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Use of Complementary Therapies in the Treatment of Rheumatoid Arthritis
Article by Louise Joel BHSc (comp med) Adv Dip Nat, Adv Dip Herb Med. 2009 Complementary therapies for rheumatoid arthritis include naturopathy, herbal medicine, psychological approaches and a number of other treatment modalities. Nutritional and dietary therapies are a well-researched area of management for rheumatoid arthritis. Contributing factors that influence the manifestation of disease may include poor lifestyle, pollutants, hormonal disturbances, infection, nutritional deficits, and their effect on predisposing genetics. The goal of the practitioner is to assess the individual in context with these factors and provide the appropriate treatment based on scientific evidence and historical clinical evidence. Rheumatoid arthritis is a systemic inflammatory autoimmune disease characterised by inflammation and damage to joint cartilage and synovial membranes (Doan, Melvold, Viselli & Waltenbaugh, 2008, p. 248). Humoral type three hypersensitivity occurs in conjunction with cell mediated type four hypersensitivity whereby damage is initiated by CD4 T-cell recognition of antigens within joints (Doan, et al., 2008, pp. 249). Elevated rheumatoid factor (RA) is a diagnostic marker for the disease involving IgM antibodies to the fc fraction of IgG (Doan, et al., 2008, p. 287). Circulating antigen-antibody complexes accumulate in vasculature and mediate the release inflammatory cytokines including tumour necrosis factor-alpha, interleukin-1, interleukin-8 and interferon-y, leading to systemic joint destruction, vasculitis, carditis and pleuritis (Doan, et al., 2008, p. 287). Human leucocyte antigen DR4 poses a relative risk of 4 for the development of rheumatoid arthritis, indicating that genetics contribute only a minor role in the development of the disease (Doan, et al., 2008, p. 250). Proteus mirabilis has an amino acid sequence similar to that on HLA DR1 and DR4 alleles, which could induce autoimmune damage via molecular mimicry (Dunn & Wilkinson, 2004, pp. 88-89). Mainline medicine for rheumatoid arthritis targets inflammatory mediators and attempts to modify the disease process with immunosuppressive and immunomodulating drugs including TNF-alpha inhibitors, glucocorticoids and methotrexate (Doan, et al., 2008, p. 287). Complementary practitioners address inflammatory pathways along with disturbances to the complex interactions between the nervous, endocrine and immune systems, which influence the manifestation of rheumatoid arthritis. Lifestyle conditions such as poor sleep habits and stress affect immune function via the hypothalamic-pituitary-axis (HPA). Patients with rheumatoid arthritis fail to mount adequate cortisol response to stressors when compared with healthy controls (Jessop & Harbuz, 2005, p. 1098). Adrenal depletion may play a role in the development of rheumatoid arthritis according to a study by The American College of Rheumatology (Meyer-Hermann, Thilo Figge & Straub, 2009 pp. 2585-2594). Circadium rhythms may be altered in rheumatoid arthritis, and cortisol levels were found to be low in relation to increased tumor necrosis factor-alpha (Meyer-Hermann, Thilo Figge & Straub, 2009 pp. 2585–2594). An increase in morning stiffness and pain may be related to a night-time elevation of tumor necrosis factor between midnight and 2:00 am, and linked to inadequate secretion of cortisol (Meyer-Hermann, Thilo Figge & Straub, 2009 pp. 2585–2594). Physiological doses of hydrocortisone are beneficial in the treatment of rheumatoid arthritis associated with low cortisol due to their anti-inflammatory effect (Doan, et al., 2008, p. 284). This therapeutic affect is also achieved with constituents of Glycyrrhiza glabra which increase cortisol levels by displacing it from its carrier molecule and inhibiting its conversion to inactive cortisone (Braun & Cohen, 2005, p. 256). In contrast to hydrocortisone and prednisolone which promote intestinal ulceration, Glycyrrhiza glabra promotes mucosal repair and alleviates the gastrointestinal inflammation and permeability often seen in rheumatoid arthritis patients (Braun & Cohen, 2005, p. 257). Adequate B vitamins are also crucial for adrenal function. Deficiency commonly occurs in inflammatory bowel conditions that may coexist with rheumatoid arthritis. Vitamin B5 is metabolised in the duodenum and is required for synthesis of coenzyme A, which is necessary for the metabolism of food and the manufacture of adrenal hormones (Braun & Cohen, 2005, p. 392). Sex hormone imbalances may play a role in the development of rheumatoid arthritis, and are influenced by the limbic system, diet and exogenous oestrogens. Women are more commonly affected by autoimmune diseases than men, reflecting their complex endocrine systems and the pro-inflammatory effects of oestrogens. Progesterone is often low in relation oestrogen in perimenopausal and postmenopausal women, particularly where environmental oestrogens are ubiquitous and compete for receptor sites. This imbalance is also relevant because progesterone a precursor of cortisone synthesis by adrenal cortex. According to a study by The American College of Rheumatology, elevated serum levels of 16-alpha hydroxylated estrogens correlate with increased tumour necrosis factor-alpha (Schmidt, Hartung, Capellino, Cutolo, Pfeifer-Leeg & Straub, 2009, p. 2919). Hydroxylated estrogens 2 and 4 inhibited this pro-inflammatory cytokine in synovial cells of rheumatoid arthritis patients (Schmidt, et al., 2009, p. 2921). Organochlorine pesticides significantly increased the formation of harmful 16 alpha-hydroxyestrone and reduced protective 2-hydroxyestrone formation (Bradlow, Lee, Davis, Gong, Sepkovic & Tiwari, 1995 pp.147-150). Lignans in flaxseed, indole-3-carbinol in brassicaceae plants, and eicosapentenoic acid from fish oil increase C-2-hydroxylation and consequently inhibit 16 alpha hydroxyestrone (Atkins, 1998, p. 209, Bradlow et al., 1995, P. 148). Various nutrients including vitamin B6, choline, inositol and methionine aid the liver’s conversion of oestradiol into estriol (Atkins, 1998, pp. 65, 79). The liver requires adequate amino acids and b-vitamins to conjugate oestrogens to glucoronic acid for excretion in bile (Murray & Pizzorno, 2005, p. 457). Dysbiosis related to poor diet and digestion raises betaglucoronidase, an enzyme which breaks this oestrogen conjugation and causes oestrogens to recirculate (Oseiki, 2005, p. 135). The addition of probiotics Lactobacillus acidophilus and Bifidobacteria, and plant fibre to the diet inhibits dysboisis by increasing the ratio of beneficial bacteria to pathogenic bacteria and reduces betaglucoronidase (Oseiki, 2005, p. 135). Digestive function is a special interest of naturopaths whom often attribute disease states to gastrointestinal permeability and the migration of immunogenic particles into the blood stream. Rheumatoid arthritis is associated with gastrointestinal lesions, which may be attributed to food allergy (Dunn & Wilkinson, 2004, p. 88-89). There is no single diagnostic test which can identify every allergy, and elimination diets are a valuable alternative approach suggested by naturopaths where common allergies are not detected by lab testing. The most common foods that exacerbate rheumatoid arthritis are wheat, dairy, corn, beef and plants of the Solanaceae family (Murray & Pizzorno, 2005, p.788). Supplemental glucosamine of 1500 mg per day aids repair of the glycosaminoglycan component of the mucosal barrier of the gastrointestinal tract, in addition to acting as an anti-inflammatory and contributing to the cartilage matrix of joints (Braun & Cohen, 2005, pp. 214-216). Glutamine supplementation may reduce intestinal permeability by repairing the gastrointestinal mucosa, along with increasing the antioxidant glutathione and decreasing release of inflammatory cytokines (Oseiki, 2005, p. 27). Dysbiosis may also cause inflammation and increased permeability in the digestive tract. These conditions may be reduced by ensuring the proper production of hydrochloric acid in the stomach followed by secretion of pancreatic enzymes which break down food and microbial proteins, reducing both inflammation and allergic response. Aside from improving digestion, protein digesting enzymes reduce circulating immune complexes as evident in rheumatoid arthritis (Murray & Pizzorno, 2005, p. 778). Prebiotic foods and probiotic supplements may further improve a disregulated immune system by reducing dysbiosis and causing a shift in the production of inflammatory cytokines, leading to the reduction of allergic symptoms (Braun & Cohen, 2005, pp. 214-216). Naturopaths promote a healthy diet containing a variety of fruits, vegetables, anti- inflammatory fats, healthy protein sources and whole grains. Supplements may be prescribed where adequate amounts are not available through diet or lab tests and signs suggest deficiency. Protein requirements are increased by inactivity and inflammation. Physical exercise enhances the metabolism of protein, justifying the addition of 15–16.5 g of essential amino acids to daily protein intake of inactive people to prevent muscle wasting, bone mineral loss and immune impairment (Guadagni & Biolo, 2009, p. 619). The protein requirements of an average healthy person are about 800 mg of protein per kilogram (Guadagni & Biolo, 2009, p. 618). Resistance exercise training reduces protein requirements needed to maintain lean body mass, however over-exercising results in increased amino acid oxidation and results in increased protein requirement (Guadagni & Biolo, 2009, p. 619). The quality of protein in conjunction with a balanced nutrient dense diet and healthy kidney function need to be taken into consideration. The risk of developing rheumatoid arthritis is increased with deficiency of antioxidants abundant in fruits and vegetables (Murray & Pizzorno, 2005, p.781). Zinc acts as a powerful anti-inflammatory in part due to its role in the synthesis of delta-6 desaturase, which has a role in the conversion of alpha-linoleic acid into EPA and DHA. Flaxseeds and their oil containing alpha-linoleic acid are often recommended for their anti-inflammatory properties but have no effect without nutritional co-factors including zinc. High doses of zinc may reduce iron levels, emphasising the importance of lab tests, especially where iron deficiency results from inflammatory processes. Zinc and copper raise a type of superoxide dismutase (SOD) that may reduce oxidative damage to joints (Murray & Pizzorno, 2005, p. 782). The anti-inflammatory action of copper bracelets may be attributed to the absorption of copper is through the skin (Murray & Pizzorno, 2005, p.778). Selenium levels may be low in rheumatoid arthritis according to a study at the University of Nebraska (Dell, Gillespie, Palmer et al, 1991 pp. 376-378). This antioxidant mineral is a co-factor in glutathione peridoxase which reduces inflammatory cytokines and leukotrines (Murray & Pizzorno, 2005, p.781). Vitamin C is also low in white blood cells and plasma of rheumatoid arthritis patients. Abundant in fruit and vegetables, vitamin C increases SOD, has anti-inflammatory effects and reduces histamine (Murray & Pizzorno, 2005, p.782). Complementary practitioners use natural methods to manipulate inflammatory pathways in rheumatoid arthritis. Mainline medicine prescribes non-steroidal anti-inflammatory drugs which affect cyclooxygenase-1 and cyclooxygenase-2 but side effects include gastric erosions and increased risk of myocardial infarctions respectively. Naturopathic treatment enhances the production of ant-inflammatory prostaglandins by increasing their synthesis with appropriate fatty acids and nutritional cofactors. Prostaglandins of series 1 and 3 are anti-inflammatory while series 2 are pro-inflammatory. Eicosapentaeonic acid (EPA) is a precursor to anti-inflammatory series 3 prostaglandins derived from fish oil. Although EPA may be converted from plant sources of alpha-linoleic acid, this conversion is limited by the availability of enzymes and their nutritional co-factors. Omega six oils derived from plants may convert to series 1 prostaglandins but a dual metabolic pathway may also convert them to arachidonic acid and pro-inflammatory series two prostaglandins. The formation of series 1 and 3 prostaglandins from plant sources may also be hindered by dietary triacylglycerides and saturated fat which compete for enzymes convert to series 2 prostaglandins. Anti-inflammatory herbal extracts include curcumin from Curcuma longa (tumeric) and Zingiber officinale (ginger) also elicit anti-inflammatory properties by inhibiting cyclooxygenase, (Murry & Pizzorno, 1998 pp. 783-784). 1200mg of Curcumin in a dose of 1200mg when compared to 300mg of phenylbutazone and achieve a similar reduction in stiffness and join inflammation associated with rheumatoid arthritis (Murry & Pizzorno, 1998 pp. 783-784). Curcumin inhibits tumor necrosis factor-alpha, otherwise targeted by mainline drugs with monoclonal antibodies and receptor inhibitors (Braun & Cohen, 2005, p. 359). Ginger exerts anti-inflammatory activity by inhibiting thromboxane synthase (Braun & Cohen, 2005, p. 187). Topical application of ginger cream may relieve joint pain in a similar way to capsicain which effects release of substance P (Braun & Cohen, 2005, p. 187). Acute joint inflammation may be alleviated by cold packs, while warm mineral baths and thermogenic herbal creams may reduce pain and stiffness associated with moderate inflammation (Murry & Pizzorno, 1998 pp. 783-784). When inflammation is under control, isometric exercise helps to maintains the range of motion of joints and strengthen surrounding muscle tissue (Murry & Pizzorno, 1998 pp. 783-784). Severe rheumatoid arthritis warrants the intervention of mainline medicine with adjunct use of complementary therapies. Rapid damage may occur to joints and heart disease may ensue without radical treatment to reduce the destructive auto-immune process. Responsible complementary practitioners make detailed case takes which help to identify individual factors linked to the disease process and refer on to other specialized practitioners where indicated. Dietary, lifestyle and environmental factors play a significant role in the management of rheumatoid arthritis, and inflammatory agents mediated by an auto-immune response may be inhibited by enhanced nutrition, physical therapeutics, stress reduction and practical lifestyle changes. References
Bradlow, H., Lee Davis, D., 2 Gong L., Sepkovic, D. & Tiwari, R. (1995). Effects of Pesticides on the Ratio of 160c/2-Hydroxyestrone: A Biologic Marker of Breast Health Perspectives, 103(7), 147-150 Braun, L. & Cohen, M. (2005). Herbs and Natural Supplements: An evidence-based guide. Doan, T., Melvold, R., Viselli, S. & Waltenbaugh, C. (2008). Immunology, Philadelphia: Guadagni, M. & Biolo, G. (2009). Effects of inflammation and/or inactivity on the need for dietary Current Opinion in Clinical Nutrition and Metabolic Care, 12, 617- 622. Hermann, M., Thilo Figge, M. & Straub, R. (2009). Mathematical Modeling of the Circadian Rhythm of Key Neuroendocrine-Immune System Players in Rheumatoid Arthritis: A Systems Biology Approach. Arthritis and rheumatism, 60(9), 2585-2594. Jessop, D. & Harbuz, M. (2005). A defect in cortisol production in rheumatoid arthritis: why are we still looking? Rheumatology, 44,1097–1100 Dunn, J. & Wilkinson, J. (2004). Naturopathic management of rheumatoid arthritis, Modern Rheumatology. Murray, M. & Pizzorno, P. (1998). Encyclopedia of Natural Medicine (rev. 2nd ed.). New O’dell, J., Lemley-Gillespie, S., Palmer, W., Weaver, A., Moore, G. & Klassen, L. (1991). Serum selenium concentrations in rheumatoid arthritis, Annals of the Rheumatic Diseases. 50, 376-378. Schmidt, M., Hartung, R., Capellino, S., Cutolo, M., Pfeifer-Leeg, A. & Straub, R. (2009). Estrone/beta-EstradiolEstradiol Conversion to, and Tumor Necrosis Factor Inhibition by Estrogen Metabolites in Synovial Cells of Patients With Rheumatoid With Osteoarthritis, Arthritis & Rheumatism, 60(10),

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