Transcript Use of Intravenous Micronutrient Therapy (IVMT) in

The Promise & Pitfalls of Intravenous
Micronutrient Therapy:
From Practice to Theory, & Back Again
David Katz, MD, MPH, FACPM, FACP
Yale Prevention Research Center
Yale University School of Medicine
ACAM
Dallas, TX
5-4-06
www.davidkatzmd.com
History of Myers’ Cocktail
(shaken, not stirred)
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Treatment pioneered by John Myers – a physician from Baltimore

Myers did not leave any published or print material on the composition of
the IV treatment

It appears that he used a combination of magnesium chloride, calcium
gluconate, thiamine, vitamin B6, vitamin B12, calcium pantothenate,
vitamin B complex, vitamin C, and dilute hydrochloric acid

Current formulations have been modified to by Dr. Alan Gaby who took
over care of Dr Myers’ patients after his death in 1984
Popular brew
Members from a wide range of national medical
associations report use of IVMT, including:
• The American College for Advancement in Medicine
(ACAM)
• The American Association of Naturopathic Physicians
(AANP)
• The American Holistic Medical Association (AHMA)
• The American Academy of Pain Management (AAPM)
• The Great Lakes College of Clinical Medicine (GLCCM)
and
• International Society of Orthomolecular Medicine (ISOM)
The Myers’ Cocktail
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Myers’ Cocktail CompositionMagnesium chloride hexahydrate (20%)
Calcium gluconate (10%)
Hydroxocobalamin (1,000 mcg/ml)
Pyridoxine hydrochloride (100 mg/ml)
Dexpanthenol (250 mg/ml)
B-complex 100*
Vitamin C (500 mg/ml)
Sterile Water
5 ml
3 ml
1 ml
1 ml
1 ml
1 ml
5 ml
20 ml
Composition, cont.

B-Complex 100 contains the following per each ml:

Thiamine HCl
Riboflavin
Pyridoxine HCl
Panthenol
Niacinamide
Benxyl Alcolhol
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100mg
2mg
2mg
2mg
100mg
2%
Theories, at least in theoryHigher Serum Concentrations
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IV administration of nutrients achieves serum concentrations
much higher than those achieved by oral or IM administration

E.g. Highest serum dose achieved after oral administration of
pharmacological dose of vitamin C is 9.2mg/dL. IV
administration of 50 g/day of vitamin C resulted in a mean
peak plasma level of 80 mg/dL
Pharmacological Effects of Nutrients

Various nutrients may exert pharmacological effects only in
concentrations achieved through IV administration
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Eg. Antiviral effect of Vitamin C demonstrated at a
concentration of 10-15 mg/dL – a level achieved through IV
therapy only
Correcting Intracellular Nutrient Deficits

Higher intracellular nutrient concentration necessary in some
cases to maintain proper cellular function
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E.g. Magnesium concentration 10 times higher in myocardial
cells as compared to extra-cellular concentrations
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in certain disease conditions cell membrane capacity to
maintain high concentrations may be compromised
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IV administration of Mg may lead to a significant though
transient increase in Mg levels
Therapeutic Applications of IVMT

IVMT has been effective in treating
----- Asthma
----- Migraines
----- Fatigue (including chronic fatigue
syndrome)
----- Fibromyalgia
----- Acute muscle spasm
---- Upper respiratory tract infections
----- Chronic sinusitis
----- Seasonal allergic rhinitis
----- Cardiovascular disease
Asthma
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IV magnesium can abort acute asthma attacks
1.
Skobeloff EM, Spivey WH, McNamara RM, Greenspon L. Intravenous magnesium sulfate for the
treatment of acute asthma in the emergency department. JAMA 1989;262:1210-1213.
Bloch H, Silverman R, Mancherje N, et al. Intravenous magnesium sulfate as an adjunct in the
treatment of acute asthma. Chest 1995;107:1576-1581.
Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with
moderate to severe acute asthma. Arch Pediatr Adolesc Med 2000;154:979-983.
Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric
asthma: results of a randomized, placebo-controlled trial. J Pediatr 1996;129:809-814.
Rowe BH, Bretzlaff JA, Bourdon C, et al. Intravenous magnesium sulfate treatment for acute asthma in
the emergency department: a systematic review of the literature. Ann Emerg Med 2000;36:181-190.
2.
3.
4.
5.
Migraine
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Beneficial effect of IVMT in treatment of
migraine has been demonstrated in some
clinical trials
1.
Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulphate
relieves migraine attacks in patients with low serum ionized magnesium levels: a
pilot study. Clin Sci 1995;89:633-636.
(29.) Demirkaya S, Vural O, Dora B, Topcuoglu MA. Efficacy of intravenous
magnesium sulfate in the treatment of acute migraine attacks. Headache 2001;41:
171-177.
(30.) Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium
sulfate relieves cluster headaches in patients with low serum ionized magnesium
levels. Headache 1995;35:597-600.
2.
3.
Fatigue
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Duration of benefit from few days to few months
1.
Manuel y Keenoy B, Moorkens G, Vertommen J, et al. Magnesium status and
parameters of the oxidant-antioxidant balance in patients with chronic fatigue:
effects of supplementation with magnesium. J Am Coll Nutr 2000;19:374-382
Howard JM, Davies S, Hunnisett A. Magnesium and chronic fatigue syndrome.
Lancet 1992;340:426.
Howard JM, Davies S, Hunnisett A. Magnesium and chronic fatigue syndrome.
Lancet 1992;340:426.
Clague JE, Edwards RH, Jackson MJ. Intravenous magnesium loading in chronic
fatigue syndrome. Lancet 1992;340:124-125
Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br
J Nutr 1973;30:277-283.
2.
3.
4.
5.
What is Fibromyalgia (FMS)?
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Clinical syndrome of unknown etiology and
pathogenesis
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Characterized by musculoskeletal pain, non
restorative sleep and fatigue, psychiatric, neurological
and other symptoms
Epidemiology
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3.7 million persons ages 18 older or 2% of the
population affected in US
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0.5 -5% of the population affected worldwide
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4-7 times more common in adult women than men;
highest prevalence in women 50-60 years of age
• Ethnic, genetic, social and cultural factors may influence
FMS predisposition
Pathophysiology Considered4 theories of pathophysiology have emerged:
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Neurogenic (Central Nervous System)
--- generalized pain
--- increase in CSF substance P
--- decrease in serum and CSF
serotonin
--- increased central sensitization
Pathophysiology, cont.
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Muscle Pathology
--- decreased oxygen tension and blood flow
--- abnormal muscle biopsies
--- weakness
Pathophysiology, cont.
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Psychopathology
--- anxiety, depression
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Immune-mediated disease
--- triggered by other infections, such as Lyme disease
Clinical Presentation
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Pain (musculoskeletal tenderness)
Lightheadedness, dizziness, syncope
Fatigue
Chronic insomnia; sleep disturbance
Cognitive deficits/short-term memory loss
Depression/anxiety
Numbness, dysesthesia in hands and feet
Diagnosis
Based on the 1990 ACR
classification guidelines:
 1 historical feature + 1 physical finding
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Historical feature = widespread (axial) pain
of 3 months or more
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Physical finding = pain in at least 3 of the 4
body segments + a finding of at least 11 tender
points on digital palpation of 18 designated
tender points
Treatment
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Patient Education
--- reading materials, videos, support groups
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Physical Exercise
--- low-grade (muscle stretches, aerobic conditioning)
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Pharmacologic Therapies
--- tricyclic antidepressants, NSAIDS, topical
capsaicin, opioids*
*Drug therapies have been used with varying degrees of success in
treating fibromyalgia
Treatment, cont.
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Complementary Treatments
--- Mind body interventions
--- Homeopathy
--- Acupuncture
--- Nutriceuticals
Practice seeking theory
(cart, seeking horse…)
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Myers’ cocktail has been a popular
“alternative” treatment for decades
No trials for FMS have been published
The anecdotal support is strong
Necessity is the mother of…
investigation.
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Current treatments do not adequately address
FMS symptoms in most patients
The apparent promise of the Myers’ Cocktail
(IVMT) called out for testing
Tribulations, prior to Trial
Lack of theoretical rationale
• Empirical evidence only
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Toxicity concerns
Need for IND status
First RCT of IVMT for FMS
(the alphabet gets a workout!)
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Study Design
--- Randomized, double blind, placebo controlled trial
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Inclusion criteria
--- Musculoskeletal pain for 3 months
--- Pain in 11 of 18 tender point sites on digital palpation
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Methods
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40 subjects randomized to treatment or control group
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Treatment
8 weekly treatments performed at one week intervals
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Control
Placebo / IV saline infusion
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Assessments
Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Index (BDI),
Visual Analog Scale (VAS) and Health Status Questionnaire (HSQ 2.0)
Evaluation
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Primary outcome: The Tender Point Index (TPI)
• The severity of pain, assessed by an algometer with a force of 4 Kg, determined
by a scoring system ranging from 0 (no reported tenderness) to 4+ (severe
pain). The TPI is the composite of scores at 18 tender point sites.
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At baseline (following 2-week run-in period)
One-week post intervention period
3-months following the intervention
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Results are now pending; trial is nearing completion
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From Practice, to Theory
Theoretical Pathway
Predisposing Factor HLA Susceptibility OR Precipitating Factors (Trauma/Medical illness)
--- Autoimmune Disorder: Formation of autoantibodies to surface proteins on myocytes or
endothelial cells
--- Deficiency in Nitric Oxide Production OR Impaired Release of, or Response to, Nitric Oxide
--- Vasomotor Dysregulation
--- Muscle Hypoperfusion
---Impaired intracellular energetics
--- Induction of Pain
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Katz DL et al. The Pain of Fibromyalgia Syndrome is due to Muscle Hypoperfusion
Induced by Regional Vasomotor Dysregulation. Medical Hypotheses: In press
And Theory to Practice: Arginine
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Precursor to NO production
Vasodilatory influence
Ameliorates endothelial function
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Also:
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Promotes production of growth hormone. FM patients have an
abnormal sleep pattern involving stages 3 and 4 of non REM
sleep. As GH is secreted predominantly during stages 3 and 4 of
non-REM sleep, it was originally hypothesized that FM patients
may have impaired GH secretion
Other Nutriceuticals
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Guai
Theory: FMS may be caused by an excess of
intracellular phosphate, and possibly oxalic acid,
which build up in the cells and depress the formation
of energy (ATP) in the cell's mitochondria. Based on
biochemical results, guai intake results in elimination
of excess phosphate and calcium from the system
Dose – Determined by individual response
300 mgm to 3,600 mgm/day
Other nutriceuticals, cont.
Vitamin B3 and B6
Theory: FMS patients may be deficient in serotonin
because the tryptophan obtained from food
metabolizes into kynurenin rather than to tryptophan
and 5-htp. For this reason, 5-htp is likely to be more
efficient than L-tryptophan in boosting serotonin.
A combination of Vitamin B3 and B6 plus tryptophan
and magnesium addresses serotonin deficiency.
Other nutriceuticals, cont.
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Zinc and calcium supplements
• Improves sleep patterns
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B Complex plus Vitamin C
• Improvement of overall nutritional status
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Antioxidants
• Theory: Inflammatory response creates damage to tissues. Antioxidants
minimize the damage.
• Natural carotenoids (carotenes, lycopenes and others), vitamin A
(retinol), bioflavonoids like rutin, hesperidin, quercetin, catechin and
the proanthocyanidins (grape seed extract, pine bark extract or
pycnogenols)
Other nutriceuticals, cont.
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Malic acid
• Theory: FMS is the result of local hypoxia to the muscles.
Patients with fibromyalgia have low muscle-tissue oxygen
pressure in affected muscles. Muscle biopsies from affected
areas showed muscle tissue glycolysis is inhibited,
reducing ATP synthesis. This stimulates the process of
gluconeogenesis, which results in muscle tissue breakdown
and mitochondrial damage.
• Malic acid reverses hypoxia induced inhibition of
glycolysis and energy production, possibly improving
energy production in fibromyalgia, and reversing the
negative effect of the relative hypoxia
Conclusions
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The needs of FMS patients are not fully met at present
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CAM / Nutriceuticals show promise
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Promising results from practice must be tested in trials
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Practice may inform theory; theory may then serve to advance
practice
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If a causal pathway for FMS can be established, we can better
direct our efforts at breaking the links
Conclusions, cont.
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IVMT appears promising for treatment of FMS
sysmptoms; trial results will be available soon
Larger trial is planned for follow-up, to include
assessment of mechanism
Use of IVMT/Myers’ Cocktail is justified at
present, although still over the line of evidence
Future efforts will need to move further
‘upstream’
Conclusions, cont.
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If promise of IVMT for fibromyalgia is
realized, a similar approach to other conditions
will be warranted:
• Delineation of theoretical causal pathways
• Controlled testing of interventions
• Evidence, not conviction, will best advance the
cause
Bibliography
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[1]
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(2): p. 160-72.
[2]
Gracely, R.H., M.A. Grant, and T. Giesecke, Evoked pain measures in fibromyalgia. Best Pract Res Clin Rheumatol, 2003. 17(4): p. 593609.
[3]
Rao, S.G. and D.J. Clauw, The management of fibromyalgia. Drugs Today (Barc), 2004. 40(6): p. 539-54.
[4]
Fietta, P., Fibromyalgia: state of the art. Minerva Med, 2004. 95(1): p. 35-47, 47-52.
[5]
Wolfe, F., et al., Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol, 1997. 24(3): p. 5559.
[6]
Lawrence, R.C., et al., Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum,
1998. 41(5): p. 778-99.
[7]
Felson, D.T., Epidemiology of the rheumatic diseases. In: Koopman WJ, editor. 1997: p. 3-34.
[8]
White, K.P. and M. Harth, Classification, epidemiology, and natural history of fibromyalgia. Curr Pain Headache Rep, 2001. 5(4): p. 3209.
[9]
Gran, J.T., The epidemiology of chronic generalized musculoskeletal pain. Best Pract Res Clin Rheumatol, 2003. 17(4): p. 547-61.
[10]
Marder, W.D., et al., The present and future adequacy of rheumatology manpower. A study of health care needs and physician supply.
Arthritis Rheum, 1991. 34(10): p. 1209-17.
[11]
Yunus, M.B., Gender differences in fibromyalgia and other related syndromes. J Gend Specif Med, 2002. 5(2): p. 42-7.
[12]
Buskila, D., et al., Assessment of nonarticular tenderness and prevalence of fibromyalgia in children. J Rheumatol, 1993. 20(2): p. 368-70.
[13]
Clark, P., et al., Prevalence of fibromyalgia in children: a clinical study of Mexican children. J Rheumatol, 1998. 25(10): p. 2009-14.
[14]
Yunus, M.B., Genetic factors in fibromyalgia syndrome. Z Rheumatol, 1998. 57 Suppl 2: p. 61-2.
[15]
Jacobsson, L.T., et al., Low prevalences of chronic widespread pain and shoulder disorders among the Pima Indians. J Rheumatol, 1996.
23(5): p. 907-9.
[16]
Neeck, G., Neuroendocrine and hormonal perturbations and relations to the serotonergic system in fibromyalgia patients. Scand J
Rheumatol Suppl, 2000. 113: p. 8-12.
[17]
Neeck, G. and W. Riedel, Neuromediator and hormonal perturbations in fibromyalgia syndrome: results of chronic stress? Baillieres Clin
Rheumatol, 1994. 8(4): p. 763-75.
[18]
Okifuji, A. and D.C. Turk, Stress and psychophysiological dysregulation in patients with fibromyalgia syndrome. Appl Psychophysiol
Biofeedback, 2002. 27(2): p. 129-41.
[19]
Garrison, R.L. and P.C. Breeding, A metabolic basis for fibromyalgia and its related disorders: the possible role of resistance to thyroid
hormone. Med Hypotheses, 2003. 61(2): p. 182-9.
[20]
Arthritis Foundation. Delivering on the Promise in Fibromyalgia. 2004 [cited; Available from:
http://www.arthritis.org/research/research_program/Fibromyalgia/default.asp.
Bibliography, cont.




















[21]
Pillemer, S.R., et al., The neuroscience and endocrinology of fibromyalgia. Arthritis Rheum, 1997. 40(11): p. 1928-39.
[22]
Bennett, R., Fibromyalgia: present to future. Curr Pain Headache Rep, 2004. 8(5): p. 379-84.
[23]
Inanici, F. and M.B. Yunus, History of fibromyalgia: past to present. Curr Pain Headache Rep, 2004. 8(5): p. 369-78.
[24]
Yunus, M.B., Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J
Rheumatol, 1992. 19(6): p. 846-50.
[25]
Daoud, K.F. and A. Barkhuizen, Rheumatic mimics and selected triggers of fibromyalgia. Curr Pain Headache Rep, 2002. 6(4): p. 284-8.
[26]
Kerschbaumer, A., et al., Fibromyalgia may mask onset of autoimmune diseases. Eur J Pain, 2003. 7(3): p. 295-6.
[27]
Staines, D.R., Is fibromyalgia an autoimmune disorder of endogenous vasoactive neuropeptides? Med Hypotheses, 2004. 62(5): p. 665-9.
[28]
Bagis, S., et al., Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder? Rheumatol Int, 2005. 25(3): p. 18890.
[29]
Sackner, M.A., E.M. Gummels, and J.A. Adams, Say NO to fibromyalgia and chronic fatigue syndrome: an alternative and complementary
therapy to aerobic exercise. Med Hypotheses, 2004. 63(1): p. 118-23.
[30]
Bennett, R., Fibromyalgia, in Textbook of Pain, Wall and Melzack, Editors. 1999, Churchill Livingstone, Inc. p. 585.
[31.
Bengtsson, A., The muscle in fibromyalgia. Rheumatology (Oxford), 2002. 41(7): p. 721-4.
[32]
Guyton, A. and J. Hall, Textbook of Medical Physiology. 10th ed. 2000: W B Saunders Co.
[33]
Mayo Clinic staff. How you feel pain. 2005 [cited; Available from: http://www.mayoclinic.com/invoke.cfm?id=PN00017.
[34]
Bruckle, W. and H. Zeidler, [Fibromyalgia - An update.]. Internist (Berl), 2005.
[35]
Schaible, H.G. and H. Vanegas, How do we manage chronic pain? Baillieres Best Pract Res Clin Rheumatol, 2000. 14(4): p. 797-811.
[36]
Muscles, Tendons, and Ligaments, in Textbook of Pain, Wall and Melzack, Editors. 1999, Churchill Livingstone, Inc. p. 585.
[37]
Lawson, K., Tricyclic antidepressants and fibromyalgia: what is the mechanism of action? Expert Opin Investig Drugs, 2002. 11(10): p.
1437-45.
[38]
Rao, S.G. and R.M. Bennett, Pharmacological therapies in fibromyalgia. Best Pract Res Clin Rheumatol, 2003. 17(4): p. 611-27.
[39]
Wolfe, F., et al., Health status and disease severity in fibromyalgia: results of a six-center longitudinal study. Arthritis Rheum, 1997. 40(9):
p. 1571-9.
[40]
Mannerkorpi, K., Exercise in fibromyalgia. Curr Opin Rheumatol, 2005. 17(2): p. 190-4.
Bibliography, cont.





















[41]
Yildiz, S., et al., A new treatment modality for fibromyalgia syndrome: hyperbaric oxygen therapy. J Int Med Res, 2004. 32(3): p. 263-7.
[42]
Hong, C.Z. and T.C. Hsueh, Difference in pain relief after trigger point injections in myofascial pain patients with and without fibromyalgia.
Arch Phys Med Rehabil, 1996. 77(11): p. 1161-6.
[43]
Bradley, L. and G. Alarcon, Fibromyalgia, in Arthritis and allied conditions, K. WJ, Editor. 1997, Williams & Wilkins: Baltimore. p. 3-34.
[44]
Singh, B.B., et al., A pilot study of cognitive behavioral therapy in fibromyalgia. Altern Ther Health Med, 1998. 4(2): p. 67-70.
[45]
Mason, L.W., P. Goolkasian, and G.A. McCain, Evaluation of multimodal treatment program for fibromyalgia. J Behav Med, 1998. 21(2): p.
163-78.
[46]
Bennett, R.M. and B.L.T.R.J.R.C.J.R.C.P.K. Kwiatek R, Beyond fibromyalgia: ideas on etiology and treatment Regional cerebral blood flow
in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. J Rheumatol Suppl, 1989.
19: p. 185-91.
[47]
Clark, S.R., Prescribing exercise for fibromyalgia patients. Arthritis Care Res, 1994. 7(4): p. 221-5.
[48]
Buckelew, S.P., et al., Biofeedback/relaxation training and exercise interventions
for fibromyalgia: a prospective trial. Arthritis Care Res, 1998. 11(3): p. 196-209.
[49]
Drexler, A.R., E.J. Mur, and V.C. Gunther, Efficacy of an EMG-biofeedback therapy in fibromyalgia patients. A comparative study of patients
with and without abnormality in (MMPI) psychological scales. Clin Exp Rheumatol, 2002. 20(5): p. 677-82.
[50]
King, S.J., et al., The effects of exercise and education, individually or combined, in women with fibromyalgia. J Rheumatol, 2002. 29(12): p.
2620-7.
[51]
Wahner-Roedler, D.L., et al., Use of complementary and alternative medical therapies by patients referred to a fibromyalgia treatment
program at a tertiary care center. Mayo Clin Proc, 2005. 80(1): p. 55-60.
[52]
Holdcraft, L.C., N. Assefi, and D. Buchwald, Complementary and alternative medicine in fibromyalgia and related syndromes. Best Pract Res
Clin Rheumatol, 2003. 17(4): p. 667-83.
[53]
Merchant, R.E., C.A. Carmack, and C.M. Wise, Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia
syndrome: a pilot study. Phytother Res, 2000. 14(3): p. 167-73.
[54]
Merchant, R.E. and C.A. Andre, 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, 2001. 7(3): p. 79-91.
[55]
Taggart, H.M., et al., Effects of T'ai Chi exercise on fibromyalgia symptoms and health-related quality of life. Orthop Nurs, 2003. 22(5): p.
353-60.
[56]
Astin, J.A., et al., The efficacy of mindfulness meditation plus Qigong movement therapy in the treatment of fibromyalgia: a randomized
controlled trial. J Rheumatol, 2003. 30(10): p. 2257-62.
[57]
Dimmock, S., P.R. Troughton, and H.A. Bird, Factors predisposing to the resort of complementary therapies in patients with fibromyalgia.
Clin Rheumatol, 1996. 15(5): p. 478-82.
[58]
Hadhazy, V.A., et al., Mind-body therapies for the treatment of fibromyalgia. A systematic review. J Rheumatol, 2000. 27(12): p. 2911-8.
[59]
Crofford, L.J. and B.E. Appleton, Complementary and alternative therapies for fibromyalgia. Curr Rheumatol Rep, 2001. 3(2): p. 147-56.
[60]
Berman, B.M. and J.P. Swyers, Complementary medicine treatments for fibromyalgia syndrome. Baillieres Best Pract Res Clin Rheumatol,
1999. 13(3): p. 487-92.
Bibliography, cont.




















[61]
Logan, A.C. and T.M. Beaulne, The treatment of small intestinal bacterial overgrowth with enteric-coated peppermint oil: a case report.
Altern Med Rev, 2002. 7(5): p. 410-7.
[62]
Pimentel, M., et al., A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Ann
Rheum Dis, 2004. 63(4): p. 450-2.
[63]
Gaby, A.R., Intravenous nutrient therapy: the "Myers' cocktail". Altern Med Rev, 2002. 7(5): p. 389-403.
[64]
Yale-Griffin Prevention Research Center, Intravenous Micronutrient Therapy (IVMT) for Fibromyalgia Syndrome: A Pilot Study. 2003:
NIH, Grant # AT 00942-01A1.
[65]
Mauskop, A. and B.M. Altura, Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci, 1998. 5(1): p. 24-7.
[66]
Mauskop, A., et al., Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot
study. Clin Sci (Lond), 1995. 89(6): p. 633-6.
[67]
Lund, E., et al., Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic
exercise. Scand J Rheumatol, 2003. 32(3): p. 138-45.
[68]
Valim, V., et al., Aerobic fitness effects in fibromyalgia. J Rheumatol, 2003. 30(5): p. 1060-9.
[69]
Nampiaparampil, D.E. and R.H. Shmerling, A review of fibromyalgia. Am J Manag Care, 2004. 10(11 Pt 1): p. 794-800.
[70] Gursoy, S., et al., Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int, 2003. 23(3): p.
104-7.
[71]
Yunus, M.B., et al., Genetic linkage analysis of multicase families with fibromyalgia syndrome. J Rheumatol, 1999. 26(2): p. 408-12.
[72]
Greenfield, S., M.A. Fitzcharles, and J.M. Esdaile, Reactive fibromyalgia syndrome. Arthritis Rheum, 1992. 35(6): p. 678-81.
[73]
Aaron, L.A., et al., Perceived physical and emotional trauma as precipitating events in fibromyalgia. Associations with health care seeking
and disability status but not pain severity. Arthritis Rheum, 1997. 40(3): p. 453-60.
[74]
White, K.P., et al., Trauma and fibromyalgia: is there an association and what does it mean? Semin Arthritis Rheum, 2000. 29(4): p. 200-16.
[75]
Crofford, L.J. and D.J. Clauw, Fibromyalgia: where are we a decade after the American College of Rheumatology classification criteria
were developed? Arthritis Rheum, 2002. 46(5): p. 1136-8.
[76]
Buskila, D., et al., Increased rates of fibromyalgia following cervical spine injury. A controlled study of 161 cases of traumatic injury.
Arthritis Rheum, 1997. 40(3): p. 446-52.
[77]
Itoh, Y., et al., Immunogenetic background of patients with autoimmune fatigue syndrome. Autoimmunity, 2000. 32(3): p. 193-7.
[78]
Nishikai, M., et al., Autoantibodies to a 68/48 kDa protein in chronic fatigue syndrome and primary fibromyalgia: a possible marker for
hypersomnia and cognitive disorders. Rheumatology (Oxford), 2001. 40(7): p. 806-10.
[79]
Smart, P.A., G.W. Waylonis, and K.V. Hackshaw, Immunologic profile of patients with fibromyalgia. Am J Phys Med Rehabil, 1997. 76(3):
p. 231-4.
[80]
Itoh, Y., et al., [Autoimmune fatigue syndrome and fibromyalgia syndrome]. Nippon Ika Daigaku Zasshi, 1999. 66(4): p. 239-44.
Bibliogrpahy, cont.
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


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
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

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



[81]
Skowera, A., et al., Antinuclear autoantibodies (ANA) in Gulf War-related illness and chronic fatigue syndrome (CFS) patients. Clin Exp Immunol, 2002.
129(2): p. 354-8.
[82]
Klein, R., M. Bansch, and P.A. Berg, Clinical relevance of antibodies against serotonin and gangliosides in patients with primary fibromyalgia syndrome.
Psychoneuroendocrinology, 1992. 17(6): p. 593-8.
[83]
Werle, E., et al., Antibodies against serotonin have no diagnostic relevance in patients with fibromyalgia syndrome. J Rheumatol, 2001. 28(3): p. 595-600.
[84]
Kwiatek, R., et al., Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine
tegmentum and thalami. Arthritis Rheum, 2000. 43(12): p. 2823-33.
[85]
Mountz, J.M., et al., Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with
low pain threshold levels. Arthritis Rheum, 1995. 38(7): p. 926-38.
[86]
Gur, A., et al., Regional cerebral blood flow and cytokines in young females with fibromyalgia. Clin Exp Rheumatol, 2002. 20(6): p. 753-60.
[87]
Eriksen, W., Linking work factors to neck myalgia: the nitric oxide/oxygen ratio hypothesis. Med Hypotheses, 2004. 62(5): p. 721-6.
[88]
Lund, N., A. Bengtsson, and P. Thorborg, Muscle tissue oxygen pressure in primary fibromyalgia. Scand J Rheumatol, 1986. 15(2): p. 165-73.
[89]
Henriksson, K.G., Chronic muscular pain: aetiology and pathogenesis. Baillieres Clin Rheumatol, 1994. 8(4): p. 703-19.
[90]
Fassbender, H.G., [Pathology of soft-tissue rheumatism]. Med Welt, 1975. 26(45): p. 2036-8.
[91]
Grassi, W., et al., Capillary permeability in fibromyalgia. J Rheumatol, 1994. 21(7): p. 1328-31.
[92]
Jeschonneck, M., et al., Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia. Rheumatology (Oxford),
2000. 39(8): p. 917-21.
[93]
Gronemann, S.T., et al., Collagen and muscle pathology in fibromyalgia patients. Rheumatology (Oxford), 2004. 43(1): p. 27-31.
[94]
Bengtsson, A., K.G. Henriksson, and J. Larsson, Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia.
Arthritis Rheum, 1986. 29(7): p. 817-21.
[95]
Lindman, R., A. Eriksson, and L.E. Thornell, Fiber type composition of the human female trapezius muscle: enzyme-histochemical characteristics. Am J
Anat, 1991. 190(4): p. 385-92.
[96]
Lindman, R., et al., Changes in muscle morphology in chronic trapezius myalgia. Scand J Work Environ Health, 1991. 17(5): p. 347-55.
[97]
Larsson, S.E., et al., Muscle changes in work-related chronic myalgia. Acta Orthop Scand, 1988. 59(5): p. 552-6.
[98]
Larsson, S.E., et al., Chronic trapezius myalgia. Morphology and blood flow studied in 17 patients. Acta Orthop Scand, 1990. 61(5): p. 394-8.
[99]
Larsson, S.E., et al., Effects of psychophysiological stress on trapezius muscles blood flow and electromyography during static load. Eur J Appl Physiol
Occup Physiol, 1995. 71(6): p. 493-8.
[100]
Sietsema, K.E., et al., Oxygen uptake during exercise in patients with primary fibromyalgia syndrome. J Rheumatol, 1993. 20(5): p. 860-5.
[101]
Valim, V., et al., Peak oxygen uptake and ventilatory anaerobic threshold in fibromyalgia. J Rheumatol, 2002. 29(2): p. 353-7.
[102]
Acero, C.O., Jr., et al., Haemodynamic responses in chronically painful, human trapezius muscle to cold pressor stimulation. Arch Oral Biol, 1999. 44(10):
p. 805-12.
[103]
Maekawa, K., G.T. Clark, and T. Kuboki, Intramuscular hypoperfusion, adrenergic receptors, and chronic muscle pain. J Pain, 2002. 3(4): p. 251-60.
[104]
Buskila, D., L. Neumann, and J. Press, Genetic factors in neuromuscular pain. CNS Spectr, 2005. 10(4): p. 281-4.
[105]
Offenbaecher, M., et al., Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region. Arthritis Rheum,
1999. 42(11): p. 2482-8.
Thank you.
David L. Katz, MD, MPH, FACPM, FACP
Director, Yale Prevention Research Center
130 Division Street
Derby, CT 06418
[email protected]
www.davidkatzmd.com