© Angela Hywood ND 2012Slide 1 Nutritional and Herbal Approaches + Functional Pathology to help...

© Angela Hywood ND 2012 Slide 1

Nutritional and Herbal Approaches+ Functional Pathology to help define the underlying causes of Fibromyalgia & CFS

Angela Hywood ND (Australia)BHSc(Naturopathy), Dip Bot Med, Dip Hom, Dip NFMMember NHAA; ANTA


Fibromyalgia

• Fibromyalgia is a disorder of unknown cause characterized by chronic widespread musculoskeletal pain and symptoms such as fatigue, sleep disturbances, gastrointestinal complaints and psychological problems.

• A key diagnostic condition is the presence of multiple tender points on the body (11 of 18 tender points should be present, as defined by the American College of Rheumatology).

• However, not all patients meet this diagnostic hurdle.

Wolfe F, Smythe HA, Yunus MB et al. (February 1990). "The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee".

Arthritis Rheum. 33 (2): 160–72 Wolfe F (February 1989). "Fibromyalgia: the clinical syndrome". Arthritis Rheum. 15 (1): 1–18


Symptoms

• Key Symptoms• Pain all over• Fatigue• Brain fog• Trouble sleeping• Exercise difficulties• Irritable bowel• Headaches• Jaw pain• Multiple sensitivities

•


Fibromyalgia

• Disease onset appears to follow physiological and/or psychological stressors.

• Prognosis for sufferers of fibromyalgia is poor. One study found no improvement in pain over two years, despite various treatments.

Wolfe F, Smythe HA, Yunus MB et al. (February 1990). "The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter

Criteria Committee". Arthritis Rheum. 33 (2): 160–72 Wolfe F (February 1989). "Fibromyalgia: the clinical syndrome". Arthritis Rheum. 15 (1): 1–18


Fibromyalgia

• There is considerable comorbidity with chronic fatigue syndrome (CFS) and multiple chemical sensitivities (MCS).

• For example, a study of a cohort of CFS sufferers found 40.6% met the criteria for MCS and 15.6% met the criteria for fibromyalgia.

• Another study found that 70% of tested CFS patients met the criteria for Fibromyalgia.

Kerry Bone "A phytotherapeutic protocol for fibromyalgia - Phytotherapy Review & Commentary". Townsend Letter for Doctors and Patients. Jan, 2011.


Fibromyalgia

• The reverse association is also strong: • 58% of a female group with fibromyalgia met

the full criteria for CFS compared to 26.1% of a control group

• For males the rates were even higher, 80.0% versus 22.2% for controls.

• There is also a strong association with depression and to a lesser extent, other psychiatric disorders.

Kerry Bone "A phytotherapeutic protocol for fibromyalgia - Phytotherapy Review & Commentary". Townsend Letter for Doctors and Patients. FindArticles.com. 02 Jan, 2011.


Fibromyalgia

• Conventional treatments include:• Pain management pharmaceuticals

– Analgesics– NSAID

• Ketamine• Interferon-alpha• More commonly antidepressant drugs (especially tricyclics).• A role for non-pharmacological therapy including exercise

and chiropractic management has been established in objective studies

Henriksson KG, Sorensen J. The promise of N-methyl-D-asparate receptor antagonists in fibromyalgia. Rheum Dis Clin North Am 2002; 28(2): 343- 351

Graven-Nielsen T, Aspegren Kendall S, Henriksson KG et al. Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain 2000; 85(3): 483-491

Russell IJ, Michalek JE, Kang YK et al. Reduction of morning stiffness and improvement in physical function in fibromyalgia syndrome patients treated sublingually with loses of human interferon-alpha. J Interferon Cytokine Res1999; 19(8): 961-96812 Sim J, Adams N.

Systematic review of randomized controlled trials of nonpharmacological interventions for fibromyalgia. Clin J Pain 2002.


Causation Hypotheses

• Genetic predispiosition• Stress• Dopamine dysfunction (hypodopaminergia)• Abnormal serotonin metabolism• Deficient growth hormone (GH) secretion• Psychological factors• Physical trauma• Aberrant immune response to intestinal bacteria

Buskila D, Sarzi-Puttini P (2006). "Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome". Arthritis Res Ther. 8 (5): 218

Cohen H, Buskila D, Neumann L, Ebstein RP (March 2002). "Confirmation of an association between fibromyalgia and serotonin transporter promoter region (5- HTTLPR) polymorphism, and relationship to anxiety-related personality traits". Arthritis Rheum. 46 (3): 845–7.

Zubieta JK, Heitzeg MM, Smith YR, et al. (February 2003). "COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor". Science (journal) 299 (5610): 1240–3

Pae CU, Luyten P, Marks DM, Han C, Park SH, Patkar AA, Masand PS, Van Houdenhove B (August 2008). "The relationship between fibromyalgia and major depressive disorder: a comprehensive review". Curr Med Res Opin 24 (8): 2359–71

Pimental M, Wallace D, Hallegua D et al. (November 1989). "A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing". J Rheumatol Suppl 19: 23–7


What Causes Fibromyalgia?

• A definitive cause is not known. • However a number of abnormalities of immune

and neuroendocrine response have been identified over the last 10 years.

• The reduced hormonal and autonomic responses appear to reflect an impairment in the hypothalamic or central nervous system response to stimuli, rather than a primary defect at the level of the pituitary or peripheral glands.


Abnormalities in Neuroendocrine Response

A recent review of pathogenic mechanisms in fibromyalgia concluded:

• “The symptomatology characterizing fibromyalgia comprises three systems: the musculoskeletal system with widespread muscular pain, neuroendocrine disorders, and psychological distress including anxiety and depression.”

Neeck G. Pathogenic mechanisms of fibromyalgia. Ageing Res Rev 2002; 1(2): 243-255



• Studies of the entire endocrine profile of fibromyalgia patients support the hypothesis that an elevated activity of corticotropin releasing hormone (CRH) neurons determines not only many symptoms of fibromyalgia but may also cause alterations observed in the hormonal axes.

• Hypothalamic CRH neurons thus may play a key role not only in resetting the various endocrine loops, but possibly also nociceptive and psychological mechanisms as well.

Neeck G. Pathogenic mechanisms of fibromyalgia. Ageing Res Rev 2002; 1(2): 243-255



• Another review on hormonal perturbations in fibromyalgia by the same research group asserted:

"Recent studies of the entire endocrine profile of FM patients following a simultaneous challenge of the hypophysis with corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone, growth hormone-releasing hormone, and luteinizing hormone-releasing hormone, support the hypothesis that an elevated activity of CRH neurons determines not only many symptoms of FM but may also cause the deviations observed in the other hormonal axes.”

Neeck G, Riedel W. Hormonal pertubations in fibromyalgia syndrome. Ann N Y Acad Sci 1999; 876: 325-338


Adrenal Stress and Fibromyalgia

• Furthering this, a Dutch research team has proposed that fibromyalgia is associated with an altered functioning of the stress response system.

• Based on a comparative study with healthy controls they conclude that: • “The present data validate and substantiate our

preliminary evidence for a dysregulation of the HPA axis in patients with FM, marked by mild hypocortisolemia, hyper- reactivity of pituitary ACTH release to CRH, and glucocorticoid feedback resistance”

Evengard B, Nilsson CG, Lindh G et al. Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue

syndrome. Pain 1998; 78(2): 153-155Russell IJ, Orr MD, Littman B et al. Elevated cerebrospinal fluid levels of substance P in patients

with the fibromyalgia syndrome. Arthritis Rheum 1994; 37(11): 1593-1601Russell IJ. The promise of substance P inhibitors in fibromyalgia. Rheum Dis Clin North Am 2002;

28(2): 329-342


Adrenal Stress and Fibromyalgia

• They propose that a reduced containment of the stress-response system by corticosteroid hormones is associated with the symptoms of fibromyalgia.

• This is possibly accompanied by adrenal hypo- responsiveness (phase 3 adrenal fatigue)• Low cortisol• Low DHEA

Griep EN, Boersma JW, Lentjes EG et al. Function of the hypothalamic- pituitary-adrenal axis in patients with fibromyalgia and low back pain. J Rheumatol 1998; 25(7): 1374-1381

Crofford LJ, Pillemer SR, Kalogeras KT et al. Hypothalamic-pituitary- adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum 1994; 37(11): 1583-1592

Griep EN, Boersma JW, de Kloet ER. Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. J Rheumatol 1993; 20(3): 418-421


Growth Hormone and Fibromyalgia

• Adult growth hormone deficiency is a well-described syndrome with many features reminiscent of fibromyalgia.

• There is a debate as to whether growth hormone (and the related insulin-like growth factor 1, IGF-1, a surrogate marker) levels are depleted in fibromyalgia.

Bennett RM. Adult growth hormone deficiency in patients with fibromyalgia. Curr Rheumatol Rep 2002; 4(4): 306-312

Landis CA, Lentz MJ, Rothermel J et al. Decreased nocturnal levels of prolactin and growth hormone in women with fibromyalgia. J Clin Endocrinol Metab 2001; 86(4): 1672-1678

Bennett RM, Cook DM, Clark SR et al. Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia. J Rheumatol 1997; 24(7): 1384-1389


Growth Hormone and Fibromyalgia

• A review concluded growth hormone deficiency (as defined in terms of a low IGF-1 level) occurs in around 30% of patients with fibromyalgia and is probably the cause of some morbidity.

• Therapy with growth hormone caused significant clinical improvement in fibromyalgia patients with low IGF-1 levels in a placebo-controlled trial.

Bagge E, Bengtsson BA, Carlsson L et al. Low growth hormone secretion in patients with fibromyalgia – a preliminary report on 10 patients and 10 controls. J Rheumatol 1998; 25(1): 145-148


Tribulus for GH and Hypoadrenal Axis

• Tribulus modulates both growth hormone and DHEA levels.

• Prescribing: • Tribulus terrastis extract equivalent to dried

herb (aerial parts), standardized to furostanol saponins as protodioscin 100mg per tablet, 3-4 tablets per day.

• Saliva adrenal hormones index testing is a sound method to evaluate adrenal involvement.

• Bloods may provide good initial screening


Adrenal Saliva Hormones


Hypoglycemia and Fibromyalgia

• When induced hypoglycemia was used as a test probe for the stress response, patients with fibromyalgia exhibited an impaired ability to activate the HP portion of the HPA axis as well as the sympatho-adrenal system.

• The corollary of this is that repeated hypoglycemia could be a precipitating factor in the pathogenesis of fibromyalgia.

Adler GK, Kinsley BT, Hurwitz S et al. Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome. Am J Med 1999; 106(5): 534-

543


Nervous System Function and Neurotransmitters

• Fibromyalgia is associated with a disturbance of autonomic nervous system function.

• Fibromyalgia patients had significantly lower heart rate variability (HRV) compared with controls.

• Power spectral analysis of the HRV patterns suggest that the basal autonomic state of patients with fibromyalgia is characterized by increased sympathetic and decreased parasympathetic tones.

• Another study using the same technique found that fibromyalgia patients have a deranged sympathetic response to orthostatic stress.

Cohen H, Neumann L, Shore M et al. Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability. Semin Arthritis Rheum 2000; 29(4): 217-227


Low Serotonin

• Serum serotonin levels were significantly lower in fibromyalgia.

• However, within the fibromyalgia group, serotonin levels were correlated with tender point count and depression.

• The link to serotonin metabolism has led to investigations of therapy with 5-hydroxytryptophan, which has been successfully trialled in fibromyalgia.

• Decreased brain serotonin levels were deduced for fibromyalgia patients, based on assessment of plasma tryptophan and its metabolites. Wolfe F, Russell IJ, Vipraio G et al. Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. J Rheumatol 1997; 24(3): 555-559Klein R, Berg PA. A comparative study on antibodies to nucleoli

and 5- hydroxytryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia-myalgia syndrome. Clin Investig 1994; 72(7): 541-549


Amino Acid Plasma Profile

• Amino Acids are the "building blocks" of proteins, are found in every tissue of the body.

• They play a major role in nearly every chemical process that affects both physical and mental function including the formation of ligaments, tendons, bones, and antibodies, as well as regulation of enzymes and blood transport proteins.

• Failure to obtain enough of even 1 of the 10 essential amino acids has serious health implications and can result in degradation of the body's proteins. Muscle and other protein structures may be dismantled to obtain the one amino acid that is needed.


Eosinophilia Myalgia Syndrome (EMS)

• Eosinophilia myalgia syndrome (EMS) has been linked to intake of contaminated tryptophan and an alteration in tryptophan metabolism.

• There are several similarities between EMS and fibromyalgia including autoantibody patterns and clinical picture.

• Adding to the theme of altered tryptophan metabolism in fibromyalgia, a recent study used a tryptophan depletion test and found a subgroup of patients who showed an activation of serotonin metabolism.

Barth H, Berg PA, Klein R. Is there any relationship between eosinophilia myalgia syndrome (EMS) and fibromyalgia syndrome (FMS)? An analysis of clinical and immunological data. Adv

Exp Med Biol 1999; 467: 487-496


Immune Function and the Role of Viruses

• It is relatively well-recognized that one of the complications of chronic hepatitis C infection can be fibromyalgia.

• Other viruses and microorganisms linked to fibromyalgia include enteroviruses and mycoplasma.

• In some cases of fibromyalgia an acute onset following a flu-like episode is described. In these patients a high prevalence of antibodies against enterovirus was found. Parvovirus has been implicated, but the association was not confirmed.

Kozanoglu E, Canataroglu A, Abayli B et al. Fibromyalgia syndrome in patients with hepatitis C infection. Pheumatol Int 2003; 23(5): 248-251

Thompson ME, Barkhuizen A. Fibromyalgia, hepatitis C infection, and the cytokine connection. Curr Pain Headache Rep 2003; 7(5): 342-347

Buskila D, Shnaider A, Neumann L et al. Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship. Arch Intern Med 1997; 157(21): 2497-2500


Mycoplasma

• Testing: Mycoplasma CPR

• Abundant research: www.neurotransmitter.net/mycoplasma.html

Nasralla M, Haier J, Nicolson GL.Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Eur J Clin Microbiol Infect Dis 1999 Dec;18(12):859-65

Nicolson GL, Gan R, Haier J.Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003 May;

111(5)557-66.

Nijs J, Nicolson GL, De Becker P, Coomans D, De Meirleir K. High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood

of chronic fatigue syndrome patients.



• Viral-induced changes in cytokines have been suggested to play a role in fibromyalgia and one study found abnormal cytokine levels but not another.

• Beta-endorphin (an endogenous opioid involved in immune regulation) levels in peripheral mononuclear cells were significantly lower in patients with CFS or fibromyalgia compared to normal controls and depressed patients.

Kozanoglu E, Canataroglu A, Abayli B et al. Fibromyalgia syndrome in patients with hepatitis C infection. Pheumatol Int 2003; 23(5): 248-251

Thompson ME, Barkhuizen A. Fibromyalgia, hepatitis C infection, and the cytokine connection. Curr Pain Headache Rep 2003; 7(5): 342-347

Buskila D, Shnaider A, Neumann L et al. Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship. Arch Intern Med 1997; 157(21): 2497-2500



• Production of various autoantibodies has been linked to fibromyalgia.

• Antinuclear antibody levels (ANA) are no higher in fibromyalgia patients compared to controls but may be predictive of more severe disease.

• Particular types of ANA have been suggested to be linked to fibromyalgia and CFS, albeit with a relatively low frequency of occurrence (15%) for one.

Yunis MB, Hussey FX, Aldag JC. Antinuclear antiodies and connective tissue disease features in fibromyalgia syndrome: a controlled study. J Rheumatol 1993; 20(9): 1557-1560

Smart PA, Waylonis GW, Hackshaw KV. Immunologic profile of patients with fibromyalgia. Am J Phys Med Rehabil 1997; 76(3): 231-234 59 Nishikai M, Tomomatsu S, Hankins RW 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): 806-810



• A defined autoantibody pattern consisting of antibodies to serotonin, gangliosides and phospholipids was found for both CFS and fibromyalgia.

• Studies support the concept that fibromyalgia and CFS may belong to the same clinical entity and manifest themselves as "psycho-neuro-endocrinological -autoimmune diseases."

• A low level coagulation activation was found in a US study which could see fibromyalgia classified as a type of antiphospholipid antibody syndrome.

Harris EN Baguley E, Asherson RA, Hughes GRV. Clinical an@ serological features of the Antiphospholipid-syndrome (APS). Br J Rheumatol 1987; 26: 19.


GIT Infections Linked to CFS and Fibromyalgia

• Blastocystis hominis • Test via CDSA• Treatment

– Saccharomyces boulardii and/ or metronidazole– Paleo diet essential

Lemle MD.Hypothesis: Chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism. Medical Hypotheses 2009;72(1):108-9. Epub 2008 Sep 16.

[email protected]

Protea Biopharma Press Conference, London 28.5.09. Prof K de Meileir, Chris Roelant, Marc Fremont.


Thyroid Function

• Thyroid hormone resistance is a factor in fibromyalgia.

• Patients with fibromyalgia were less responsive to injections of thyrotropin-releasing hormone in terms of thyrotropin and thyroid hormone production.

Garrison RL, Breeding PC. A metabolic basis for fibromyalgia and its related disorders: the possible role of resistance to thyroid hormone. Med Hypotheses 2003; 61(2): 182-189

Neeck G, Riedel W. Thyroid function in patients with fibromyalgia syndrome. J Rheumatol 1992; 19(7): 1120-1122


“Integrative” Thyroid Panel

• TSH• Free T3• Free T4• Reverse T3• Thyroid antibodies• Spot urinary iodine• Serum selenium, zinc, copper, B6

– Better still, red blood cell mineral analysis

• Pyrroluria testing• D3• Iron studies• Possible urinary element or mineral hair analysis (heavy

metal toxicity)


Muscle and Connective Tissue Metabolism

• Disorders of muscle metabolism and structure have been suggested by some studies although this is disputed as a relevant issue.

• So many practitioners simply focus on magnesium therapy for fibromyalgia for muscle relieve, however, we can see it is a more complex issue.

Lund E, Kendall SA, Janerot-Sjoberg B et al. Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise. Scand J Rheumatol 2003;

32(3): 138-145Park JH, Niermann KJ, Olsen N. Evidence for metabolic abnormalities in the muscles of patients with

fibromyalgia. Curr Rheumatol Rep 2000; 2(2): 131-140Eisinger J, Plantamura A, Ayavou T. Glycolysis abnormalities in fibromyalgia. J Am Coll Nutr 1994;

13(2): 144-148Drewes AM, Andreasen A, Schroder HD et al. Pathology of skeletal muscle in fibromyalgia: a histo-

immuno-chemical and ultrastructural study. Br J Rheumatol 1993; 32(6): 479-483


Circulatory Abnormalities

• Reduced regional pontine tegmental cerebral blood flow was a recent new finding in fibromyalgia.

• Other changes in regional blood flows consistent with chronic pain syndromes were also found.

• Patients with fibromyalgia showed small overnight falls in arterial oxygen saturation. These observations were not due to sleep apnoea syndrome - it may be relevant to musculoskeletal pathophysiology in fibromyalgia.Kwiatek R, Barnden L, Tedman R et al. Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalmi. Arthritis Rheum 2000;

43(12); 2823-2833Mountz JM, Bradley LA, Modell JG 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): 926-938

Alvarez Lario B, Alonso Valdivielso JL, Alegre Lopez J et al. Fibromyalgia syndrome: overnight falls in arterial oxygen saturation. Am J med 1996; 101(1): 54-60


Other Possible Factors

• Increased levels of homocysteine were found in the CNS of patients with both fibromyalgia and CFS. This may suggest folate and B12 deficiency (i.e. poor methylators)

Regland B, Andersson M, Abrahamsson L et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol

1997; 26(4): 301-307


Other Possible Factors

Vitamin D Deficiency• Medical researchers are discussing the possibility of

raising the recommended daily allowance of vitamin D, in response to a barrage of evidence that the vitamin has a major role in preventing cancer, autoimmune diseases, CFS and fibromyalgia.

www.rednova.com/news/display/?id=126369


Vitamin D Deficiency

• Because the typical symptoms are aching bones and muscle discomfort, vitamin D deficiency is often misdiagnosed as fibromyalgia or chronic fatigue syndrome, according to Michael F. Holick, MD, PhD, of the Boston University School of Medicine.

www.rednova.com/news/display/?id=126369


Vitamin D Deficiency

• Vitamin D supplement of at least 1000 IU per day is recommended, pending blood test results

• In cases of established vitamin D deficiency, supplementation with 2000-10,000 IU per day for at least 1 month is required to replete body stores.

• Optimal levels of D3 in serum ~ 80- 100 nmol/L


The Role of Magnesium and Malic Acid

• In recent years, evidence has accumulated to suggest that fibromyalgia is the result of local hypoxia to the muscles.

• For instance, patients with fibromyalgia have low muscle-tissue oxygen pressure in affected muscles, and to a lesser degree the same is true of other tissues.

• Muscle biopsies from affected areas showed muscle tissue glycolysis is inhibited, reducing ATP synthesis.

Townsend Letter, 247:28-30, February/March 2004.2. Abraham G.E., Flechas, J.D., Management of Fibromyalgia: Rationale for the Use of Magnesium and Malic Acid. J. Nutr. Med., 3:49-59, 1992.3. Russell, J., et al, Treatment of Fibromyalgia Syndrome with Super Malic[R]: A Randomized, Double Blind, Placebo

Controlled, Crossover Pilot Study. J. Rheumatol., 22:953-958, 1995.



• This stimulates the process of gluconeogenesis, which results in muscle tissue breakdown and mitochondrial damage.

• Additionally, low levels of the high-energy phosphates ATP, ADP, and phosphocreatine were found.

• It is hypothesized that in hypoxic muscle tissue, glycolysis is inhibited, reducing ATP synthesis.



• This muscle tissue breakdown, which has been observed in muscle biopsies taken from fibromyalgia patients, is hypothesized to result in the muscle pain characteristic of CFS & fibromyalgia.





• Malic acid is both derived from food sources and synthesized in the body through the citric acid cycle.

• Its importance to the production of energy in the body during both aerobic and anaerobic conditions is well established.

• Under aerobic conditions, the oxidation of malate to oxaloacetate provides reducing equivalents to the mitochondria through the malateaspartate redox shuttle.





• During anaerobic conditions, where a buildup of excess of reducing equivalents inhibits glycolysis, malic acid’s simultaneous reduction to succinate and oxidation to oxaloacetate is capable of removing the accumulating reducing equivalents.

• This allows malic acid to reverse hypoxia’s inhibition of glycolysis and energy production, possibly improving energy production in fibromyalgia, and reversing the negative effect of the relative hypoxia that has been found in these patients.

Townsend Letter, 247:28-30, February/March 2004.2. Abraham G.E., Flechas, J.D., Management of Fibromyalgia: Rationale for the Use of Magnesium and Malic Acid. J. Nutr. Med., 3:49-59, 1992.3.

Russell, J., et al, Treatment of Fibromyalgia Syndrome with Super Malic[R]: A Randomized, Double Blind, Placebo Controlled, Crossover Pilot Study. J. Rheumatol., 22:953-958, 1995.



• Because of its obvious relationship to energy depletion during exercise, malic acid may be of benefit to healthy individuals interested in maximizing their energy production, as well as those with Fibromyalgia, or CFS.

Townsend Letter, 247:28-30, February/March 2004.2. Abraham G.E., Flechas, J.D., Management of Fibromyalgia: Rationale for the Use of Magnesium and Malic Acid. J. Nutr. Med., 3:49-59, 1992.3.

Russell, J., et al, Treatment of Fibromyalgia Syndrome with Super Malic[R]: A Randomized, Double Blind, Placebo Controlled, Crossover Pilot Study. J. Rheumatol., 22:953-958, 1995.



• As a result of the compelling evidence that malic acid plays a central role in energy production, especially during hypoxic conditions, malic acid supplements have been examined for their effects on fibromyalgia.

• Subjective improvement in pain was observed within 48 hours of supplementation with 1200-2400 mg of malic acid, and this improvement was lost following the discontinuation of malic acid for 48 hours.





• Lab studies show that many patients with fibromyalgia & chronic fatigue have low magnesium levels.

• Magnesium supplementation enhanced the treatment of both conditions. Its benefits appear to result, at least in part, from its positive impact on serotonin function.

• Combining 5-HTP with St. John's Wort extract, malic acid, and magnesium, is part of an overall fibromyalgia treatment plan, providing excellent results - due in large measure to its improvement of sleep quality and mood.



• While these studies also used magnesium supplements, due to the fact that magnesium is often low in fibromyalgia patients, the rapid improvement following malic acid, as well as the rapid deterioration after discontinuation, suggests that malic acid is the most important component.

• This interesting theory of localized hypoxia in fibromyalgia, and the ability of malic acid to overcome the block in energy production that this causes, should provide hope for fibromyalgia sufferers

• The potential for malic acid supplements however, reaches much further than fibromyalgia.


Treatment Approaches

• It appears there is not one single “cure” for fibromyalgia- each patients aetiology and pathophysiology is unique and different.

• Herbal and nutritional treatments can provide valuable support and symptom alleviation.

• When taken over extended periods (months to years) herbs and nutrients can eventually resolve or minimise the impact of this condition.



Adrenal Adaptogens• Given the disordered response of the HPA axis

and the role of stress in fibromyalgia, there is a clear role for tonic and adaptogenic herbs:• Korean Ginseng 1:2 root extract, containing 10.5mg/mL

ginsenosides with Rg1 & Rb1 greater than or equal to 0.5 by HPLC, 2-4 mL daily

• Withania 2:1 root extract, containing a minimum of 4.0mg/mL withanolides, 1.4-4.2 mL per day

• Eleutherococccus senticosus 1:2 root extract, containing a minimum 0.5mg/mL eleutheroside E, 2-8 mL per day

• Rhodiola 2:1 root extract, containing 3.0mg/mL rosavin & 1.0mg/mL salidroside, 10 mL per day



Adrenal Tonics• The hypo responsiveness of the adrenal glands

suggests a degree of adrenal exhaustion and a role for adrenal tonic herbs such as:• Licorice 1:1 root extract, containing minimum

30mg/mL glycyrrhizin, 2-4 mL per day• Rehmannia 1:2 root extract, 5-8 mL per day

Bone K. Clinical Guide to Blending Liquid Herbs. Churchill Livingston, Edinburgh, 2003


Safety Concerns with Use of Licorice

Commission E advises that high dose of 5-15g of Licorice (equivalent to 200-600 mg glycyrrhizin) should not be taken for longer than 6 to 8 weeks. Lower doses are safe for long term use

If used longer term, advise patient to take a high potassium/low sodium diet.

K+ sources: Green leafy vegetables, avocado, dried apricots, banana, dandelion leaf tea.

Monitor patients blood pressure at each visit

Bone K. Clinical Guide to Blending Liquid Herbs. Churchill Livingston, Edinburgh, 2003



Nutritional Support for adrenal fatigue, fibromyalgia, CFS:

• Comprehensive B Multi, 1 per day• Magnesium, 300-600 mg per day (++)• Malic Acid, 1200-2400 mg per day• Inositol, 1200 mg per day, especially at night for

sleep quality• 5 HTP, 100-400 mg per day• Tyrosine, 500-1500 mg per day• Vitamin C, 2500-5000 mg per day• B12, 200-400 mcg per day• D3, 1000-10,000 IU per day



For pain and anxiety Management• Kava 3.2g (equiv. to 50mg kavalactone), 1

tablet 3 times daily• 5 HTP, 100- 400mg per day



Nervine and Sedative Herbs• St. John's wort can have an important role to

play due to its antiviral and antidepressant activity (although fibromyalgia sufferers may not be clinically depressed, St. John's wort could have a beneficial effect on central nervous system neurotransmitters and sleep patterns).• St Johns Wort 1:2 flowering tops extract,

containing minimum 0.2mg/mL hypericin, 2-6mL per day



Sleep quality needs to be improved through use of herbs & nutritionals, such as:

• Valerian 1:2 root extract, 5- 10 mL at night• Skullcap 1:2 herb extract, 5- 10 mL at night• Passionflower 1:2 herb extract, 5- 10 mL at night• Zizyphus 1:2 seed extract, 5-10 mL per day• Phosphatidylserine, 100-400 mg per day • 5 HTP 100-200mg at night• Magnesium 300-600mg at night• Calcium 600-800mg at night



Immune Modulators• Although it is possibly controversial, the

implication of viral or mycoplasma infections and abnormal immune response suggests a role for long-term therapy with Echinacea. • Echinacea angustifolia 1:2 root extract,

containing minimum 1.6 mg/mL alkylamides, 5mL per day

• Cat’s Claw (uncaria tomtentosa) 1:2 Inner bark extract, containing minimum 1.5mg/mL POA, 4 - 12 mL per day

• Andrographis 1:2, 2-4 mL per day



Immune Modulators (for auto immune involvement)

• Other immune modulating or anti-inflammatory herbs could be useful such as Hemidesmus, Rehmannia and Bupleurum• Patients will experienced good success with the use of

these three herbs in combination for fibromyalgia pain and tenderness (as a long-term therapy).

• Hemidesmus 1:2 root extract, 3.5-8.5 mL per day

• Rehmannia 1:2 root extract, 4-8 mL per day• Bupleurum 1:2 root extract, 3.5-9 mL per day



Circulatory Stimulants• The abnormal cerebral circulation and

hematological parameters suggest a role for Ginkgo and Ginger.

• Ginger has 5HT3 antagonist activity which has been shown to be of value in fibromyalgia• Ginkgo biloba 2:1 root extract, containing

minimum 9.6mg/mL ginkgo flavone glycosides, 3-4 mL per day

• Ginger 1:2 rhizome extract, 1-2 mL per day



Herbs for Symptom Management• Other useful anti-inflammatory herbs include:

• Feverfew 1:5 leaf extract, containing minimum 0.3 mg/mL parthenolide 1-2 mL per day

• Boswellia solid extract equivalent to dry gum oleoresin, standardized to contain bowellic acid 180mg, 4-16g per day

• Turmeric 1:1 rhizome extract, 5- 15mL per day• Ginger 1:2 rhizome extract, 1-2 mL per day• Celery seed 1:2 fruit extract, containing

mimimum 10mg/mL phthalide as butylphthalide and sedanenolide 4-8mL petr day



• Willow bark as the modern high-dose extract can be a useful analgesic for some patients.

• Salix purpurea (willow) extract equivalent to dry ste, bark, standardised to contain salicin 0.75m/g, 16-32 g per day• Clinical pearl: always prescribe a probiotic

as Willow bark. Willowbark requires gut flora to become “bioactive”


Case Study


Case Presentation

• Male patient aged 63 presented in Feb 2011 with Polymyalgia Rheumatica & fibromyalgia, diagnosed in 2008

• “I used to be energetic, vibrant, life of the party… and now I feel like a train wreck”

• Occupation: Builder, physical laborer all of this professional life, now retired, due to physical incapacity, not by choice

• Chemical exposure to polyurethane, wood dust, varnish, oils, solvents (40+ years daily exposure?)

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Case Presentation

• Symptom Picture:• Constant pain• Slowly slipped onto depressive state, negative state of

mind, terribly irritable & snappy, over reactive, emotional

• Headaches- frontal & temporal- can vary from ½ hour to all day. Change each day. Worrying intensity

• Severe epileptic like fits at night- about 3-4 episodes per week. MRI and full medical investigation revealed no neurological abnormalities

• Constant involuntary neurlogical “nodding” of head• Blood pressure variable but mostly low• Poor sleep. Waking every hour or so with pain and

sweats or fits62


Case Presentation

• Symptom Profile continued• Back pain- constant but to varying degrees

– Lower back- Lumbar L2-5 + Sacral region– Has a serious work accident (fall) 1990. A lot of pain

since• Joint and muscle pains

– Can be difference locations each day- wandering– As the condition progresses, more global

• Very sore dry eyes- can no long read• Sore behind the eyes, esp. since prednisolone Rx• Itchy- back, legs, arms• Stuttering- past 9 months• Bloating, gas, diarrhea over past 2 years

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Case Presentation

• No prior history of ill health- he was strong and robust

• Robustly healthy all of his adult life and throughout his childhood

• Family: he was the first born of 7 siblings to Polish immigrant parents

• Born and raised in small country town country in NSW

• Happily married and great relationship with his wife

• Father of 4 children

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Case Presentation

• Pharmaceutical Management:• Prednisolone 25 mg per day• Zoloft 100mg per day• Panadeine Forte 2-8 per day

• The Rheumatologist mentioned next steps in drug treatment trial would involved methotrexate

• He became alarmed when he read the warnings.

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Pathology Investigation

• We arranged pathology testing with an integrative doctor to investigate:

• Thyroid function test– TSH– Free T4– Free T4

– Lupus anticoagulant– Serum Copper– Serum Zinc– Serum Magnesium– AM fasting resting cortisol

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• Hormones• Testosterone total• Testosterone Free• SHBG• Free Androgen

Index• DHEA-S

• 25-OH-D• Mycoplama CPR• Coeliac Serology• Cardiolopin • ANA• Full Blood Count + ESR• LFT• Biochemistry• Urinary Mineral

Analysis post chelation challenge

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Treatment Plan

• Initial Rx• Herbal formulation: 15mL twice a day,

morning and mid afternoon after food– Licorice 50mL– Rehmannia 100mL– Passionflower 50mL– Burpleurum 100mL– Turmeric 100mL – Siberian Ginseng 100mL – TOTAL 500mL

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Treatment Plan

• Magnesium + Malic Acid Powder• 1 teaspoon twice a day into a glass of water• Morning and before bed

• Tyrosine + B Vitamin Formula• 2 tablets in the morning 15 minutes before

breakfast• 1 tablet mid afternoon 15 minutes before snack

• Omega 3 EFA• 2 capsules three times a day before food

• Desiccated Adrenal Formula (USA)• 2 tablets each morning

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March 2011 AppointmentResults Review

• 4 weeks passed and he came in for follow up consultation/ results review.

• Treatment feedback to date:• Everyone had noticed an improvement!• Mood: brighter, more assertive• He has dropped prednisolone dose to 10mg

per day as a “test” as his pain/ discomfort has reduced

• Myalgia pain ~ 30% less severe• Stuttering and head nodding 100% resolved• No fitting episodes in 3 weeks + 2 days

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March 2011 AppointmentResults Review

• Background dizziness was still evident• Less irritable overall- but still could be vastly

improved• Headaches decreased ~ 40% in frequency &

severity• Down to 1-2 x Panadeine Forte on “bad” days only –

not needing pain relief every day• Sleep: sleeping longer spells but still not good.

Continues to wake feeling very fatigued.• Stopped drinking coffee & coke upon request

• Increased hydration to 2L per day +1 sachet electrolytes per day

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Pathology Results

• Thyroid function test– TSH 0.66 (0.4-

4) normal– Free T4 12.2 (9-

19) low end normal

– Low Iodine +/-Tyrosine?

– Free T3 5 (2.6-6) normal

• Lupus anticoagulant- negative

• Serum Copper 16 (12-22) normal

• Serum Zinc 6 (10-18) Very low. Deficient

• Serum Magnesium 0.47 (0.65-1) Low Deficient

• AM fasting resting cortisol 169 Low Deficient

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Pathology Results

• Reproductive Hormones• Testosterone total 8.5 (9.5-28) Low- Deficient• Testosterone Free 14.8 (37-85) Low- Deficient• SHBG 29 (15-50) normal• Free Androgen Index 29.3 (15-100) Subclincal low• DHEA-S 0.5 (1-8) Low- Deficient

• 25-OH-D 57 (51-140) Low- Deficient• Mycoplama CPR- negative• Coeliac Serology

– Gliaden IgA Abs 7 (0-20) Low positive. Digestive symptoms?– tTG IgA/IgG 7 (0-20) Low positive Digestive symptoms?– Endomysial IgA Abs Not Detected

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Pathology Results

• Cardiolipin- no evidence of phospholipid antibodies• ANA- not detected• Full Blood Count + ESR

• RBC count all normal• WCC all normal• ESR- 23 High- Inflammation

• Full Biochemistry• all normal

• Liver Function– Bili Total 25 (4-20) High Evidence of Liver Damage– LD (Lactate dehydrogenase) 275 (120-250) High +

+ Evidence of kidney/ liver damage

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• Urinary Mineral Analysis with Chelation Challenge• No evidence of heavy metal toxicity

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Summary of Findings

• Nutritional Deficiency• Iodine• Tyrosine• D3• Magnesium• Zinc

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Summary of Findings

• Endocrine Findings• Testosterone deficiency - Andropausal• Low cortisol• Low DHEA

– Adrenal fatigue

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Summary of Findings

• Immunological Findings• Gluten sensitivity

– Recommend Gluten Free Diet

• Inflammatory Markers• Elevated ESR

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Androgen Deficiency

Symptoms • Fatigue• Poor muscle strength• Muscle and joint pain• Low mood and irritability• Poor concentration• Low interest in sex

(decreased libido)• Osteoporosis (thinning of

bones)• Difficulty getting and

keeping erections

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March Treatment Plan RevisionStage 2

• Rx• Herbal formulation: 15mL twice a day,

morning and mid afternoon after food– St Mary’s Thistle 100mL (Liver Support)– Damiana 100mL (** replaced Passionflower ANS)– Burpleurum 100mL (liver support, mood

regulation)– Turmeric 100mL (inflammation management,

liver support)– Tribulus 100mL (adrenal adaptogen; low

testosterone, low DHEA)– TOTAL 500mL

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• Magnesium & Malic Acid powder• 1 teaspoon twice a day into a glass of water• Morning and before bed• Address functional Mg deficiency

• Tyrosine & B vitamin formula• 2 tablets in the morning 15 minutes before

breakfast• 1 tablet mid afternoon 15 minutes before snack• Support Iodine/ Tyrosine levels• Support HPA Axis

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• Omega 3 EFAs• 2 capsules three times a day before food• Reduce elevated ESR• Inflammation management

• Licorice and Rehmannia Formula tablets• 2 tablets each morning and 2 tablets mid afternoon• Withdrew short term use of Desiccated Adrenal and

replaced with herbal adrenal cortex support• Also indicated to offset side effects associated with

corticosteroids as patient is “weaning” off under doctors co management.

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• D3 5000 IU per day• To treat deficiency

• Zinc Citrate 25mg• 1 tablet at bedtime• To treat deficiency and androgen deficiency

• Diet• Gluten free• No caffeine• No Sugar• 1 serve of protein 4-5 times a day daily

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3rd ConsultationMay 2011

May 2011• Down to 4mg

Prednisolone• Pain reduced ~ 80%

• Muscles, joints vastly improved

• No headaches• Sleeping 5 hours per

night, waking to use toilet and then falling back to sleep. AM fatigue vastly improved

• No further neurological “nodding” “fits” “tics”

• No dizziness• Mood vastly improved

• Feelings of happiness, joking again, laughing

• As been back in his shed doing wood work- first time in 2+ years! This is his passion.

• No diarrhea or gas- digestion feels great

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June 2011 Follow Up Pathology Tests

June 2011•Thyroid function test

– Free T4 14.8 (9-19) Improved•Serum Zinc 20 (10-18) Deficient resolved•Serum Magnesium 0.85 (0.65-1) Improved•AM fasting resting cortisol 345 Improved. Still low end. More time in treatment required

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• Reproductive Hormones• Testosterone total 9.6 (9.5-28) Improved• Testosterone Free 35 (37-85) Improved• Free Androgen Index 39.2 (15-100)

Improved• DHEA-S 0.9 (1-8) Improved

• Vitamin D (25-OH-D) 69 (51-140) Improved

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• ESR 09 Normalized

• Liver Function– Bili Total 12 (4-20) Improved– LD (Lactate dehydrogenase) 190 (120-250)

Improved

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June 2011 Pharmaceuticals

• Current Pharmaceutical Rx• Prednisolone 2 mg per day

– Expected to be off this completely by July 2011

• Zoloft 100mg per day ceased in May 2011• Panadeine Forte 2-10 per day ceased in May

2011

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Thank you

Q & A


Grateful acknowledgements to my mentor & colleague for support and contribution to materials within this

presentationAssociate Professor Kerry Bonewww.herbaleducation.com.au

© Angela Hywood ND 2012Slide 1 Nutritional and Herbal Approaches + Functional Pathology to help...

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