Painful menstrual periods in women.

Other Syndromes Related to FMS: Chronic Fatigue Syndrome, Multiple Chemical Sensitivities, Tension/migraine headaches, Depression/affective disorders, Temporomandibular Joint Disorder, Sleep Disorders, Irritable Bowel Syndrome, Esophageal dysmotility, Idiopathic Low Back Pain, Nondermatomal paresthesias, Vestibular Dysfunction, Sicca syndrome, Vasomotor rhinitis, Neurally mediated hypotension, Mitral valve prolapse, Noncardiac chest pain, Interstitial Cystitis, Female urethral syndrome, Chronic Pelvic Pain, Endometriosis (Aaron, Arch Int Med 2000).

FMS Symptoms in Children. Although symptoms are similar in children, some experts suggest that they often have no set number of pain tender points. In one study, children had an average of 9.7 tender point locations compared to the minimum of 11 in adults. In general, children with fibromyalgia most often experience sleep disorders and diffuse pain, and less frequently headache, general fatigue, and morning stiffness.

Who Gets Chronic Fatigue Syndrome & Fibromyalgia?

CFS/ME

In studies of large patient groups, 25% of people complain of fatigue and 4% have a fatiguing illness lasting greater than 6 months and of these only a small number meet CDC criteria for CFS. The CDC performed a national survey in 2004 which revealed that 1-2% of the general population meets criteria for CFS but they were not examined to rule out other causes. All age groups had CFS but adults were most common and women were greater than men by 2-5 times. Minorities were at increase risk along with those in lower socio-economic groups.

Of those people who meet criteria for CFS, 16% also meet criteria for FMS and 41% meet criteria for Multiple Chemical Sensitivity Syndrome.

FMS

Studies report that 4% of the general population meet the diagnostic criteria for fibromyalgia (Wolfe, et al, 1990). Some evidence suggests that a number of  factors may predispose people to fibromyalgia, including being female, having had difficult experiences in childhood, having a psychological vulnerability to stress, and coming from a very stressful culture or environment.

·    Gender. The prevalence of fibromyalgia is higher in women (3.4%) than in men (0.5%). Women's symptoms are also more severe than men's are.

·    Age. The disorder usually occurs in people between 20 to 60 years of age and peaks at age 35. In one study, however, fibromyalgia increased with age and had a prevalence of over 7% in patients between 60 and 79 years of age.

·    A condition called juvenile primary fibromyalgia, which appears in children, is uncommon, but studies indicate that its incidence is increasing. One study found that 1.2% of school children, all girls, met the criteria for fibromyalgia. Other studies have found an even higher prevalence of fibromyalgia in children. A 2000 study reported that in one specialty center it typically developed in children after age 13 and was most commonly diagnosed at 15. Symptoms were similar but outcome appears to be better in young people than adults.

·    Family Factors. Studies report a higher incidence of fibromyalgia among family members. It is not clear if genetic or psychological factors or both are involved. Some studies reporting some relationship are as follows:

o   One reported that 28% of the children of mothers with fibromyalgia also develop the disorder. There were no differences in psychological disorders between offspring who developed fibromyalgia and those who did not, however.

o    Another study noted that 66% of parents of children with fibromyalgia reported some sort of chronic pain, and about 10% had fibromyalgia itself. Close-knit families, oddly enough, were more likely to be associated with severe cases of childhood fibromyalgia.

What Causes These Disorders?

Chronic Fatigue Syndrome/Myalgic Encephalopathy

Theories abound about the causes of chronic fatigue syndrome. Unfortunately, many physicians still doubt that CFS is an actual disease but believe that it is a component of a psychological disorder or a symptom of other problems, similar to anemia and high blood pressure. Indeed, no primary cause has been found that explains all cases of CFS, but a number of experts believe that the chief possible causes of CFS include:

·        Infectious agents (viral, bacterial, other germs)

·        Immune system defects

·        Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysfunction

·        Orthostatic Hypotension

·        Environmental Chemicals- pesticides, solvents, heavy metals

Other factors may include genetic factors and brain abnormalities. Still, although many of these elements appear to be at work in most cases of CFS, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. And these elements may produce similar symptoms across all individuals but not produce consistent biologic factors that would allow objective testing. Personality and psychological factors do not appear to be a direct cause of CFS but may increase a person's susceptibility to the syndrome after exposure to mental or physical stresses, such as viral infections.

Many experts believe that FMS is not a disease but rather a dysfunctional disorder which is "set" by the genes we are born with but then modified or exacerbated by our environmental influences or stressors. The "Stressors" capable of triggering FMS include (Clauw D. Neuroimmunomodulation 1997):

• Peripheral Pain Syndromes
• Infections (EBV, Parvovirus, Lyme Disease, Q fever)
• Physical trauma (automobile accidents)
• Psychological stress/distress
• Hormonal alterations (hypothyroidism)
• Drugs
• Vaccines
• Certain catastrophic events (war, but not natural disasters)

In our opinion, the underlying cause of these conditions is long-term unremitting stress (we will look at the long list of stressors in more detail later). Where such stress has reduced the vitality of the body it can often only take one or two more severe stress incidents to throw the individual into the full-blown Chronic Fatigue state. While this last stress is the one that usually gets blamed for the condition, it is only the “straw that broke the camel’s back.”

Each of us has our own breaking point dependent upon the vitality of our endocrine (adrenal) glands and immune system. Some individuals have inherited such a weak immune system that they will suffer from this condition no matter what measures they take to prevent it (Even these can be helped, however). On the other hand, there are still a few left whose systems are so strong that they will never develop this condition no matter what may come along. The great majority of us lie somewhere between these two extremes.

In our opinion, the reason that this CFS/FMS is now the fastest growing epidemic in our nation can be laid at the feet of the modern dictum, “Better Living through Chemistry.” The traditional stresses of physical strain, emotional strife, bacterial and viral invaders, trauma, natural poisons, etc. have been with us since the earliest days of mankind and yet we have few verified cases of Chronic Fatigue during these years. What has changed in our lives today is the explosion of man made toxic chemical substances for which the body has had no time to create the needed internal antidotes. A list of these assaulting agents would have to include but are not limited to pesticides, water pollution, air pollution, almost all modern medical drugs including the overuse and abuse of antibiotics, multiple vaccinations and food additives. As each new generation has its collective immune systems assaulted by an increasing number of these “unnatural” substances our children are born with ever-weaker immune systems and so the predisposition to this condition grows exponentially with each new generation.

Causes of Secondary Fibromyalgia

 Secondary Fibromyalgia is a condition with fibromyalgia symptoms that are caused by specific disorders:

• Physical Injury: In one study, for example, secondary Fibromyalgia developed in over 20% of patients who had neck injuries. The symptoms are identical to those of primary Fibromyalgia but are harder to treat. Once study reported a high incidence of Fibromyalgia in workers complaining of repetitive stress injuries, although it is not clear which condition caused the other.

• Ankylosing Spondylitis

• Surgery

• Lyme Disease. According to one study between 10% and 25% of patients with Lyme disease subsequently developed Fibromyalgia, which did not respond to standard Lyme treatment using antibiotics.

• Hepatitis C

 

Body Area and Organ Dysfunctions found in CFS/FMS

Central Nervous System (Brain)

Brain dysfunction appears to be a key abnormality for understanding the features of CFS/FMS. Although IQ does not appear to be affected, cognitive impairment (problems with thinking, memory and attention) has been documented by psychometric testing in both CFS and FMS patients. These include deficiencies in complex information processing (dealing with multiple tasks at the same time), information processing speed, initial acquisition of new information and learning/recalling complex verbal material. It has been shown that these cognitive deficiencies are not the result of depression or other mental health disorders (Tiersky LA, et al. J Clin Exp Neuropsychol 1997). An analysis on reaction times between CFS patients and healthy controls revealed slowed reaction times that worsened and stay worse after exercise (Snell C. IACFS 2007).

 

There are several non-specific abnormalities in the central nervous system, including pinpoint spots of brain inflammation found on MRI (Lange, et al. JNS, 17:3, 1999), decreased regional blood flow to the brain by SPECT and SPET scans, specifically in the temporal lobes, cingulate cortex and frontal lobes (Abu-Judeh 1998, Kuratsune 2002, Garcia A. AICFS 2007), hypometabolism by PET scan, and abnormalities in spinal fluid ( Natelson, BH. Abstract, AACFS, 2003). Furthermore, brain blood flow was demonstrated to be decreased in CFS whether they had depression or not. (Yoshiuchi K, Nateson BH, AACFS, Oct 2004). Brain SPET uptake worsened after performing a physical-mental stress test (Garcia-Quintana A. IACFS 2007).

 

On dynamic neruoimaging studies, CFS patients perform as accurately as healthy controls but their brain activation patterns are different and there is a clear deficit on speed of brain processing (Lange, IACFS 2007). CFS patients demonstrate longer information processing times after controlling for variables (including depression) that confound the interpretation of information processing speed. Simply put, CFS patients have to work harder to do simple tasks and this is not explained by depression (Togo, F. IACFS 2007).

 

Research has reported that some patients with CFS have high levels of serotonin, a neurotransmitter (chemical messenger in the brain); such elevated levels in the brain are associated with fatigue. However, another study revealed low levels of serotonin transporters in the part of the brain (the anterior cingulated cortex) of CFS patients which is very different from the areas involved in depression (Kuratsune H, AACFS, Oct 2004). Other studies have revealed reduced serotonin neurotransmitter system across brain, specifically the hippocampus (Cleare 2005) and anterior cingulate.

 

Some critics of CFS feel that this condition is just a form of primary depression or anxiety. However, CFS patients were found to have elevated lactate in the ventricles and low N-acetyl-aspartate in the hippocampus of their brains compared to healthy individuals and patients with the diagnosis of generalized anxiety disorder (GAD). The elevated lactate suggests oxidative stress and mitochondrial dysfunction are playing a role brain abnormalities in CFS. These findings support that there is biochemical differences in the brains of individuals with "pure" CFS when compared to healthy individuals and those with generalized anxiety disorder.(Nestadt, P. IACFS 2007)

 

Autonomic Nervous System (ANS) Dysfunction

Vagus Nerve Dysfunction: One study found that after CFS patients exercise, they exhibit slight abnormalities in the activity of the vagus nerves on the heart; the vagus nerves run down each side of the neck and end at the intestines and affect many bodily functions.

 

Postural Orthostatic Tachycardia Syndrome (POTS) is the most common form of autonomic imbalance in CFS and occurs frequently in young people with CFS.

 

Neurally Mediated Hypotension (NMH): Some studies have suggested that a subgroup of patients who fit the strict criteria for chronic fatigue syndrome may have a condition known as neurally mediated hypotension (NMH). This is confirmed with a tilt table test. NMH causes a dramatic drop in blood pressure when standing up, even for as short a time as ten minutes. It is the result of an abnormality in the central nervous system that signals the heart to slow down and lower blood pressure when a person stands up; blood pools in the feet and legs before circulating back up to the heart, sometimes causing light-headedness, nausea, and fainting. One 1999 study suggested that such patients tend to be younger and to recover from CFS sooner than patients whose symptoms are not due to NMH. Some experts believe that in these cases, a virus or infection may cause injury to the central nervous system that results in the hypotension abnormality. This could help explain why so many patients report a viral infection before developing chronic fatigue syndrome. Major studies need to be done and the results repeated with larger patient groups before they can be applied to the majority of CFS patients.

 

Low Blood Volume

Some (a subset) of patients with CFS have low blood volume (low blood cell mass) that adds to the orthostatic intolerance described above. A well designed placebo controlled, double-blinded study was performed at the University of Miami examining the role of an injectable drug, Epoetin Alpha in CFS patients with documented low blood volume. This injectable treatment relieved the symptoms of dizziness and the suspectibility to orthostatic syncope but it did not improve the fatigue severity in these patients (Hurwitz B. Miami Epoetin Alpha Clinical Trial, IACFS 2007).

 

Chronic Sleep Disturbance

Although there is not one specific sleep disturbance that is purely defining of CFS or FMS, both CFS and FMS patients have non-restorative sleep, which means that they do not have normal deep sleep. Other abnormalities include difficulty in initiating and maintaining sleep (DIMS), apnea, periodic limb movement of sleep (PLMS), nocturnal myoclonus (NM), vivid nightmarish dreams, "tired but wired", phase shifting, and dysania (Lapp, C. IACFS 2007).  Scientific studies have reveal sleep abnormalities 88-95% of CFS patients (Reeves, BMC neurol 2006, Fossey M. J Behavo Med 2004; May KP, Am J MEd 2004, Drupp L, J Psychsom Res 1993). OSA was the most common sleep disturbance found in these studies. Poor sleep quality was found in CFS patients (but not in healthy controls) and was associated with weakness in the parasympathetic nervous system during sleep (Tajima, S. IACFS 2007).

 

FMS patients have been shown to have decreased amount of the deep stages of sleep (stage III and IV) and increased incidence of sleep apnea, restless legs syndrome, periodic limb movement disorder (PLMD) which is a form of restless legs syndrome during sleep and bruxism (jaw clenching and teeth grinding) (Shaver, J. IACFS 2007).

Upper Airway Resistance Syndrome- UARS is chracterized by erratic breathing but not meeting criteria for Obstructive Sleep Apnea (OSA), oxygenation drops, frequent arousals and is associated with daytime fatigue, headaches, Irritable Bowel Syndrome and low BP (Lario BA Am J Med 1996; Sergi Eur Resp J 1999). This syndrome may be involved in FMS as of 28 subjects with FM, 26 were found to have UARS by a sleep study and CPAP treatment resulted in 40% improvement in their daytime symptoms (Gold AR Sleep 2004). UARS is more common in women.

Some experts believe that fibromyalgia does not cause disturbed sleeping patterns, but that sleep disturbances may be the precipitating factor for many cases of fibromyalgia pain. In one study, non-fibromyalgia volunteers reported fibromyalgia-like pain after they had been subjected to disrupted deep sleep. Disturbed sleep appears to trigger factors in the immune system that cause inflammation, pain, fatigue, and decreased pain threshold.

 

Abnormal Pain Perception

Some studies have suggested that the lowered pain thresholds experienced by fibromyalgia patients may represent a central defect in the way fibromyalgia patients process pain. Brain scans of fibromyalgia patients have, in fact, suggested abnormalities in pain processing centers (Gracely, R. et al. fMRI analysis in fibromyalgia and chronic fatigue syndrome. Abstracts, AACFS, 2003). Of particular interest is research that has detected up to three times the normal level of substance P (a neurotransmitter associated with increased pain perception) in the cerebrospinal fluid of fibromyalgia patients. Such abnormalities along with other factors (such as chronic sleep deprivation or physical injury) may produce a state called generalized hyper vigilance, which is an amplification of sensation. People with this condition are oversensitive to external stimulation and are preoccupied with the sensation of pain.

For example one study compared three groups of individuals: fibromyalgia patients, rheumatoid arthritis patients, and people without these disorders. They were given a questionnaire to assess their response to pain and noise. Of the three groups, the fibromyalgia patients were least tolerant and most attentive to such stimuli.

 

Hormonal Abnormalities & The Hypothalamic-Pituitary-Adrenal (HPA) Axis

Adrenal Stress Hormones. Strong adrenal glands are key to optimum energy. The adrenal glands regulate the body's minerals as well as work with the thyroid gland to produce and maintain energy levels. We are exposed daily to many different kinds of stress including emotional, physical, environmental and work-related stress. Dietary factors such as refined and over-processed foods, preservatives, and pesticides are also stressors. These stresses make the adrenals over respond by producing extra amounts of hormones for energy. However, long periods of stress cause the adrenals to work overtime, eventually robbing the body’s reserve of energy and nutrients – which can create adrenal fatigue and chronic tiredness. Of particular interest to researchers are possible abnormalities in the brain system known as the hypothalamus-pituitary-adrenal axis (HPA), which controls important functions, including sleep, response to stress, and depression.

·        A number of studies on CFS patients have observed deficiencies in cortisol levels, a stress hormone produced in the hypothalamus (Cleare AJ, et al. Constrasting neuroendocrine responses in depression and chronic fatigue syndrome. Journal of Affective Disorders. 1995; 35: 283-289). Cortisol is a powerful suppressor of the immune system. One central hypothesis for CFS suggests that after a person with cortisol deficiency (hypoadrenalism) is exposed to a viral infection or some other physical or emotional stress, the immune system over responds and causes symptoms typical of chronic fatigue syndrome/FMS.

·        Riccardo Baschetti, M.D., states “Chronic Fatigue Syndrome (CFS) shares 39 features with primary adrenal insufficiency, including all the physical and neuropsychological symptoms listed in both the original and the revised criteria for CFS, as well as many other abnormalities.” Dr. Baschetti concludes, “I believe that adrenal insufficiency, rather than alteration in cardiac function, may primarily account for the reduction in exercise capacity in CFS.” (Riccardo Baschetti, M.D. Editor’s Correpsondence regarding: De Becker P, Roeykens J, Reynders M, Mc Gregor N, De Meirleir K. Exercise capacity in chronic fatigue syndrome. Arch Intern Med. 2000;160:3270-3277)

·        DHEA response to stimulation- One study investigated the response of the adrenal glands in 22 patients with CFS and 14 healthy controls. In both groups, they measured DHEA in serum after ACTH stimulation during 60 minutes. Although the researchers found normal basal (pre-stimulation) DHEA levels, they noted a ‘blunted’ serum DHEA response curve to the ACTH injection. This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. (De Becker et al, Horm Metab Res 1999 Jan;31 (1):18-21)

·        Small Adrenal Glands in CFS- The first study to use imaging methods to measure adrenal gland size in CFS revealed significant adrenal atrophy in a group of 8 CFS patients with abnormal endocrine parameters. The right and left adrenal gland bodies were reduced by over 50% in the CFS subjects compared to those from a group of 55 healthy subjects. (Scott et al, Psychoneuroendocrinology 1999 Oct;24 (7):759-68)

·        Abnormalities in the hypothalamus-pituitary-adrenal gland (HPA) axis have also been reported in fibromyalgia patients. Studies have revealed an impaired ability to activate the hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis as well as the sympathoadrenal system, leading to reduced ACTH and epinephrine responses to hypoglycemia (Adler GK, et al, "Reduced Hypothalamic-Pituitary and Sympathoadrenal Responses to Hypoglycemia in Women With Fibromyalgia Syndrome," Am J Med, May, 1999;106:534-543.)

 

Low Growth Hormone Levels. A third of FMS patients have low insulin growth factor (IGF) levels. Low levels of growth hormone have been associated with impaired mental functioning, lack of energy, muscle weakness, and intolerance to cold. See the medical therapy section for more information on growth hormone therapy in FMS/CFS.

 

Female Menses. Dr. Rowe reported in a small study that severe dysmenorrhea (painful menses) was more common in young women with CFS/ME and additionally, their CFS symptoms were worse during the time of their menses (Rowe K. IACFS 2007). Female hormone levels (estrogen, progesterone, testosterone) did not correlate directly with pain severity in 74 FMS women when compared to women without FMS (Okifuji 2006)

 

Infections

In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition. Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome. Most cases of CFS occur sporadically, cropping up individually without appearing to be contagious, and there is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact. It is likely that a subset of CFS/FMS patients have infection as a major reason for their illness, especially those with significant neuro-cognitive (brain) symptoms (Peterson, D. Abstract, AACFS, 2003).

Although over 30 infectious germs have been suggested to cause CFS over the years, no single germ agent have been proven to cause CFS including Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLVs), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus. Specifically, most studies (9 of them) suggest HHV6 as the most common infectious trigger to this disorder, but other studies (2) have failed to confirm this. Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS symptoms. Another theory referred to as "hit and run" suggests that chronic fatigue syndrome might be the result of a virus or bacteria that infects the body, causes immune abnormalities, and is then eliminated. It leaves behind a damaged imbalanced and dysregulated immune system, however, that continues to cause flu-like symptoms even in the absence of the virus (this is called Th2 activation). Other theories pose that immune system or neurologic abnormalities cause a reactivation of a viral or bacterial infection that had presumably resolved but had persisted in a latent (inactive) stage.

So far, there has been no study proving that CFS is “contagious.” However, one small pilot study suggests the possibility that an infectious agent which can cause CFS may persist in at least some CFS patients and can given to another individual, especially those living closely with the CFS patient (Underhill, O’Gorman, AACFS, Oct 2004).

 

Viral Infections

There have been 20 or more viruses somehow associated with CFS. Of these, two viruses seem to be the most prominent in recent studies: Human Herpes Virus 6 (HHV-6) and Epstein Barr Virus (EBV) (IACFS 2007). Other viruses linked to CFS include Parvovirus B19, enteroviruses (Coxackie B like viruses), Ross River virus, Coxiella burnetti (Q fever virus). In one small sample of 20 CFS patients, 9 (45%) were found positive to either EBV or HHV-6 compared to 12 healthy controls (Levine S. IACFS 2007). More information about HHV-6 can be found at the HHV-6 Foundation, www.hhv-6foundation.org

 

A common symptom found in many CFS patients is chronic stomach pain. Dr. Chia found evidence that 80% of 108 CFS patients had an enterovirus infection of their stomach proven by endoscopic biopsy (Chia J. IACFS 2007).

 

Mycoplasma Infections: Dr. Nicolson and co-workers have been interested in the potential role that chronic infections may play in FMS/CFS. Although the causes of chronic illnesses are for the most part unknown, the complex signs and symptoms that evolve in many FMS, CFS, Gulf War Illness (GWI) patients may be due, in part, to systemic chronic infections (bacteria, viruses, fungi). Such infections can follow acute or chronic chemical, environmental or other insults (trauma, acute viral illness, etc.) that have the potential to suppress the immune system and cause metabolic imbalances (Nicolson, G.L., et al. Mycoplasmal infections in chronic illnesses: Fibromyalgia and Chronic Fatigue Syndromes, Gulf War Illness, HIV-AIDS and Rheumatoid Arthritis. Med. Sentinel 1999; 4: 172-176 and Nicolson, N.L. Chronic fatigue illness and Operation Desert Storm. J. Occup. Environ. Med. 1996; 38: 14-16)

 

Dr. Nicolson previously found that more than 60% of patients with Chronic Fatigue Syndrome/ Fibromyalgia Syndrome had mycoplasma blood infections, such as M. fermentans. In a more recent study, patients with chronic Fatigue Syndrome/Fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A total of 91 patients diagnosed with Chronic Fatigue Syndrome/ Fibromyalgia Syndrome and with a positive test for any mycoplasmal infection were investigated for the presence of M. fermentans, M. pneumoniae, M. hominis and M. penetrans infections using forensic polymerase chain reaction. Infections were detected with M. pneumoniae (54/91), M. fermentans (44/91), M. hominis (28/91) and M. penetrans (18/91) of mycoplasma-positive patients, respectively. Multiple mycoplasmal infections were found in 48 of 91 patients, with double infections being detected in 30.8% or triple infections in 22%, but only when one of the species was M. pneumoniae and/or M. fermentans. Patients infected with different Mycoplasma spp. generally had a longer history of illness, suggesting that patients may have contracted additional mycoplasmal infections with time. (Nasralla M, Nicolson G. Multiple Mycoplasmal Infections Detected in Blood of Chronic Fatigue Syndrome and Fibromyalgia Syndrome Patients. European J of Clin Microbiology & Inf Dis 1999; 18: 859-865). Dr. Kamaroff found no evidence of M. fermentens in CFS patients (1993) but another report found evidence of M. fermentens in roughly 30% of CFS patients (Vojdani A. Detection of Mycoplasma genus and Mycoplasma fermentens by PCR in patients with CFS. FEMS Immunol Med Microbiol 1998; 22:355-65). More information on Mycoplasma can be found at http://www.cfsresearch.org/mycoplasma/index.htm

 

Intestinal bacterial overgrowth (Dysbiosis) may also play a role in these disorders. The data from a recent study suggests that bowel symptoms in fibromyalgia may be caused by small intestinal bacterial overgrowth.  There have been associations made between fibromyalgia symptoms and Chlamydia species as well as Borrelia burgdorferi.  In animal models, small intestinal bacterial overgrowth can result in bacterial translocation to mesenteric lymph nodes and can produce systemic effects.  These systemic effects are believed to be mediated by endotoxins from Gram-negative bacteria.  These endotoxin effects may explain the soft tissue hyperalgesia that is seen in fibromyalgia syndrome since injections of the endotoxin into lab animals results in similar hyperalgesia.  The authors conclude that the intestinal symptoms of fibromyalgia patients may be related to small intestinal bacterial overgrowth, and treatment of small intestinal bacterial overgrowth can result in overall improvement in intestinal symptoms. (Pimentel M, et al, "Small Intestinal Bacterial Overgrowth:  A Possible Association With Fibromyalgia,", J Musculoskeletal Pain, 2001;9(3):107-113)

 

Yeast Infections or Overgrowth

Although the “Yeast Over-growth Syndrome” remains controversial in medicine, one researcher found evidence of increased Candida albicans with an abnormal immune response in some CFS patients (Cozon, G. et al. In vivo and in vitro abnormal cellular reactivity to Candida albicans in patients with CFS. Abstract, AACFS, 2003). A small study on 20 CFS patients in an "acute phase of illness" found elevated levels of Candida albicans in stool samples when compared to 19 healthy individuals without CFS (Evengard B. IACFS 2007).

 

Immune System Abnormalities

CFS has been referred to as the "chronic fatigue - immune dysfunction syndrome" because studies have found dysfunction of the immune system, in which some components appear to be over reactive (termed “activated”), whereas other parts of the immune system have impaired function. Researchers have detected a number of chronic immune abnormalities in CFS patients, but no consistent or major abnormality that could indicate a primary cause. Researchers have identified certain auto-antibodies in many Fibromyalgia patients that affect neurologic and hormonal systems.

 

In one study, those patients with severe CFS symptoms, had higher-than-normal numbers of infection-fighting white blood cells known as killer T cells, which launch attacks on invading viruses and other disease-causing microorganisms. These same people had lower-than-normal levels of another white blood cell known as the suppressor T cell, which helps to shut down the immune response once the invading organisms have been killed. In such cases, the immune system becomes persistently overactive (activated) and produces fatigue, muscle aches, and other symptoms of CFS. Other studies have indicated lower amounts of natural killer (NK) cells and cytotoxic T cells in some CFS patients, which might make them more susceptible to viral and other infections. (Maher, K, Klimas, N, Fletcher, MA. Molecular defects associated with chronic fatigue syndrome. Abstract, AACFS, 2003). Abnormal NK cell function was found to be abnormal in both CFS patients and Gulf War Illness patients compared to healthy controls (Fletcher M. Klimas, N. IACFS 2007). Furthermore, these “activated” lymphocytes can pass through the blood-brain barrier and produce inflammatory chemicals called “cytokines” which leads to chronic low-level immune activation and inflammation in the brain (CDC Cold Spring Harbor Conference, Sept 2004)

 

Another area of research involves increase in the immune defense molecules “2-5A Synthetase” and “Rnase L.” Early studies revealed increased levels of these immune markers in CFS patients, in other words, the antiviral defense pathway is working overtime or is "upregulated" (Suhadolnik, R, et al. Clin Inf Dis, 18 (S96), 1994; Vojdani A, J Clin Lab Immunol, 1998; and Suhadolnik R, J CFS, 5,223, 1999). More recently, Dr. Suhadolnik demonstrated abnormalities of the RNase-L pathway and impaired function of natural killer cells in CFS patients but not in healthy “control” subjects or in patients with primary depression. Furthermore, these abnormalities correlated with elevated symptom scores (Suhadolnik R, et al.. Clinical and Biochemical Characteristics Differentiating CFS from Major Depression and Healthy Control Populations: Relation to Dysfunction of RNase L Pathway. J CFS 2004).  

 

To summarize, the evidence is very convincing that CFS patients have increased number of "activated T cells," poorly functioning natural killer (NK) cells, abnormal 2-5A Synthetase and RNase L pathway dysfunction, and elevated pro-inflammatory cytokines (TNF-a, IL-1, IL-6, INF-y) (Komaroff A. IACFS 2007).

 

Allergies and Contributing Environmental Factors

Allergies- are the only consistent immune system abnormality among CFS patients. Some studies have reported that up to 80% of CFS patients have allergies to food, pollen, metals (such as nickel or mercury) or other substances, although other studies have found no greater incidence of allergies in CFS patients than in the general population. In any case, allergies appear to make CFS symptoms worse in those who have them. Elimination diets may help determine whether allergies to specific foods are present. Most allergic people, however, do not have CFS. Some research indicates that in some cases people with both allergies and emotional disorders, such as anxiety or depression, are more vulnerable to the effects of the inflammatory response, which is triggered by allergens. This response triggers the release of a number of immune factors, importantly cytokines, powerful factors that can cause fatigue, joint aches, and fever and which can also affect the hypothalamus-pituitary-adrenal system in the brain. Another study found a similar relationship between depression, allergies, and low back pain.

 

Heavy Metal Toxicity (namely Mercury) has been implicated in CFS/FMS (Clauw DJ, "The pathogenesis of chronic pain and fatigue syndromes: fibromyalgia" Med Hypothesis, 1995, 44:369-78; & Hanson S, Fibromyalgia, glutamate, and mercury. Heavy Metal Bulletin, Issue 4, 1999, p3-6) and (Sterzl I, et al. Mercury and nickel allergy: risk factors in fatigue and autoimmunity. Neuroendocrinology Letters 1999; 20:221-228). In our experience, those patients who test high in mercury need to have this toxicity addressed for optimal treatment of their underlying CFS/FMS.

 

Metabolic (Mitochondrial) Dysfunction

Mutations in Mitochondria- Another theory about the cause of CFS, as well as fibromyalgia and other illnesses, concerns mutations of the mitochondria, the part of each cell that supplies energy. Inherited disorders involving  mutations that affect mitochondria are known to cause fatigue and muscle pain. One study reported that a specific genetic mitochondrial mutation called cytochrome b was associated with intolerance to exercise and aches and pains in a group of patients who had no known family history of mitochondrial genetic disease. Some research suggests that the mutation may be caused by free radicals, damaging particles released by the body's chemical processes. Two recent studies document increased free radicals and oxidant stress in CFS patients compared to healthy control subjects. (Kennedy, G, et al. Increased plasma isoprotanes and other markers of oxidative stress in chronic fatigue syndrome. Abstract, AACFS, 2003 and Vecchiet J, et al. Antioxidiant status in chronic fatigue syndrome, CFS. Abstract, AACFS, 2003). More work is warranted on this interesting observation to determine if such a mutation may account for some cases of CFS, especially concerning the role of antioxidants.

 

A theory that may help tie in the various conditions associated with CFS suggests that a combination of factors, including allergies, stress, and infections, may impair metabolic function by depleting adenosine triphosphate (ATP). This chemical stores energy in cells, and low levels are common in CFS patients. One study showing symptom improvement using a coenzyme called NADH that increased ATP levels lends support to this theory.

Muscle Abnormalities in FMS

·    Patients with CFS sometimes complain that they feel so weak that it seems as if their muscles are no longer working properly. It has been proposed that a defect in skeletal muscle could be the cause of the fatigue. However, physical, chemical, and metabolic studies have not yet been found in the  majority of CFS patients. Some research has detected muscle defects in fibromyalgia patients, which can be classified as follows:

o   Biochemical abnormalities. (Eg, One study reported that fibromyalgia patients had lower levels of the muscle-cell chemicals phosphocreatine and adenosine triphosphate (ATP). Such chemicals regulate the ebb and flow of calcium in muscle cells, an important component in their ability to contract and relax. If ATP levels are low, calcium is not "pushed back" into the cells and the muscle remains contracted. Such abnormal chemical levels could derive from signals in the brain.)

o   Structural abnormalities. (Eg, some researchers have observed overly thickened capillaries in the muscle tissue of fibromyalgia patients, which could produce lower chemical levels as well as reduce the flow of oxygen-rich blood in the muscle tissue.)

o   Functional abnormalities. (Pain and stress of the disease itself can impair muscle function.)

 

Coagulation Abnormalities

Dr. Berg has documented a unique “hypercoagulable state” in patients with CFS, FMS, Gulf War Illness and other conditions like Infertility and Multiple Sclerosis. He has named this abnormality “Immune System Activation of Coagulation (ISAC).” His model proposes that a variety of infectious agents (CMV, HHV6, Mycoplasma, Chlamydia, etc), toxins, allergens, or even vaccine contaminants stimulates the immune system to produce inflammatory chemicals (cytokines) which then results in increased blood viscosity (thickness) and microscopic “clotting” which causes localized decrease in blood flow and oxygenation to varies body tissues including the brain. These markers of hypercoagulation include fibrinogen, prothrombin fragment 1&2, thrombin anti-thrombin complexes and soluble fibrin monomer. He proposes the use of heparin (which must be injected into the skin or vein) for treatment of this abnormality. (Hannan KL, Berg E, et al. Activation of the coagulation system in Gulf War Illness: a potential pathophysiologic link with chronic fatigue syndrome: a laboratory approach to diagnosis. Blood Coag Fibrinolysis 2000, 11:7). A follow up study of these coagulation factors revealed the possibility that a hereditary gene defect combined with the immune system activation of coagulation work together to produce the end result of microscopic clotting and decreased blood flow to the body’s tissues in the CFS/FM patient. (Harrison H, et al. Procoagulant genetic factor in a pooled cohort of 582 chronic fatigue syndrome, fibromyalgia and related chornic illnesses, AACFS, Oct 2004).

Psychological and Social Effects

Although not primary causes, psychological and social factors may contribute to CFS/FMS in three ways:

·        They could make individuals susceptible to CFS/FMS

·        They may play some role in triggering the onset of the condition.

·        They may help perpetuate it by stressing the immune system

 

Studies have reported a greater incidence of severe experiences of victimization from emotional and physical abuse in patients with fibromyalgia than in the general population. Most often the abuse originated from family or partners. This suggests that post-traumatic stress syndrome or chronic stress may play a strong role in the development of this disorder in some patients. Post-traumatic stress disorder (PTSD) is an anxiety disorder that is a reaction to a specific traumatic event. Symptoms of this condition, which can occur for years after the traumatic event, include emotional withdrawal, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle response to noise. There is some evidence that PTSD actually results in changes in the brain, possibly from long-term overexposure to stress hormones.

Gulf War Illness: Chronic Fatigue-like Symptoms after the Gulf War

Gulf War veterans have been intensively studied because of a high percentage reporting CFS symptoms. One major study reported that 45% of Gulf War veterans met the overall criteria for chronic fatigue syndrome, with 6% having severe cases. Women veterans had three times the risk as men. Interestingly, 15% of the noncombat personnel, representing the general population, reported the same problems, although the cases in general were less severe than in the veterans. Because such symptoms have occurred in other veteran groups, some experts suspect that post-traumatic stress syndrome may be responsible for the symptoms in some cases. After finding that stress weakens the blood-brain barrier, some experts believe that, in extremely stressful situations such as the Gulf War, this weakened barrier may allow agents, such as small viruses, to pass into the brain causing damage and triggering CFS symptoms. Whether uncovering the causes of the syndrome in Gulf War soldiers can be applied to civilian cases of CFS, however, is not known. One 2000 study has heavily implicated multiple vaccinations given to military personnel during the Gulf War (but not those given before). More than a dozen different illnesses have been detected in over 70,000 soldiers examined for this problem. Some researchers identified an unusual bacteria-like organism known as Mycoplasma fermentans in nearly half the veterans who suffered from Gulf War syndrome, and one scientist speculated that it might have been developed for biological warfare. Some researchers suspect that the symptoms were caused by an experimental vaccine that contained a substance called squalene. High levels of antibodies to this compound have been found in the blood of veterans with CFS symptoms. An investigation is underway. Still other studies have found that up to 20,000 troops may have been exposed to low levels of the nerve gas sarin.

How is CFS/FMS Diagnosed?

Diagnostic Criteria

There is no unequivocal objective method for diagnosing these sister conditions. The criteria used for studying CFS and FMS are very helpful, particularly if the patient does not have any accompanying disorder, such as depression or arthritis, that could complicate the diagnosis. Failure to meet the criteria, however, does not rule them out. It should be suspected in any patients with severe fatigue and muscle or pain when no identifiable cause has been found.

Medical and Personal History

A physician should always take a careful personal and family medical history, which would include a psychological profile and a history of any factors that might be indicative of disorders other than fibromyalgia. Such factors might include recent weight change, physical injuries, infectious diseases, muscle weakness, rashes, and any instances of sexual, physical, or substance or alcohol abuse. The patient should report any drugs being taken, including vitamins and over-the-counter or herbal medications.

Physical Examination

Pressure on Tender Spots. Any physical examination for fibromyalgia requires that the physician press firmly on all potential tender spots. They must be painful when pressed, not simply tender. In addition, for a diagnosis of fibromyalgia, these tender sites are not typically accompanied by signs of inflammation, such as redness, swelling, or heat in the joints and soft tissue. The pressure points may also change in location and sensitivity over time. A physician, then, may re-check pressure points that do not respond the first time in patients who have other significant symptoms.

Detection of Other Causes of Symptoms. A physical examination also includes scrutiny of nails, skin, mucous membranes, joints, spine, muscles, and bones to help rule out arthritis, thyroid disease, and other disorders.

Other Tests

There are no blood, urine, or other laboratory tests that can proof the the specific diagnosis of CFS or FMS. Tests for specific diseases depend on family histories and other symptoms. They may include thyroid and liver function tests, blood count, tests of certain antibodies, and sedimentation rate.

Simply measuring blood pressure will not identify CFS patients whose condition might be caused by Neurally Mediated Hypotension (an abnormal drop in blood pressure). A tilt test, whereby an individual lies on a table tilted upright at a 70-degree angle for a prolonged period, may confirm CFS caused by Neurally Mediated Hypotension if the patient feels lightheaded, sick, and faint after several minutes. A specialized test of the autonomic nervous system (ANSAR) can be easily performed in the office and detects abnormalities in the autonomic nervous system without the stress of a tilt table test.

Other specialized tests may include growth hormone, adrenal hormone assay, tests for heavy metal toxicity, stool tests for bacterial/fungal overgrowths, for infections (RNase-L, EBV, HHV6, Mycoplasma, Lyme, etc), and subtle inflammation markers like HS-CRP. Some experts are hoping that this or other markers may reveal a biologic basis for CFS and also establish a method for diagnosing it. Follow-up psychological profile testing may be suggested if laboratory results do not indicate a specific disease.

Cardiac stress tests with oxygen consumption measurements can sometimes be helpful in finding physiologic abnormalities in CFS patients. However, a recent small study of CFS patients versus healthy controls revealed that CFS patients had a significant worsening of their oxygen consumption when the test was repeated 24 hours later whereas healthy individuals had normal results on both the initial and repeat test (Ciccolella, M. IACFS 2007). This two-step cardiac stress test with oxygen consumption analysis appears to document the significant post-exertional exhaustion that is the hall mark of CFS.

How Serious Are These Conditions?

Severity of Symptoms

The severity of chronic fatigue syndrome varies. In extreme cases, patients are bedridden and can do virtually nothing, including even light housework. More often, CFS sufferers can work at least part-time. Most commonly, patients with CFS report that they have trouble fulfilling both home and work responsibilities. Most patients say that while fatigue is the most incapacitating symptom, those of mental impairment, such as an inability to concentrate, are the most distressing. Some studies indicate that although general intelligence is not impaired, CFS patients test lower in certain mental functions, particularly speed and efficiency in processing complex information. In such studies, this impaired mental function occurs regardless of the presence or absence of depression or other psychiatric disorders. One study found that the mental impairment in CFS patients parallels the degree of their physical impairment, indicating that the disease process itself may exert a neurologic effect.

Like CFS, Fibromyalgia can be mild or disabling, and the emotional repercussions can be substantial. About half of all patients have difficulty with or are unable to perform routine daily activities. Estimates of patients who have had to stop work or change jobs range from 30% to 40%. The pain, emotional repercussions, or sleep disturbances may lead to self-medication and overuse of sleeping pills, alcohol, drugs, or caffeine.

 

Long-term Outlook in Adults

Because the illness has been undefined and there are few objective measures for recovery, experts have found it difficult to determine the long-term outlook of CFS. Some physicians have observed that patients whose symptoms began abruptly following a severe viral illness recovered completely after six months to a year, whereas patients whose problems developed slowly and insidiously experienced symptoms for a longer period of time. Patients who report that they can think clearly most of the time, who do not have other physical or emotional complaints beyond CFS symptoms, and who sleep well are more likely than other CFS patients to experience improvements in their fatigue over time. Nevertheless, studies have reported that between 58% and 72% of patients who complain of chronic fatigue (whether CFS or idiopathic fatigue) continue to experience it after a year and in one study nearly 60% were still fatigued at two years. One small 1999 study observed that even after four years few patients with severe CFS had returned to their pre-illness state. Yet another study, however, found that when patients with severe CFS were treated with a multidisciplinary rehabilitation program, nearly all improved significantly and the gains were maintained for at least a year afterward. Many patients with less severe chronic fatigue have reported turning a corner after a year or two and slowly regaining energy despite some setbacks along the way. Some patients get progressively worse, but the disorder is not fatal. Although children with symptoms of chronic fatigue have not been rigorously studied, some studies indicate that children generally have a better prognosis than adults and recover after one to four years in up to 95% of cases.

Some studies indicate that fibromyalgia symptoms remain stable over the long term, while others report a better outlook, with 25% of patients in remission two years after diagnosis. Although the disease is chronic, it is neither progressive nor fatal, and remission can occur in many patients who participate in disease management programs. Patients with secondary fibromyalgia, particularly when it is caused by injury, tend to have a more severe and less easily treated condition than those with primary fibromyalgia.

Outlook in Children

Children with Fibromyalgia tend to have better outlooks than adults do. In adult patients who were studied for four and a half years, those who had adequate exercise had the most promising outcome; those with a significant life crisis or who were on disability had a poorer outcome than others. Outcome was determined by improvements in the patients' capacity to work, their own feelings about their condition, pain sensation, disturbed sleep, fatigue, and depression.

General Treatment Guidelines

Since there is no one cause for CFS/FMS, there is no one treatment! Treatments can be thought of in two distinct categories and are usually given concurrently.

·    Symptomatic therapies that address the worst symptoms in each individual patient (ie. pain medication, sleep agents, antidepressants).

·    Therapies designed to address those specific HPA axis dysfunctions, immune dysfunctions, infections, toxic, hormonal or metabolic disturbances found in each person evaluated in a comprehensive manner.

If the specific underlying factors can be isolated to each given individual patient and targeted with specific therapies for those specific abnormalities, then less symptomatic therapy is required and improvement ensues. Treatments usually involves a combination of a variety of therapies the achieve the maximum results for each person.

The specific tender points and generalized pain suffered by Fibromyalgia patients are most likely the end-points of a disease process that starts in the brain. Therefore, treatments should involve not just dealing with the pain centers but must be a multi-faceted approach. One study found that interdisciplinary treatment programs were effective in significantly improving pain in 42% of patients. After treatment stopped, improvements in pain and other symptoms, including depression and sense of physical capability, persisted for at least six months, although patients tended to become fatigued again. The effectiveness of the treatments tended to depend on how depressed the patients were, the sense of their own disability, personal support networks, and whether the cause was known. The severity of the pain at the start of treatment had little to do with outcome.

Dr. Teitelbaum demonstrated success with the multi-factorial treatment of 72 FMS patients (38 active, 34 placebo; 69 also met CFS criteria). All patients  received all active or all placebo therapies as a unified intervention. Patients were treated, as indicated by symptoms and/or lab testing, for: (1) subclinical thyroid, gonadal, and/or adrenal insufficiency, (2) disordered sleep, (3) suspected Neurally Mediated Hypotension (NMH), (4) opportunistic infections, and (5) suspected nutritional deficiencies. His conclusions: significantly greater benefits were seen in the active group than in the placebo group for all primary outcomes. Using an integrated treatment approach, effective treatment is now available for FMS/CFS. (Teitlebaum J, et al. Effective Treatment Of Chronic Fatigue Syndrome (CFIDS) & Fibromyalgia (FMS) - A Randomized, Double-Blind, Placebo-Controlled, Intent To Treat Study. J CFS 2001 8:2)

Preparation for Treatment

·        Patients must have realistic expectations about the long-term outlook and their own individual capabilities. It is important to understand that the condition can be managed and patients can live a full life. The following tips may be helpful in embarking on a treatment program for fibromyalgia:

·        Patients must begin all treatments with the attitude that they are trial and error. No physician, even an expert, has a clear treatment solution, because little significant research has been conducted on this disorder. For example, there were no major trials on drug therapies for fibromyalgia reported during 2000. Patients and doctors need to work together to make the best choices for individual symptoms and concerns.

·        Therapies are prolonged, in some cases life-long, and patients should not be discouraged by relapses.

·        Enlisting family, partners, and close friends, particularly with exercise and stretching programs, can be helpful.

·        Becoming involved with support groups of fellow-patients has also benefited many patients. Support groups may also benefit family members, particularly parents of children with fibromyalgia. One study noted that the severity of the disorder increased in children whose parents were less able to cope with their children's pain.

·        Improvement is subjective, and some patients are pleased with only a 10% reduction in pain and other symptoms.

General Treatments Categories

·        Exercise and Physical Therapy

·        Lifestyle Modification: Stress Management, Diet, Sleep Hygeine

·        Psychological Therapies such a Cognitive Behavior Therapy

·        Medical Therapies: Medication, hormone therapies

·        Body Based Therapies: Osteopathic/Chiropractic Manipulation, Massage, Acupunture, etc

·        Complementary and Alternative Therapies: Herbs, Vitamin Therapies

Physical Therapy and Exercise

Most CFS patients experience profound fatigue following even mild to modest exercise, and it is the primary factor in the low-activity levels in these patients. A recent study found, however, that 75% of patients who were able to engage in exercise, particularly aerobic exercise, reported improvement in fatigue, normal functioning, and fitness after a year. Another recent study demonstrated that light intensity interval training for CFS patients can be beneficial and slowly produced improvements in their exercise capacity and physical functioning without increased fatigue or other CFS symptoms (Gudrun, L., et al. Low intensity, interval training in women with chronic fatigue syndrome. Abstract, AACFS, 2003). Low intensity exercise was again found to increase physical capacity without worsening CFS/ME symptoms in a study of 14 women who completed a 10 week low intensive interval training program (Lennartsson C. IACFS 2007).

It is necessary to go slowly, however, to prevent relapse as some studies have shown too aggressive exercise to make some CFS patients worse (Whiteside, 2004; Paul, 1999; Blackwood, 1998). Patients should gradually increase activity level, keeping within limits and avoiding over-exertion. This is termed Activity Pacing. An incremental program of activity, beginning with as little as two minutes of moderate exercise a day, is suggested, although capacity varies greatly among CFS sufferers. The goal is to increase activity by about 20% every two to three weeks. Setbacks will occur, but patients should not become discouraged. Rather, they should experiment with various forms of physical activity that suit their available energy levels. Some patients report great benefits from Yoga or Tai chi, which combine exercise with meditation.

One of the best things you can do if you have fibromyalgia is exercise. Exercise relieves much of the pain fibromyalgia causes. Some people find that exercise makes all their pain go away. You will also feel better if you have some control over your own care and well-being. Physical activity prevents muscle atrophy, increases a sense of well-being, and, over time, reduces fatigue and pain itself. Many studies have indicated that exercise is the most effective component in managing fibromyalgia, and patients must expect to undergo a long-term exercise program. ("Effect of a Randomized, Controlled Trial of Exercise on Mood and Physical Function in Individuals With Fibromyalgia," Gowans SE, et al, Arthritis Care Res, December 2001;45(6):519-529.) 

 

·         Some patients with fibromyalgia avoid exercise for fear it will exacerbate their pain. However, according to studies, any pain caused by exercising subsides within 30 minutes. A very gradual incremental program of activity, beginning with mild exercise and building over time, is important to help patients comply with exercise.

·         Start your exercise program slowly, because at the beginning, exercise may make your pain worse. Begin with stretching exercises and gentle, low-impact activity, such as walking or bicycling. Some muscle soreness is normal when you're starting to exercise, but sharp pain may be a sign that you have overworked your muscles. Patients who attempt strenuous exercise too early actually experience an increase in pain and are likely to become discouraged and quit. It should be noted that even walking two or three times a week is helpful. Some may need to start out with 5 minutes of exercise per week, and add 1 minute per week- in over half a year, you will be up to 30 minutes of exercise per day.

·         As you progress with exercise, it will become more comfortable for you. In order for exercise to help, you must do it regularly. The goal is to get started and keep going, to gain relief from pain and to improve sleep. Some tips may be helpful:

·         Walking: Start slowly by walking for 5 minutes the first day. The next day, add a minute to this total. Keep adding 1 or 2 minutes a day until you are walking for 60 minutes a day. When you reach this point, walk for at least 1 hour, 3 or 4 times a week. If you find yourself struggling as you're working your way up to walking for 60 minutes, go back to a length of time that was comfortable for you and continue walking for this period of time for several days. Then continue to increase the minutes again until you reach the goal of 60 minutes. Try as many times as you need to reach the goal of walking for 60 minutes.

·         Walking/jogging: After you feel comfortable with walking 3 or 4 times a week, you can alternate walking with slow jogging. Walk for 2 blocks, then jog for 1 block, walk for 2 blocks, jog for 1 block, and so on. Do this as often as feels comfortable, and extend your exercise for longer periods if you feel comfortable.

·         Bicycling: Stationary bicycles (exercise bikes) offer the benefit of exercising indoors. Keep track of your mileage, or set a goal of exercising for 60 minutes.

·         Tai Chi and Yoga: Can be excellent choices for the FM patient as they are low impact and involve stretching and motion without excessive exhaustion.

The type of exercise you choose is up to you. The important thing is that you start exercising and keep doing it. Every patient must be prepared for relapse and setbacks, which are nearly universal, but this should not dissuade the patient from exercising. Patients should experiment with various forms of physical activity that can be tolerated using their available energy levels.

 

Aerobic and Strength Training Exercise. Strength training and regular low-impact aerobic exercise are very helpful for raising the pain threshold, although it may take months to perceive benefits. Desirable exercises are walking, swimming, and using stationary bikes. Swimming and water therapy, which eliminate weight-bearing, appear to be excellent choices for getting started.

Training Index. Some experts recommend the use of a training index for gauging progress and establishing a goal. This index is the product of three calculations:

·                     The duration of exercise in minutes.

·                     Number of days per week that the patient exercises.

·                     The percentage of maximum heart rate. See Determining Percentage of Maximum Heart Rate below.

People just beginning an exercise program should start with an index of 10 to 25 and aim over time for at least 42. The following are some examples for determining these indexes using exercise goals.

·                     To achieve an initial index of 15 the patient strives for the following exercise goals: A maximum heart rate percentage of 60% (.60) during exercise performed for 5 minutes 5 times a week. (the index is calculated in such a case by multiplying .60 x 5 x 5)

·                     The later goal of an index of 42 could be achieved with the following a maximum heart rate percentage of 70% that occurs with 20-minute exercises three days a week (.70 x 20 x 3 = 42).

Stretching exercises should be performed for about 10 minutes before aerobic exercise, but they are not considered part of the total exercise time that the patient uses in calculating the index goal.

Determining Percentage of Maximum Heart Rate

·                     Determine the maximum heart rate by subtracting one's age from 220.

·                     Determine the heart rate by measuring the pulse either at the carotid artery on the neck or on the inside of the wrist during a workout. It's easiest to count pulse beats for 10 seconds, then multiply by six for the per-minute total.

·                     Calculate the percentage of maximum heart rate, by dividing the exercise heart rate by the maximum heart rate and multiply by 100

Physical Therapy. The use of physical therapy may be very helpful. One study suggests that such therapy may reduce muscle overload, reduce fatigue from poor posture and positioning, and help condition weak muscles.

Life Style Modification Therapies

Establish Regular Sleep Routines

Sleep is essential, particularly since pain is aggravated by disturbed sleep. Improvement is low in those who are unable to sleep consistently and at night. Swing shift work, for example, is extremely hard on fibromyalgia patients. (For tips on improving sleep, see our handout on Sleep Hygeine)

 

Diet

Some fats may be beneficial. Some studies report some improved symptoms in patients who consumed black currant, evening primrose and fish oils. These oils contain a polyunsaturated fatty acid known as gamma linoleic acid, which seems to block the release of cytokines and prostaglandins, important immune factors that play major destructive roles in inflammatory diseases. For those with demonstrated low blood pressure, increasing the amount of salt in the diet may be helpful.

A small 2000 study in Finland suggested that a vegan diet (no meat, dairy, or eggs plus uncooked fruits, vegetables, nuts, and germinated seeds) had beneficial effects on fibromyalgia symptoms including pain, stiffness, and quality of sleep. In addition, the diet was associated with lower weight and cholesterol levels. There are no large scale studies telling us that any specific dietary factor is effective in managing fibromyalgia. Oils containing omega-3 fatty acids are of  particular interest for arthritic pain. Such oils are found in cold water fish and can be purchased as supplements called EPA-DHA or omega 3.

We have found a “low starch/low grain diet” generally beneficial:

Breakfast Suggestions

·                     Organic oatmeal, milk, soymilk, or goat’s milk, 3 Tbsp. fresh ground flaxmeal

·                     Hot brown rice cereal w/cinnamon, green tea

·         Organic cottage cheese with flax oil, organic fruit or raw nuts (almonds, walnuts), green tea

·                     Organic yogurt (no sugar), 1 Tbsp. flax oil or 3 Tbsp. ground flaxmeal,

·                     ½ cup organic berries

·                     Poached organic omega-3 eggs or three egg omelet, sweet potatoes w/rosemary

·                     2 organic eggs any style, 1 slice whole grain toast, 3 tablespoons freshly ground flaxmeal

Lunch and Dinner Suggestions

·                     Season sardines in water (green and white label), green salad

·                     Flank steak, baked potato, green salad with flax oil dressing

·                     Broiled red snapper, steamed broccoli, baked yams

·                     Large mixed green salad w/ oil and lemon juice, small can of tuna, chopped yellow and sweet red pepper

·                     Broiled red snapper, steamed broccoli, green beans or other vegetable

·                     Beef, lentil and vegetable soup, (celery, carrots, onion, cabbage)

·                     Chicken salad made with sugar-free mayonnaise, roasted vegetables, spinach salad

·                     1 cup cottage cheese or yogurt, 1 tablespoon flax oil, 1 tablespoon natural preserves

·                     1 chicken breast with rosemary, ½ cup black eyed peas, roasted onions or garlic, spinach salad.

Snacks

·                     Protein shakes with freshly ground flaxseeds added, handful of raw almonds, hazelnuts, walnuts, brazil nuts, or  sesame seeds, an organic apple, pear, or grapes, sugar-free yogurt, rice cakes with nut butter

·                     Green vegetable juices: three 6-ounce glasses per day freshly made only from green vegetables (celery, spinach, dandelion, zucchini work well).

·                     Herbal teas: licorice, ginseng, and green tea.

Avoid

·                     Sugar, hydrogenated oils, corn oils, soft drinks, alcohol

 

Coping and Stress Reduction Techniques

Relaxation and stress-reduction techniques are proving to be helpful in managing chronic pain. There is certainly evidence that people with fibromyalgia have a more stressful response to daily conflicts and encounters than those without the disorder. (For more information, see our Stress Fitness Handout). A number of relaxation and stress-reduction techniques have proven to be helpful in managing chronic pain:

• Deep breathing exercises
• Muscle relaxation techniques
• Imagery techniques
• Hypnosis
• Biofeedback

Hypnosis. In one controlled study, hypnosis was more effective than physical therapy in improving function and reducing pain.

Biofeedback. Evidence suggests that biofeedback techniques may be helpful for fibromyalgia patients. During biofeedback, electric leads are taped to a subject's head. The person is encouraged to relax using methods such as those described above. Brain waves are measured and an auditory signal is emitted when alpha waves are detected, a frequency that coincides with a state of deep relaxation. By repeating the process, subjects associate the sound with the relaxed state and learn to achieve relaxation by themselves.

One study showed that biofeedback/relaxation training and structured exercise programs produced short- and long-term benefits for individuals with fibromyalgia in the areas of self-efficacy, disease severity and physical activity.  In general, the improvements were modest. (Buckelew SP, et al, "Biofeedback/Relaxation Training and Exercise Interventions for Fibromyalgia:  A Prospective Trial," Arthritis Care and Res, June, 1998;11(3):196-209)

 

Coping Help: The Stanford Self Management Model has been validated and found very helpful in other chronic medical conditions. Its premise is logical, rational and has attributes that could be very beneficial for the CFS/FMS patient. There exists a Self Help Manual "Living a healthy life with Chronic conditions." In addition, there is an online site which is based upon the Stanford Model: www.cfidsselfhelp.org

Medical Therapies

The primary goal of drug therapy is to address the most significant symptoms in these conditions: improve sleep, improve fatigue and thinking, improve depression, improve autonomic dysfunction and pain management.  

Symptomatic Treatments

Treatments for Depression and Anxiety

Studies suggest that antidepressants help between a third and a half of patients with FSM. Doses used for fibromyalgia are generally lower than for depression, so combinations may be an option. Benefits may be strongest with a combination of drugs from two classes, the tricyclics and SSRIs. However, none have been well researched. It should be noted that some patients report worse symptoms with antidepressants.

·        Saint John’s Wort- has been shown beneficial for mild to moderate depression, anxiety, insomnia (enhances REM sleep) and also has anti-viral and anti-inflammatory activity. There have been no studies with SJW in CFS or FMS.

·        Tricyclics. Tricyclics not only help relieve depression but they also have properties that reduce sleeplessness and muscle pain. The tricyclic drug most commonly used for fibromyalgia is amitriptyline (Elavil, Endep), which produces modest benefits with pain, but which can lose effectiveness over time. Other tricyclics include desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), amoxapine (Asendin), and nortriptyline (Pamelor, Aventyl). Generally only small doses are necessary for relief of fibromyalgia, so, although tricyclics have a number of side effects, they may occur less frequently in fibromyalgia patients than in those taking tricyclics for depression. Side effects most often reported include dry mouth, blurred vision, sexual dysfunction, weight gain, difficulty in urinating, disturbances in heart rhythm, drowsiness, and dizziness. Amitriptyline, doxepin and trazodone are the most sedating and desipramine is the least sedating. Like all medications, tricyclics must be taken as directed; overdose can be life threatening.

·        Selective Serotonin-Reuptake Inhibitors (SSRIs). Selective serotonin-reuptake inhibitors (SSRIs) increase serotonin levels in the brain. Serotonin is a chemical messenger important for feelings of well being. Commonly prescribed SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox) and Lexapro. In some patients, they may improve sleep, fatigue, pain, and well-being. SSRIs should be taken in the morning, since they may cause insomnia. Common side effects are agitation, nausea, and sexual dysfunction, including delayed or loss of orgasm and low sexual drive.

o       One study of 60 women with FMS found that that Fluoxetine (prozac) was effective on most outcome measures and generally well tolerated in women with fibromyalgia but the effects on tender points and myalgic scores were not so clear-cut. (L. Arnold. "A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia" The American Journal of Medicine 2002;112(3):191-197)

o       Another study revealed the combination of prozac with amitriptyline was better than either one alone for FMS symptom improvement (Goldenberg D, et al. A randomized, double blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Arthritis Rheum 1996, 39:1852-9)

o       SSRI medications appear to have little value for CFS beyond treating any accompanying depression.

·        Other Antidepressants

o       Nefazodone (Serzone) a newer, so-called designer SSRI, produced moderate benefits in CFS patients' mood, fatigue, and sleep disturbance in one small 1999 study.

o       Trazodone (Desyrel) is an antidepressant that might be specifically helpful for fibromyalgia suffers. It is also very sedating.

o       Venlafaxine (Effexor)- Is an antidepressant that increases both serotonin and norepinephrine in the brain. It may be of use in FMS (Ninan PT. Use of venlafaxine in other psychiatric disorders. Depress Anxiety 2000, 12 Suppl 1:90-4)

·        Anti-Anxiety Medications: If anxiety is also a problem, an anxiety-relieving drug, such as alprazolam (Xanax) or Lorazepan (, may be prescribed, although anti-anxiety drugs can become addictive if used for prolonged periods and are not usually recommended.

·        Phototherapy-The use of phototherapy may be effective treatment for patients with CFS whose symptoms have a seasonal variability (worse in the winter time) that is similar to those of patients with seasonal affective disorder (SAD). Patients with SAD experience more depression during winter than summer months. With phototherapy, the patient sits a few feet away from a box-like device that emits very bright fluorescent light (10,000 lux) for about 30 minutes every day. It is best performed immediately after awakening in the morning.

Muscle Relaxants

Cyclobenzaprine (Flexeril) relaxes muscle spasms in specific locations without affecting overall muscle function. It is related to the tricyclic antidepressants and has similar side effects, the most common being dry mouth, drowsiness, and dizziness. Other muscle relaxants include Soma and Zanaflex.

Sleep Medications

Non Prescription Natural Agents

·        Melatonin- 3-10 mg -1 at bedtime

·        5 HTP (5 Hydroxytryptophan) -100 to 400mg at night. Naturally stimulates Serotonin. 5-HTP has been shown to be effective in treating a wide variety of conditions, including fibromyalgia and depression (Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev 1998; 3:271-80)

·        Passion Flower (Passiflora) -100 to 200mg at night. This is also good for anxiety during the day.

·        Kava Kava -30% extract -250mg capsules -1 to 3 capsules at night (if a rash develops add a B-complex ,50mg at night -and stop/decrease the dose/frequency of use. There are recent reports in Germany of rare occurrence of liver dysfunction in patients taking Kava and liver enzymes should be monitored if this therapy is attempted.

Prescription Medications

·        Doxylamine (Unisom For Sleep) -25 mg at night (an antihistamine).

·        Benadryl (dihydramine)- 25-50mg at bedtime (an antihistamine).

·        Ambien (zolpidem) -10 mg- ½ to 1 at bedtime. If you tend to wake during the night, leave an extra 1/2 to 1 tablet at bedside and you can take it as needed to help you sleep through the night.

·        Elavil (amitriptyline) -10 mg- ½ to 5 tablets at bedtime. May cause weight gain or dry mouth. Good for nerve pain and vulvadynia.

·        Doxepin (sinequan)- 10mg capsule at bedtime. May cause weight gain or dry mouth. Good for nerve pain and vulvadynia.

·        Desyrel (trazodone) -50 mg – ½ to 6 at bedtime. Although sedating, it can be used (50-250mg at a time) for anxiety. Do not take over 450mg a day (or 150mg a day if on other antidepressants). Increases stage III and IV sleep.

·        Klonopin (clonazepam) – ½ mg -begin slowly and work your way up as sedation allows. Take ½ tablet at bedtime increasing up to 6 tablets at bedtime as needed. Can be effective for sleep, pain and Restless Legs. The combination of klonopin ande doxepin may be more useful than either alone.

·        Soma (carisprodol) – ½ to 1 at bedtime. This is very good if pain is severe.

·        Flexeril (cyclobenzaprine) -10 mg- ½ to 2 at bedtime. Muscle relaxant --can cause dry mouth.

·        Remeron (mirtazapine) -15mg -1 to 3 tablets at bedtime (especially helpful if you feel like you're "hibernating" during the day). Increases stage III and IV sleep

·        Serzone (nefazodone)- Increases stage III and IV sleep

·        Xanax (alprazolam) – ½ mg – ½ to 4 tablets at bedtime. This is short-acting and gives a good 3 to 5 hours sleep with less hangover in the morning.

·        Sinemet 10/100- 1 at 6 to 9PM each evening for Restless Leg Syndrome.

Pain Relievers

Pain relief is of major concern for patients with fibromyalgia and frequently required in CFS.

·        Acetaminophen (Tylenol) is most often recommended but can reduce glutathione levels (felt important by some researchers for liver and brain detoxification). See our monograph on Glutathione for further information on this very important antioxidant/detoxifier.

·        Anti-inflammatory drugs, which are commonly used for arthritic conditions are mush less useful for the pain of fibromyalgia, since the pain is not caused by muscle or joint inflammation. Such drugs include corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Advil), and others.

·        Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has helped some people and was thought not to be addictive, although dependence and abuse have been reported. It can cause nausea.

·        Tricyclic antidepressants (elavil, doxepin, norpramin) decrease the pain sensations in the brain and thus can be useful in chronic pain states.

·        SNRI's (Venlafaxine, Milnacipran, Duloxetine)- These agents, which work on both serotonin and norepinephrine receptors appear to provide benefits in the type of pain found in FMS.

·        Gabapentin (Neurontin) and Pregabalin are anti-seizure medications that can help neuralgic type pain.  that is helpful for some neuralgic type pain. Other anti-seizure medications that may be useful include Lamictal, Trileptal and Topomax.

·        Opioids (Oxycontin, Morphine, etc) have been shown to be not helpful in the kind of pain that FMS/CFS patients experience, called "central pain." Since this class of pain relievers are not beneficial and may lead to dependence and addiction, opioids should be avoided.

·        Intravenous Lidocaine has been suggested to be helpful in chronic pain conditions in several small studies. Mexilitine (oral form of lidocaine) may also be tried.

            Targeting Pressure Points and Stretching Techniques

Much of the pain experienced by patients occurs where muscles join tendons or bones, particularly when the muscles are stretched. Stretching, or flexibility exercises, are part of the warm-up and cool-down routines of any regular program. Stretching technique used for muscle relaxation and pain reduction in fibromyalgia, however, are different and employ injections or cooling agents to inactivate the pressure points so that muscles can be stretched. These techniques must be performed by a person other than the patient, usually a family member or close friend. With use of either injections or the spray, the benefits may last from a few days to weeks. Neither the spray nor the injection is useful without muscle stretching.

Spray and Stretch:  Tender points are sprayed with a “freezing” spray and then manually stretched

Trigger-Point Injections. In some cases, "trigger-point injections" of an anesthetic may be used for particularly painful tender points as an aid to stretching.

·                     The injection causes intense, transient pain in the trigger point. After the medication has taken effect, however, the ability to stretch the muscle is greatly enhanced.

·                     There is some soreness afterward, which can be severe. After an injection, spraying the whole muscle with cooling agents may inactivate less severe tender points.

·                     In some cases, injections may be needed two or three times over six to eight weeks.

It should be noted that the benefits of this treatment may not be apparent immediately.

Treatment of Specific Abnormalities

Treatment for Low Stress (Adrenal) Hormones

Cortisone Therapy- Some evidence exists that patients with CFS may be deficient in cortisol, a steroid hormone. Studies testing the steroid drug hydrocortisone have reported increased energy and less fatigue in patients taking it. However, side effects including insomnia, increased appetite, weight gain, and, more seriously, suppression of the adrenal gland, make this therapy unacceptable.

·        A recent study reporting improvement with very low doses of cortisone (5 mg to 10 mg daily) with only minor side effects may make this therapy feasible for some patients. In this trial, 32 CFS patients treated with 5-10mg hydrocortisone for 28 days and showed ‘significant reduction in self-rated fatigue and disability in patients with chronic fatigue syndrome’ (Cleare et al; The Lancet, 1999, Vol. 353 February 6, p455-32.)

·        However, in another randomized controlled trial of hydrocortisone therapy (McKenzie at al) used a higher dose of hydrocortisone treatment of 25 - 35mg daily. They found that this dose was associated with some improvements in symptoms but caused significant adrenal and immune suppression.

·        Neither of these research teams currently recommend the use of hydrocortisone as a treatment for ME/CFS. They stress that further studies, involving longer durations of treatment and follow-up, are required to assess the long-term effectiveness and safety of this treatment.

DHEA- DHEA is another adrenal hormone that is often found to be low in CFS/FMS patients. 60% of CFS patients who received “optimal” doses of DHEA by lymphocyte drug sensitivity testing (LDST) revealed clinical improvement in CFS symptoms. (McCoy J. Immunomodulatory properties of DHEA as a potential treatment for CFIDS. The CFIDS Chronicle Physician’s Forum, Fall, 1993.)

In our opinion, diagnosis and treatment of adrenal dysfunction is cornerstone of successful treatment of these disorders. We aggressively support the adrenal with the use of adrenal glandular extracts, licorice, phosphatidyl serine derivatives and DHEA as indicated by specific adrenal testing. See the section on Complementary and Alternative Therapies for more information on these agents.

Treatment of Neurally Mediated Hypotension (Autonomic Nervous System Dysfunction)

In one study, 76% of patients diagnosed with and specifically treated for neurally mediated hypotension (NMH) experienced improvement within a month, and in 40% of these patients, chronic fatigue symptoms completely or nearly completely resolved. For treating NHM, the physician might first recommend nonmedicinal measures, such as increasing salt content in the diet. Patients are instructed to perform exercises before getting out of bed that flex the feet so that the blood moves up toward the head. They are encouraged to avoid excessive activity after meals. They should not use medications that reduce blood pressure. Special support garments may help to prevent circulating blood from pooling in the lower part of the body and to return it to the heart. If the condition does not improve, certain medications may be tried in combination or alone. Midodrine (ProAmatine) is a drug that increases smooth muscle tone and blood pressure and reduces symptoms of NMH. Adverse effects include itching, numbness, and tingling, but the drug is well tolerated. A wide range of drugs normally used for other disorders have been used to treat NMH, but physicians have had difficulty adjusting them so that they would be effective for NMH without causing distressing side effects. Such medications include fludrocortisone (an oral steroid), phenylpropanolamine or ephedrine (decongestants), indomethacin or ibuprofen (nonsteroidal anti-inflammatory drugs or NSAIDs), disopyramide (an anti-arrhythmic drug), beta-blockers (drugs normally used to prevent hypertension), and recombinant erythropoietin epoetin alfa (used to increase red blood cells). It should be stressed that no one should take measures to raise blood pressure without a clear diagnosis of NMH or without a physician's approval, since increasing blood pressure can be very dangerous in individuals with existing normal or high blood pressure. There is also no clear evidence yet that NMH is a major cause of chronic fatigue syndrome.

Treatment of Low Growth Hormone

Some studies have suggested that growth hormones may benefit some patients with fibromyalgia who show evidence of deficiencies. It stimulates the growth of muscles and bones, helps regulate metabolism, slows the production of fatty tissue, helps maintain blood sugar levels for the brain, helps regulate all other hormones, and mobilizes fat, making it available to the cells as an alternative fuel. GH is associated with stage four sleep. A major spike should also occur in the middle of your "night", whenever that maybe. GH and stage 4 sleep are interdependent, like the chicken and the egg: no GH, no stage four sleep; no stage four sleep, no GH. At 3 a.m. the liver comes up and maximally detoxifies. Isn’t it interesting that the body spikes GH not long before the liver needs it? It primes the liver. If you don’t get the priming with GH at midnight, then your liver doesn’t work and you become more toxic." (Paul Cheney, MD)

Forty-five women with fibromyalgia and low insulin-like growth factor-1 levels were enrolled in a double-blind, randomized, placebo-controlled trial of 9 months duration.  Twenty-two of the women were given a dose of growth hormone at 0.0125 mg/kg daily for the first month, and then the dose was adjusted, at monthly intervals, to maintain an insulin-like growth factor-1 level of about 250 ng/ml; 23 women received placebo.  If there were side effects such as edema, arthralgia or carpal tunnel syndrome, the dose was reduced to 0.0125 mg/kg/day until the problem subsided.  The treatment group had a significant improvement over the placebo group at 9 months in both the Fibromyalgia Impact Questionnaire score and the tender point score. Fifteen of the growth hormone group and 6 of the control group experienced global improvement. Most patients experienced improvement at the 6-month mark.  After discontinuing growth hormone, patients experienced a worsening of symptoms. Carpal tunnel syndrome was more prevalent in the growth hormone group.  No other adverse effects were noted.  Secondary growth hormone deficiency may be responsible for some of the symptoms of fibromyalgia. (Bennett, Robert M., M.D., et al, "A Randomized, Double-Blind, Placebo- Controlled Study of Growth Hormone in the Treatment of Fibromyalgia," American Journal of Medicine, 1998;104:227-231)

Treatment of Infections

Antibiotic Treatments: When microorganism infections are identified, these patients can be treated with antibiotic therapy. The majority of patients with confirmed pathogenic mycoplasmal infections eventually recover from 50-100% of their premorbid health on therapies that are directed specifically against their chronic infections. The recommended treatment for confirmed mycoplasmal blood infections is long-term antibiotic therapy, usually multiple 6-week cycles of doxycycline (200-300 mg/day), ciprofloxacin or Cipro (1,500 mg/day), azithromycin or Zithromax (500 mg/day) or clarithromycin or Biaxin (750-1,000 mg/day). Multiple cycles are required, because few patients recover after only a few cycles [4-6], possibly because of the intracellular locations of the infections, the slow-growing nature of these microorganisms and their inherent insensitivity to antibiotics. Dr. Nicholson recommends that patients who have been diagnosed with blood infections receive continuous oral antibiotics for at least 6 months before using the 6-week cycles of treatment. (Nicolson, G.L. and Nicolson, N.L. Doxycycline treatment and Desert Storm. JAMA 1995; 273: 618-619 and Nicolson, G.L. Considerations when undergoing treatment for chronic infections found in Chronic Fatigue Syndrome, Fibromyalgia Syndrome and Gulf War Illnesses. (Part 1). Antibiotics Recommended when indicated for treatment of Gulf War Illness/CFIDS/FMS (Part 2). Intern. J. Med. 1998; 1: 115-117, 123-128). More information on antibiotic therapy can be found @ Dr. Nicolson’s web site: www.immed.org

Anti- Viral Therapies

• Ampligen. The intravenous antiviral drug, polyl:polyC12U (Ampligen) is one of the most studied anti-CFS drugs at this time. In an analysis of studies, after 24 weeks of Ampligen therapy patients had a 31% improvement in CFS symptoms compared to a 10% improvement in patients on placebo. Patients taking Ampligen progressed from needing daily assistance of normal activities to needing assistance only once a week. However, there has been some controversy concerning the 25-year old drug, which has been studied without success for many cancers and for AIDS.

• Valganciclovir (VGCV) or Valcyte- This is an anti-viral drug given either by vein (intravenous) or orally that was studied in a small open label trial in CFS patients. Of 25 CFS patients that were found to have elevated antibodies to the viruses EBV and HHV6. The drug was given for 6 months and 9 of 12 (75%) improved their CFS symptoms along with improvements in their blood tests. This trial was performed at Standford Univ. School of Medicine (Montoya, J. IACFS 2007). Another small phase 1 trial with valacyclovir (valtrex) or valganciclovir at the Univ. of Michigan also revealed benefits in 37 CFS patients with either EBV or CMV infections (Lerner, M. IACFS 2007). Stanford Univ. School of Medicine plans a definitive placebo controlled trial to verify these preliminary findings.

Anti Fungal Therapies

Although the “Yeast Over-growth Syndrome” remains controversial in medicine, we find some CFS/FMS patients improve with “anti fungal therapies” along with diet treatment. There are several anti fungal prescription medications and numerous “natural” and fungal agents available. One researcher found evidence of increased Candida albicans with an abnormal immune response in some CFS patients (Cozon, G. et al. In vivo and in vitro abnormal cellular reactivity to Candida albicans in patients with CFS. Abstract, AACFS, 2003)

·        Nystatin- A 4 week randomized, double blind, placebo controlled trial revealed that nystatin combined with a “yeast diet” revealed overall symptom improvement in “polysymptomatic patients” (Santelmann, H, et al. Effectiveness of nystatin in polysymptomatic patients. Family Practice, 2001; 18(3):258-265)

Other Agents for Infection

·        Transfer Factors. Of interest is a substance called transfer factor (TF), a small protein molecule that can actually transfer immunity from an immunized mammal to a non-immune one. TF stimulates interferon, an anti-viral protein. Transfer factor with activity against specific herpes viruses (such as Immodin) may prove useful for some patients with CFS. Younger patients appear to benefit significantly more than older patients from transfer factor treatment.

One study revealed improvement in CFS patients (with positive HHV-6 levels) and an therapeutic increase in NK cell levels in patients taking a colostrums/transfer factor that was specific for HHV-6 but not a general transfer factor product. (Brewer, JH, et al. Abstract, AACFS, 2003)

·        Olive Leaf Extract- This natural herb has demonstrated anti viral, anti fungal, anti bacterial activity and anti mycoplasma activity. It is being used by some physicians including ourselves with variable success (some appear to benefit very well, while others it does not seem to help much).

·        Interferon. Preliminary studies are reporting some improvement in morning stiffness and physical function when fibromyalgia patients take small doses of oral interferon-alpha, an agent used for chronic hepatitis. Oral interferon-alpha is available from Canada with a prescription (http://www.amarbio.com/).

Treatment of Mitochondrial Dysfunction

Carnitine- Carnitine is essential for mitochondrial energy production. Without enough carnitine, a person’s cells can’t break down fatty acids or remove toxic wastes.

o     A 1994 Japanese study done at Osaka University Graduate School of Medicine showed CFS patients had an acylcarnitine deficiency. (Kuratsune H, et al. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 1994 Jan;18 Suppl 1:S62-7)

o     A year later, a study done by AV Plioplys of Mercy Hospital and Medical Center in Chicago found CFS patients had significantly lower serum total carnitine, free carnitine and acylcarnitine levels, and found a correlation between levels of total and free carnitine and symptoms. (The higher the carnitine levels, the better people felt.) (Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology 1995;32(3):132-8)

o     A 1998 Japanese study found low levels of acylcarnitine in the blood of CFS and Hepatitis C patients, but not in some other diseases (Kuratsune H, et al. Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases. Int J Mol Med 1998 Jul;2(1):51-6 50 and  Matsumoto Y. Fibromyalgia syndrome [Article in Japanese] Nippon Rinsho 1999 Feb;57(2):364-9). A study by the same team a year later found lower levels of serum acylcarnitine in CFS patients but not in a majority of patients with fibromyalgia.

o     A Dutch study done by a team at the University of Nijmegen in the Netherlands in 2000 which measured the levels of total carnitine, free carnitine, acylcarnitine and carnitine esters in 25 female CFS patients and 25 healthy, matched controls found normal levels in CFS patients. (Soetekouw PM, et al. Normal carnitine levels in patients with chronic fatigue syndrome. Neth J Med 2000 Jul;57(1):20-4)

o     One study found oral L-carnitine supplementation improved many CFS symptoms after just eight weeks of treatment.(Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology 1997;35(1):16-23) 

 

NADH: A natural antioxidant agent called nicotinamide adenine dinucleotide, or NADH (Enada), is also in trials. This substance boosts serotonin and triggers adenosine triphosphate (ATP) an enzyme found in every cell that is necessary for conversion of food into energy. Typical dose is 5-10 mg per day. Take it on an empty stomach first thing in the morning (leave it by your bedside in the bottle or foil wrap with a glass of water) at least ½ hour before eating, drinking coffee/juice or taking any medication or supplements (except thyroid, which you can take with the NADH). It takes 2 months to see if it works. 15 to 20 mg a day may be more effective and is safe. Don't take vitamin C, Malic Acid, Lipoic Acid or other acids within 2 to 3 hours of NADH, as acid destroys NADH

·     A small randomized, double-blind, placebo-controlled crossover study showed 31 percent of the CFS patients who got the NADH reported improvements in fatigue, decreases in other symptoms, and improved overall quality of life, compared with only 8 percent of those who received a placebo. Improved symptoms continued even after 18 months. Although the study was small, these results showed promise. (L. Forsyth, et al. NADH: A new therapeutic approach in chronic fatigue syndrome (CFS). Annals of AAI, 82:2, 1999). The statistical analysis of this study was subsequently challenged, however.(Colquhoun and Senn. Annals of AAI 84: 639. 2000. Cited in Goudsmit, E. Capita Selecta http://freespace.virgin.net/david.axford/melist2.htm )

·     NADH has also been shown to reduce the effects of jet lag on cognitive performance and sleepiness.( Kay GG, et al. Stabilized NADH as a countermeasure for jet lag Abstract presented and published in the proceedings of the 48th International Congress of Aviation and Space Medicine, September 2000)

 

NT Factor- is a phospholipid/anti-oxidant nutritional combination designed to improve mitochondrial function. Dr. Nicolson reported a 33-35% reduction in fatigue severity in CFS patients with moderate levels of fatigue after 8 to 12 weeks of use (Nicolson G. IACFS 2007). He also reported positive findings in a the following journal article: (Nicolson GL, Ellithorpe E. Lipid replacement and antioxidant nutritional therapy for restoring mitochondrial function and reducing fatigue in Chronic Fatigue Syndrome and other fatiguing illnesses. J CFS 2006;13(1):57-68).

 

Coagulation Abnormalities

Heparin- Some practitioners recommend injectable heparin to treat the hypercoagulation if found positive on specialized testing. Others feel this treatment is too risky and recommend more natural therapies such as bromelain, garlic, Nattokinase from the Japanese food “Natto” or phosphatidyl choline. Of all the natural therapies, Nattokinase appears most promising but has not yet been formally tested in CFS/FMS patients.

Other Drugs

Some treatments being tried for CFS/FMS are experimental and have potentially toxic side effects and interactions with other drugs. Patients should be sure to inform their physicians of any other drugs, including so-called natural remedies, that they are taking.

·         Guaifenesin. Dr. Amand reported improvement with guaifenesin, an agent that loosens mucus and is used in some common cough medications, but another well controlled study confirmed that its benefits were only due to placebo effects (however, this study did not eliminate salicylates as recommended by Dr. Amand)

·         Tropisetron. Tropisetron (Navoban) is a serotonin receptor antagonist and used to reduce vomiting during chemotherapy. At 5mg per day, European studies are suggesting it may also help patients with fibromyalgia, including reducing pain, dizziness, and depression and improving sleep. Gastrointestinal symptoms and headaches were the most common side effects. (Haus U, et al. Oral treatment of fibromyalgia with tropisetron given over 28 days : influence of functional and vegetative symptoms, psychometric parameters and pain. Scand J Rheumatol Suppl 2000; 113:55-8 and Farber L, et al. Efficacy and tolerability of tropisetron in primary fibromyalgia- a highly selective and competitive 5-HT3 receptor antagonist. German Fibromylagia Study Group. Scand J Rheumatol Suppl 2000;113:49-54)

Body Based Therapies

·        Acupuncture. Acupuncture may be effective for some patients. It should be noted, however, that there is some concern that it may actually intensify symptoms in certain patients.

o       In a data base search, 7 studies (of which 3 were randomized controlled trials and 4 were cohort studies) were evaluated for the effectiveness of acupuncture in the treatment of fibromyalgia syndrome. 

o       Although the data are limited, evidence suggests real acupuncture is more effective than sham acupuncture for improving symptoms of patients with fibromyalgia syndrome.  (Berman, BM, et al, "Is Acupuncture Effective in the Treatment of Fibromyalgia?" J Family Practice, March, 1999;48(3):213-218)

·        Osteopathic/Chiropractic Manipulation. Chiropractic care may also improve symptoms for some patients. In one study 21 patients improved after four weeks of spinal manipulation compared to those receiving only medications. It may be less effective, however, in older patients with severe symptoms. (It should be noted that in rare cases manipulation of the neck has been known to cause stroke or damage to the arteries.)

·        Massage Therapy. Massage therapy is thought to stimulate the parasympathetic nervous system, which slows down the heart and relaxes the body. Rather than causing drowsiness, massage actually increases alertness; the reduction of stress and anxiety levels and the resulting relaxation, however, do contribute to better sleep.

Other Complementary & Alternative Treatments

Because of the difficulties in treating CFS/FMS, many patients seek alternative treatments. Major analyses have indicated that mind-body therapies, such as biofeedback or hypnosis, are more effective than no treatment at all, but less effective than moderate to intense exercise. It is extremely important for patients to realize that any herbal remedy or natural medicine that has positive effects may also have negative side effects and toxic reactions, just as any conventional drug does.

Those with CFS/FM usually have deficiencies as a result of those illnesses— one study done in 2000 by Dr. Werbach suggests they are low in the B vitamins, vitamin C, magnesium, sodium, zinc, L-tryptophan, L-carnitine, coenzyme Q10, and essential fatty acids “primarily due to the illness process rather than to inadequate diets.” Werbach suggests identifying deficiencies with objective testing when possible, treating them effectively, and testing again after treatment to ensure the deficiencies get resolved. But when that’s impossible, he suggests supplementing CFS patients with these nutrients, along with a general high-potency vitamin/mineral supplement, at least for a trial period. Why? “Because it’s often difficult to rule out marginal deficiencies, because serious adverse reactions are rare, and because nutritional supplements offer a therapeutic benefit,” he said in his study. In other words, it probably won’t hurt and it’s likely to help.

In our experience, many CFS/FMS patients require nutritional supplements but are “intolerant” to them and have many variable “reactions.” These must be handled carefully by an healing practitioner with experience in this area.

It should be strongly noted that alternative or natural remedies are not regulated and their quality is not publicly controlled. In addition, any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. Everyone is strongly advised to consult a physician before using any untested products or dietary supplements, and to discuss potential interactions with any medications being taken. The following website is building a database of natural remedy brands that it tests and rates. Not all are available yet. http://www.ConsumerLab.com/

 

·    B Vitamins- One study found preliminary evidence of reduced functional B vitamin levels, particularly pyridoxine (B-6), in CFS patients.( Heap LC, Peters TJ, Wessely S. Vitamin B status in patients with chronic fatigue syndrome. J R Soc Med 1999 Apr;92(4):183-5)

·    B1 as Thiamine pyrophosphate-

·    B12- There are 3 forms of vitamin B12- “cyanocobalamin”, “hydroxycobalamin” and “methylcobalamin.” Our preferred form of B12 is methylcobalamin.

o    In one preliminary trial, 2,500-5,000 mcg of vitamin B12 given by injection every two to three days led to improvement in 50-80 percent of a group of CFS patients; most improvement appeared after several weeks. (Lapp CW, Cheney PR. The rationale for using high-dose cobalamin (vitamin B12). CFIDS Chronicle Physicians' Forum 1993;Fall:19-20).

o    One small preliminary study found that CFS and FM patients had increased levels of homocysteine in their cerebrospinal fluid, which the study authors believed to be due to low levels of B-12 in the fluid.(Regland B; et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol (Norway) 1997, 26 (4) p301-7) This study also found a correlation between homocysteine and fatigue levels. (Vitamin B12 acts with folic acid and vitamin B6 to control homocysteine levels. An excess of homocysteine may increase the risk of heart disease, stroke, and perhaps osteoporosis and Alzheimer’s disease.) Dr. Britt Ahlrot-Westerlund from Sweden has had success treating CFS and FM with methylcobalamin. She uses it conjunction with folic acid, Vitamin B6 and antioxidants.

·    Branched-Chained Amino Acids (Valine, leucine, and isoleucine)- It is hypothesized that a deficiency of BCAAs may play a role in the pathophysiology of FM since these amino acids supply energy to the muscle and supplementation may be beneficial (Maes M, et al. Serotonergic markers and lowered plasma branched-chain-amino acid concentrations in fibromyalgia. Psychiatry Res 2000;97:11-20)

·    Vitamin C- Vitamin C mobilizes your body's self-defense mechanisms that assist your immune system in overcoming disease. It is also a powerful antioxidant required to produce collagen, the main supportive protein in cartilage, tendon and connective tissue. A potent antioxidant, Vitamin C is also credited with destroying or minimizing the effects of free radicals and carcinogens. Although most animals manufacture their own vitamin C — on average, a 150-pound animal produces 4,000 to 13,000 mg. of vitamin C daily— human beings are among only a handful of animals that do not. For those CFS patients with low blood pressure and low blood volume, the form of vitamin C caused "Sodium Ascorbate" may be the preferred form.

o    An interesting 1996 Japanese study showed that CFS patients improved after taking intravenous infusions of vitamin C and DHEA.(Kodama M, et al. The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). In Vivo 1996 Nov-Dec;10(6):585-96)

o    In Dr. Jesse Stoff’s study of 1,357 patients, which he treated using 1000 mg of vitamin C three times daily and Biomune OSF, an immune-modulating substance, he claimed 88 percent of those who had one detected viral infection improved within one year. Those with multiple infections improved at roughly half that rate.(Chronic Fatigue Complex Natural Health Consultants, available at http://www.naturalhealthconsult.com/fatigue.html )

·    Chlorella: In 55 subjects with fibromyalgia, 33 with hypertension and 9 with ulcerative colitis who participated in a double-blind, placebo-controlled, randomized trial, subjects took 10 g of pure chlorella in tablet form and 100 ml of a liquid which contained a chlorella extract each day for 2 or 3 months. Results showed reductions in blood pressure and serum cholesterol levels, enhanced wound healing and immune function, improved sleep and reduced anxiety levels in fibromyalgia patients and a decline in the Disease Activity Index for ulcerative colitis symptoms. (Merchant RE, Andre CA. A Review of Recent Clinical Trials of the Nutritional Supplement Chlorella pyrenoidosa in the Treatment of Fibromyalgia, Hypertension, and Ulcerative Colitis,, Altern Ther Health Med, May/June 2001;7(3):79-91.)

·    Collagen Hydrolysat: In one 2000 study collagen hydrolysat, a food supplement, significantly decreased pain in fibromyalgia patients with accompanying temporomandibular joint problems.

·    CoQ 10- Low CoQ10 levels have been found in one small study on CFS patients and further decreased after exercise that did not resume to baseline after overnight rest. Exercise intolerance improved after supplementation with 100mg/d (Judy W. Coenzyme Q10. Presentated at Am College of Nutrition 37^th Annual Conference, 1996)

·    Vitamin D- Vitamin D is very important for proper immune function and levels were found to be deficient in roughly 20% of patients with CFS/FMS (Wynants H & Moorkens, G. Magnesium and Vitamin D status in female patients with CFS, fibromyalgia or autonomic dysfunction. Abstract, AACFS, 2003).

·    Essential Fatty Acids (Gamma Linoleic Acid)- A double-blind placebo controlled trial of long chain essential fatty acid supplementation produced improvement in the majority of CFS patients. (Behan Po, et al. Effect of high doses of essential fatty acids on the post viral fatigue syndrome. Acta Neurol Scand 82:209-216, 1990.)

·    Glutathione- A potent antioxidant, glutathione eliminates free radicals, detoxifies and removes heavy metals like lead, mercury and cadmium from the body, recycles oxidized vitamin C back to useful vitamin C, and protects cells from damage from oxidative stress. Unfortunately, oral glutathione does not pas the digestive tract even taken in massive oral doses and either intra-muscular or intravenous routes are required.

o     Glutathione levels have been found to be low in CFS patients ((Kennedy, G, et al. Increased plasma isoprotanes and other markers of oxidative stress in chronic fatigue syndrome. Abstract, AACFS, 2003). A healthy person produces several grams of glutathione daily.

o     Dr. Patricia Salvato of Houston, Texas, recommends intramuscular injections of glutathione. Some CFS patients have taken 100 mg. glutathione combined with 1 mg. of ATP injections twice weekly with good results. (In a study of 276 CFIDS patients —218 women and 58 men— who received weekly injections of glutathione/ATP injections, 82 percent (226 patients) reported less fatigue and 196 experienced improvement in memory and concentration, while 171 experienced lower levels of pain. A few patients had heart palpitations thought to have come from the ATP.)

o     It may help to take magnesium and glutathione together: in a high-quality study in Belgium, patients who were magnesium deficient (47 percent) had significantly lower total antioxidant capacity in their blood. Magnesium deficient patients whose magnesium stores didn’t improve even after oral supplementation with 10 mg magnesium per day also had persistently lower blood glutathione levels.(40)

o     NAC (N-Acetyl -L -Cysteine) may naturally increase glutathione levels in the body

o     Whey protein products have also shown to increase glutathione levels. (see below for more information on whey)

·    Hyperbaric Oxygen Therapy (HBOT)- One small study of 29 patients with CFS (15 of which were infected with Mycoplasma species) revealed reduced fatigue, increased levels of activity and an improved reaction time along with improved quality of life, functional status (Van Hoof E., De Meirleir K. Hyperbaric Therapy in Chronic Fatigue Syndrome. J CFS 11(3): 37-49)

·    Licorice (glycyrrhiza glabra) – Augments adrenal hormones with mineralcorticoid activity and potentiates glucocorticoid activity (it helps hold onto salt and blood volume and increased cortisol activity in the body). (Baschetti R. Chronic fatigue syndrome and liquorice. N  Z Med J. 108:156-7,259, 1995.)

·     Magnesium- Magnesium deficiency can cause dysregulation of the immune and autonomic nervous systems, and clinical or experimental magnesium deficiency produces fatigue, depression, poor exercise tolerance, and decreased resistance to psychological stress. Ideal dose to reach for is 500-750 mg of magnesium/day- the number one side effect of large doses is loose stools/diarrhea.

o   One case control study of 18 CFS patients matched with 20 healthy controls revealed significantly lower RBC magnesium levels. 32 patients were randomly assigned to receive intra-muscular Mg sulfate weekly or placebo. RBC magnesium levels normalized with treatment as did improvement scores. (Cox JM, et al. Red blood cell magnesium and chronic fatigue syndrome. Lancet 337:757-60, 1991.)

o   A study in Paris found a link between magnesium deficiency, chronic fatigue syndrome and mitral valve prolapse (MVP), an abnormality in which the valve between the heart’s left atrium and ventricle malfunctions or is weakened and blood cannot circulate through the heart in the way it should. As many as 75 percent of those with fibromyalgia have MVP. (Durlach J, et al. Neurotic, neuromuscular and autonomic nervous form of magnesium imbalance. Magnes Res 1997 Jun;10(2):169-95)

o    24% of CFS patients, 27% of FMS patients and 53% of patients with autonomic dysfunction had low magnesium levels (Wynants H & Moorkens, G. Magnesium and Vitamin D status in female patients with CFS, fibromyalgia or autonomic dysfunction. Abstract, AACFS, 2003).

o     The specific form of magnesium called “magnesium malate” was found helpful in FMS patients (Abraham GE, Flechas JD. Rationale for the use of magnesium and malic acid in fibromyalgia treatment. Journal of Nutritional Medicine, 1992, 3:40-52.)

o    In 21 female and 3 male patients (mean age of 49 years) with fibromyalgia compared with 16 female and 2 male subjects (mean age of 50 years), participants consumed 200 mg of malic acid and 50 mg of magnesium in tablet form at a dose of 3 tablets, 2 times a day, compared with a placebo for 4 weeks/course, followed by a 6-month, open-label trial escalating up to 6 tablets, 2 times a day. There was shown no clear benefit of malic acid supplementation in the low-dose trial. With escalating doses and a longer duration of treatment in the open-label trial, there were significant reductions in the severity of all 3 primary pain/tenderness measures. Malic acid and magnesium may help with carbohydrate metabolism, which could lead to increased production of ATP. Enhanced energy production through ATP may help improve muscle tender points. (Russell IJ, Michalek JE, Flechas JD, Abraham GE "Treatment of Fibromyalgia Syndrome With Super Malic : A Randomized, Double Blind, Placebo Controlled, Crossover Pilot Study,", J Rheumatol, 1995;22(5):953-958)

·    Magnet Therapy. Magnet therapy has received some attention. One study using magnets that were only slightly more powerful than refrigerator magnets showed some benefits, although there is no strong evidence to confirm their benefits.

·    Melatonin: a natural hormone associated with the sleep-wake cycles may have benefits for some patients with fibromyalgia.

·        MSM- MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. 6-20 grams/day.

·        Mud Pack Treatments. One 1999 Italian study suggested that taking an antidepressant and undergoing mud-pack treatment may release natural steroids that reduce inflammation and relieve pain. Further research is needed to confirm any benefits.

·        Phosphatidyl Serine- Phosphatidylserine (PS) is vital to brain cell structure and function, and plays an important role in the brain’s neurotransmitter systems, metabolism, and maintaining nerve connections. This natural hormone supports communication between brain cells and promotes improved memory function. Typical doses are 100-300mg or more per day.

·        S-adenosylmethionine (SAMe): is a natural substance that has antidepressant, anti-inflammatory, and analgesic properties. It has shown some benefit in controlled studies. SAMe is a methyl donor in many methylation reactions that occur in the brain.

o        Thirty patients with secondary fibromyalgia syndrome in a double-blind protocol were given 400 mg/day of SAMe or a placebo for 15 days by intravenous injection. All 30 patients completed the study. There was a significant decrease in pain. The scores for both the Hamilton and SAD tests decreased significantly after SAMe therapy. SAMe may be a good candidate for the treatment of secondary fibromyalgia syndrome. (Tavoni, A., MD, et al, "Evaluation of S-Adenosylmethionine in Secondary Fibromyalgia:  A Double-Blind Study," Clinical and Experimental Rheumatology, 1998:106-107)

·        Whey Protein (Undenatured)- The Physician Desk Reference (PDR) states the following properties to whey protein: support gastrointestinal health, promotes repair of RNA and DNA, promotes removal of toxic metals from the body, aids in wound healing, supports production of hemoglobin, enzymes and antibodies and creation of new muscle mass. These effects make whey protein supplementation attractive for the CFS patient.

o        One unpublished study demonstrated an undenatured whey protein (ImmunoPro) significantly increased NK cell function in CFS patient’s blood samples (Herst C, et al. The ex vivo effects of ImmunPro on the induction of natural killer cells in patients with chronic fatigue syndrome. Unpublished)

o        Another unpublished study revealed HHV-6 reduction in CFS patients taking whey protein (ImmunoPro) and in combination with the drug foscarnet lowered high levels of HHV-6 in CFS patients (Abrahams, M. In vitro study of the efficacy of ImmunoPro and foscarnet in eliminating the infectivity of HHV-6A. Unpublished, 2003)

Psychological Therapies

Cognitive-Behavioral Therapy

Studies continue to show that when CFS/FMS patients increase their psychological capacity to deal with the specific conditions of their disorder and their lives, they are more apt to experience physical improvement. Cognitive-behavioral therapy is an effective method for enhancing patients' belief in their own abilities and to develop methods for dealing with stressful situations.

The Goals of Cognitive-Behavioral Therapy. The primary goals of cognitive-behavioral therapy are to change any distorted perceptions that individuals have of the world and of themselves and to change their behavior accordingly. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that pain is only one negative factor and, to a degree, a manageable experience among many positive ones.

Cognitive therapy is particularly helpful in defining and setting limits, behavior that is extremely important for these patients. Many fibromyalgia patients live their lives in extremes. They first become heroes or martyrs, doggedly pushing themselves past the point of endurance until they collapse and withdraw. This inevitable backlash reverses their self-perception, and they then view themselves as complete failures, unable to cope with the simplest task. One important aim of cognitive therapy is to help such patients discover a middle route, whereby they can prioritize their responsibilities and drop some of the less important tasks or delegate them to others. Such behavior will eventually lead to a more manageable life and to less of an absolutist perspective on themselves and others.

The Procedure. Cognitive therapy may be expensive and not covered by insurance, although it is usually of short duration, typically six to 20 one-hour sessions. Patients are also given homework, which usually includes keeping a diary and attempting tasks that they have avoided because of negative thinking.

A typical cognitive therapy program may involve the following measures:

• Keep a Diary. The patient is almost always asked to keep a diary, an it is usually a key component of cognitive therapy. The diary serves as a general guide for setting limits and planning activities. The patient uses the diary to track any stress factors, such as a job or a relationship, that may be making the pain worse or better.
• Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs ("eg, I'm not good enough to control this disease, so I'm a total failure.") to using coping statements ("Where is the evidence that I can control this disease?")
• Set Limits. Limits are designed to keep both mental and physical stress within a manageable framework so that patients do not get discouraged by forcing themselves into situations in which they are likely to fail. For example, tasks are broken down into incremental steps, and patients focus on one at a time.
• Seek out Pleasurable Activities. List a number of enjoyable low-energy activities that can be conveniently scheduled.
• Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.
• Accept Relapses. Over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of treatment- or self-failure.

Cognitive therapy may be expensive and not covered by insurance. An alternative that may be as beneficial for some patients are strong, intelligently managed support groups. In one center, educational discussion groups were as effective, or even more so, than a cognitive therapy program. Such results cannot necessarily be applied to all centers, of course. Therapeutic success varies widely depending on the skill of the therapist.

Other Resource Information for CFS/FM

Organizations

International Association for Chronic Fatigue Syndrome/Myalgic Encephalothy.
 http://www.IACFS.net )
Formed by health professionals to promote dissemination of information on CFS.

American Association of Medical Acupuncture, 5820 Wilshire Blvd., Suite 500, Los Angeles, CA 90036. On the internet, http://www.medicalacupuncture.org . This organization will provide information about physician acupuncturists in particular areas.

American Chronic Pain Association, P.O. Box 850, Rocklin, CA 95677. Call (916) 632-0922 or on the Internet (http://www.theacpa.org/ )

American Fibromyalgia Syndrome Association, Inc., 6380 E. Tanque Verde Rd., Suite D, Tucson, AZ 85715. Call (520-733-1570) or on the Internet (http://www.afsafund.org/ ).

American Pain Society, 4700 W. Lake Avenue, Glenview, IL 60025. Call (847-375-4715) or on the Internet http://www.ampainsoc.org/

Centers for Disease Control and Prevention, Division of Viral Diseases, Building 6, Rm. 120, Atlanta, GA 30333. Call (404-332-4555) or on the Internet http://www.cdc.gov/ncidod/diseases/

American Society of Clinical Hypnosis, 2200 E. Devon Avenue, Suite 291, Des Plaines, IL 60018-4534

The Arthritis Foundation, 1330 West Peachtree Street, Atlanta, Georgia 30309. Call(800-283-7800) or on the Internet (http://www.arthritis.org/ )

The Chronic Fatigue and Immune Dysfunction Syndrome Association of America, PO Box 220398, Charlotte, NC 28222-0398. Call (800-44-CFIDS or 442-3437) or on the Internet (http://www.cfids.org )

Fibromyalgia Network, PO Box 31750, Tucson, AZ 85751-1750.
Call (800-853-2929) or on the Internet (http://www.fmnetnews.com/ ).
The FM Network offers information on support groups, and health care specialists by area. Their web site has useful advice and information.

International Association for the Study of Pain, 909 NE 43rd St., Suite 306, Seattle, WA 98105-6020. Call (206-547-6409) or on the Internet http://dasnet02.dokkyomed.ac.jp/IASPM/IASP.html

National Arthritis and Musculoskeletal and Skin Diseases, Information Clearinghouse (NAMSIC), NIH, 1 AMS Circle, Bethesda, MD 20892-3675.
Call (301-495-4484) or on the Internet (http://www.nih.gov/niams/ )

National Chronic Fatigue Syndrome and Fibromyalgia Association, PO Box 18426, Kansas City, MO 64133. Call (816-313-2000)
This organization is a good source of accurate information on CFS. Send self-addressed envelope for information. They will return phone calls using a collect call.

National Chronic Pain Outreach Association. 7979 Old Georgetown Road, Suite 100, Bethesda, MD 20814-2429. Call (301) 652-4948, or on the internet at http://neurosurgery.mgh.harvard.edu/ncpainoa.htm

National Institute of Allergy and Infectious Diseases (NIAID), Office of Communications, Building 31, Rm. 7A50, 31 Center Dr., MSC 2520, Bethesda, MD 20892-2520. Write for the publication Chronic Fatigue Syndrome, NIH Publication No. 96-484 or on the Internet www.niaid.nih.gov

The Oregon Fibromyalgia Foundation, PO Box 500, Salem, OR 97302.
On the Internet (http://www.myalgia.com/ )

The Society for Clinical and Experimental Hypnosis, 3905 Vincennes Rd, Suite 304, Indianapolis, IN 46268

Tai Chi Chuan Foundation, 5 East 17 Street, New York, NY 10003. Call 212-645-7010)

Other Informational Resources:

Healing Research Centers' Chronic Fatigue Syndrome and Fibromyalgia (www.chronicfatigue.org )

Cheney Clinic Information Service (CCIS) (www.fnmedcenter.com/ccis )

ConsumerLab, on the internet at http://www.consumerlab.com . Provides research on the quality of herbal products and dietary supplements.
MEDWATCH, a Food and Drug Administration program called for people to report adverse reactions to medical products, including drugs, herbal remedies and vitamins. Call 800-332-1088.

From Fatigue to Fantastic, Dr. Tietelbaum’s Web Site, www.endfatigue.com

Immune Support.com; http://www.immunesupport.com/

Institute for Molecular Medicine (714) 903-2900 for information pack in mycoplasma infection, and read the research at www.immed.org

Journal of Chronic Fatigue Syndrome (http://www.cfs-news.org/

http://www.ahmf.org/

Appendix A: The Biologic (Adrenal) Reaction to Stress