood, and community studies have reported that it is somewhat more common in people of African, Hispanic,
or Native American descent compared to those of European or Asian ancestry (Afari 2003; Dinos 2009).
CFS often occurs concurrently with other conditions that cause similar symptoms. Studies have reported that US Centers
for Disease Control and Prevention (CDC) CFS criteria (see Diagnosis section) have been met by 88% of people with
multiple chemical sensitivity (Ziem 1999), 20-70% of people with fibromyalgia (Afari 2003), and 15.7% of veterans in the
US VA Gulf War Registry (Kipen 1999). Given the similarities between CFS and fibromyalgia, and their high degree of
concurrence, studies on fibromyalgia are often viewed as potentially relevant to CFS, and integrative practitioners frequently
apply similar approaches to the two conditions.

Viral Infections
Viral infection may cause prolonged fatigue during active infection, and some studies suggest that viruses such as human
herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) may play a role in the development of CFS (Morelli 2011; Bansal
2012; Klimas 2007; Montoya 2013). However, the exact mechanisms by which viral infection may trigger CFS are poorly
understood. Some scientists have suggested that post-viral alterations in the hosts immune system may underlie CFS, but
this theory is debated (Moss-Morris 2013; Hickie 2006). Chronic viral infections may alter white blood cell activity (such as
triggering abnormalities in T cell function and decreasing activity of natural killer cells) and damage mitochondrial function
(Klimas 2007; Bansal 2012).

Allergies and Food Sensitivities

Some evidence suggests that allergies may play a role in CFS (Bellanti 2005; Straus 1988); however, understanding the link
between the two is complicated by the fact that not all CFS patients have allergies (Jones 2011). Similar to viral infections, it
has been proposed that allergies may trigger immune abnormalities that lead to CFS (UMMC 2013). One study found that
drug allergies were more frequently reported by people with CFS than healthy controls (Ferr Ybarz 2005). Additionally,
certain measures of allergic reactions (ie, eosinophil activation) were increased in patients with CFS (Conti 1996).
Food sensitivities have also been considered as a potential cause or cofactor in CFS (Lind 2013; Trabal 2012; Berstad 2012).
In one study, it was reported that 54% of a sample of CFS patients tried dietary modifications; of those, 73% reported
reduced fatigue (Logan 2001). In an Australian study, 90% of CFS patients who eliminated wheat, milk, benzoates, nitrites,
nitrates, and food colorings reported that the severity of their symptoms improved (Logan 2001; Emms 2001).

Inflammation
Many individuals with CFS show signs of excessive inflammation and increased levels of the pro-inflammatory factors
interleukin-1, leptin, and tumor necrosis factor-alpha (TNF-) (Bansal 2012; Maes 2012; Stringer 2013). A 2014 brain
imaging study found that individuals with CFS had significantly more neuroinflammation in many areas of the brain
compared to healthy controls (Nakatomi 2014). Evidence from an animal model suggests that induction of an activated,
pro-inflammatory state in the resident immune cells of the central nervous system, microglial cells, may be involved in the
heightened pain sensitivity observed in CFS (Yasui 2014). Animal models also demonstrated that fatigue arises when a
stimulus induces activation of microglial cells and/or there is an increase in inflammatory chemicals within the brain
(Harrington 2012).

Mitochondrial Dysfunction
Mitochondria are organelles within cells that are responsible for most of the cells supply of energy in the form of a chemical
called adenosine triphosphate (ATP), which is used throughout the body (Myhill 2009). Research suggests dysfunction of
mitochondria and mitochondrial enzymes may be associated with chronic fatigue and fibromyalgia. The proinflammatory
cellular milieu seen in many individuals with CFS can impair mitochondrial functions and may reduce production of ATP in
cells. An electron microscopy study of muscle biopsies from 50 CFS subjects reported that 80% had mitochondrial
degeneration (Behan 1991).

Orthostatic Hypotension
Orthostatic hypotension is a syndrome comprised of low blood pressure, weakness, or faintness after moving from a lying
or sitting position to a standing position (Lanier 2011). One study reported that 96% of subjects with CFS experienced
orthostatic hypotension. Many of these subjects were on low-salt diets. Following treatment with a balanced diet and
adequate amounts of liquid and salt, chronic fatigue was completely resolved in 39% of subjects. Some of these patients were
also treated with the corticosteroid fludrocortisone (Florinef) to help increase blood pressure (Bou-Holaigah 1995). Studies
in Australia and the UK, respectively, reported that 11% and 13% of those who met the CDC or Canadian CFS diagnostic
criteria also met criteria for postural orthostatic hypotension (Reynolds 2014; Lewis 2013). Some researchers have suggested
that measuring blood pressure at various postures may be a useful diagnostic tool for CFS (Frith 2012).

Diagnosis
There is no specific diagnostic test for CFS, and it may be difficult to distinguish CFS from fatigue secondary to other health
conditions. A diagnosis of CFS requires that other potential causes of fatigue be ruled out. Examples of such causes include:
obstructive sleep apnea (Norman 2008; Lieberman 2009)
depression (Skapinakis 2004)
hypothyroidism (Yancey 2012)
toxin exposures (Ziem 1999; Curtis 2004)
autoimmune diseases such as lupus or multiple sclerosis (Yancey 2012)
cancer (Yancey 2012)
traumatic brain injury (Mott 2012)
heart failure (King 2012)
anemia (Guralnik 2005; Jones 2011)
irritable bowel syndrome (Frissora 2005)
diabetes (Yancey 2012)
chronic or sub-acute infection (Jones 2011)
ongoing adverse reactions to medications (Jones 2011)
There are several diagnostic guidelines for CFS. A commonly used definition for CFS was developed at the US Centers for
Disease Control and Prevention (CDC). These criteria include subjects who have experienced chronic, unexplained fatigue for
at least six months, which is of new onset (ie, not a lifelong problem), is not the result of ongoing exertion, is not
substantially relieved by rest, and hinders occupational, social, or personal activities. In addition, at least four of the
following symptoms must be present 50% of the time for at least six months (Fukuda 1994; Jones 2011; Ferri 2014):
1) Unrefreshing sleep

5) Aching or stiff muscles

2) Impaired memory or concentration

6) Multi-joint pain

3) Sore throat

7) Headache of new type, pattern, or

severity

4) Tender lymph nodes in neck or armpit

areas

8) Post-exercise malaise or illness feeling

which lasts more than 24 hours

Although there is no single diagnostic test for CFS, the following tests are used to help rule out other common causes of
fatigue (Yancey 2012; Ferri 2014; Sawchuck 2013; Jones 2011):
basic blood chemistries and complete blood count (to check for anemia and other conditions)
thyroid hormone levels (to check for hypothyroidism)
blood sugar levels (to check for diabetes)
urinalysis (to check for kidney disease)
serum vitamin B12; serum and urinary methylmalonic acid (to check for vitamin B12 deficiency and insufficiency)
CFS is considered by some researchers to be the result of a chronic infection; however, testing for EBV, HHV-6, and Borrelia
burgdorferi, which causes Lyme disease, are not routinely recommended. These tests can be considered on a case-by-case
basis, depending on the patient's clinical presentation and history (Eymard 1993; Jones 2011). Other infections may be
mistaken for CFS, so tests for tuberculosis; hepatitis A, B, and C; and HIV/AIDS should also be considered. Testing blood
levels of 25-hydroxyvitamin D may be helpful as well, since vitamin D deficiency symptoms (ie, weakness, muscle pain)
may sometimes overlap with CFS symptoms (Kennel 2010; Jones 2011). Psychological conditions, such as depression and
substance abuse, should be ruled out as well (Jones 2011; Eymard 1993).
Sleep studies have been suggested for all CFS patients with symptoms suggestive of sleep disorders, as chronic sleep
problems such as sleep apnea or insomnia can cause fatigue and be mistaken for CFS (Buchwald 1994; Neu 2014; Mariman
2013). A comprehensive discussion of several sleep disorders and methods of treating them is available in the Insomnia
protocol.
Some researchers have suggested that sex hormone imbalances may contribute to CFS, especially in women, although the
evidence is inconsistent (Harlow 1998; Boneva 2011). A full evaluation of hormonal status may be useful in understanding
individual cases of CFS, with blood tests measuring levels of hormones such as DHEA-S, pregnenolone, estrogen, and
testosterone. If levels are low, bioidentical hormone replacement may be a useful treatment or adjunct therapy. For more
specific information on bioidentical hormone replacement and hormone testing, see the Female Hormone Restoration and
Male Hormone Restoration protocols.

Conventional Treatment
Cognitive Behavioral Therapy and Graded Exercise
Cognitive behavioral therapy and graded exercise therapy are generally agreed to have the highest level of evidence for
success in treating CFS (Jones 2011; Moss-Morris 2013). Cognitive behavioral therapy involves systematically adjusting
behavior and may encompass improved exercise, dietary, and sleep habits; relaxation; and getting support from others (Cox
2004). Graded exercise therapy involves initiating a low-intensity exercise program and slowly increasing the intensity over
time (CDC 2013). Adaptive pacing therapy, which also may be useful in treating CFS, involves carefully controlling the
amount of activity and exercise in accordance with tolerance (Cox 2004).
Although exercise can be quite helpful for individuals with CFS, exercise regimens must begin at a low level (such as walking
a few blocks or bicycling a few miles) and gradually build up to longer and more intense exercise. Many people with CFS
may experience worsened fatigue if they initially try to exercise or work at intensive levels without gradually building up
stamina over time (Nijs 2008). One study randomly assigned 29 CFS subjects to a program of graded aerobic exercise and 30

CFS subjects to flexibility and relaxation exercises. The exercise group started with 5-15 minutes of slow walking with
gradual increases in speed and duration; they light swimming or bicycling. The other group performed flexibility and
relaxation exercises for 10 minutes a day, gradually increasing to 30 minutes. After 12 weeks of treatment, improvement
occurred in both groups, though twice as many subjects in the exercise group (55%) rated themselves as very much or
much better compared to the flexibility group (27%) (Fulcher 1997).

Stimulant Drugs
Stimulant drugs such as methylphenidate (Ritalin, Concerta) or amphetamine/dextroamphetamine (Adderall) have been used
to treat CFS. In a randomized controlled trial on 60 CFS subjects, treatment with 10 mg methylphenidate twice daily
resulted in significantly less fatigue and better concentration compared to placebo (Blockmans 2006). A study of 10 CFS
subjects reported that fatigue was significantly reduced in 90% of subjects treated with 5 or 10 mg of Adderall twice daily
for four weeks compared to 40% who improved in the placebo group (Olson 2003). Another study treated CFS subjects
who had deficits in cognitive function with either lisdexamfetamine dimesylate (Vyvanse, 30-70 mg daily), an amphetamine
stimulant that has been used to treat ADHD in children and adults (Hutson 2014), or placebo. After six weeks of treatment,
the Vyvanse-treated subjects had significantly better emotional control and working memory as well as significantly less
fatigue and generalized pain compared to subjects who received placebo (Young 2013). A study to evaluate the effects of
daily low dose (5-10 mg) methylphenidate coupled with either a multifaceted nutritional supplement (containing vitamins,
amino acids, and mitochondrial nutrients such as magnesium, coenzyme Q10 [CoQ10], and L-carnitine) or placebo is
underway as of the time of this writing (Montoya 2014).
Stimulant drugs have a number of common adverse side effects including insomnia, loss of appetite, potential heart problems,
as well as the potential for addiction and misuse (Chavez 2009; Reddy 2013). There is some evidence that such medications
may alter normal brain function, including neurotransmission, and only limited information is available on the long-term
effects of stimulant medication (Hyman 1996; Wang 2013; Vitiello 2001; Berman 2009).

Antidepressants
About 33-50% of CFS patients also experience depression (Morelli 2011). Selective serotonin reuptake inhibitor (SSRI)
anti-depressant medications (such as fluoxetine [Prozac], sertraline [Zoloft], paroxetine [Paxil], and citalopram [Celexa]) are
frequently prescribed to people with CFS. Some published studies have reported that antidepressant medications are of
some help, although the topic has been the subject of little rigorous research. A double-blind study on 96 adults with CFS
reported that six months of treatment with 20 mg fluoxetine was associated with significantly less depression but not
significantly less fatigue compared with placebo (Wearden 1998). A small study of 16 CFS subjects reported that 10-20 mg
of citalopram daily was associated with significantly less fatigue and depression after 12 weeks (Amsterdam 2008).

Novel and Emerging Therapies

Rintatolimod
Rintatolimod (Ampligen) is a drug with antiviral and immunomodulating properties. In a double-blind study, 234 subjects
with severe CFS were treated with either 400 mg rintatolimod or placebo twice weekly. After 40 weeks of treatment, the
rintatolimod-treated subjects had significantly higher exercise tolerance compared to subjects given placebo (Strayer 2012).
An earlier study with 92 CFS subjects reported that after 24 weeks of rintatolimod treatment, subjects showed improved
cognitive and physical performance, better functioning, and decreased symptoms compared to placebo (Strayer 1994).
However, the US Food and Drug Administration (FDA) has stated that the data provided by these two trials was
insufficient to allow approval of rintatolimod to go to market. More studies on the safety and efficacy of rintatolimod are
needed (FDA 2013).

Valacyclovir
Valacyclovir (Valtrex) is an oral antiviral drug used to treat herpes virus infections. In one study, 27 CFS patients were
treated with valacyclovir four times daily or placebo. After six months, the treatment group was judged to be more active,
based on an estimate of energy expended in one day, compared to the placebo group (Lerner 2007). In another study, 15
children aged 8-18 years with treatment-resistant depression who met the CDC definition for CFS were treated with
valacyclovir. After an average of over two years of treatment with 500-1000 mg twice daily, subjects experienced significant
improvements in fatigue and vigor and markedly increased natural killer cell counts in their blood. Fourteen of fifteen study
participants experienced a positive response after eight months of treatment. The author concluded The studys data
support an intriguing hypothesis that a portion of treatment-resistant depression may in fact be undiagnosed CFS or other
chronic viral infection (Henderson 2014).

Valganciclovir
Valganciclovir (Valcyte), another oral antiviral medication, was the subject of an uncontrolled study in 61 CFS patients.
Roughly half the subjects reported substantial improvement in physical and mental functioning, and their response was
independent of initial viral infection severity tests (titers). Longer treatment yielded better results in this population (Watt
2012). A randomized controlled trial of valganciclovir treatment for six months was conducted in 30 CFS patients with
elevated immunoglobulin G antibody titers against HHV-6 and EBV. Treatment produced significant improvements in mental
fatigue, fatigue severity, and cognitive function. The improvement was noted within three months and was still present after
an additional nine months (Montoya 2013).

Biofeedback
Brain-centered therapies such as biofeedback may be helpful for individuals with fibromyalgia and CFS (James 1996; Babu
2007; Boyer 2014). Biofeedback is a system in which several physiological parameters (such as brain waves and heart rate)
are monitored with electrodes and computers while the patient receives visual and auditory feedback. The goal of
biofeedback is to help the patient consciously control, at least to some degree, autonomous physiological functions. A case
report of a CFS patient treated with an electroencephalography (EEG)-based biofeedback regimen indicated significant
improvements in cognitive ability, functional skill level, and quality of life (James 1996). As mentioned earlier, 20-70% of
people with fibromyalgia meet US CDC criteria for CFS, which makes the following study of interest regarding biofeedback
therapy for CFS: six days of biofeedback training in a group of 15 fibromyalgia subjects was associated with significant
reductions in tender points compared with 15 fibromyalgia subjects given a placebo treatment that imitated biofeedback but
without therapeutic value (Babu 2007).

Repetitive Transcranial Magnetic Stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that involves passing an electromagnetic
field through parts of the brain to modulate neural circuitry. rTMS has been successfully used for several conditions,
including treatment-resistant depression, schizophrenia, and recovery in stroke patients (Hovington 2013; Hsu 2012). rTMS
may also be helpful for those with fibromyalgia and CFS. One study compared rTMS treatment in 20 fibromyalgia patients
to sham rTMS treatment (placebo). After 14 rTMS treatments, fatigue, pain, and stiffness were significantly reduced, and
sleep significantly improved in the treatment but not the placebo group (Mhalla 2011). Although more studies are needed to
evaluate the efficacy of rTMS in CFS, some researchers suggest this modality may be useful in conditions involving
unexplained pain, such as CFS, as it may alter central pain processing (Nijs 2011).

Hormone Replacement Therapy

Deficiencies of testosterone and estrogen are common in aging adults, and low levels of these hormones are associated with
fatigue (Stanworth 2008; Thornton 2013; Moller 2013; Schwartz 2011). In addition, dehydroepiandrosterone (DHEA) levels
have been found to be significantly lower in individuals with CFS compared to healthy controls (Scott 1999; Kuratsune
1998).
DHEA, a hormone produced mostly by the adrenal glands, declines with age to as little as 10-20% of the amount of a
30-year old by the 8th decade of life (Racchi 2003; Himmel 1999; Maggio 2013). DHEA is a precursor to several other
hormones including testosterone and estrogens (Himmel 1999). DHEA has important antiviral, pro-immunity, and insulinregulating effects (Torres 2012; Chang 2005; Mauriege 2003; Weiss 2011; Sawalha 2008; Himmel 1999). A study of 23
women who had CFS and levels of DHEA-S below 2 mcg/mL reported that six months of supplementation with 25 mg of
oral DHEA daily was associated with significant improvements in fatigue, pain, memory, and concentration (Himmel 1999).
A study that interviewed individuals with unexplained chronic fatigue reported that 11 of 17 subjects who self-treated with
DHEA supplementation experienced positive results (Bentler 2005).
There is some evidence that CFS may be accompanied or partially caused by a dysfunction in the hypothalamic-pituitaryadrenal (HPA) axis (Papadopoulos 2012). HPA axis hormone regulation abnormalities often seen in CFS include modest but
clinically meaningful reductions in cortisol levels; changes in 24-hour cortisol patterns; and inadequate cortisol response to
stimuli that should provoke cortisol release, known as enhanced negative feedback (Nijhof 2014; Papadopoulos 2012).
More information about the benefits of hormone replacement can be found in the Male Hormone Restoration and Female
Hormone Restoration protocols, and a comprehensive discussion of strategies to manage stress and help balance the HPA
axis is available in the Stress Management protocol.

Immune/Stem Cell Mobilization Therapy

There is an FDA-approved drug called granulocyte colony stimulating factor given to certain cancer patients that helps
protect their immune system against the toxic effects of chemotherapy (NCI 2013).
Granulocyte colony stimulating factor induces the bone marrow to produce and release huge numbers of stem cells and
immune cells into the circulation (Xu 2000; Ozguner 2014; Maharaj 1995).
A pioneering doctor wondered what would happen if granulocyte colony stimulating factorwere given to patients who
suffered from diseases other than cancer. His hypothesis was that the mobilization of stem cells from ones own bone
marrow might have a systemic regenerative effect.
A before and after SPECT scan of the brain of a chronic fatigue syndrome patient showed remarkable restoration of cerebral
blood flow and metabolic activity, along with marked clinical and symptomatic improvement.
Below is a case history report of this chronic fatigue syndrome patient successfully treated with granulocyte colony
stimulating factor:
The patient, identified as patient LS, began experiencing total body pain in 2010 and later received a diagnosis of
fibromyalgia. In early 2013, she was diagnosed with heavy metal toxicity, gut dysbiosis, severe micronutrient deficiencies,
food sensitivities, hormone imbalance, immune dysfunction, H. pylori infection, and chronic fatigue syndrome.
After undergoing extensive treatment (eg, opioid pain medication, IV nutrient therapy, hormone replacement therapy, etc.),
patient LS continued to experience chronic pain in her head, neck, arms, and legs.
On 7/29/2013, patient LS began undergoing six weeks of treatment with a stem cell mobilization protocol in conjunction
with an anti-inflammatory diet, stress management techniques, and nutritional supplementation.
Just two weeks after completing her treatment, patient LS noted relief of her total body and neck/back pain. She was able to

significantly decrease her pain medication dosage and reported improved cognition.
A single-photon emission computed tomography (SPECT) scan of patient LSs brain on 7/18/2013, before treatment,
revealed reduced blood flow to parts of the brain or an ongoing neuroinflammatory process. The follow up SPECT scan on
9/12/2013, after treatment, revealed a significant improvement in blood flow to parts of the brain (BMSCTI 2014).
This doctor has now treated about 100 patients with various disorders including Parkinsons, diabetes, and chronic fatigue
syndrome. Clinical improvements in these diseased patients have ranged from good to astounding. Not only was their
primary disorder responding to granulocyte colony stimulating factor, but they are reporting alleviation or elimination of
other age-associated debilities like chronic pain, cognitive impairment and frailty (BMSCTI 2014).
These were not mere placebo effects, as clinical measurements of blood pressure, inflammation, gait, body composition, and
cerebral perfusion markedly improved. Blood levels of glucose and lipids fell while HDL levels rose.
These are all indications of systemic age-reversal occurring in response to the mobilization and release of stem cells and
healthy immune cells from the bone marrow of these patients.
A downside to this treatment is that drug expenses are quite high and not covered by most health insurance programs. To
inquire about this program, contact the South Florida Bone Marrow/Stem Cell Transplant Institute at 561-752-5522.
Their website is www.bmscti.org

Dietary and Lifestyle Considerations

Avoid Smoking and Chemical Exposures
People with CFS should avoid, as much as possible, exposure to tobacco smoke, toxic chemicals, and pollutants. Smoke
contains many toxicants, including carbon monoxide and nicotine, which can cause fatigue, damage the nervous system, and
increase risk of chronic pain (Balzan 1996; Shi 2010; Kirkpatrick 1987; Zvolensky 2009; Jay 2000). Exposure to cigarette
smoke, even secondhand, is pro-inflammatory and suppresses or disorders immune response (Lugade 2014; Lee, Taneja
2012; Orosz 2007). In a large study of 984 fibromyalgia subjects of which 145 (14.7%) were tobacco users, the
tobacco-using subgroup had significantly greater pain, joint stiffness, anxiety, depression, and fatigue compared to nonusers
(Weingarten 2009).
Exposure to toxic compounds (including mercury, lead, petrochemical solvents, pesticides, and molds) has been linked to
CFS-like symptoms (Brown 2014; Curtis 2004; Nacul 2009). Many people with chemical sensitivity also have severe
chronic fatigue (Ziem 1999; Katerndahl 2012). Several studies have reported that a variety of generalized and multiple organ
system symptoms have resolved in chemically sensitive subjects who reduce or eliminate toxicant exposure (Hillert 2013;
Brown 2007; Yun 2013; Katerndahl 2012).
Heavy indoor exposure to molds has been linked to asthma, sinus problems, chronic fatigue, and significantly reduced levels
of hormones essential for energy production such as growth hormone and thyroid hormones (Curtis 2004; Dennis 2009). In a
study on 79 subjects with chronic fatigue, chronic sinusitis, and a history of mold exposure, 51% were deficient in growth
hormone and 81% were deficient in the thyroid hormones T4 and/or T3. The subjects were then placed on a multifaceted
treatment program including: cleanup of subjects indoor environment to greatly reduce mold and moisture conditions that
foster mold growth; saline nasal sprays; oral and nasal antibacterial and antifungal drugs; hormone replacement treatment
with growth hormone, thyroid hormone, and other hormones as needed; and a broad range of nutritional supplements
including vitamins, minerals, herbs, CoQ10 and L-carnitine. Following this treatment, sinusitis resolved in 93% of
participants who achieved a normal indoor mold count; and fatigue improved in all 37 participants who received growth
hormone and cortisol and/or thyroid hormone replacement based on a diagnosed deficiency in these hormones (Dennis 2009).

If possible, those with CFS should also live and work in well-ventilated buildings. Indoor levels of pollutants such as
solvents, pesticides, and dust are generally higher in buildings that do not receive enough outdoor air ventilation, or in which
the external air intake is improperly filtered or positioned. In a large study of 4106 office workers, symptoms of fatigue or
difficulty concentrating were 38% less common in well-ventilated buildings (ie, ventilated with 100% outdoor air) compared
to less well-ventilated buildings (Mendell 2008). Using an air purifier may also be advisable (Yun 2013).

Detoxification Regimens
Nutritional detoxification regimens may also be helpful for CFS. In a group of 111 patients with metal hypersensitivity and
symptoms resembling CFS, removing mercury-containing dental amalgams was associated with major long-term health
improvements in 76% of subjects (Stejskal 1999). A case series reported that treatment with oral vitamin C (ascorbate) and
choline was associated with significant reduction in both fatigue and blood levels of organochlorine pesticides in four CFS
subjects (Richardson 2000; Erkekoglu 2010; Mehedint 2013; Corbin 2012). Another case series of women with CFS
reported that 35 days of once-daily thermal therapy (15 minutes of far-infrared dry sauna followed by 30 minutes resting in
a very warm room) was associated with improvements in sleep, energy level, and concentration, as well as a reduction in
depression (Masuda 2005). Sauna use may support detoxification, has sleep enhancing effects, and relieves muscular spasms
related to muscle contraction and pain (Cecchini 2007; Crinnion 2007; Masuda 2005).
A review of detoxification strategies is available in the Metabolic Detoxification protocol.

Massage and Qigong

Alternative therapies such as massage and Qigong are often used by CFS patients. Qigong is a specialized form of gentle
exercise that harmonizes breathing, posture, body movements, and mind in order to prevent and heal disease and improve
quality of life (Dorcas 2003; Sun 2008; Alraek 2011). A small study of 20 CFS subjects reported that undergoing massage
therapy twice weekly for five weeks was associated with significant reductions in pain and fatigue compared to placebo
(which involved sham transcutaneous electrical nerve stimulation). Another study of 31 CFS cases reported that practicing
Qigong and meditation for two hours weekly for 12 weeks was associated with significantly less fatigue and significantly
greater work capacity compared with cases given no treatment (Alraek 2011).

Candida Treatment
Candida albicans (a yeast) is a common resident of the healthy human intestinal tract. However, overgrowth of Candida may
cause health problems, including CFS-like symptoms, and may be involved in CFS in some individuals (Evengrd 2007). One
author reported on the treatment of 1100 CFS subjects with the oral anti-fungal drug ketoconazole (Nizoral) and a special
diet that eliminated refined sugar, fruit juice, and alcohol. A favorable response was noted in 84% of CFS subjects after 3-12
months of treatment. Before treatment, 685 of these subjects were on disability, and after treatment, only 12 subjects were
on disability (Cater 1995).
More information on fungal infections and Candida is available in the Fungal Infections (Candida) protocol.

Integrative Interventions
Magnesium
Magnesium is an essential mineral involved in hundreds of enzymatic reactions in humans, and its deficiency may be linked
to chronic fatigue (Wicks 1999; Rude 2009). Magnesium deficiency is a common and often underestimated problem
(Rosanoff 2012). For example, a nationwide US survey reported that adult women consumed an average of 71% of the US
Recommended Daily Allowance (RDA) of 320 mg (Rude 2009).

Some, but not all, studies have reported that supplemental magnesium is helpful for people with CFS or fibromyalgia. One
study reported that 20 adults with CFS had significantly lower red blood cell magnesium levels compared to 20 healthy
controls. In a follow-up placebo-controlled clinical trial, 15 CFS patients were randomly chosen to receive a weekly 1 g
intramuscular injection of magnesium sulfate for six weeks. Members of the treatment group had significantly improved
energy levels and less pain, were less emotionally reactive, and perceived significant overall improvement compared to the
subjects receiving placebo. Eighty percent of magnesium-treated subjects reported benefit from the treatment versus 18% of
controls (Cox 1991). Although not a CFS study, an uncontrolled trial of up to 600 mg magnesium and 2400 mg malic acid
daily in 24 fibromyalgia subjects reported significant declines in pain and tenderness (Russell 1995).
The traditional test for magnesium levels (ie, serum magnesium) can be misleading. Serum magnesium levels are considered
unreliable, as they only show fairly severe deficiency, which has created confusion in some studies that test serum
magnesium and conclude that magnesium status is adequate (Ismail 2010). While the perfect test for magnesium status has
not yet been developed, red blood cell magnesium is the preferred method for assessing stores of this important mineral
(Witkowski 2011).

B-Vitamins
B-complex vitamins such as B1 (thiamine), B2 (riboflavin), and B6 (pyridoxine) play a critical role in many energyproducing reactions in the body, while other B vitamins, such as folate and B12 (methylcobalamin), are important for the
creation of new cells, repair of damaged ones, and normal function of the central nervous system (Woolf 2006; Reynolds
2006). One study found significantly lower vitamin B1, B2, and B6-related enzyme activities in 12 CFS patients compared
with 18 age- and gender-matched controls (Heap 1999). Another study reported that serum folate was abnormally low in 30
of 60 CFS patients (Jacobson 1993). Yet another trial compared placebo to treatment with a daily low potency
multivitamin/mineral supplement containing B vitamins in 38 women aged 18-50 years who had CFS. Along with other
nutrients, the supplement contained B vitamins in the following amounts: 4.2 mg B1, 4.8 mg B2, 6 mg B6, 54 mg niacin, 600
mcg folate and 3 mcg B12. After two months, the women receiving the supplement had significantly less fatigue, better
sleep, and fewer and less intense headaches compared to women receiving placebo (Maric 2014). A multi-nutrient
intravenous nutrition formula (ie, Myers cocktail) that includes B-vitamins, magnesium, and other nutrients has been
reported to help CFS patients (Gaby 2002).

Zinc
Zinc is a mineral involved in immunity, wound healing, protection against oxidative damage, and other essential functions
(Tate 1999; Rostan 2002). A study that compared 21 CFS patients to healthy controls found significantly lower blood zinc
levels in patients; moreover, lower zinc was positively correlated with markers of inflammation and immune activation
(Maes 2006). A study in 10 healthy but sedentary young men reported that daily zinc supplementation at a dosage of 3
mg/kg bodyweight prevented an exercise-related decrease in thyroid hormone and testosterone. The author concluded that
this result indicates supplemental zinc may improve performance (Kilic 2007). Another author, reviewing integrative
treatments for CFS, wrote that despite a lack of clinical trials of supplemental zinc for CFS, it is a worthwhile candidate for
further investigation (Brown 2014).

Vitamin C
While a number of studies have reported that supplemental vitamin C can improve immunity, reduce inflammation and
oxidation damage, and improve blood vessel health, research examining vitamin C supplementation in CFS is sparse (Qian
2001; Bryer 2006; Werbach 2000). A study of 25 disabled CFS patients reported that intravenous treatment with 15 g of
vitamin C corrected, within a matter of minutes, red blood cell abnormalities in 100% of CFS patients compared to only 10%
of controls (Werbach 2000).

Vitamin D
One study of 221 people with CFS demonstrated average vitamin D blood levels of only 18 ng/mL significantly lower than
healthy controls (Berkovitz 2009) and far below optimal levels of 5080 ng/mL. It has also been found that, among people
with CFS, low vitamin D levels correlate with markers of increased cardiovascular risk, inflammation, and oxidative stress.
The authors underscored the complex relationship between vitamin D levels and CFS symptoms; they also highlighted the
need to perform additional studies with different methodological approaches to better understand this correlation (Witham
2014). Vitamin D supplementation may benefit those affected by CFS; a small case series reported that fatigue was reduced
in four adults with CFS who were treated with 5000-10000 IU of vitamin D plus minerals and trace elements daily (Hock
2000). Other researchers have proposed that vitamin D may be a useful treatment for CFS by modulating inflammatory
pathways thought to be involved in the condition, namely the NF-B pathway. Vitamin Ds active metabolite,
1,25-dihydroxyvitamin D, represses activation of the NF-B pathway, which drives inflammation and whose chronic
activation has been implicated in CFS symptomatology (Hoeck 2011).

Omega-3 Fatty Acids

Omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are abundant in marine
oils such as fish and krill oil, effectively modulate inflammatory pathways in the body (Flock 2013). They are also
important for supporting the integrity of cell membranes and can favorably impact blood lipid levels (Riediger 2009; Ginter
2010).
In a study on 63 adults with postviral fatigue syndrome, subjects were treated daily with either a 4 g mixture of evening
primrose oil and fish oil or 4 g of sunflower oil (placebo). The total daily dose in the evening primrose/fish oil group was 288
mg of the omega-6 fatty acid gamma-linolenic acid (GLA) from evening primrose oil, 136 mg EPA, 88 mg DHA, and 80 mg
vitamin E. At three months, 85% of the evening primrose/fish oil group reported significant improvement compared to only
17% of the placebo group (Behan 1990). An uncontrolled study in four CFS patients found that 12 weeks of daily
supplementation with 1116 mg EPA, 348 mg DHA, and 120 mg GLA resulted in symptomatic improvement in all subjects
(Puri 2004).

CFS May Respond Best to a Multifaceted Treatment Approach

CFS appears to have many interrelated causes and triggers that affect multiple organs and systems in the body, making
multifaceted treatment more likely to produce noticeable and sustainable improvement (Teitelbaum 2001). Several published
studies have investigated the effects of multiple nutrient and herbal extract combinations or nutrient/drug combinations.
In a pilot study, 34 adults (average age 50 years) suffering from severe fatigue took a comprehensive, multi-nutrient
supplement two or three times daily. Each supplement pack contained a broad range of ingredients including vitamins,
minerals, herbal and plant extracts, amino acids, and essential fatty acids. After eight weeks of treatment, fatigue levels fell
by 33% (Ellithorpe 2003).
An earlier study of a multiple nutrient and drug intervention protocol in 72 adults with fibromyalgia randomly assigned 38
subjects to receive treatment ; 96% of subjects also met CDC criteria for CFS. The reported average duration of CFS
symptoms, before entering the study, was 8.3 years. Chronic fatigue and fibromyalgia symptom outcomes were analyzed
using subject interviews and indexes of tender points and disability (Teitelbaum 2001).
The multi-faceted treatment program included:
1. Nutritional supplements. The treatment group received a daily multivitamin and mineral supplement; a magnesium
and malic acid supplement; valerian; and 3-10 mg of melatonin at bedtime to improve sleep. Twenty-four subjects
received additional iron and 30 received additional vitamin B12.

2. Thyroid hormone replacement. Patients were treated with thyroid medication (18 with levothyroxine [Synthroid]
and 15 with natural porcine thyroid [Armour]) if needed.
3. Adrenal hormone replacement. Adrenal function was tested and subjects received treatment with oral
hydrocortisone (Cortef) if needed (29 people).
4. Fibromyalgia and depression treatment. To improve sleep, 29 subjects received anti-depressant drugs including
sertraline, paroxetine, nefazodone (Serzone), and fluoxetine. In addition, the muscle relaxant cyclobenzaprine (Flexeril)
was prescribed to 10 subjects with neuromuscular symptoms.
5. Treatment of candida overgrowth. Thirty-five subjects were treated with nystatin and 27 with itraconazole
(Sporanox).
6. Steroid hormone replacement. Patients were tested for hormone levels and supplemented if indicated. Hormone
replacement included DHEA (24 people), oxytocin (Pitocin) (15 people), testosterone (eg, Depo-Testosterone) (12
people), progesterone (eg, Prometrium) (9 patients), estradiol (Estrace) (7 people), and a mix of estrone, estradiol, and
estriol (Tri-estrogen) (6 people).
At the end of the trial, the treatment group had significantly fewer symptoms of fibromyalgia and chronic fatigue and
significantly fewer tender lymph nodes than the placebo group; side effects were comparable between the two groups.
Ninety-one percent of treated subjects assessed their conditions as better or much better versus only 36% of placebo
subjects (Teitelbaum 2001). Further studies are needed to help identify effective multifaceted treatment regimens for CFS,
fibromyalgia, and similar conditions.

Amino Acids
Amino acid deficiencies may be linked to CFS. An analysis of 25 CFS subjects demonstrated that levels of the following
amino acids were below reference values: tryptophan (80%), phenylalanine (72%), taurine (64%), isoleucine (60%), leucine
(52%), arginine (24%), and methionine (20%). In an uncontrolled trial, a 15 g free form amino acid mixture was prescribed
based on individual test results. Of the 20 who completed the three-month treatment phase, 15 reported a 50-100%
improvement in symptoms, three reported a 25-50% improvement, and two reported no improvement (Bralley 1994).

Cocoa Bean Polyphenols and Flavonoids

Dark chocolate is made from cocoa beans, which contain a wide range of phytochemicals (such as polyphenols and other
flavonoids) that have a variety of health benefits, including possibly reducing the risk of cardiovascular disease and cancer.
Dark chocolate may have a role in the treatment of CFS. A study treated 10 adults with CFS using 15 g of polyphenol-rich
dark chocolate three times daily. After eight weeks of treatment, fatigue, depression, and anxiety scores all declined
significantly. Then, following a two-week period of no treatment, participants were given another preparation of 15 g of
low-polyphenol, simulated chocolate three times daily. During this time, their condition deteriorated significantly. The
simulated chocolate had other differences besides the lower polyphenol content; it contained whole milk powder (active
treatment contained none) and almost twice the percentage of sugar and more than twice the percentage of carbohydrate as
the active treatment. Chocolate has been shown to increase neurotransmitters (eg, serotonin), and an imbalance of
neurotransmitters has been reported in CFS subjects. The researchers hypothesized that by modulating neurotransmitters,
polyphenol-rich chocolate reduced symptoms of CFS (Sathyapalan 2010).

Melatonin
Melatonin is a natural hormone produced by the pineal gland in the brain (Arendt 1998; Wu 2005). It regulates the
sleep-wake cycle and is an efficient antioxidant (Cipolla-Neto 2014; Romero 2014). An analysis of 14 published studies
revealed that melatonin taken shortly before bedtime significantly reduced sleep latency (time to fall asleep) in persons with
delayed sleep phase syndrome, or difficulty falling asleep (Buscemi 2005). One promising study gives reason to suspect that
melatonin may be helpful for some people with CFS. In an uncontrolled trial in 29 adults with CFS who had chronic fatigue

for at least 12 months, subjects were administered 5 mg melatonin daily. After three months of treatment, subject scores on a
standardized assessment of fatigue, concentration, and activity all significantly improved. Excessive fatigue was eliminated
entirely in eight of the subjects during treatment (Van Heukelom 2006). Individuals with Parkinsons disease often develop
chronic and unremitting fatigue that meets the diagnostic criteria for CFS. In a study on 30 Parkinsons patients with CFS
symptoms, treatment with melatonin led to a significant reduction in fatigue and anxiety scores on standardized assessments
as well as improvements in quality of life; sleep quality also improved following melatonin treatment (Datieva 2013).

Probiotics
A number of studies have found that probiotic bacteria such as Lactobacillus and Bifidobacterium may decrease symptoms
of CFS. A controlled trial in 29 healthy adults aged 60-81 years reported that daily consumption of 100 g of a fermented
milk drink containing live Lactobacillus helveticus for three weeks significantly improved sleep compared to a placebo
beverage that contained no probiotics (Yamamura 2009). A study of 15 subjects who met the CDC criteria for CFS reported
that treatment with 20 billion colony forming units (CFUs) of Lactobacillus paracasei, Lactobacillus acidophilus,and
Bifidobacterium lactis bacteria twice daily for 30 days reduced CFS-related symptoms in 40% of subjects (Sullivan 2009). In
a placebo-controlled pilot study of probiotics for CFS, 39 adults were given a probiotic mixture containing eight billion live
Lactobacillus casei bacteria three times daily. Treatment significantly reduced anxiety compared to placebo (Rao 2009).

Ribose
Ribose plays a key role in synthesizing many important compounds such as RNA and DNA (the cells genetic material), as
well as many compounds involved in energy production (such as CoA, ATP, NADH, and FADH). A pilot study analyzed
36 subjects with CFS and/or fibromyalgia who took 5 g of D-ribose three times daily. After an average of 25 days of
treatment, subjects reported experiencing significantly less fatigue and improved overall well-being, better sleep, increased
mental clarity, and a decreased pain threshold (Teitelbaum 2006).

Adaptogenic Herbs for Chronic Fatigue

Several medicinal plants, known as adaptogens, have shown a non-specific ability to enhance the bodys overall resistance to
mental and physical stress. Although the precise mechanisms are unclear, there is evidence that they may influence the HPA
axis and several biochemical pathways involved in the bodys stress response (Panossian 2009).
Adaptogenic herbs are of particular interest in CFS due to their reputation for boosting energy as well as their possible
effects on the HPA axis and on supporting healthy immune system function. Some adaptogens considered promising for CFS
include:
Ginseng Panax ginseng, a perennial herb native to Asia, is one of the most studied of all botanical medicines
(Kiefer 2003; Kim, Son 2013; Jo 2011). It is reputed to have adaptogenic and fatigue-relieving qualities (Lee, Yoo
2012; Wang 2010). In a 2013 randomized controlled trial comparing a 1g or 2g daily dose of ginseng extract to placebo
in a group of individuals with unexplained chronic fatigue, the 2g dose resulted in significantly less fatigue, better
mental function, and less oxidative stress (Kim, Cho 2013).
Rhodiola Rhodiola rosea is a small biennial herb that grows in cool climates around the world. It is one of the most
promising adaptogenic herbs and in the past decade has rapidly grown in reputation. Rhodiola has been studied for its
effect in non-CFS physical and mental fatigue, though with unclear results (Ishaque 2012). It has been suggested that
rhodiolaextract may help improve cognitive function and attention in those with CFS (Panossian 2009; Lee 2009).
Ashwagandha Withania somnifera has a long history of use in traditional Indian medicine (Ayurveda) as a
rejuvenator and has come to be considered a useful and powerful adaptogen (Singh 2011). It has been studied for
conditions affecting the central nervous system, including stress, drug addiction, and neurodegenerative diseases such
as Parkinsons and Alzheimers (Kulkarni 2008).

Additional information on adaptogens can be found in the Stress Management protocol.

Nutrients to Support Mitochondrial Function

The mitochondria are the energy powerhouses of cells; they generate chemical energy in the form of ATP, which is used to
fuel cellular reactions throughout the body. Thus, supporting mitochondrial function may be beneficial in conditions
involving diminished energy or fatigue, such as CFS (Maassen 2002; McBride 2006; Nicolson 2013).
NADH. NADH is a coenzyme and cellular metabolite related to niacin (vitamin B3) (Jones 1996); it is involved in many
energy-producing reactions within the body. In an open-label trial, 20 individuals with CFS were randomized to treatment as
follows: 12 subjects received 5 mg of oral NADH daily, escalating to 10 mg if not symptomatic improvements were noted,
and eight subjects received other nutritional supplements plus psychotherapy. After three months, the NADH group had a
significantly greater reduction in mean CFS symptom score (Santaella 2004). Another study of 26 subjects who met CDC
criteria for CFS reported that 31% responded favorably to four weeks of daily supplementation with 10 mg NADH
compared to only 8% of subjects given placebo (Forsyth 1999).
Coenzyme Q10 (CoQ10). CoQ10, a nutrient with potent antioxidant properties, is a crucial component in the production
of ATP within mitochondria (Maes 2009). CoQ10 is found in meat and synthesized in small quantities in the body, though
in healthy individuals it is abundant in the mitochondria (Molyneux 2008). A study of 58 people with CFS reported that up
to 45% had blood CoQ10 levels below normal (ie, below 0.49 g/mL), while none of the 22 healthy controls had blood
CoQ10 levels below this level. CFS subjects with very low CoQ10 levels (ie, below 0.39 g/mL) had significantly more
problems with fatigue, concentration, and memory compared to CFS subjects with higher levels (Maes 2009). A randomized,
controlled trial in fibromyalgia subjects reported significantly lower levels of fatigue, pain, and tender points in 10 subjects
who received 100 mg CoQ10 three times daily for 40 days compared to 10 placebo-treated fibromyalgia subjects (Cordero,
Alcocer-Gmez, de Miguel 2013). Other researchers have reported that CoQ10 supplementation reduced production of
pro-inflammatory interleukins IL-1 and IL-18 in subjects with fibromyalgia (Cordero, Alcocer-Gmez, Culic 2013).
L-carnitine. L-carnitine is an amino acid derivative that plays two important roles in energy production. First, L-carnitine
and its derivatives acetyl-L-carnitine and propionyl-L-carnitine transport fatty acids into the mitochondria where they are
oxidized for energy. Second, L-carnitine also upregulates several enzymes involved in energy production (Scioli 2014; Kudoh
2014; Huertas 1992; Mingorance 2011; Mazzio 2003; Kuratsune 1994). Some evidence suggests that L-carnitine may be
useful for people with CFS or other conditions characterized by fatigue. Two studies reported significantly lower blood
carnitine and acylcarnitine in CFS patients compared to controls (Kuratsune 1994; Plioplys 1995). In the second study,
higher blood carnitine levels corresponded to better clinical status. A 2-month study of 30 CFS subjects compared the drug
amantadine (Symmetrel), an FDA-approved antiviral medication, with 1 g of L-carnitine three times daily; authors concluded
that L-carnitine was better tolerated and produced significantly greater clinical improvement (Plioplys 1997). Another group
of researchers treated CFS patients with either 2 g acetyl-L-carnitine, 2 g propionyl-L-carnitine, or 2 g of each (4 g total)
daily; there were 30 subjects in each of the three groups. After 24 weeks of treatment, considerable improvements (as
measured by the clinical global impression score) were experienced by 59%, 63%, and 37% of subjects in the acetylL-carnitine, propionyl-L-carnitine, and combined groups, respectively. In a preliminary open-label study, authors also
reported greater improvement in a lower dose group (2 g) than a higher dose group (4 g) indicating increased efficacy for CFS
with a 2 g dose. Acetyl-L-carnitine demonstrated a significant effect on mental fatigue and concentration whereas propionylL-carnitine showed most improvement in general and physical fatigue (Vermeulen 2004).
Carnitine may also be useful for other conditions that cause prolonged fatigue. A randomized controlled trial compared
acetyl-L-carnitine to the drug amantadine for the treatment of chronic fatigue in individuals with multiple sclerosis. Patients
who received 1 g acetyl-L-carnitine twice daily for 90 days experienceda significantly greater reduction in fatigue severity
than those treated with 100 mg daily of amantadine (Tomassini 2004).

Roburin-rich French Oak Wood Extract

Roburins are constituents of oak wood; they belong to the class of phytochemicals known as ellagitannins (Natella 2014).
Roburins have been consumed by humans for centuries in wine and spirits aged in oak barrels. Ellagitannins are a type of
polyphenol, which are capable of modulating inflammatory responses within the body (Natella 2014; Piwowarski 2013). A
roburin-rich French oak wood extract has been demonstrated to relieve a wide range of CFS symptoms (Belcaro 2014). It is
believed to have this impact at least partially as a result of its ability to improve the functioning of ribosomes, a type of
cellular machinery responsible for translating genetic information into usable proteins and peptides (Bhavsar 2010; Natella
2014). Thus, ribosomes are indispensable to every body function and organ system, and their dysregulation is implicated in
the symptoms of CFS and chronic viral syndromes.
In an open-label trial that evaluated 85 patients with verified CFS, 45 received oak wood extract and 40 served as controls.
After a thorough medical evaluation to exclude other causes of fatigue, subjects were followed up for at least six months.
Researchers tracked the physical symptoms and mood of the CFS patients as well as measures of oxidative stress. At three
and six months, the roburin-rich French oak wood extract group showed a significant decrease in oxidative stress as measured
in whole blood, whereas there was no significant change in the control group (Belcaro 2014).
The oak wood-supplemented group experienced marked trends toward reductions in nearly every parameter of CFS
symptom scores measured, especially after six months, whereas the control group experienced minimal improvement, or in
some cases, worsening of symptoms at three and six months. Oak wood extract was shown to modestly improve sleep;
memory or concentration; muscle and joint pain; headaches; and tender lymph nodes. Of the nine secondary symptoms
evaluated, the control group experienced little change in symptoms, and in some cases, worsening of symptoms at three and
six months, whereas the roburin extract-supplemented group had marked improvement in sensitivity to noise, food,
medication, and chemicals; dizziness or lightheadedness; depression; mood swings; weight change; allergy symptoms; and
visual symptoms (Belcaro 2014).

Life Extension Suggestions

Magnesium: 500 1500 mg daily
Coenzyme Q10 (CoQ10) (as ubiquinol): 100 200 mg daily
DHEA (Dehydroepiandrosterone): 15 75 mg daily (depending on blood test results)
L-Carnitine (as Acetyl L-Carnitine, Acetyl L-Carnitine Arginate and Propionyl L-Carnitine): 2100 mg daily
Vitamin B1 (thiamine): 100 mg daily
Vitamin B2 (riboflavin): 50 100 mg daily
Vitamin B3 (niacin): 500 1000 mg daily
Vitamin B6 (pyridoxine): 250 mg daily
Folate (as L-Methylfolate): 1000 mcg daily
Vitamin B12 (as methylcobalamin): 1 8 mg daily, sometimes up to 40 mg daily
Vitamin D: 5000 8000 IU daily; depending upon blood levels of 25-OH-vitamin D
NADH: 5 mg daily
Vitamin C: 500-1000 mg daily
Zinc: 50 mg daily
Probiotics (including Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus paracasei): 15 billion colony
forming units (CFUs) daily
Melatonin: 0.3 5 mg 30 to 60 minutes before bedtime
Ribose: 5100 mg daily
Fish Oil (with olive polyphenols and sesame lignans): 1400 mg EPA and 1000 mg DHA daily
Gamma-linolenic acid (GLA): 299 1495 mg daily
Panax ginseng: 250 1000 mg daily

Rhodiola rosea: 250 mg daily

Ashwagandha extract (std. to 8% withanolide glycoside conjugates [10 mg] and 32% oligosaccharides [40 mg]): 250
mg daily
Dark Chocolate: 45 g of a polyphenol-rich dark chocolate daily
5-HTP (5-Hydroxytryptophan): 50 200 mg daily
French oak wood extract: 200 mg daily
In addition, the following blood tests may provide helpful information:
Chronic Fatigue Profile
Chemistry Panel & Complete Blood Count (CBC)
Thyroid Panel (including TSH, T4, and T3)
Urinalysis
Vitamin D, 25-Hydroxy
Cytomegalovirus (CMV) Antibodies
Hepatitis Panel (A, B, C), Acute
Estrogens, Total
Pregnenolone
Dehydroepiandrosterone Sulfate (DHEA-S)
Testosterone (Free with Total)
Serum Vitamin B12, Serum and Urine Methylmalonic Acid

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other
qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change
intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or
other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any
protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified.
Product labels may contain important safety information and the most recent product information provided by the product
manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National,
state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the
risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to
persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the
information contained herein.
The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can
guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and
expressly disclaim responsibility for any error in literature.

References
Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry 2003;160: 221-236.
Alraek T, Lee MS, Choi TY, Liu J. Complementary and alternative medicine for patients with chronic fatigue syndrome: A
systematic review. BMC Complementary Altern Med 2011;11:87.
Amsterdam JD, Shults J, Rutherford N. Open-label study of s-citalopram therapy in chronic fatigue syndrome and
co-morbid major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 2008;32:100-106.

Anderson JS, Ferrans CE. The quality of life in person with chronic fatigue syndrome. J Nervous Mental Dis
1997;185:359-367.
Arendt J. Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology. Reviews of
reproduction. Jan 1998;3(1):13-22.
Aschbacher K, Adam EK, Crofford LJ, Kemeny ME, Demitrack MA, Ben-Zvi A. Linking disease symptoms and subtypes
with personalized systems-based phenotypes: a proof of concept study. Brain, behavior, and immunity. Oct
2012;26(7):1047-1056.
Babu AS, Mathew E, Danda D, Prakash H. Management of patients with fibromyalgia using biofeedback: A randomized
control trial. Indian J Med Sci 2007;67:455-461.
Balzan MV, Agius G, Galea Debono A. Carbon monoxide poisoning: easy to treat but difficult to recognise. Postgraduate
medical journal. Aug 1996;72(850):470-473.
Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral
infection. Brain Behavior Immun 2012;26:24-31.
Belcaro G, Cornelli U, Luzzi R, Cesarone M, Dugall M, Feragalli B, . . . Ippolito E. Improved management of primary
chronic fatigue syndrome with the supplement French oak wood extract (Robuvit): a pilot, registry evaluation.
Panminerva medica. 2014;56(1):63-72.
Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta
Neurol Scand 1990;82:209-216.
Behan WMH, More AR, Behan PO. Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol
1991;83:61-65.
Bellanti JA, Sabra A, Castro HJ, Chavez JR, Malka-Rais J, de Inocencio JM. Are attention deficit hyperactivity disorder
and chronic fatigue syndrome allergy related? what is fibromyalgia? Allergy and asthma proceedings : the official journal of
regional and state allergy societies. Jan-Feb 2005;26(1):19-28.
Bentler SE, Hartz AJ, Kuhn EM. Prospective observational study of treatments for unexplained chronic fatigue. J Clin
Psychiatry 2005;66:625-632.
Berkovitz S, Ambler G, Jenkins M, Thurgood S. Serum 25-hydroxy vitamin D levels in chronic fatigue syndrome: a
retrospective study. Int J Vitam Nutr Res 2009;79:250-254.
Berman SM, Kuczenski R, McCracken JT, London ED. Potential adverse effects of amphetamine treatment on brain and
behavior: a review. Molecular psychiatry. Feb 2009;14(2):123-142.
Berstad A, Undseth R, Lind R, Valeur J. Functional bowel symptoms, fibromyalgia and fatigue: a food-induced triad?
Scandinavian journal of gastroenterology. Sep 2012;47(8-9):914-919.
Bhavsar RB, Makley LN, Tsonis PA. The other lives of ribosomal proteins. Human genomics. Jun 2010;4(5):327-344.
Blockmans D, Persoons P, Van Houdenhove B, Bobbaers H. Does methylphenidate reduce the symptoms of chronic fatigue
syndrome? Am J Med 2006;119:167.e23-167.e30.
BMSCTI. South Florida Bone Marrow/StemCell Transplant Institute. Available at: http://www.bmscti.org/index.htm
(homepage). Accessed: 8/18/2014.

Boneva RS, Maloney EM, Lin JM, Jones JF, Wieser F, Nater UM, . . . Reeves WC. Gynecological history in chronic fatigue
syndrome: a population-based case-control study. Journal of women's health (2002). Jan 2011;20(1):21-28.
Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic
fatigue syndrome. JAMA 1995;274:961-967
Boyer L, Dousset A, Roussel P, Dossetto N, Cammilleri S, Piano V, . . . Guedj E. rTMS in fibromyalgia: a randomized trial
evaluating QoL and its brain metabolic substrate. Neurology. Apr 8 2014;82(14):1231-1238.
Bralley JA, Lord RS. Treatment of chronic fatigue syndrome with specific amino acid supplementation. J Appl Nutr
1994;46:74-78.
Brown BI. Chronic fatigue syndrome: A personalized integrative medicine approach. Alternative Therapies 2014;20:29-40.
Brown MM, Jason LA. Functioning in individuals with chronic fatigue syndrome: increased impairment with co-occurring
multiple chemical sensitivity and fibromyalgia. Dynamic medicine: DM. 2007;6:6.
Bryer SC, Goldfarb AH. Effect of high dose vitamin C supplementation on muscle soreness, damage, function, and oxidative
stress to eccentric exercise. International journal of sport nutrition and exercise metabolism. Jun 2006;16(3):270-280.
Buchwald D, Pascualy R, Bombardier C, Kith P. Sleep disorders in patients with chronic fatigue syndrome. Clinical
Infectious Dis 1994;18(supp 1)S78-S72.
Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, et al. The efficacy and safety of exogenous
melatonin for primary sleep disorders. J Gen Intern Med 2005;20:1151-1158.
Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occupational medicine
(Oxford, England). Jan 2005;55(1):20-31.
Cater RE. Chronic intestinal candidiasis as a possible etiological risk factor in the chronic fatigue syndrome. Medical
Hypotheses 1995;44:507-515.
CDC. Centers for Disease Control and Prevention. Chronic Fatigue Syndrome (CFS): Who's at Risk? Available at:
http://www.cdc.gov/cfs/causes/risk-groups.html. Accessed 07/16/2014. 2012.
CDC. Centers for Disease Control and Prevention. Chronic Fatigue Syndrome (CFS). Managing Activities and Exercise.
Available at: http://www.cdc.gov/cfs/management/managing-activities.html. 2/14/2013. Accessed 5/8/2014.
Cecchini M, LoPresti V. Drug residues store in the body following cessation of use: impacts on neuroendocrine balance and
behavior--use of the Hubbard sauna regimen to remove toxins and restore health. Medical hypotheses. 2007;68(4):868-879.
Cella M, Sharpe M, Chalder T. Measuring disability in patients with chronic fatigue syndrome: reliability and validity of the
Work and Social Adjustment Scale. Journal of psychosomatic research. 2011;71(3):124-128.
Chang CC, Ou YC, Raung SL, Chen CJ. Antiviral effect of dehydroepiandrosterone on Japanese encephalitis virus infection.
The Journal of general virology. Sep 2005;86(Pt 9):2513-2523.
Chavez B, Sopko MA, Ehret MJ, Paulino RE, Goldberg KR, Angstadt K, Bogart GT. An update on central nervous system
stimulant formulations in children and adolescents with attention-deficit/hyperactivity disorder. Ann Pharmacother
2009;43:1084-1095.
Ciccone DS, Chandler HD, Natelson BH. Illness trajectories in the chronic fatigue symdrome: a longitudinal study of
improvers versus non-improvers. J Nerv Ment Dis. 2010;198(7):486-93.

Cipolla-Neto J, Amaral FG, Afeche SC, Tan DX, Reiter RJ. Melatonin, energy metabolism, and obesity: a review. Journal of
pineal research. May 2014;56(4):371-381.
Conti F, Magrini L, Priori R, Valesini G, Bonini S. Eosinophil cationic protein serum levels and allergy in chronic fatigue
syndrome. Allergy. Feb 1996;51(2):124-127.
Corbin KD, Zeisel SH. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression.
Current opinion in gastroenterology. Mar 2012;28(2):159-165.
Cordero MD, Alcocer-Gomez E, Culic O, Carrion AM, De Miguel M, Diaz-Parrado E, et al. NLRP3 inflammasome is
activated in fibromyalgia: The effect of coenzyme Q10. Antioxidants Redox Signal 2013; In Press.
Cordero MD, Alcocer-Gomez E, De Miguel M, Culic O, Carrion AM, Alvarez-Suarez JM, et al. Can coenzyme Q10
improve clinical and molecular parameters in fibromyalgia? Antioxidants Redox Signal 2013;19:1356-1361.
Cox D, Ludlam S, Mason L, Wagner S, Sharpe M. PACE Manual for Therapists, Adaptive Pacing Therapy, 2004. Accessed
1/25/2014 at http://www.pacetrial.org/docs/apt-therapist-manual.pdf
Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991;337:757-760.
Crinnion W. Components of practical clinical detox programs--sauna as a therapeutic tool. Alternative therapies in health and
medicine. Mar-Apr 2007;13(2):S154-156.
Curtis L, Lieberman A, Stark M, Rea W, Vetter M. Adverse health effects of indoor molds. J Nutr Environ Med
2004;14:261-274.
Datieva VK, Rosinskaia AV, Levin OS. [The use of melatonin in the treatment of chronic fatigue syndrome and circadian
rhythm disorders in Parkinson's disease]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo
zdravookhraneniia i meditsinskoi promyshlennosti Rossiiskoi Federatsii, Vserossiiskoe obshchestvo nevrologov [i]
Vserossiiskoe obshchestvo psikhiat. 2013;113(7 Pt 2):77-81.
Dennis D, Robertson D, Curtis L, Black J. Fungal exposure endocrinopathy in sinusitis with growth hormone deficiency:
Dennis Robertson syndrome. Toxicology Industrial Health 2009;25:669-680.
Dinos S, Khoshaba B, Ashby D, White PD, Nazroo J, Wessely S, Bhui KS. A systematic review of chronic fatigue, its
syndromes and ethnicity: prevalence, severity, co-morbidity and coping. Int J Epidemiol 2009;38:1554-1570.
Dorcas A, Yung P. Qigong: harmonising the breath, the body and the mind. Complementary therapies in nursing &
midwifery. Nov 2003;9(4):198-202.
Ellithorpe RR, Settineri RA, Nicolson GL. Pilot study: Reduction of fatigue by use of a dietary supplement containing
glycophospholipids. J Am Nutraceutical Assoc 2003;6: 23-28.
Emms TM, Robers TK, Butt HL, et al. Food intolerance in chronic fatigue syndrome. Abstract #15 presented at the
American Association for Chronic Fatigue Syndrome conference. January 2001. Seattle, WA
Erkekoglu P, Baydar T. Evaluation of the protective effect of ascorbic acid on nitrite- and nitrosamine-induced cytotoxicity
and genotoxicity in human hepatoma line. Toxicology mechanisms and methods. Feb 2010;20(2):45-52.
Evengrd B, Grans H, Wahlund E, Nord CE. Increased number of Candida albicans in the faecal microflora of chronic fatigue
syndrome patients during the acute phase of illness. Scandinavian journal of gastroenterology. Dec 2007;42(12):1514-1515.
Eymard D, Lebel F, Miller M, Turgeon F. Human herpesvirus 6 and chronic fatigue syndrome. The Canadian journal of

infectious diseases = Journal canadien des maladies infectieuses. Jul 1993;4(4):199-202.

FDA. U.S. Food and Drug Administration website. Drugs page. Drug Development for Myalgic Encephalomyelitis and
Chronic Fatigue Syndrome (ME and CFS): Questions and Answers. Available at: http://www.fda.gov/Drugs/NewsEvents
/ucm337759.htm. Last updated 2/5/2013. Accessed 5/23/2014.
Ferr Ybarz L, Cardona Dahl V, Cadahia Garcia A, Ruiz E, Vazquez A, Fernandez de Sevilla T, Alegre Martin J. [Prevalence
of atopy in chronic fatigue syndrome]. Allergologia et immunopathologia. Jan-Feb 2005;33(1):42-47.
Ferri FF. Ferris Clinical Advisor. Chronic Fatigue Syndrome. Available at: www.clinicalkey.com. Copyright 2014.
Accessed 5/23/2014.
Flock MR, Rogers CJ, Prabhu KS, et al. Immunometabolic role of long-chain omega-3 fatty acids in obesity-induced
inflammation. Diabetes Metab Res Rev. 2013;29(6):431-45.
Forsyth LM, Preuss HG, MacDowell AL, Chiazze L, Birkmayer GD, Bellanti JA. Therapeutic effects of oral NADH on
the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol 1999;82:185-191.
Frissora CL, Koch KL. Symptom overlap and commorbidity or irritable bowel syndrome with other conditions. Current
Gastroenterol Rep 2005;7:264-271.
Frith J, Zalewski P, Klawe JJ, Pairman J, Bitner A, Tafil-Klawe M et al. Impaired blood pressure variability in chronic
fatigue syndrome a potential biomarker. QJ Med 2012;105:831-838.
Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The Chronic Fatigue Syndrome: A comprehensive
approach to its definition and study. Ann Intern Med 1994;121:953-959.
Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ
1997;314:1647-1652.
Gaby AR. Intravenous nutrient therapy: the Myers cocktail. Altern Med Rev. 2002;7(5):389-403.
Ginter E, Simko V. Polyunsaturated fatty acids n-3; new data on heart disease, cancer, immune resistance, and mental
depression. Bratislavia Lek Listy 2010;111:680-685.
Griffith JP, Zarrouf FA. A systematic review of chronic fatigue syndrome: don't assume it's depression. Primary care
companion to the Journal of clinical psychiatry. 2008;10(2):120-128.
Guralnik JM, Ershler WB, Schrier SL, Picozzi VJ. Anemia in the elderly: a public health crisis in hematology. Am Soc
Hematol 2005;528-530.
Harlow BL, Signorello LB, Hall JE, Dailey C, Komaroff AL. Reproductive correlates of chronic fatigue syndrome. The
American journal of medicine. Sep 28 1998;105(3a):94s-99s.
Harrington ME. Neurobiological studies of fatigue. Progress in neurobiology. Nov 2012;99(2):93-105.
Heap LC, Peters TJ, Wessely S. Vitamin D status in patients with chronic fatigue syndrome. J Royal Soc Med
1999;92:183-185.
Henderson TA. Valacyclovir treatment of chronic fatigue in adolescents. Advances Mind Body Med 2014;28:4-14.
Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, . . . Lloyd A. Post-infective and chronic
fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ (Clinical research ed.). Sep
16 2006;333(7568):575.

Hickie I, Lloyd A, Wakefield D, Parker G. The psychiatric status of patients with the chronic fatigue syndrome. Br J
Psychiatry 1990;156:534-540.
Hillert L, Jovanovic H, Ahs F, Savic I. Women with multiple chemical sensitivity have increased harm avoidance and reduced
5-HT(1A) receptor binding potential in the anterior cingulate and amygdala. PloS one. 2013;8(1):e54781.
Himmel PB, Seligman. A pilot study employing dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue
syndrome. J Clin Rheumatol 1999;5:56-59.
Hock AD. Divalent cations, hormone, psyche and soma: Four case reports. J Chronic Fatigue Syndrome 2000;6:117-131.
Hoeck AD, Pall ML. Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue?
Medical hypotheses. Feb 2011;76(2):208-213.
Hovington CL, McGirr A, Lepage M, Berlim MT. Repetitive transcranial magnetic stimulation (rTMS) for treating major
depression and schizophrenia: a systematic review of recent meta-analyses. Ann Med 2013;45:308-321.
Hsu WY, Cheng CH, Liao KK, Lee IH, Lin YY. Effects of repetitive transcranial magnetic stimulation on motor functions in
patients with stroke: A meta-analysis. Stroke 2012;43:1849-1857.
Huertas R, Campos Y, Diaz E, Esteban J, Vechietti L, Montanari G, . . . Arenas J. Respiratory chain enzymes in muscle of
endurance athletes: effect of L-carnitine. Biochemical and biophysical research communications. Oct 15
1992;188(1):102-107.
Hutson PH, Pennick M, Secker R. Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: A novel
d-amphetamine pro-drug. Neuropharmacology. Mar 1 2014.
Hyman SE, Nestler EJ. Initiation and adaptation: a paradigm for understanding psychotropic drug action. The American
journal of psychiatry. Feb 1996;153(2):151-162.
Ishaque S, Shamseer L, Bukutu C, Vohra S. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC
Complement Alt Med 2012;12:70.
Ismail Y, Ismail AA, Ismail AA. The underestimated problem of using serum magnesium measurements to exclude
magnesium deficiency in adults; a health warning is needed for "normal" results. Clinical chemistry and laboratory medicine:
CCLM / FESCC. Mar 2010;48(3):323-327.
Jacobson W, Saich T, Borysiewicz LK, Behan WM, Behan PO, Wreghitt TG. Serum folate and chronic fatigue syndrome.
Neurology 1993;43:2645-2647.
James LC, Folen RA. EEG biofeedback as a treatment for chronic fatigue syndrome: a controlled case report. Behavioral
medicine (Washington, D.C.). Summer 1996;22(2):77-81.
Jason L. Problems with the New CDC CFS Prevalence Estimates. International Association for Chronic Fatigue Syndrome /
Myalgic Encephalitis. Available at: http://www.iacfsme.org/IssueswithCDCEmpiricalCaseDefinitionandPrev/tabid
/105/Default.aspx. Accessed 07/16/2014. 2013.
Jay SJ. Tobacco use and chronic fatigue syndrome, fibromyalgia and tempomandibular disorder. Arch Intern Med
2000;160:2398-2399.
Jo IH, Bang KH, Kim YC, Lee JW, Seo AY, Seong BJ, . . . Kim HS. Rapid Identification of Ginseng Cultivars (Panax ginseng
Meyer) Using Novel SNP-Based Probes. Journal of ginseng research. Nov 2011;35(4):504-513.

Jones R, Brasington R, Shepherd R, Baustian GH, Murray JL. Clinical Key: First Consult. Chronic fatigue syndrome.
Available at www.clinicalkey.com. Revised 4/1/2011. Accessed 4/10/14.
Jones WM, van Ophem PW, Pospischil MA, Ringe D, Petsko G, Soda K, Manning JM. The ubiquitous cofactor NADH
protects against substrate-induced inhibition of a pyridoxal enzyme. Protein science: a publication of the Protein Society.
Dec 1996;5(12):2545-2551.
Katerndahl DA, Bell IR, Palmer RF, Miller CS. Chemical intolerance in primary care settings: Prevalence, comorbidity, and
outcomes. Ann Family Med 2012;10:357-365.
Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clinic
proceedings. Aug 2010;85(8):752-757; quiz 757-758.
Kiefer D, Pantuso T. Panax ginseng. American family physician. Oct 15 2003;68(8):1539-1542.
Kilic M. Effect of fatiguing bicycle exercise on thyroid hormone and testosterone levels in sedentary males supplemented
with oral zinc. Neuro Endocrinol Lett 2007;681-685.
Kim HG, Cho JH, Yoo Sr, Lee JS, Han JM, Lee NH, et al. Anti-fatigue effects of Panax ginseng C.A. Meyer: A randomized,
double-blind, placebo-controlled trial. PLOS ONE 2013;8:e61271.
Kim JA, Son JH, Song SB, Yang SY, Kim YH. Sterols isolated from seeds of Panax ginseng and their antiinflammatory
activities. Pharmacognosy magazine. Apr 2013;9(34):182-185.
King M, Kingery J, Casey B. Diagnosis and evaluation of heart failure. Am Fam Physician 2012;85:1161-1168.
Kipen HW, Hallman W, Kang H, Fielder N, Natelson BH. Prevalence of chronic fatigue and chemical sensitivities in Gulf
Registry Veterans. Arch Environ Health 1999;54:313-318.
Kirkpatrick JN. Occult carbon monoxide poisoning. The Western journal of medicine. Jan 1987;146(1):52-56.
Klimas NG, Koneru AO. Chronic fatigue syndrome: Inflammation, immune function, and neuroendocrine interactions. Curr
Rheumatology Rep 2007;9:482-487.
Koslik HJ, Hamilton G, Golomb BA. Mitochondrial dysfunction in Gulf War illness revealed by 31Phosphorus Magnetic
Resonance Spectroscopy: a case-control study. PloS one. 2014;9(3):e92887.
Kudoh Y, Aoyama S, Torii T, Chen Q, Nagahara D, Sakata H, Nozawa A. The effects of oral L-carnitine supplementation on
physical capacity and lipid metabolism in chronic hemodialysis patients. Nephron extra. Jan 2014;4(1):33-41.
Kulkarni SK, Dhir A. Withania somnifera: an Indian ginseng. Progress in neuro-psychopharmacology & biological
psychiatry. Jul 1 2008;32(5):1093-1105.
Kuratsune H, Yamaguti K, Sawada M, Kodate S, Machii T, Kanakura Y, Kitani T. Dehydroepiandrosterone sulfate
deficiency in chronic fatigue syndrome. Int J Mole Med 1998;1:143-146.
Kuratsune H, Yamaguti K, Takahashi M, Misaki H, Tagawa S, Kitani T. Acylcarnitine deficiency in chronic fatigue
syndrome. Clin Infect Dis 1994;18(supplement 1):S62-S67.
Lanier JB, Mote MB, Clay EC. Evaluation and management of orthostatic hypotension. American family physician. Sep 1
2011;84(5):527-536.
Lee FT, Kuo TY, Liou SY, Chien CT. Chronic Rhodiola rosea extract supplementation enforces exhaustive swimming
tolerance. The American journal of Chinese medicine. 2009;37(3):557-572.

Lee J, Taneja V, Vassallo R. Cigarette smoking and inflammation: cellular and molecular mechanisms. Journal of dental
research. Feb 2012;91(2):142-149.
Lee NH, Yoo SR, Kim HG, Cho JH, Son CG. Safety and tolerability of Panax ginseng root extract: a randomized, placebocontrolled, clinical trial in healthy Korean volunteers. Journal of alternative and complementary medicine (New York, N.Y.).
Nov 2012;18(11):1061-1069.
Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir treatment in Epstein-Barr Virus subset chronic fatigue
syndrome: thirty-six month follow up. In Vivo 2007;21:707-714.
Lewis I, Pairman J, Spickett G, Newton JL. Clinical chararcteristics of a novel subgroup of chronic fatigue syndrome
patients with postural orthostatic tachycardia syndrome. J Internal Medicine 2013;273:501-510.
Lieberman JA. Obstructive sleep apnea (OSA) and excessive sleepiness associated with OSA: recognition in the primary
care setting. Postgrad Med 2009;121:33-41.
Lind R, Berstad A, Hatlebakk J, Valeur J. Chronic fatigue in patients with unexplained self-reported food hypersensitivity
and irritable bowel syndrome: validation of a Norwegian translation of the Fatigue Impact Scale. Clinical and experimental
gastroenterology. 2013;6:101-107.
Logan AC, Wong C. Chronic fatigue syndrome: oxidative stress and dietary modifications. Alternative medicine review : a
journal of clinical therapeutic. Oct 2001;6(5):450-459.
Lugade AA, Bogner PN, Thatcher TH, Sime PJ, Phipps RP, Thanavala Y. Cigarette smoke exposure exacerbates lung
inflammation and compromises immunity to bacterial infection. Journal of immunology (Baltimore, Md. : 1950). Jun 1
2014;192(11):5226-5235.
Maassen JA, Janssen GM, Lemkes HH. Mitochondrial diabetes mellitus. Journal of endocrinological investigation. May
2002;25(5):477-484.
Maes M, Mihaylova I, De Ruyter M. Lower serum zinc in chronic fatigue syndrome (CFS): Relationships to immune
dysfunctions and relevance for the oxidative stress status in CFS. J Affective Disorders 2006;90:141-147.
Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E. Coenzyme Q10 deficiency in myalgic
encephalomyelitis/chronic fatigue syndrome is related to fatigue, autonomic, and neurocognitive symptoms and is another
risk factor explaining the early mortality in ME/CFS due to cardiovascular disorders. Neuoendrocrinol Lett 2009;30:470-478.
Maes M, Twisk FNM, Ringel K. Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis / chronic
fatigue syndrome and depression: Inflammatory markers are higher in myalgic encephalomyelitis / chronic fatigue than in
depression. Psychother Psychosom 2012;81:286-295.
Maggio M, Colizzi E, Fisichella A, Valenti G, Ceresini G, DallAglio E, et al. Stress hormones, sleep deprivation and
cognition in older adults. Maturitas 2013;76:22-44.
Maharaj D, Gomez-Marin O, Lewis-Ximenez LL, Riley R, Albarracin C. Serum G-CSF levels in patients undergoing
G-CSF/chemotherapy mobilized peripheral stem cell harvest and predictors of neutrophil and platelet recovery. Leukemia.
Oct 1995;9 Suppl 1:S113-117.
Maric D, Brkic S, Mikic AN, Tomic S, Cebovic T, Turkulov V. Multivitamin mineral supplementation in patients with
chronic fatigue syndrome. Med Sci Monitor 2014;20:47-53.
Mariman A, Delesie L, Tobback E, Hanoulle I, Sermijn E, Vermeir P, . . . Vogelaers D. Undiagnosed and comorbid disorders in
patients with presumed chronic fatigue syndrome. Journal of psychosomatic research. Nov 2013;75(5):491-496.

Masuda A, Kihara T, Fukudome T, Shinsato T, Minagoe S, Tei C. The effects of repeated thermal therapy for two patients
with chronic fatigue syndrome. J Psychosomat Res 2005;58:383-387.
Mauriege P, Martel C, Langin D, Lacaille M, Despres JP, Belanger A, . . . Deshaies Y. Chronic effects of
dehydroepiandrosterone on rat adipose tissue metabolism. Metabolism: clinical and experimental. Mar 2003;52(3):264-272.
Mazzio E, Yoon KJ, Soliman KF. Acetyl-L-carnitine cytoprotection against 1-methyl-4-phenylpyridinium toxicity in
neuroblastoma cells. Biochemical pharmacology. Jul 15 2003;66(2):297-306.
McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Current biology: CB. Jul 25
2006;16(14):R551-560.
Mehedint MG, Zeisel SH. Choline's role in maintaining liver function: new evidence for epigenetic mechanisms. Current
opinion in clinical nutrition and metabolic care. May 2013;16(3):339-345.
Mendell MJ, Lei-Gomez Q, Mirer AG, Seppanen O, Brunner G. Risk factors in heating, ventilating, and air-conditioning
systems for occupant symptoms in US office buildings: The USA EPA BASE Study. Indoor Air 2008:18:301-306.
Mhalla A, Baudic S, Ciampi de Andrade D, Gautron M, Perrot S, Teixeira MJ, et al. Long term maintenance of the analgesic
effects of transcranial magnetic stimulation in fibromyalgia. Pain 2011;152:1478-1485.
Mingorance C, Rodriguez-Rodriguez R, Justo ML, Alvarez de Sotomayor M, Herrera MD. Critical update for the clinical
use of L-carnitine analogs in cardiometabolic disorders. Vascular health and risk management. 2011;7:169-176.
Moller MC, Radestad AF, Von Schoultz B, Bartfai A. Effect of estrogen and testosterone replacement therapy on cognitive
fatigue. Gynecol Endocrinol 2013;29:173-176.
Molyneux SL, Young JM, Florkowski CM, Lever M, George PM. Coenzyme Q10: is there a clinical role and a case for
measurement? The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists. May 2008;29(2):71-82.
Montoya J. Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of
Methylphenidate Hydrochloride as a Treatment for Chronic Fatigue Syndrome in Patients Taking a CFS-Specific Nutrient
Formula. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 5/7/2014. Available at:
https://clinicaltrials.gov/ct2/show/NCT01966276?term=NCT01966276&rank=1. NLM Identifier: NCT01966276.
Montoya JG, Kogelnik AM, Bhangoo M, Lunn MR, Flamand L, Merrihew LE, . . . Desai M. Randomized clinical trial to
evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. Journal of medical
virology. Dec 2013;85(12):2101-2109.
Morelli V. Fatigue and chronic fatigue in the elderly: Definitions, diagnoses, and treatments. Clin Geriatr Med
2011;27:673-686.
Morris G, Maes M. Mitochondrial dysfunction in myalgic encephalomyelitis/ chronic fatigye syndrome explained by
activated immune-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis 2014;29:19-36.
Moss-Morris R, Deary V, Castell B. Chronic fatigue syndrome. Handbook of clinical neurology. 2013;110:303-314.
Mott TF, McConnon ML, Rieger BP. Subacute to chronic mild traumatic brain injury. Am Fam Physician.
2012;86(11):1045-51.
Myhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. International journal of
clinical and experimental medicine. 2009;2(1):1-16.

Nacul LC, Lacerda EM, Campion P, Pheby D, DeDrachler M Leite JC, et al. The functional status and well being of people
with mylagic encephalomyelitis/chronic fatigue syndromes and their careers. BMC Public Health 2011;11:402.
Nacul LC, Lacerda EM, Sakellariou D.Is there an association between exposure to chemicals and chronic fatigue syndrome?
Review of the evidence. Bulletin IACFS/ME 2009;17:3-15.
Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, et al. Neuroinflammation in patients with chronic fatigue
syndrome/myalgic encephalomyelitis: An 11C-(R)-PK11195 PET study. J Nucl Med. 2014; 55(6):945-950.
Natella F, Leoni G, Maldini M, Natarelli L, Comitato R, Schonlau F, . . . Canali R. Absorption, Metabolism, and Effects at
Transcriptome Level of a Standardized French Oak Wood Extract, Robuvit, in Healthy Volunteers: Pilot Study. Journal of
agricultural and food chemistry. 2014;62(2):443-453.
NCI. National Cancer Institute. Cancer Drug Information: Filgrastim. Available at: http://www.cancer.gov/cancertopics
/druginfo/filgrastimUpdated 7/10/2013. Accessed: 8/18/2014.
Neu D, Mairesse O, Montana X, Gilson M, Corazza F, Lefevre N, . . . Verbanck P. Dimensions of pure chronic fatigue:
psychophysical, cognitive and biological correlates in the chronic fatigue syndrome. European journal of applied physiology.
May 31 2014.
Nicolson GL. Mitochondrial dysfunction and chronic disease: treatment with natural supplements. Alt Ther Health Med
2013;19: In Press
Nijhof SL, Rutten JM, Uiterwaal CS, Bleijenberg G, Kimpen JL, Putte EM. The role of hypocortisolism in chronic fatigue
syndrome. Psychoneuroendocrinology. Apr 2014;42:199-206.
Nijs J, Meeus M, Van Oosterwijck J, Roussel N, De Kooning M, Ickmans K, Matic M. Treatment of central sensitization in
patients with 'unexplained' chronic pain: what options do we have? Expert opinion on pharmacotherapy. May
2011;12(7):1087-1098.
Nijs J, Paul L, Wallman K. Chronic fatigue syndrome: An approach combining self-management with graded exercise to avoid
exacerbations. J Rehabil Med 2008;40:241-247.
Norman D, Loredo JS. Obstructive sleep apnea in older adults. Clin Geriatr Med 2008;24:151-165.
Olson LG, Ambrogetti A, Sutherland DC. A pilot randomized controlled trial of dexamphetamine in patients with chronic
fatigue syndrome. Psychosomatics 2003;44: 38-43.
Orosz Z, Csiszar A, Labinskyy N, Smith K, Kaminski PM, Ferdinandy P, . . . Ungvari Z. Cigarette smoke-induced
proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. American journal of
physiology. Heart and circulatory physiology. Jan 2007;292(1):H130-139.
Ozguner M, Azik MF, Tavil B, Bozkaya I, Koksal Y, Canal E, . . . Tunc B. Do two different stem cell grafts: G-CSF
stimulated and unstimulated bone marrow differ according to hematopoietic colony forming capacity? Transfusion and
apheresis science : official journal of the World Apheresis Association : official journal of the European Society for
Haemapheresis. Jun 2014;50(3):467-472.
Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stressprotective activity. Current clinical pharmacology. Sep 2009;4(3):198-219.
Papadopoulos AS, Cleare AJ. Hypothalmic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev
Endocrinol 2012;8:22-32.

Piwowarski J, Granica S, Kiss A. Influence of gut flora-derived ellagitannins' metabolites-urolithins on production and release
of pro-inflammatory factors from stimulated neutrophils in the context of cardiovascular disease prevention. Planta medica.
2013;79(13):SL52.
Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsychobiology
1997;35:16-23.
Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology
1995;32:132-138.
Puri BK. The use of eicosapentaenoic acid in the treatment of chronic fatigue syndrome. Prostaglandins, Leukotrienes
Essential Fatty Acids 2004;70:399-401.
Qian L, Pan N, Gong J. [Change of NOS activity in hypoxia and cold-induced blood vessels damage and its biological
significance]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. Jan 2001;35(1):57-60.
Racchi M, Balduzzi C, Corsini E. Dehydroepiandrosterone (DHEA) and the aging brain: flipping a coin in the "fountain of
youth". CNS drug reviews. Spring 2003;9(1):21-40.
Rao AV, Bested AC, Beuline TM, Katzman MA, Iorio C, Berardi JM, et al. A randomized, double-blind, placebo-controlled
pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathogens 2009;1:6
Reddy DS. Current pharmacotherapy of attention deficit hyperactivity disorder. Drugs today (Barc) 2013;49:647-665.
Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet neurology. Nov 2006;5(11):949-960.
Reynolds GK, Lewis DP, Richardson AM, Lidbury BA. Comorbidity of postural orthostatic tachycardia syndrome and
chronic fatigue syndrome in an Australian cohort. J Internal Medicine 2014;275:409-417.
Richardson J. Four cases of pesticide poisoning presenting as ME treated with a choline and ascorbic acid mixture. J
Chronic Fatigue Syndrome 2000;6:11-21.
Riediger ND, Othman RA, Suh M, Moghadasian MA. A systemic review of the roles of n-3 fatty acids in health and
disease. J Am Dietetic Assoc 2009;668-679.
Romero A, Ramos E, de Los Rios C, Egea J, Del Pino J, Reiter RJ. A review of metal-catalyzed molecular damage:
protection by melatonin. Journal of pineal research. May 2014;56(4):343-370.
Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences
underestimated? Nutrition Rev 2012;70:153-164.
Ross SD, Estok RP, Frame D, Stone LR, Ludensky V, Levine CB. Disability and chronic fatigue syndrome. Arch Intern Med
2004;164:1098-1107.
Rostan EF, DeBuys HV, Madey DL, Pinnell SR. Evidence supporting zinc as an important antioxidant for skin. International
journal of dermatology. Sep 2002;41(9):606-611.
Rude RK, Singer ER, Gruber HE. Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr 2009;28:131-141.
Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with SuperMalic: A randomized,
double blind, placebo controlled, crossover pilot study. J Rheumatol 1995;22:953-958.
Santaella ML, Font I, Disdier OM. Comparison of oral nicotinamide adenine dinuculeotide (NADH) versus conventional
therapy for chronic fatigue syndrome. Puerto Rico Health Sci J 2004;23:89-93.

Sathyapalan T, Beckett S, Rigby AS, Mellor DD, Atkin SL. High cocoa polyphenol rich chocolate may reduce the burden of
symptoms in chronic fatigue syndrome. Nutrition J 2010;9:55.
Sawalha AH, Kovats S. Dehydroepiandrosterone in systemic lupus erythematosus. Current rheumatology reports. Aug
2008;10(4):286-291.
Sawchuck CN, Buchwald D. Chronic fatigue syndrome. Epocrates 6/17/2013. Accesed 3/26/2014 at
https://online.epocrates.com/u/2911277/chronic+fatigue+syndrome
Schwartz E, Holtof K. Hormone replacement therapy in the geriatric patient: Current state of the evidence and questions for
the future. Estrogen, progesterone, testosterone, and thyroid hormone augmentation in geriatric clinic practice. Clin Geriatr
Med 2011;27:541-559.
Scioli MG, Stasi MA, Passeri D, Doldo E, Costanza G, Camerini R, . . . Orlandi A. Propionyl-L-Carnitine is Efficacious in
Ulcerative Colitis Through its Action on the Immune Function and Microvasculature. Clinical and translational
gastroenterology. 2014;5:e55.
Scott LV, Salahuddin F, Cooney J, Svec F, Dinan TG. Differences in adrenal steroid profile in chronic fatigue syndrome, in
depression and in health. J Affect Disorders 1999;54:129-137.
Shi Y, Weingarten TN, Mantilla CB, Hooten WM, Warner DO. Smoking and pain: pathophysiology and clinical implications.
Anesthesiology. Oct 2010;113(4):977-992.
Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. African
journal of traditional, complementary, and alternative medicines: AJTCAM / African Networks on Ethnomedicines. 2011;8(5
Suppl):208-213.
Skapinakis P, Lewis G, Mavreas V. Temporal relations between unexplained fatigue and depression: Longitudinal data from
an international study in primary care. Psychosomatic Med. 2004;66:330-335.
Stanworth RD, Jones TH. Testosterone for the aging male; current evidence and recommended practice. Clinical
interventions in aging. 2008;3(1):25-44.
Stejskal VD, Danersund A, Lindvall A, Hudecek R, Nordman V, Yaqob A, et al. Metal-specific lymphocytes: biomarkers of
sensitivity in man. Neuro Endocrinol Lett 1999;20: 289-298.
Straus SE, Dale JK, Wright R, Metcalfe DD. Allergy and the chronic fatigue syndrome. The Journal of allergy and clinical
immunology. May 1988;81(5 Pt 1):791-795.
Strayer DR, Carter WA, Brodsky I, Cheney P, Peterson D, Salvato P, et al. A controlled clinical trial with a specifically
configured RNA drug, Poly(I).poly(C12U), in chronic fatigue syndrome. Clin Infect Dis 1994;18 Supplement 1:S88-S95.
Strayer DR, Carter WA, Stouch BC, Stevens SR, Bateman L, Cimoch PJ, et al. A double-blind, placebo-controlled,
randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLOS ONE
2012;7:e31334.
Stringer EA, Baker KS, Carroll IR, Montoya JG, Chu L, Maecker HT, Younger JW. Daily cytokine fluctuations, driven by
leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. Journal of
translational medicine. 2013;11:93.
Sullivan A, Nord CE, Evengard B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity
in patients with chronic fatigue syndrome. Nutr J 2009;8:4.

Sun GC. Qigong: bio-energy medicine. Journal of alternative and complementary medicine (New York, N.Y.). Oct
2008;14(8):893.
Tate DJ, Jr., Miceli MV, Newsome DA. Zinc protects against oxidative damage in cultured human retinal pigment epithelial
cells. Free radical biology & medicine. Mar 1999;26(5-6):704-713.
Taylor RR, OBrien J, Kielhofner G, Lee SW, Katz B, Mears C. The occupational and quality of life consequences of
chronic fatigue syndrome / malgic encephalomyelitis in young people. Br J Occupat Therapy 2010;73:524-530.
Teitelbaum JE, Bird B, Greenfield RM, Weiss A, Muenz L, Gould L. Effective treatment of chronic fatigue syndrome: A
randomized, double-blind, placebo-controlled, intent to treat study. J Chronic Fatigue Syndrome 2001;8:3-28.
Teitelbaum JE, Johnson C, St. Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: A pilot study. J
Altern Compliment Med 2006;12:857-862.
Thornton MJ. Estrogens and aging skin. Dermato-endocrinology. Apr 1 2013;5(2):264-270.
Tomassini V, Pozzilli C, Onesit E, Pasqualetti P, Marinelli F, Pisani A, et al. Comparison of the effects of acetyl L-carnitine
and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomized, double-blind, crossover trial.
J Neurol Sci 2004; 218:103-108
Torres NI, Castilla V, Bruttomesso AC, Eiras J, Galagovsky LR, Wachsman MB. In vitro antiviral activity of
dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1. Antiviral research.
Jul 2012;95(1):37-48.
Trabal J, Leyes P, Fernandez-Sola J, Forga M, Fernandez-Huerta J. Patterns of food avoidance in chronic fatigue syndrome:
is there a case for dietary recommendations? Nutricion hospitalaria. Mar-Apr 2012;27(2):659-662.
UMMC. University of Maryland Medical Center. Chronic fatigue syndrome. Available at: http://umm.edu/health/medical
/reports/articles/chronic-fatigue-syndrome. Last updated 6/21/2013. Accessed 8/1/2014.
Van Den Eede F, Moorkens G, Van Houdenhove B, Cosyns P, Claes SJ. Hypothalamic-pituitary-adrenal axis function in
chronic fatigue syndrome. Neuropsychobiology. 2007;55(2):112-120.
Van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic
fatigue syndrome and late melatonin secretion. Eur J Neurology 2006;13:55-60.
Vermeulen RCW, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue
syndrome. Psychosomatic Med 2004;66:276-282.
Vitiello B. Long-term effects of stimulant medications on the brain: possible relevance to the treatment of attention deficit
hyperactivity disorder. Journal of child and adolescent psychopharmacology. Spring 2001;11(1):25-34.
Wang GJ, Volkow ND, Wigal T, Kollins SH, Newcorn JH, Telang F, . . . Swanson JM. Long-term stimulant treatment affects
brain dopamine transporter level in patients with attention deficit hyperactive disorder. PloS one. 2013;8(5):e63023.
Wang J, Li S, Fan Y, Chen Y, Liu D, Cheng H, . . . Zhou Y. Anti-fatigue activity of the water-soluble polysaccharides isolated
from Panax ginseng C. A. Meyer. Journal of ethnopharmacology. Jul 20 2010;130(2):421-423.
Ward MH, DeLisle H, Shores JH, Slocum PC, Foresman BH. Chronic fatigue complaints in primary care: incidence and
diagnostic patterns. The Journal of the American Osteopathic Association. Jan 1996;96(1):34-46, 41.
Watt T, Oberfoell S, Balise R, et al. Respose to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6

and Epstein-Barr virus IgG antibody titer. J Med Virol. 2012;84(12):1967-74.

Wearden AJ, Morriss RK, Mullis R, Strickland PL, Pearson DJ, Appleby L, et al. Randomised, double-blind, placebocontrolled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry 1998;172:485-490.
Weingarten TN, Podduturu VR, Hooten WM, Thompson JM, Luedtke CA, Oh TH. Impact of tobacco use in patients
presenting to a multidisciplinary outpatient treatment program for fibromyalgia. Clin J Pain 2009;25:39-43.
Weiss EP, Villareal DT, Fontana L, Han DH, Holloszy JO. Dehydroepiandrosterone (DHEA) replacement decreases insulin
resistance and lowers inflammatory cytokines in aging humans. Aging. May 2011;3(5):533-542.
Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Alt Med Rev 2000;5:93-108.
Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. Psychological symptoms, somatic symptoms, and psychiatric disorder
in chronic fatigue and chronic fatigue syndrome: a prospective study in the primary care setting. The American journal of
psychiatry. Aug 1996;153(8):1050-1059.
Wicks TC. AANA Journal course: update for nurse anesthetists--magnesium homeostasis and deficiency. AANA journal.
Apr 1999;67(2):171-179.
Witham M, Kennedy G, Belch J, Hill A, Khan F. Association between vitamin D status and markers of vascular health in
patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). International journal of cardiology. Apr 2
2014.
Witkowski M, Hubert J, Mazur A. Methods of assessment of magnesium status in humans: a systematic review.
Magnesium research: official organ of the International Society for the Development of Research on Magnesium. Dec
2011;24(4):163-180.
Woolf K, Manore MM. B-vitamins and exercise: does exercise alter requirements? Int J Nutr Exerc Metab 2006;16:453-484.
Wu YH, Swaab DF. The human pineal gland and melatonin in aging and Alzheimer's disease. Journal of pineal research. Apr
2005;38(3):145-152.
Xu S, Hoglund M, Hakansson L, Venge P. Granulocyte colony-stimulating factor (G-CSF) induces the production of
cytokines in vivo. British journal of haematology. Mar 2000;108(4):848-853.
Yamamura S, Morishima H, Kumano-go T, Suganuma N, Matsumoto H, Adachi H, et al. The effect of Lactobacillus
helveticus fermented milk on sleep and health perception in elderly subjects. Eur J Clin Nutr 2009;63:100-105.
Yancey JR, Thomas SM. Chronic fatigue syndrome: Diagnosis and treatment. Am Fam Physician 2012;86:741-746.
Yasui M, Yoshimura T, Takeuchi S, Tokizane K, Tsuda M, Inoue K, Kiyama H. A Chronic fatigue syndrome model
demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation. Glia. Sep
2014;62(9):1407-1417.
Yoshiuchi K. [Psychological symptoms in chronic fatigue syndrome]. Nihon rinsho. Japanese journal of clinical medicine.
Jun 2007;65(6):1023-1027.
Young JL. Use of lisdexamfetamine dimesylate in treatment of executive functioning deficits and chronic fatigue syndrome: A
double-blind, placebo-controlled study. Psychiatry Res 2013;207:127-133.
Yun MJ, Kang DM, Lee KH, Kim YK, Kim JE. Multiple chemical sensitivity caused by exposure to ignition coal fumes: a
case report. Annals of occupational and environmental medicine. 2013;25(1):32.

Ziem G Understanding patients with multiple chemical sensitivity. Am Family Physician 1999;59:2001
Zvolensky MJ, McMillan K, Gonzalez A, Asmundson GJ. Chronic pain and cigarette smoking and nicotine dependence
among a representative sample of adults. Nicotine & tobacco research: official journal of the Society for Research on Nicotine
and Tobacco. Dec 2009;11(12):1407-1414.

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