Rheumatoid arthritis is a chronic inflammatory condition affecting the entire body but especially synovial membranes of joints, joints involved: hands, feet, wrists, ankles, and knees; affects 1-3% of the population; females outnumber males 3:1, age of onset is 20-40 years, but may begin at any age; onset gradual, but occasionally quite abrupt; several joints usually involved at onset in symmetrical pattern (both hands, wrists, or ankles); in one-third of cases, initially confined to one or a few joints; effected joints warm, tender, and swollen; overlying skin has ruddy purplish hue; disease progression-joint deformities in hands and feet (“swank neck”, “boutonniere”, and “cock-up toes”).

Pathogenesis

Autoimmune reaction-antibodies against components of joint tissues; triggering mechanism unknown; factors are genetic susceptibility, abnormal bowel permeability, lifestyle and nutritional factors, food allergies, and microorganisms; classic multifactorial disease involving genetic and environmental factors.

• Genetic factors: histocompatibility antigen HLA-DRw4 in 70% of RA patients vs. 28% of controls; severe RA at four times expected rate in first degree relatives of those with seropositive disease; environmental factors are necessary for disease development – are demonstrated in monosygotic twins.

• Abnormal bowel permeability: RA patients have increased intestinal permeability to dietary and bacterial antigens plus alterations in bowel flora; food allergies may contribute to increased permeability; NSAIDs implicated; permeability to gut-derived antigens increases endotoxins (lipopolysaccharide components of cell walls of Gram-negative bacteria) and immune complexes characteristic of RA; permeability and inappropriate bacterial flora can increase absorption of antigens similar to antigens in joint tissues; antibodies to microbial antigens may cross-react with joint tissue antigens – antibodies to Campylobacter, Salmonella, and Shigella cross-react with collagen, while antibodies to Klebsiella pneumoniae, Proteus vulgaris and Yersinia enterocolitica cross-react with other joint tissues.

• Dysbiosis and small intestinal bacterial overgrowth: many RA patients exhibit altered microbial flora and small intestinal bacterial overgrowth (SIBO); degree of SIBO is linked to severity of symptoms and disease activity.

• Abnormal antibodies and immune complexes: serum and joint fluid of nearly all RA patients contain rheumatoid factor (RF) = antibodies against Fc fragment of IgG; RF antibodies belong to IgM, and IgA classes, but only IgM RF is readily measured – by latex agglutination, bentonite flocculation, and sensitised sheep or human RBC test; most of RF formed locally in affected joints by infiltration of activated B-cells and plasma cells; serum titer of RF correlates with severity of symptoms; circulating immune complexes contribute to pathogenesis-cell mediated, humoral, and non-specific immune responses to immune complexes leads to proliferative inflammation; abnormalities similar to Arthus reaction and serum sickness, immune complex-induced reactions dependent upon neutrophils, and complement activation; amount of circulating immune complexes is not correlated with disease activity, but immune complexes and abnormal antibodies plus sequelae are major factors in RA.

• Microbial hypotheses: not in themselves comprehensive enough to explain all events observed in RA; variety of suggested microbes: Epstein-Barr virus, rubella virus, amoebic organisms, and mycoplasma; no microbial agent consistently isolated in RA patients; attempts to isolate whole organisms from synovial fluids and antibodies to viable, whole organisms, and failure to isolate offending organisms, are suggestive, to some researchers, of atypical viral-like agent(s); microbial factors (immune complexes) contribute, but a single causative microbe is unlikely.

• Decreased DHEA levels: defective androgen synthesis proposed as predisposing factor; dehydroepiandrosterone sulphate (DHEAS) levels are lower in postmenopausal women (aged 45-65 ) with RA than postmenopausal controls; supplemental DHEA (200mg q.d.) is beneficial in systemic lupis erythematosus (SLE): may be beneficial for RA despite absence of double-blind clinical studies; can be used conservatively to correct physiological deficit; use 24-h urinary test; can be used aggressively to impact RA – dosage required > 50mg q.d.; major side-effect is mild to severe acne and possibly increased androgenization in women.

Therapeutic considerations

Study of therapeutic efficacy requires 20 years follow-up; study of RA patients after 20 years of aggressive conventional treatment-only 18% able to lead normal lives; most patients (54%) with either dead (35%) or severely disabled (19%); most mortalities were directly related to RA; RA is a multifactorial condition requiring comprehensive approach focused on reducing contributing factors (gut permeability, circulating immune complexes, free radicals, immune dysfunction, etc.), controlling inflammation, and promoting joint regeneration; foremost in natural approach – use diet to control inflammation.

Diet

Strongly implicated in RA-cause and cure; RA not found in societies that eat ‘primitive’ diet; found at relatively  high rate in societies consuming ‘Western’ diet; diet rich in whole foods, vegetables, and fiber, and low in sugar, meat, refined carbohydrate, and saturated fat is protective against RA; eliminate food allergens; follow vegetarian diet; change dietary fats and oils; increase antioxidant nutrients.

• Food allergy: eliminating allergic foods is very beneficial to some RA patients; any food can aggravate RA; most common offending foods are wheat, corn, milk and dairy, beef, and nightshade (tomato, potato, eggplant, peppers and tobacco) plus food additives; short-term fasting (vegetable broth and juices) followed by vegetarian diet substantially reduces disease activity in many patients – eliminates food allergens, improves dietary fatty acids, and colon flora.

• Colon microflora: altered flora linked to RA and other autoimmune diseases > 400 different spices; there is significant alteration in intestinal flora when patients change from omnivorous to a vegetarian diet; positive changes in colon flora correlate with improvements in RA; total surface area of GI system = 300-400 m2; only single epithelial layer separates host from enormous amounts of dietary and microbial antigens; gut associated lymphoid tissue (largest lymphoid organ) is protective; alterations in intestinal flora change antigenic challenge, with significant impact on disease activity; gas-liquid chromatography of fatty acids in stool samples may be relatively quick and easy method of forecasting clinical improvement in RA.

• Digestion: incompletely digested food molecules can be inappropriately absorbed; many patients with RA are deficient in HCL and pancreatic enzymes-incomplete digestion may be a major factor; digestive aids are warranted; pancreatic enzymes offer additional benefits; proteases in pancreatin reduce circulating levels of immune complexes in autoimmune diseases (RA, SLE, periarteritis nodosa, scleroderma, ulcerative colitis, Crohn’s disease, MS, AIDS); as clinical improvement corresponds with decreased immune complexes (use ESR as rough indicator), pancreatin or bromelain supplements are often warranted.

• Dietary fats: fatty acids are precursors of inflammatory prostaglandins, thromboxanes, and leukotrienes; altering dietary fatty acids can increase or decrease inflammation depending on preponderant type ingested; goals are to reduce arachidonic acid (AA) and increase DHGLA  and EPA; vegetarian diets are beneficial, in part, by decreasing AA for conversion to inflammatory eicosanoids, while supplying linoleic and linolenic acids; cold-water fish (mackerel, herring, sardines, and salmon) are rich sources of EPA, which competes with AA for prostaglandin and leukotriene production; net effect is reduced inflammatory/allergic response; consumption of broiled or baked fish correlates with decreased risk of RA – dose-dependent response was noted: 2+ servings/week more protective than one serving/week; best diet for RA is vegetarian diet with exception of cold-water ocean fish; flaxseed oils is also useful.

Nutritional supplements    

           
• GLA: evening primrose (EPO), black current, and borage oil contain gamma-linolenic acid, an omega-6 fatty acid, precursor to anti-inflammatory prostaglandins of 1 series; although quite popular, research on GLA in RA is controversial and not as strong as research on omega-3 oils; long-term GLA supplementation increases tissue AA and decreases tissue EPA-contrary to treatment goal; key factor is whether or not subjects are allowed to take anti-inflammatory drugs – drugs inhibit formation of inflammatory prostaglandins-mask negative effects of altered tissue fatty acid profile produced by GLA; dosage for RA = 1.4 g q.d.; EPO is 9% GLA; 31-500mg caps EPO required q.d. at cost of E100/month; omega-3 oils are better choice; GLA can be formed from linoleic acid-difficult to determine whether effects are due to GLA vs. linoleic acid; most sources of GLA are much richer in linoleic acid than GLA; (EPO contains 9% GLA, but 72% linoleic acid).

• Omega-3 fatty acids: fish oil EPA studies show less morning stiffness and tender joints; reduces production of inflammatory compounds secreted by WBCs; but not all, commercially available fish oils have high levels of lipid peroxides; use cold-water fish and flaxseed oil or lab-certified fish oil; flaxseed oil is not as effective in increasing tissue EPA and lowering tissue AA as fish oils; for flax oil to be effective, patients must minimize dietary omega-6 fatty acids (other vegetable oils) while supplementing with 13g (1 tbsp) flaxseed oil q.d.; flax can inhibit autoimmune reaction as well as EPA; conversion of alpha-linolenic acid to EPA requires adequate zinc nutriture; zinc deficiency is common in RA.

• Dietary antioxidants: fresh fruit and vegetables are the best sources of dietary antioxidants; vitamin C, beta-carotene, vitamin E, selenium, and zinc are well-recognised as antioxidants; flavonoids neutralize inflammation and support collagen structures; risk of RA is highest in people with lowest levels of nutrient antioxidants (serum alpha-tocopherol, beta-carotene, and vitamin C).

• Selenium and vitamin E: selenium levels are low in RA patients; Se is an antioxidant and cofactor in free radical scavenging enzyme glutathione peroxidase-reducing inflammatory prostaglandins and leukotrienes; selenium plus vitamin E have positive effect; food sources; Brazil nuts, fish, and whole grains; amount of Se in grains and other plant foods is related to amount of Se in soil.

• Zinc: antioxidant and cofactor in antioxidant enzyme superoxidase dismutase (copper-zinc SOD); slight therapeutic effect alone; prefer zinc picolinate, monomethionine, or citrate forms; foods rich in zinc are oysters, whole grains, nuts and seeds.

• Manganese and superoxide dismutase: manganese functions in different form of superoxide dismutase (manganese SOD); Mn-SOD is deficient in RA patients. RA patients low in manganese; dietary sources are nuts, whole grains, dried fruits, and green leafy vegetables; meats, dairy, poultry, and seafood are poor sources of manganese.

• Vitamin C: antioxidant; WBC and plasma ascorbate significantly decreased in RA patients; vitamin C supplements increase SOD activity, decrease histamine levels, and provide some anti-inflammatory effects; food sources are broccoli, Brussels sprouts, cabbage, citrus fruits, tomatoes, and berries.

• Pantothenic acid: whole blood pantothenic acid is lower in RA patients vs. normal controls; disease activity is inversely correlated with pantothenic acid levels; correcting low pantothenic acid levels to normal improve improves duration of morning stiffness, degree of disability, and severity of pain; dietary sources; whole grains and legumes.

• Copper: copper aspirinate (salicylate) yields better results in reducing pain and inflammation than standard aspirin; wearing of copper bracelets is a long-time folk remedy; copper is absorbed through the skin and is chelated to another compound able to exert anti-inflammatory action; copper is a component (with zinc) in one type of SOD (copper-zinc SOD); deficiency may increase susceptibility to free radical damage; excess intake of copper is detrimental due to ability to combine with peroxides and damage joint tissues.

• Sulphur: sulphur (cysteine) content is fingernails of arthritics is lower than healthy controls; intraglutual colloidal sulphur alleviates pain and swelling; increased consumption of sulphur-rich foods (legumes, garlic, onions, Brussels sprouts, and cabbage) or supplements may be benefical.

• Niacinamide: Kaufman and Hoffer – treatment of RA and osteoarthritis (OA) using high-dose niacinamide confirmed in OA.

Botanical Medicines : used alone or in combination; severe inflammation and joint destruction require more aggressive therapy; history of corticosteroid use and those weaning of corticosteroids- Bupleuro falcatum (Chinese thoroughwax), licorice and panax ginseng to prevent and/or reverse adrenal atrophy. The following additional herbs have also been found to exert therapeutic action to RA patients they include: Curcuma longa (tumeric), Bromelain, and Zingiber officinalis (ginger),

Physical Medicine

Has a major role in managing RA; not curative, but improves comfort and preserves joint and muscle function; heat relieves stiffness and pain, relaxes muscles, and increases range of motion (ROM); moist heat (moist packs and hot baths) are more effective than dry heat (heating pad); paraffin baths used if skin irritation from water immersion develops; cold packs are valuable during acute flare-ups; strengthening and ROM exercises preserves joint function; well-developed disease and inflammation-begin with progressive, passive ROM and isometrics; as inflammation subsides-active ROM and isotonics exercises.

• Balneotherapy: therapeutic mineral baths and mud packs are a European tradition; confirmed by Israeli studies of Dead Sea spa therapy in conditions of high barometric pressures, low humidity, high temperatures, paucity of rainfall, and absence of air pollution; modalities are mud packs, sulphur baths, and bathing in Dead Sea; provides significant improvement in duration of morning stiffness, 15m walk time, grip strength, activities of daily living assessment, patient’s assessment of disease activity, number of active joints, and Ritchie articular index; improvement noted with Dead Sea bathing superior to regular hot baths with table salt; trace elements (zinc and copper-components to superoxidase dismutase-plus boron, selenium, rubidium, etc.) may be absorbed through skin; no side-effects or aggravation of disease noted.    

ICIM Medics believe that effective treatment requires controlling as many contributing factors as possible; foremost – dietary measures to reduce causes and amelioration symptoms; symptom relief through conventional physical therapy (exercise, heat, cold, massage, diathermy, lasers, and paraffin baths), anti-inflammatory botanicals and nutrients and, as appropriate, bowel detox; severe cases –NSAIDs may be necessary in acute phase; natural measures enhance efficacy of drugs-lower dosages required; when drugs given, prescribe deglycyrrhizinated licorice (DGL) to protect against peptic ulcers.

• Diet: therapeutic fast or elimination diet followed by careful reintroduction of foods to detect those which initiate symptoms; any food can aggravate RA; most common offenders are wheat, corn, milk and other, beef, nightshade (Solanum) family foods (tomato, potato, aubergines, peppers, and tobacco; after isolating and eliminating allergens, eat healthy diet rich in whole foods, vegetables, and fiber, and low in sugar, meat, refined carbohydrates, and animal fats; particularly beneficial-cold water fish (mackerel, herring, sardines, and salmon) and flavonoid-rich berries (cherries, hawthorn berries, blueberries, blackberries, etc.) and their extracts.

• Supplements: DHEA, EPA, niacinamide, pantothenic acid, quercetin, tryptophan, vitamin C, vitamin E, copper, manganese, selenium, zinc, betaine HCL, pancreatin are the main supplements indicated for RA patients. However, should be supervised by a medical practitioner.

• Botanical medicines: curcurmin (tumeric), bupleuri falcatum, panax ginseng and glycyrrhiza glabra (licorice) used alone or in combination are beneficial.

• Physical medicine: heat (moist packs, hot baths, etc.), cold packs for acute flare-ups, paraffin baths (if skin irritation caused by hot water), active ROM exercises, progressive isometic exercises and massage further support RA patients.

For further information contact the Irish Centre of Integrated Medicine, St. Johns Grove, Johnstown, Naas, Co. Kildare. Tel. 045 844 819.