Pain free 1-2-3! Eliminating fibromyalgia pain.

Overview

Chronic fatigue syndrome (CFS) and its often simultaneously present cousins fibromyalgia syndrome (FMS) and myofascial pain syndrome (MPS) are common names for an overlapping spectrum of disabling syndromes. It is estimated that FMS alone affects over 3 to 6 million Americans, causing more disability than rheumatoid arthritis. (1) Myofacial pain syndrome (MPS) affects many millions more. These syndromes can cause severe pain. Though the pharmacologic focus (using the three new FDA-approved drugs Lyrica, Cymbalta, and Savella) focus predominently on masking the pain, we have found it far more effective to treat its underlying cause--often resulting in long-term relief.

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Although we still have much to learn, effective treatment is now available for the large majority of patients with these illnesses. (2,3) CFS/FMS/MPS represents a spectrum of processes with a common end point. As the majority of patients I see in clinical practice who have CFS also have FMS and MPS, I will often refer to the three together.

Recent research has implicated mitochondrial and hypothalamic and dysfunction as common denominators in these syndromes. (4-7) These processes therefore reflect a human energy crisis. Dysfunction of hormonal, sleep, and autonomic control (all centered in the hypothalamus) and energy production centers can explain the large number of symptoms and why most patients have a similar set of complaints.

To make it easier to explain to patients, we use the model of a circuit breaker in a house: If the energy demands on your body are more than it can meet, your body "blows a fuse." The ensuing fatigue forces you to use less energy, protecting you from harm. On the other hand, although a circuit breaker may protect the circuitry in the home, it does little good if you do not know how to turn it back on or that it even exists.

This analogy reflects what actually occurs. Research in genetic mitochondrial diseases shows not simply myopathic changes, but also marked hypothalamic disruption. As energy stores are depleted, hypothalamic dysfunction occurs early on, resulting in the disordered sleep, autonomic dysfunction, low body temperatures, and hormonal dysfunctions commonly seen in these syndromes. In addition, inadequate energy stores in a muscle results in muscle shortening (think of rigor mortis) and pain, which is further accentuated by the loss of deep sleep. Therefore, restoring adequate energy production and eliminating the stresses that overutilize energy (e.g., infections, situational stresses, etc.) renew function in the hypothalamic "circuit breaker" and also let muscles release--allowing pain to resolve. Our placebo-controlled study showed that when this is done, 91 % of patients improve, with an average 90% improvement in quality of life and a dramatic decrease in pain. In fact, the majority of patients no longer qualified as having FMS by the end of three months. (3)

Diagnosis

The criteria for diagnosing CFS and FMS are readily available elsewhere. There is a simpler approach to diagnosis that is very effective clinically. If the patient has the paradox of severe fatigue combined with insomnia (if one is exhausted, one should sleep all night), she does not have severe primary depression, and these symptoms do not go away with vacation, she likely will have a CFS-related process. If she also has widespread pain, fibromyalgia is probably present as well. Both respond well to proper treatment as discussed below.

Anything that results in inadequate energy production or energy needs greater than the body's production ability can trigger hypothalamic dysfunction. This may include infections, disrupted sleep, pregnancy, hormonal deficiencies, toxin exposures, and other physical and/or situational stresses.

Fortunately, two studies (including our published RCT) showed an average 90% improvement rate when using the SHINE protocol. (2,3) SHINE stands for Sleep, Hormonal support, Infections, Nutritional support, and Exercise as able. When a patient has fatigue and insomnia coupled with widespread pain, see him as having a bodywide "energy crisis." Treating with the SHINE approach will help him. An editorial published in the journal of the American Academy of Pain Management notes: "This study by Dr. Teitelbaum et al. confirms what years of clinical success have shown ... that sub clinical abnormalities are important, and that the comprehensive and aggressive metabolic approach to treatment in Teitelbaum's study is highly successful and ... an excellent and powerfully effective part of the standard of practice for treatment of people who suffer from FMS and MPS." (9)

Treatment

Using the SHINE protocol will simplify treatment of these patients. Although this article will give you an excellent start in treating CFS/FMS/MPS, our treatment checklist offers over 270 useful natural and prescription therapies with resources and detailed instructions for use (organized by category). For example, there are 26 sleep therapies reviewed. I will be happy to e-mail you this file, plus patient questionnaires that you can modify for use in your office. Using these free tools will dramatically simplify the care of these patients. Simply e-mail me at Endfatigue@ aol.com. I would note as an aside that, although I am very picky about what products I recommend, I have a policy of not taking money from any natural or pharmaceutical companies, and 100% of the royalties for my products go to charity.

As an additional tool, our free Symptom Analysis Program at www.endfatigue.com can analyze your CFS/ FMS/MPS patients' symptoms (and even labs if available), determine the likely contributing diagnoses, and tailor a treatment protocol to their cases, which they can then bring to their practitioners to implement.

The long program will elicit a detailed history and analyze the symptoms and labs to create a complete medical record of their case, including a detailed treatment protocol.

Although nutritional support is the foundation of getting well and eliminating pain in CFS/FMS, it is critical that the entire process be treated for optimal results. Let's begin with "S" for sleep.

Disordered Sleep

A foundation of CFS/FMS is the sleep disorder. Using medications that increase deep restorative sleep, so that the patient gets seven to nine hours of solid rest, is critical. Start treatment with natural therapies or with a low dose of sleep medications that do not decrease stage 3-4 sleep. Continue to adjust the treatments each night until the patient is sleeping eight hours a night without a hangover.

The natural remedies that I recommend you begin with include the following:

1. Herbal preparations containing a mix of valerian root, wild lettuce, Jamaican dogwood, passionflower, hops, and theanine. These are all combined in an excellent product called the Revitalizing Sleep Formula by Integrative Therapeutics (888-849-5069 or 920-737-8828). Patients can take 1 to 4 caps at bedtime. These six herbs can help muscle pain and libido as well as improving sleep. (11-15)

2. Melatonin: 0.5-1mg at bedtime.

3. 5-HTP (5-Hydroxytryptophan): 200 to 400 mg at night.

4. Calcium and magnesium at bedtime, as these help sleep.

If natural remedies are not adequate to result in at least 8 hours a night of sleep, consider these medications:

* Zolpidem (Ambien), 5 to 20 mg qhs.

* Neurontin 100-900 mg hs can help sleep, pain, and restless leg syndrome (RLS) as well.

* Cyclobenzaprine (Flexeril) 10 mg, Klonopin 0.5 mg, and/or carisprodol (Soma), 350 mg.

* Trazodone (Desyrel), 50 mg. Use 0.5 to 6 tablets qhs.

Some patients will sleep well with natural therapies and/or 5 mg of Ambien and 25 mg of Desyrel. Others will require a surprisingly large amount of sleep support, because the malfunctioning hypothalamus controls sleep. Because of next-day sedation and each medication's having its own independent half-life, CFS/FMS patients do better with combining natural therapies and then (if needed) adding low doses of several medications than with a high dose of one.

Although less common, three other sleep disturbances must be considered and, if present, treated. These are sleep apnea, UARS (upper airway resistance syndrome), and RLS, which is also fairly common in fibromyalgia. (16)

Evaluation and Treatment of Associated Hormonal Dysfunction

Hormonal imbalances are associated with FMS. Sources of imbalance include hypothalamic dysfunction, adrenal exhaustion from chronic stress, environmental toxins, and autoimmune processes such as Hashimoto's thyroiditis. Most blood tests use two standard deviations to define blood test norms. By definition, only the lowest or highest 2.5% of the population is in the abnormal (treatment) range. This does not work well if over 2.5% of the population has a problem. For example, it is estimated that as many as 20% of women over 60 are hypothyroid. Other tests use late signs of deficiency such as anemia for iron or B12 levels to define an abnormal lab value.

The goal in CFS/FMS management is to restore optimal function while keeping labs in the normal range for safety. One way to convey the difference between the "normal" range based on 2 standard deviations and the optimal range that the patient would maintain if she did not have FMS is as follows:

Pretend your lab test uses 2 standard deviations to diagnose a "shoe problem." If you accidentally put on someone else's shoes and had on a size 12 when you wore a size 5, the normal range derived from the standard deviation would indicate that you had absolutely no problem. You would insist that the shoes did not fit, although your shoe size would be in the normal range. Similarly, if you lost your shoes, the doctor would pick any shoes out of the "normal-range pile" and expect them to fit you.

Thyroid Function

Suboptimal thyroid function is very common, and it is important to treat all chronic myalgia patients with thyroid hormone replacement if their free T4 blood levels are below even the 50th percentile of normal (Janet Travell--personal communication). Many CFS/FMS patients also have difficulty in converting T4, which is fairly inactive, to T3, the active hormone. Additionally, T3 receptor resistance may be present, requiring higher levels. (17), (18) in most CFS/ FMS patients, I give an empiric trial of Armour Thyroid, 0.5 to 3 grains every morning, adjusted to the dose that feels best to the patient as long as the free T4 is not above the upper limit of normal.

TSH testing is not reliable, as hypothalamic hypothyroidism is common and the patient's TSH can be low, normal, or high. (19) The inadequacy of thyroid testing is further suggested by studies that show:

* that most patients with thyroid problems have normal blood results (20), (21);

* that when patients with symptoms of hypothyroidism and normal labs were treated with thyroid hormone (in this study, Synthroid at an average dose of 120 meg every day), a large majority improved sigificantly. (20)

In addition, remember that thyroid supplementation can increase a patient's Cortisol metabolism and unmask a case of subclinical adrenal insufficiency. If the patient feels worse on low-dose thyroid replacement, he may need adrenal support as well.

Adrenal Insufficiency

The hypothalamic-pituitary-adrenal (HPA) axis does not function well in CFS/FMS. (4), (22), (23) Because early researchers were not aware of physiologic doses of Cortisol, they treated with high doses and their patients developed severe complications. These side effects are not seen with physiologic dosing of Cortef; that is, up to 20 mg a day. (24) Twenty mg of hydrocortisone (Cortef) is approximately equivalent in potency to 4 to 5 mg of prednisone.

Our study did not show adrenal suppression using lower Cortef dosing. (3) Dr. Jefferies, with thousands of patient-years' experience in using low-dose Cortef, recommends an empiric trial of 20 mg a day of Cortef in all patients with severe, unexplained fatigue and has found this to be quite safe for long-term use. (24), (25) Our research and clinical experience suggests that using Cortef at 20 mg or less a day in CFS and fibromyalgia patients is safe and often very helpful (most patients need 5-12.5 mg).

Symptoms of an underactive adrenal include weakness, hypotension, dizziness, sugar craving, and recurrent infections--all of which are common in CFS/ FMS. Although a baseline morning Cortisol of > 6 mcg/ dl is often considered "normal," most healthy people run approximately 16 to 22 mcg/dl at 8 a.m.

If the baseline Cortisol is less than 16 mcg/dl or if the patient's symptoms suggest inadequate adrenal function, I treat with a therapeutic trial of 5 to 15 mg Cortef in the morning, 2.5 to 10 mg at lunchtime, and 0 to 2.5 mg at 4 p.m. (maximum of 20 mg a day). After 9 to 18 months, the patient can often taper off the Cortef. More is not better.26 For an excellent review of the safety and effectiveness of ultra-low-dose Cortisol in CFS, see www.endfatigue.com/bool_notes/Fftf_chapter_4.html#safety_2.

A nonprescription glandular that actually contains (I've been told) 2.5 mg of hydrocortisone per pellet is called Isocort (available from Bezwekian at 800-743-2256). This would carry the same risks as Cortef and is not standardized, so I would avoid going over 6 pellets/day. An excellent glandular/herbal for adrenal support that is very safe and effective is Adrenal Stress End (from Integrative Therapeutics). Give 1 to 2 capsules each morning (or 1 to 2 in the morning and 1 at noon).

DHEA

Dehydroepiandrosterone (DHEA) is a major adrenal hormone that has recently been getting a lot of media attention as a "fountain of youth" supplement. (28) It is stored as DHEA-sulfate (DHEA-S), and levels of the active free DHEA fluctuate throughout the day. Because of this, I recommend checking DHEA-S levels and not DHEA levels.

Many CFS/FMS patients have suboptimal DHEA-S levels, and the benefit of treatment is often dramatic. Most women need 5 to 25 mg a day and most men 25 to 50 mg a day. I use the middle of normal range for a 29-year-old, keeping the DHEA-S level at 150 to 180 mcg/dl in women and 350 to 480 mcg/dl in men.

Low Estrogen and Testosterone

Although we are trained to diagnose menopause by cessation of periods, hot flashes, and elevated FSH and LH, these are late findings. Estrogen deficiency often beings many years before, and may coincide with the onset of CFS/FMS. (29) To compound the problem, research done by Sarrel shows that the majority of women who have a hysterectomy, even with the ovaries left in, begin menopause within six months to two years. (29)

The initial symptoms of estrogen deficiency are poor sleep, poor libido, brain fog, achiness, and especially worsening of CFS/FMS symptoms in the 3 to 7 days before the period. I prefer to have the compounding pharmacist make a combination of Bi-Est 1.25-2.5 mg plus progesterone 30-50 mg, plus testosterone 1-3 mg, all in 1/10 or 2/10 of a CC of cream (which can be applied to the mucosal surface of the labia each evening). Nonprescription Bi-Est and/or natural progesterone can also be obtained from Bezwekian. Early data on estriol suggest that it does not raise breast cancer risk and may actually lower it.

Testosterone Deficiency

Among my CFS/FMS patients 70% of men and many women have free testosterone levels in the lowest quartile, while their total testosterone levels are normal. A recently completed study found that treating low testosterone in women decreases FMS pain. As noted above, supplementation can be done easily by adding 1 to 3 milligrams of testosterone to the estrogen cream.

In men taking thyroid supplements, testosterone supplementation can also cause elevated thyroid hormone levels. Despite the concerns about athletes' using very high levels of synthetic testosterone, it is important to remember that research shows that raising a low testosterone level in men using natural in lower cholesterol, decreased angina and depression, and improved diabetes. (30)

Immune Dysfunction and Infections

Immune dysfunction is part of the process. Opportunistic infections present in CFS/FMS include yeast/candida, chronic URIs (upper respiratory-tract infections) and sinusitis, bowel infections, and chronic low-grade prostatitis. These need to be treated.

Chronic sinusitis responds poorly to antibiotics but well to antifungals. (31) Bowel infections with alterations of normal bacterial flora, fungal overgrowth, and parasitic infections are also generally present. This is reflected by the patient's bowel symptoms. Because of the lack of a definitive test for yeast overgrowth, there is little research published in this area and treatment is controversial. Treatment is empiric and based on the patient's history. Yeast vaginitis; onychomycosis; sinusitis; a history of frequent antibiotic use such as tetracycline for acne; or gas, bloating, diarrhea, or constipation warrant an empiric therapeutic antifungal trial. Many CFS/FMS patients who have failed other therapies for spastic colon or sinusitis have responded dramatically to antifungal treatments. I give an empiric trial of antifungal therapy in most CFS patients.

I treat with sugar avoidance, a mix of antifungal herbs (Anti-Yeast from Ultraceuticals, 2 twice a day), and Acidophilus Pearls (Integrative Therapeutics), 2 twice a day. These are given for 5 months. After four weeks on the Anti-Yeast, add 200 mg of fluconazole (Diflucan--use the less expensive generic) a day for six weeks.

Parasitic infections, occult infections such as Chlamydia and Mycoplasma incognitus and human herpesvirus-6, cytomegalovirus, and Epstein-Barr virus are also sometimes active in CFS/FMS. In these cases, I often use an excellent immune stimulant called Pro-Boost: 1 packet sublingually t.i.d. for 3 months (Klabin Marketing: 800-933-9440). This thymic hormone mimic is excellent for acute infections as well.

Nutritional Deficiencies

CFS/FMS patients are often nutritionally deficient. B-vitamins, magnesium, iron, coenzyme Q10, malic acid, and acetyl-L-camitine are essential for mitochondrial function. (7), (32) These nutrients are also critical for many other processes. Although blood testing is not reliable or necessary for most nutrients, I do recommend that you check B12, Fe, TIBC, and ferritin levels.

I begin patients with CFS/FMS on the following nutritional regimen:

1. A quality multivitamin suited for their needs. It should contain at least a 50 mg B complex, 150 mg magnesium glycinate, 900 mg malic acid, 600 mg vitamin D, 500 mg vitamin C, zinc 200 mg, selenium 200 mcg, chromium 200 mcg, and amino acids. Because there are dozens of important nutrients, and patients got tired of taking handfuls of tablets, I now use a powdered multivitamin called the Energy Revitalization System (by Integrative Therapeutics) in almost all of my patients, even those without CFS, for overall nutritional support. It contains over 50 nutrients, and 1 capsule plus a single drink daily replaces over 35 tablets or capsules of supplements each day. This should be taken long term, and I recommend it as excellent overall nutritional support for almost everyone (whether or not they have fibromyalgia).

2. Ribose is an excellent nutrient for enhancing energy production, and I use it in all of my CFS/FMS patients as well as patients with heart disease. We recently published a study showing that ribose increased energy an average of 45% in patients with CFS/FMS. If you are not familiar with this nutrient, you will find it to have a dramatic benefit in your practice. (For a more detailed article that I have written on ribose, see www.endfatigue.com/tools-support/D-ribose.html.) Proper dosing is critical. Use 5 g (5000 mg) t.i.d. for 3 weeks, then 5 g twice a day. Give it 6 weeks to see the full clinical effect, so we have patients get a 280 g container of ribose (Corvalen from Bioenergy: 763-757-0032) as a therapeutic trial. For my article on nutritional support in heart disease, see www.endfatigue.com/health_articles_f-n/Heart-overview_treating_heart_problems_naturally.html.

3. If the B12 level is under 540 pg/ml, I recommend B12 injections, 3000 micrograms IM three times a week for 15 weeks, then as needed based on the patient's clinical response. (33-36)

4. Coenzyme Q10, 100 to 200 mg a day. I use the Integrative Therapeutics chewable 200 mg wafers.

5. Acetyl-L- carnitine 500 mg twice daily for 4 months.

6. The patient should avoid sugar and caffeine, and water intake should be increased as well.

7. If the iron saturation is under 22% or the ferritin is under 40 mg/ml, supplement with iron. This will also help decrease RLS when present.

Exercise As Able

Although conditioning is important, these patients cannot make adequate energy, and therefore beyond a certain amount of exercise will crash instead of conditioning. Because of this, they should walk as able (where they feel "good tired" afterward and better the next day). After 8 to 10 weeks on the SHINE Protocol, they can begin to increase their walking by up to 1 minute a day (again, as able). When up to walking an hour a day, they can increase the exercise intensity.

General Pain Relief

Although many kinds of pain will often resolve within three months of simply treating with SHINE as discussed above, it is also critical to eliminate pain directly. Many studies show a marked analgesic and anti-inflammatory effect from adequate doses of two herbals, willow bark (containing at least 240 mg of salicin/day) and Boswellia (900 + mg), which have been shown to be at least as effective as NSAIDs and COX 2 inhibitors but without the Gl or other toxicity. (37-54) These herbals are excellent for arthritic, inflammatory, and other pains as well, and are combined with cherry in the Pain Formula herbal mix by Integrative Therapeutics. I would use 1 to 4 tabs t.i.d. for 6 weeks (effectiveness increases over time) or until pain is controlled, and then use as needed. The herbs discussed above (Revitalizing Sleep Formula) under "Disordered Sleep" can also help muscle pain. My book Pain Free 1-2-3! reviews more than 100 natural and prescription pain therapies and gives an overview of pain management in general. As medications for CFS/FMS/MPS pain, Neurontin, Ultram, and Skelaxin are far more effective than NSAIDs such as Lyrica, Cymbalta, and milnacipran (Savella), which may be helpful but are often more toxic and certainly much more expensive.

Psychological Weil-Being

Many illnesses are associated with various psychological profiles. In, a common profile is a "mega-Type A" personality who, because of childhood low self-esteem, overachieves to get approval. They tend to be perfectionists and have difficulties protecting their boundaries--that is, they say yes to requests when they feel like saying no. Instead of responding to their bodies' signal of fatigue by resting, they redouble their efforts. Taking time to rest, and getting and staying out of abusive personal and work environments is critical. Teach patients (and yourself) to only do and keep their attention on things that, from a centered place, feel good. Joseph Campbell put it beautifully and succinctly when he said, "Follow your bliss"!

Dr. Teitelbaum is a board-certified internist and medical director of the Fibromyalgia and Fatigue Centers nationally (www.FibroandFatigue.com). Having suffered with and overcome CFS and fibromyalgia in 1975, he spent the next 30 years creating, researching, and teaching about effective therapies for fatigue and pain. He is the senior author of the landmark studies "Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia: a Placebo-Controlled Study" and "Effective Treatment of CFS and Fibromyalgia with D-Ribose."

He lectures internationally. He is also the author of the best-selling books From Fatigued to Fantastic! (3rd ed. Penguin/Avery October 2007) and Pain Free 1-2-3: A Proven Program for Eliminating Chronic Pain Now (McGraw Hill 2006). He makes numerous media appearances, including Good Morning America, CNN, and FOX National News and is a frequent guest on Oprah & Friends with Dr. Mehmet Oz. His website is www.endfatigue.com.

Note: The Fibromyalgia and Fatigue Centers (see www.fibroandfatigue.com ) are hiring MDs and DOs as they continue to expand. If interested, contact Dr. Teitelbaum at [e-mail].

Notes

(1.) Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis and Rheumatism 38 (1) (January 1995): 19-28.

(2.) Teitelbaum J, Bird B. Effective treatment of severe chronic fatigue: a report of a series of 64 patients. I Musculoskelet Pain. 1995;3(4): 91-110.

(3.) Teitelbaum JE, Bird B, Greenfield RM, et al. Effective treatment of CFS and FMS: a randomized, double-blind placebo controlled study. I Chronic Fatigue Syndr. 2001;8(2). The full text of the study can be found at: http://www.endfatigue.com/resources/Effective-Treatment-Of-Severe-Chronic-Fatigue-States.html.

(4.) Demitrack MA, Dale K, Straus SE, et al. Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. J Clin Endocrinol Metab. December 1991;73(6): 1223-1234.

(5.) Teitelbaum J. Estrogen and testosterone in CFIDS/FMS. From Fatigued to Fantastic Newsletter. February 1997.

(6.) Behan PO. Post-viral fatigue syndrome research. In: Hyde B, Goldstein ), Levine P eds. The Clinical and Scientific Basis of Myalgic Encephalitis and Chronic Fatigue Syndrome. Ottawa, ON: Nightingale Research Foundation; 1992:238.

(7.) Teitelbaum J. Mitochondrial dysfunction [in CFS/FMS]. From Fatigued to Fantastic Newsletter. 1997;1(2).

(8.) Wolfe F et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the Multicenter Criteria Committee," Arthritis Rheum. 1990;33:160-172.

(9.) Blatman H. Editorial. I Am Acad Pain Manage. April 2002.

(10.) Conference on the Neuroscience and Endocrinology of Fibromyalgia Syndrome, sponsored by the National Institutes of Health, 16-17 July 1996.

(11.) Fleming T, ed. Jamaica dogwood. PDR for Herbal Medicines. 1998:428-429.

(12.) Humulus lupus (monograph]. A/tern Med Rev. 8(2)2003.190-192.

(13.) Cronin JR. Passionflower--reigniting male libido and other potential uses. Altern Complement Ther. April 2003:89-92.

(14.) Dhawan K et al. Reversal of morphine tolerance and dependence by Passiflora incarnata. Pharm Biol. 2002;40(8):576-580.

(15.) Hadley S et al. Valerian. Am Fam Physician. 2003;67(8):1755-1758.

(16.) Yunus MB, Aldag JC. Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study. Br Med I. 25 May 1996;312(7042):1339.

(17.) Lowe IC, Garrison RL, Reichman Aj, Yellin J, Thompson M, Kaufman D. Effectiveness and safety of T3 therapy for euthyroid fibromyalgia: a double-blind, placebo-controlled response driven crossover study. Clinical Bulletin of Myofascial Therapy 1997:2 (2/3):31-58.

(18.) Lowe JC, Reichman AJ, Yellin J. The process of change during T3 treatment for euthyroid fibromyalgia: a double-blind, placebo-controlled, crossover study. Clin Bull Myofascial Ther. 1997;2(2/3):91-124.

(19.) Faglia G, Bitensky L, Pinchera A, et al. Thyrotropin secretion in patients with central hypothyroidism: evidence for reduced biological activity of immunoreactive thyrotropin. J Clin Endocrinol Metab. June 1979;48(6):989-998.

(20.) Skinner GRB, Holmes D, Ahmad A, et al. Clinical response to thyroxine sodium in clinically hypothyroid but biochemically euthyroid patients, J Nutr Envir Med. June 2000;10(2):115-125.

(21.) Nordyke RA, Reppun TS, Madanay LD, et al. Alternative sequences of thyrotropin and free thyroxine assays for routine thyroid function testing, quality and cost. Arch Int Med. 9 February 1998;158(3):266-272.

(22.) Griep FN, Boersma JN, de Kloet ER. Altered reactivity of the hypothalamic-pituitary axis in the primary fibromyalgia syndrome. J Rheumatol. March 1993;20(3):469-474.

(23.) McCain GA, Tilbe KS. Diurnal hormone variation in fibromyalgia syndrome and a comparison with rheumatoid arthritis. J Rheumatol. 1993;25:469-474.

(24.) Jefferies WM. Safe Uses of Cortisol. 2nd ed. Springfield, IL: Charles C. Thomas; 1996.

(25.) Jefferies WM. Low-dosage glucocorticoid therapy, an appraisal of its safety and mode of action in clinical disorders, including rheumatoid arthritis. Arch Int Med. March l967;119(3):265-278.

(26.) McKenzie R, O'Fallon A, Dale J, et al. Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial. JAMA. September 23-30 1998;280(12):1061-1066.

(27.) Teitelbaum JE, Bird B, Weiss A, et al. Low dose hydrocortisone for chronic fatigue syndrome. JAMA. 1999;281:1887-1888.

(28.) Morales AJ, Nolan JJ, Nelson JC, et al. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. J Clin Endocrinol Metab. June 1994;78(6):1360-1367.

(29.) Vliet EL. Screaming to Be Heard: Hormone Connections Women Suspect ... and Doctors Ignore. New York: M. Evans and Company; 1995.

(30.) Wright JV, Lenard L. Maximize Your Vitality & Potency: for Men over 40. Smart Publications; 1999. An excellent reference for those who would like to explore the topic: further.

(31.) Ivker RS. Sinus Survival. New York: Tarcher/Putnam; 2000.

(32.) Becker WM, Reece JB, Poenie MF, et al. The World of The Cell. 3rd ed. San Francisco: Benjamin Cummings; 1996.

(33.) Regland B, Andersson M, Abrahamsson L, et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scan J Rheumatol. 1997;26(4):30l-307.

(34.) Lindenbaum J, Rosenberg IH, Wilson PW, et al. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. July 1994;60(1):2-11.

(35.) Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytoses. N Engl J Med. 30 June 1988;318(26)-.1720-1728.

(36.) Beck WS. Cobalmin and the nervous system [editorial]. N Engl J Med. 30 June 1988;318(26):1752-1 754.

(37.) Beck WS, op. cit; Chrubasik S. et al. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am I Med. 2000 Jul; 109(1):9-14.

(38.) Chrubasik S, Kunzel O, et al. Potential economic impact of using a proprietary willow bark extract in outpatient treatment of low back pain: an open non-randomized study. Phytomedicine. 2001 Jul; 8(4):241-51.

(39.) Marz RW, Kemper F. Willow bark extract--effects and effectiveness. Status of current knowledge regarding pharmacology, toxicology and clinical aspects. [In German.] Wien Med Woch&ischr. 2002;152(15-161:354-359.

(40.) Schmid B et al. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res. 2001 Jun;15(4):344-350.

(41.) Highfield ES, Kemper KJ. White willow [monograph]. Longwood Herbal Task Force. Available at: http://www.mcp.edu/herbal/willowbark/willow.pdf.

(42.) Hedner T Everts B. The early clinical history of salicylates in rheumatology and pain. Clin Rheumatoi 1998;17:17-25.

(43.) Chrubasik S, Eisenberg E. Treatment of rheumatic pain with herbal medicine in Europe. Pain Dig.1998;8:231-236.

(44.) Meier B, Sticher O, Julkunen-Tiitto R. Pharmaceutical aspects of the use of willows in herbal remedies. Planta Med. 1988:559-560.

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(50.) Sander O, Herborn G, Rau R. Is H15 (Resin extract of Boswellia serrata, "incense") a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. [In German.] Z Rheumatol. 1998;57:11-16.

(51.) Sharma ML et al. Agents Actions. 1988;24:161.

(52.) Etzel R. Pnytomed/dne. l996;3(1):91-94.

(53.) Kimmatkar N, Thawani V, Hingorarii L, et al. Phytomedicine. 2003; 10(1 ):3-7.

(54.) Safayhi H et al. Inhibition by Boswellic acids of human leukocyte elastase. J Pharmacol Exp Theory. 1997 Apr; 281(1):460-463.

by Jacob Teitelbaum, MD

www.Vitality 101.com