Rheumatoid Arthritis

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What Is?
What is Rheumatoid Arthritis
How to Treat Rheumatoid Arthritis
Natural Treatments for Rheumatoid Arthritis

What is rheumatoid arthritis?

Rheumatoid arthritis is a chronic, systemic, generally progressive, autoimmune inflammatory disease, which chiefly affects the synovial membranes of multiple joints, and the connective tissue elements of tendons and ligaments. Of the inflammatory arthritis conditions, rheumatoid arthritis is the most common.

In severe disease, inflammatory degeneration of the organs may also occur, particularly involving the heart, lung and kidney, and exhibits a wide clinical spectrum with considerable variability in the joint and extra-articular manifestations.

Rheumatoid arthritis affects 1 to 3% of the general population. Before menopause women are three to four times more likely to develop the disease compared with men. The peak age of onset is between 20 to 40 years of age. How¬ever, acute onset may commence at any age and juvenile rheumatoid arthritis can develop in children.

The cause of this inflammatory polyarthritis remains ill defined. Genetic factors play a significant role. In the case of identical twins, if one twin develops rheumatoid arthritis the other twin will develop the disease in 40% of cases. A person whose identical twins has rheumatoid arthritis is five times more likely to develop rheumatoid arthritis compared with non-identical twins.

The disease appears to be strongly related to the immune response genes of the major histo compatibility complex that code for class II HLA. Population surveys reveal a strong association between specific alleles at the HLA-DRB1 locus and disease susceptibility, with relative risk varying from twofold for HLA-DR1 to more than sixfold for HLA-DR4.

Thus, in patients with severe seropositive erosive arthritis, more than 70% of patients are HLA-DR4 positive compared to a 25% incidence in the unaffected population. In the more severe forms of rheumatoid arthritis, the specific Dw4 subtype of DR4 shows an increased frequency, with the majority of DR4 homozygotes exhibiting a Dw4/Dw14 genotype.

The genetic contribution accounts for approximately 30% of the disease incidence. Environmental factors strongly influence initiation and maintenance of the autoimmune disease process. Many infectious disorders have shown the capacity to initiate immunologically mediated, inflammatory reactive arthritis, for example following gastroenteric infection with Chlamydia, Salmonella, Campylobacter, Shigella and Yersinia, or systemic viral infection, such as Ross River Virus, Barmah Forest Virus and Parvovirus. Thus, a variety of infectious agents have been postulated to cause rheumatoid arthritis, either by covert joint tissue infection, as for mycoplasma, rickettsiae and chlamydiae species, or immunological reactivity against organisms that exhibit tissue antigen molecular mimicry, as for proteus and Klebsiella organisms.

Pathologic examination of the joint tissues invariably demonstrates a severe inflammatory synovitis with hypertrophic tissue changes, called a pannus, which is infiltrated with large numbers of inflammatory cells including activated tissue macrophages, dendritic cells, plasma cells, and T and B lymphocytes – predominantly CD4-helper T lymphocytes.

Collagen autoimmunity has been implicated in the development of rheumatoid arthritis and, though circulating antibodies to type II collagen are detectable in rheumatoid patients, intra-articular cartilage and synovium contain a far greater prevalence of type II collagen antibodies than serum, which suggests an intra-articular antigen-driven immune process is responsible.

On a molecular level, the plasma cells secrete large quantities of immunoglobulins, mainly IgM and IgG rheumatoid factor, which react with self-IgG, activating complement proteins that initiate and maintain the inflammatory process. Complement breakdown products act as potent chemokines, attracting and activating polymorphonuclear leucocytes and stimulating release of proteases, lysosomal enzymes, collagenases, prostaglandins and TNF-alpha, which results in inflammatory erosion of cartilage and bone, breakdown of ligaments and tendons, and systemic cytokine-mediated inflammatory effects. Rheumatoid arthritis symptoms can include fever, energy loss, protein catabolism, myalgia and arthralgia.

During the acute phase, an inflammatory joint effusion will develop resulting in severe pain, redness and swelling. During the later stages, joint destruction, instability, and loss of function will develop resulting in secondary joint tissue fibrosis, misalignment of joints, and gross disturbance of joint movement.

Widespread inflammatory will often occur in other tissues, including myositis, tendonitis and tenosynovitis, endothelial vasculitis, and inflammatory granulomata in the subdermal connective tissues and organs, such as the heart, heart valves, lungs, spleen, and kidneys.

What are the symptoms of rheumatoid arthritis?

What are the symptoms of rheumatoid arthritis?

According to the Australian Department of Health, the most common symptoms of rheumatoid arthritis:

  • General feeling of ill-health and fatigue
  • Pain in the affected joints
  • Swelling and heating of the joints
  • Stiffness, which restricts movement
  • Muscle weakness as a result of inactivity due to inflammation
What are the risk factors for rheumatoid arthritis?

What are the risk factors for rheumatoid arthritis?

The exact cause of rheumatoid arthritis remains unclear. The likelihood of developing rheumatoid arthritis increases with increasing age, in particular in people more that 45 years of age. The disease is more common among families, so having a family member with rheumatoid arthritis increases a person’s chance of developing rheumatoid arthritis.

Gender and hormones play a role as risk factors. Premenopausal women are more likely to be affected than men. Cigarette smoking may also increase the risk of rheumatoid arthritis, especially for individuals at risk.

The aims of treatment for rheumatoid arthritis are to suppress joint inflammation in order to prevent day-to-day pain and stiffness, and long-term joint damage.

How is rheumatoid arthritis diagnosed?

How is rheumatoid arthritis diagnosed?

The clinical features of rheumatoid arthritis:

  • Onset is highly variable, and may present as acute onset arthritis, recurrent episodic arthritis or a slow but progressive arthritis.
  • Early symptoms – malaise, fever, weight loss, periarticular pain and tenderness, sweating and paraesthesia in the hands and feet, prolonged morning joint stiffness
  • Overt inflammatory swelling of the small peripheral joints, with marked pain, redness, heat and joint dysfunction and, with progressive disease, periarticular soft tissue fibrosis and thickening, joint subluxation, flexion deformities
  • Joint involvement is usually symmetric, curved deformity
  • Blood tests invariably show evidence of acute inflammation
  • X-ray findings – joint effusion and bony erosions, narrowing and distortion of the joint spaces, juxta-articular soft-tissue swelling, osteoporosis
  • Extra-articular manifestations – tendonitis and tenosynovitis, muscle soreness and atrophy, subdermal granulomas
  • Systemic symptoms of immune hyperactivation include: episodic low level fever, anorexia, fatigue, weakness, weight loss, dermal atrophy and dryness of eyes, mouth and other mucous membranes (Sjogren’s syndrome)

Blood tests usually reveal the presence of severe inflammation with:

  • Increased serum levels of acute-phase proteins – C-reactive protein (CRP), ferritin, fibrinogen and caeruloplasmin
  • Decreased or elevated complement proteins – usually low C3 and normal or elevated C4 levels
  • Elevated Erythrocyte Sedimentation rate (ESR)
  • Increased leucocyte and platelet count, particularly neutrophilia
  • Mildly reduced haemoglobin level and low red cell count
  • Positive autoimmune antibodies, usually rheumatoid factor and anti-ANA antibody
  • Increased cytokine levels, particularly IL-6, TNF-alpha and IL-2R
Antinuclear antibodies associated with autoimmune disease
Antibody Disease association
Rheumatoid Factor Rheumatoid arthritis
Antinuclear antibodies:
Systemic Lupus Erythematosus (SLE)
Rheumatoid arthritis, SLE and other connective tissue diseases
Extractable nuclear antigens:
Scl 70
U1 RNP centromere
Sjögren’s syndrome, SLE
Sjögren’s syndrome, SLE
SLE with membranous nephritis
Systemic sclerosis (scleroderma)
Mixed connective tissue disease and limited scleroderma
Other common autoantibodies:
Antineutrophil cytoplasmic antibody
Anticardiolipin antibody
Systemic vasculitis
Antiphospholipid antibody syndrome, SLE, other connective tissue disease
NB: low-titre anti-ANA < 1:128 is not uncommonly found in apparently healthy people and at this low titre does not signify disease.
Derived from the Oxford Textbook of Medicine, Third Edition, p.2952

Blood tests usually reveal the presence of severe inflammation with:

  • Increased serum levels of acute-phase proteins – C-reactive protein (CRP), ferritin, fibrinogen and caeruloplasmin
  • Decreased or elevated complement proteins – usually low C3 and normal or elevated C4 levels
  • Elevated Erythrocyte Sedimentation rate (ESR)
  • Increased leucocyte and platelet count, particularly neutrophilia
  • Mildly reduced haemoglobin level and low red cell count
  • Positive autoimmune antibodies, usually rheumatoid factor and anti-ANA antibody
  • Increased cytokine levels, particularly IL-6, TNF-alpha and IL-2R

Conventional medical treatment for rheumatoid arthritis

Unfortunately no cure for rheumatoid arthritis is available and only rarely does the problem goes away. Effective management of rheumatoid arthritis requires a multi disciplinary approach based on early and accurate diagnosis, which will enable appropriate therapy, patient education about joint protection, future planning to delay with potential disability, and adequate social support.

Medical treatment should include physical therapy, and pharmaceutical therapy, which usually work well, but most take several weeks to months to take full effect. In advanced disease, surgery may be necessary to replace a diseased joint, to enable improved mobility.

Physical therapy should emphasise:

  • Joint protection measures ranging from merely resting affected joints to splinting of joints, particularly at night to avoid future joint deformity, or for joints that are too painful or unstable for use
  • Local application of heat or cold or regular massage with analgesic or healing creams and lotions (topical NSAID creams, Dead Sea mud packs and sulphur baths)
  • Stretching exercises to prevent joint contracture
  • Active resistance exercise to maintain muscle strength and tone
  • Supportive orthotic footwear to prevent foot deformity or enable the patient with deformed feet to maintain mobility

Pharmaceutical therapy that is focused on:

  • Analgesia and anti-inflammatory relief – aspirin and aspirin derivatives; NSAIDS such as ibuprofen, piroxicam and sulindac; and the new COX-2 inhibitor medications celecoxib and rofecoxib
  • Disease-modifying medications that are believed to influence the underlying rheumatoid pathology, though they exhibit substantial adverse effects, requiring careful patient monitoring. Drugs in this class include: gold salts; sulphasalazine; D-penicillamine and the antimalarial medication hydroxychloroquine.
  • Steroidal anti-inflammatory therapy – substantially reduces inflammation and modifies disease progression, but adverse affects of iatrogenic Cushing’s syndrome, immune system depression and osteoporosis limit the use to short-term intervention preferably. Synthetic steroid prednisone and prednisolone are potent agents and cortisone acetate in low doses on an intermittent basis as required is preferable.
  • Cytotoxic chemotherapy agents in low dose destroy lymphocytes and leucocytes and include: methotrexate, cyclophosphamide and azathioprine. In low-dose they exhibit little acute adverse effects, though acute infection due to secondary immune system depression is not uncommon, but long-term adverse effects are problematical.
  • Novel immune-targeted therapies include: leflunomide, a lymphocyte suppression medication that shows good clinical efficacy but also exhibits serious adverse hepato¬toxic and bone marrow suppressive effects; and anti-TNF-alpha agents that are currently undergoing clinical trials.

Surgery is sometimes necessary to maintain function or reduce pain, and may include:

  • Soft tissue procedures, as in repair of tendon rupture, tendon transfer, nerve decompression
  • Synovectomy and excision arthroplasty to correct persistent synovitis and joint deformity
  • Arthrodesis to fuse painful and unstable joints, particularly neck and foot joints
  • Joint replacement arthroplasty, particularly of the hip and knee joints

Contemporary outcome studies report that pharmaceutical therapy has little beneficial impact on disease progression or overall mortality, with some reports that cytotoxic therapy may even reduce life expectancy.

Symptoms of rheumatoid arthritis may include painful swelling, inflammation, and stiffness in the fingers, arms, legs, and wrists occurring in the same joints on both sides of the body, especially upon awakening.

Nutritional medicine treatment for rheumatoid arthritis

For years people have believed that foods are an important trigger in the development of rheumatoid arthritis. Many sufferers notice an improvement in their condition when they avoid dairy products, citrus fruits, tomatoes, eggplant, meat, and sugar-rich and processed foods. For example omega-3 fatty acid supplements, and a gluten-free vegan diet have been show to benefit some people with rheumatoid arthritis.

From a nutritional medicine perspective, a variety of precipitating factors appear to be causally related to the development of the immune system hyper-reactivity, the prime characteristic of rheumatoid arthritis. These causal factors include both genetic and environ¬mental factors that interact to produce a hyper-inflammatory immunological state, with altered tissue macrophage antigen presentation, excessive production of cytokines and inflammatory mediators, and a shift in T-lymphocyte activity that results in production of autoimmune antibodies.

Genetic susceptibility

Genetic susceptibility

Genetic susceptibility is related to the cell membrane expression of the HLA-DR gene, particularly the HLA-Dw4 and Dw14 subtypes, on macrophages, dendritic cells and B-lymphocytes, which are all involved in antigen presentation to the CD4 T-lymphocytes. Contemporary studies report that monocyte HLA-DR expression was substantially inhibited, both in vitro and in vivo, by omega-3 fatty acid supplementation, as was expression of intercellular adhesion molecule-1 and leukocyte-function-associated antigen-1. Thus, genetic susceptibility to rheumatoid arthritis is adversely affected by early dietary omega-3 fatty acid insufficiency, which is common in the modern diet. Supplementation with omega-3 will help prevent or delay disease onset.

Ideally, therefore, prevention of gene-related rheumatoid disease, and other autoimmune diseases, should commence in childhood, with identification of genetic susceptibility and approp¬riate essential fatty acid dietary modification. Experts believe that the ideal ratio for omega-6/omega-3 fatty acids should range from 1:1 to 5:1. (Mel to check)

Gastroenteric mucosal macrophage antigen uptake

Gastroenteric mucosal macrophage antigen uptake

Gastroenteric mucosal macrophage antigen uptake and presentation to enteric CD4 T-helper lymphocytes is strongly implicated as a major initiator of immune system activation, generating release of pro-inflammatory cytokines, TNF-alpha and interleukins IL-1, Il-6 and Il-8.

Gastroenteric mucosal exposure to provocative molecules, such as incomplete food digestates containing mixed nucleotides, antigenic oligopeptides, and food allergen epitopes, increase mucosal macrophage activity and cytokine production. An elemental amino acid diet enhances the jejunal sCD8/sCD4 ratio and down¬regulates immunological activity.

Gastroenteric-related immuno-stimulation may be increased by a number of factors, including:

a) Enteric infection with pathogenic organisms is acknowledged to induce substantial cytokine production and immune system activation, with widespread systemic effects. Enteric infection by a wide range of organisms, bacterial, viral, protozoal, and mycoplasma species, has been associated with systemic joint and connective tissue inflammation.

Persistent immune system hyperactivation may result from:

  • Incomplete elimination of infectious organisms or their derived antigens
  • Latent or unidentified colonisation with gram-negative toxigenic bacteria (Proteus, Klebsiella and Clostridium species)
  • Sub-clinical enteric candida overgrowth
  • Enteric colonisation by parasitic organisms such as Giardia llamblia, Blastocystis, Dientamoeba, Strongyloides and Endolimax.

The resultant upregulated cytokine release, particularly of TNF-alpha, induces low-grade connective tissue inflammatory reactions that lead to progressive Polymorphonuclear cells (PMN) activation and collagen degradation.

PMN release of reactive oxygen species, lysosomal proteases and o-quinones results in the formation of novel immunogenetic protein molecules that, in genetically susceptible persons, triggers B-lymphocyte activation and production of autoimmune antibodies. This process may be enhanced or even precipitated by bacterial antigenic material that mimics epitopes of cell-surface histocompatibility antigens, such as that reported between HLA-DR and Proteus vulgaris antigens or HLA-B27 and Klebsiella.

b) Increased mucosal permeability occurs secondary to mucosal damage induced by enteric infection, dysbiotic colonisation, or immunoglobulin (Ige, IgA or IgG) mediated food allergy reactions. This results in enhanced absorption of bacterial antigens and endotoxins, as well as food-related antigens and chemicals, promoting macrophage activation and cytokine production and further contributing to systemic inflammatory reactions development of further food sensitivity.

It should be also noted that aspirin, NSAIDs, and cytotoxic therapy are well documented to also engender intestinal mucosal damage and increase mucosal permeability, thereby contributing to enhanced immune system upregulation and maintenance of the autoimmune disease process.

c) Impaired gastric acid secretion, induced by consumption of high GI diets and food allergy reactions, secondarily reduces pancreatic enzyme production, by moderating the stimulus for CCK and Secretin release, resulting in impaired digestion of food proteins, nucleotides, and proteoglycans. Partial digestates of these food-derived molecules are reported to enhance mucosal macrophage activation and cytokine production and augment immune system hyper-reactivity, thereby promoting autoimmune disease processes.

Hypochlorhydria also encourages small intestinal bacterial growth. A 1993 study reported that 32% of rheumatoid arthritis patients demonstrated hypochlorhydria on testing, while 50% of these hypochlorhydric patients and the achlorhydric controls had proven bacterial overgrowth.

However, 35% of the rheumatoid patients with normal gastric acid secretion also exhibited small intestine bacterial overgrowth compared with none of the normal controls. Disease activity indices and rheumatoid factor titres were significantly higher in rheumatoid arthritis patients with bacterial overgrowth than in those without.

d) Bowel dysbiosis with gram-negative bacterial overgrowth and yeast mycelial growth (candidiasis) may be induced by antibiotic therapy, dietary food imbalance, oral steroid therapy (including contraceptive pills), nutrient deficiency, immunodeficiency, and bowel surgery and stasis.

Dysbiosis in the stomach and small intestine is predominantly related to hypochlorhydria, food allergy reactions, excessive intake of sugar and refined carbohydrate foods in the presence of low fibre intake, and antibiotic therapy. Intestinal colonisation with gram-positive aerobic coccal-form bacteria is enhanced, as is mycelial yeast growth, whilst lactobacillus growth is reduced.

Mucosal damage produced by bacterial protease action interferes with pancreatic and intestinal brush border enzyme function, causing maldiges-tion and impaired mucosal permeability that stimulates immunogenic activity, resulting in sensitisation to bowel organisms and commonly consumed foods.

Large bowel dysbiosis is predominantly related to excessive fat intake and low insoluble fibre intake, but is also encouraged by chronic bowel motility problems and antibiotic therapy. An overgrowth of anaerobic bacteroides and Enterobacter species with reduced growth of bifidobacteria is characteristic of large bowel dysbiosis.

In rheumatoid arthritis patients, increased colonic populations of Proteus vulgaris and clostridium species has been reported and has been associated with production of antibacterial antibodies, some of which demonstrate cross-reactivity with HLA-DR antigens. Bacterial enzyme deconjugation of bile salts and conjugated steroidal hormones results in toxic secondary metabolites that are absorbed into the hepatoenteric circulation, promoting hepatotoxicity and hormone imbalance and contributing to excessive free radical genesis, glutathione insufficiency, and TNF-alpha production.

Correction of dysbiotic flora is essential to the effective management of immune hyper-reactivity and autoimmune disease. An integrated program of dietary correction, probiotic replacement, and judicious antibacterial therapy may achieve this. Either natural antibacterial agents or antibiotics can be used to treat intestinal dysbiosis. Natural treatments include grapefruit seed extract, artemisia or burberry extracts. Antibiotics include metronidazole or minocycline for small bowel and ciprofloxacin for large bowel.

Dietary fatty acid imbalance

Dietary fatty acid imbalance

Dietary fatty acid imbalance related to consumption of saturated fats, trans-fatty acids, and arachidonic acid from animal meat and dairy products with associated inadequate intake of both gamma-linolenic acid, the omega-6 fatty acid precursor of PGE2, and the omega-3 fatty acids.

Excess saturated fat intake promotes tissue mast cell activation and macrophage activity, resulting in greater than usual release of vasoactive inflammatory kinins and cytokines, which upregulate inflammatory responses and CD4 T-cell activation. A reduction in dietary saturated fats will reduce inflammatory processes and immune hypersensitisation. Several studies have shown that approp¬riately constructed vegetarian diets substantially reduce joint inflammation and pain in rheumatoid arthritis patients.

The three omega-3 fatty acids are alpha-lipoic acid (ALA), which is found in plant oils, EPA, and DHA, both of which are found in marine oils. Inadequate omega-3 fatty acid intake results in excessive arachidonic acid accumulation in cell membranes, which increases phospholipase A2 activity and cellular release of lipolytic hydroxy-peroxy fatty acids, as well as Prostaglandin E2, Thromboxane A2 and the 4-series leukotrienes.

These eicosanoids amplify inflammatory mediator release, Substance P and other kinins, further escalating local tissue damage and inflammatory reactions, PMN activity and free radical genesis, and cytokine release and immuno-reactivity.

Raising omega-3 fatty acid intake, through dietary manipulation and supplements, has been shown to increase PGE3 and 5-series leukotrienes, which will reduce inflammation and pain, and downregulate TNF-alpha production and immuno-reactivity.

Omega-6 fatty acid intake correlates with proinflammatory cytokine and leukotriene production, except at very high intake levels, and exerts counter¬productive activity on inflammation control.

Controlled interventional trials of combined GLA plus EPA and DHA have helped in the treatment of rheumatoid arthritis patients. Several studies have reported that gamma-linolenic acid (GLA) supplements appear to exhibit a synergistic effect with omega-3 fatty acids, raising membrane-bound EPA and DHA concentrations and reducing production of proinflammatory eicosanoids and cytokines, to a greater extent than that induced by sole omega-3 fatty acid supplementation.

Individual antioxidant capacity

Individual antioxidant capacity

Antioxidant capacity is heavily compromised in patients with rheumatoid arthritis, both locally within inflamed joints and systemically. Antioxidant supplementation has been documented in multiple studies to beneficially reduce joint inflammation, pain, and immune hyper-reactivity. Nevertheless, the use of antioxidant therapy remains conspicuously absent in conventional medical treatment.

Individual patient assessment of antioxidant capacity, including the status of nutrients essential to endogenous antioxidant production, is required for a comprehensive supp¬lemen¬tation program. Antioxidants that have been shown to be low in patients with rheumatoid arthritis include ascorbate, vitamins E and D, bioflavonoids, Coenzyme-Q10, sulphydryl groups (methionine and cysteine), selenium, glutathione peroxi¬dase and super¬oxide dismutase.

Glutathione peroxidase insufficiency has been reported in a majority of rheumatoid arthritis patients, particularly in patients with severe disease, and appears to be partially related to impaired synthesis and response to oxidative challenge as well as selenium deficiency. In addition, zinc and manganese, which are essential to superoxide dismutase activity, can be depleted in rheumatoid arthritis patients and supplementation may raise superoxide dismutases (SOD) activity, which provides important anti-oxidantion protection.

In addition to an integrated antioxidant regimen, high-dose vitamin E (at least 2000U/day) may also exhibit a beneficial action, as several studies report that high-dose vitamin E reduces lymphocyte and PMN activity, which should be worth attempting in rheumatoid arthritis patients. Though no specific studies have addressed this issue, practitioners’ clinical experiences report significant benefit at this level of supplementation.

High-dose bioflavonoid therapy with quercetin and citrus bioflavonoids is reported to exhibit substantial anti-inflammatory benefits in rheumatoid arthritis, and other auto¬immune diseases, and is reported to:

  • Inhibit Mast cell degranulation and histamine production
  • Reduce PMN activation and free radical genesis
  • Inhibit phospholipase A2 activity and eicosanoid production
  • Exhibit potent antioxidant activity, reducing oxidative damage and conserving ascorbate and vitamint E activity, and
  • Inhibit hyaluronidase and protease enzyme activity, retarding connective tissue breakdown and stabilising the tissue collagen matrix.

Thus, antioxidant therapy with a range of bioactive nutrients exerts significant beneficial anti-inflammatory and immuno-modulatory activity that is synergistic with those derived from appropriate essential fatty acid modulation.

Hepatic detoxification pathways

Hepatic detoxification pathways

Hepatic detoxification pathways are often compromised in rheumatoid arthritis patients, often related to prior medication use, bowel dysbiosis, unduly high free radical genesis, and genetic polymorphism of detoxification enzymes.

Phase I enzyme activity may be either upregulated or downregulated, while Phase II conjugation pathways are generally constrained, particularly the sulphate and glutathione conjugation pathways.

Cytochrome P450 activity enzymes are a family of mixed-function-oxidase enzymes that exhibit remarkable polymorphism and are responsible for transformation of fat-soluble bioactive molecules, hormones, and toxins into oxidised water-soluble metabolites. Reduced Cyt-P450 activity results in impaired clearance of endogenous and exogenous toxins, drugs, and hormones, resulting in mitochondrial and cytosolic enzyme dysfunction and reduced cellular metabolism, particularly of liver and brain. Patient exposure to environmental chemicals, medications, and enteric bacterial endotoxins increases cellular dysfunction that may cause medication adverse effects with hepatocellular or neurological damage.

As many rheumatoid arthritis patients have received treatment with a variety of medications that are known to inhibit Cyt-P450 activity, most patients require a nutritional regimen to upregulate Phase I activity. This may be achieved by adequate supplementation with antioxidants, protein, magnesium, zinc, and B-complex vitamins, through added niacin and pyridoxine, selenium, and glutathione.

The majority of rheumatoid arthritis patients demonstrate impaired sulphur conjugation capacity, with down regulation of both sulphoxidation and sulphotransferase enzyme activity, which appears to be due to genetic polymorphism.

Impaired sulphoxidation enzyme activity results in impaired ability to metabolise sulphite with increased sensitivity to dietary sulphites and sulphur-containing medications and chemicals and may be detected by an increased urinary sulphite excretion following consumption of sulphur-containing amino acids. A simple clinical identification of these patients is to determine if excretion of odiferous urine follows ingestion of asparagus, as incomplete oxidation of the sulphur compounds in asparagus implicates impaired sulphoxidation.

Impaired sulphoxidation activity results in impaired sulphate conjugation and increased load on glutathione and glucuronidation pathways and is identified by a low urinary sulphate/creatinine ratio following acetaminophen challenge. In the presence of selenium depletion and impaired glutathione metabolism, as reported in a majority of rheumatoid arthritis patients, glutathione conjugation may well be similarly impaired and contribute to hepatotoxicity and excessive pro-oxidant genesis.

Patients exhibiting impaired sulphoxidation generally have a latent molybdenum deficiency, which may be corrected by increasing molybdenum-rich foods, such as meat, fish, poultry, legumes and Brazil nuts, or supplements may be required. However, excessive molybdenum supplementation has been reported to reduce sulphate conjugation, thus urinary sulphite excretion must be monitored and supplement dosage adjusted as sulphite excretion normalises. Patients with impaired sulphate and glutathione conjugation may benefit from supp¬lementary inorganic sulphur and N-acetylcysteine, glutathione, and taurine.

Neuroendocrine disturbance

Neuroendocrine disturbance

Neuroendocrine disturbance is commonly reported in rheumatoid patients affecting production of a variety of hormones and interfering with neurotransmitter receptor response. Dysregulation of hypothalamic control of adrenal cortisol secretion is common and may be related to chronic stress, prolonged high-level cytokine production, or altered neurotransmitter receptor activity secondary to food allergy reactions, endotoxin and xenobiotic toxin exposure, and nutrient deficiency. Reduced cortisol, oestrogen, and androgen secretion and elevated prolactin production may contribute to immune system hyperactivation and inflammation, while reduced androgen and DHEA production may enhance protein catabolism and lean-weight atrophy.

Detailed assessment and correction of impaired hormonal and neurotransmitter activity is essential to a well-balanced recovery program.

Therapeutic Considerations

Therapeutic Considerations

Therapeutic Considerations

  • Protect gastroenteric integrity and support digestive efficacy
  • Assess for food sensitivity reactions; define and exclude provocative foods
  • Utilise a well balanced protein sufficient, high-fibre diet
  • Reduce saturated fat intake and optimise essential fatty acid balance
  • Consider a vegetarian diet or even a period of elemental diet or fasting
  • Optimise intake of antioxidant nutrients and phytonutrients
  • Correct for bowel dysbiosis and impaired hepatic detoxification
  • Consider supplemental vitamins C and E, selenium, zinc, manganese, niacin, pantethine, glutathione and sulphur-containing amino acids
  • Add anti-inflammatory phytonutrients – Quercetin and citrus bioflavonoids, Bromelain, Curcuma longa, Zingiber officinalis and Boswellia
  • Assess and correct for hormonal imbalance
  • Add adjunctive physical therapy such as balneotherapy (mineral baths and mudpacks) , heat packs and cold packs, approriate physical exercises


Antiphospholipid antibody syndrome
Arthralgia – painful joints
Barmah Forest Virus – mosquito-borne infectious disease, which was discovered in Barmah Forest in Victoria
Bowel dysbiosis – an imbalance in the intestinal microbiome
Campylobacter – infectious disease of intestine causing diarrhoea
Candidiasis – fungal infection from the yeast genus Candida. Candida albicans is the most common agent of candidiasis in humans.
CD4-helper T lymphocytes – play an important role in the immune system
Collagenases – enzymes that target connective tissue and break the peptide bonds in collagen in presence of bacterial infection
Chemokines – family of small cytokines, or signaling proteins secreted by cells
Chlamydia – a sexually transmitted disease
Cytochrome p450 (CYP) – large and diverse group of hemoprotein enzymes called monoxygenases that catalyse the oxidation of organic substances
DHEA – didehydroepiandrosterone is an important endogenous steroid hormone
Endothelial vasculitis – inflammation of the endothelial layer of blood vessels
Extra-articular – outside a joint
Histocompatibility – having the same alleles of a set of genes called the major histocompatibility complex
Hypochlorhydria – when the stomach gastric juices are low or absent
Granulomata – pleural of granuloma, a collection of macrophages formed when the body walls-off a foreign substance
Histocompatibility complex – set of cell surface molecules encoded by a large gene family in all vertebrates
HLA (Class I and Class II) – gene family that provides instructions for making a group of related proteins called the human leukocyte antigen complex, which aide the immune system to distinguish between foreign virus and bacteria and the body’s own protein
Immune hyperactivation – causing the immune system to over-react
Intra-articular – within a joint
Juxta-articular – near a joint
Klebsiella organisms – non-motile, gram-negative bacteria
Lysosomal enzymes – enzymes in the subcellular organelles for food digestion, including glycosidases, protease, acid phosphatases, sulfatases and lipases
Myalgia – painful muscles
Mycoplasma – genus of bacteria that lack a cell wall and are unaffected by common antibiotics
Myositis – muscle inflammation
Parasthesia – numbness
Parvovirus – contagious DNA virus
Periarticular – tissues around a joint
Phytonutrients – chemical compounds that occur naturally in plants
Polyarthritis – any type of arthritis that affects five joint or more
Poly-morphonuclear leucocytes – a white blood cell containing a segmented lobular nucleus; an eosinophil, basophil, or neutrophil
Prostaglandins – non-endocrine hormones derived from fatty acids that are important to human physiology and have a wide variety of effects
Protein catabolism – break down of protein from body tissues
Proteases – type of enzyme that begins protein breakdown
Proteus organisms – gram-negative enterobacteria
Quercetin – a flavonoid (plant pigment) found in fruits, vegetables, leaves, and grains
Rickettsiae (spotted fever, typhus and scrub typhus) – gram-negative pleomorphic bacteria carried by ticks, fleas and lice
Ross River Virus – mosquito-borne infectious disease, which originated from the Ross River in Townsville
Salmonella – gram-negative enterobacteria
Seropositive erosive arthritis – when rheumatoid factor present in blood
Shigella – gram-negative enterobacteria closely related to Salmonella
Sjogren’s syndrome – systemic autoimmune disease that affects the exocrine glands that produce tears and saliva
Subluxation – joint dislocation
Superoxide dismutases (SOD) – important antioxidant defence in nearly all cells exposed to oxygen
Systemic lupus erythematosus – a systemic autoimmune disease that attacks healthy tissue, such as skin, joints, intestine, lung, heart, kidneys, and brain.
Tendonitis – inflammation of a tendon
Tenosynovitis – inflammation of the fluid-filled sheath that surrounds a tendon
TNF-alpha – tumour necrosis factor part of acute phase reaction in systemic inflammation
Vasculitis – blood vessel inflammation
Yersinia – gram-negative enterobacteria, one of the causes of reactive arthritis and associated with gout