• Fatigue, low-grade fever, weakness, weight loss, joint stiffness, and vague joint pain may precede the appearance of painful, swollen joints by several weeks
• Severe joint pain with considerable inflammation that usually begins in the small joints and progresses to eventually affect all joints
• X-ray findings usually show soft tissue swelling, erosion of cartilage, and joint space narrowing
• Rheumatoid factor is present in the blood
Rheumatoid arthritis (RA) is a chronic inflammatory condition that affects the entire body, but especially the joints. The joints typically involved are the hands, feet, wrists, ankles, and knees. Between 1% and 3% of the population is affected, and the number of women with RA exceeds the number of males by almost three to one. The usual age of onset is 20 to 40, although rheumatoid arthritis may begin at any age.
The onset of RA is usually gradual but occasionally is quite abrupt. Several joints are usually involved in the onset, typically in a symmetrical fashion (i.e., both hands, wrists, or ankles). In about one-third of people with RA, initial involvement is confined to one or a few joints.
Involved joints will characteristically be quite warm, tender, and swollen, with prolonged morning stiffness. The skin over the joint will take on a ruddy purplish hue. As the disease progresses, deformities develop in the joints of the hands and feet. The common terms used to describe these deformities include swan neck, boutonniere, and cock-up toes.
The diagnosis of RA is based upon the presence of pain and inflammation in at least one joint, with no alternative explanation, and (see table below) a score of 6 or greater in a four-tier rubric.1
Joint involvement (select the one with highest point value):
1 medium-large joint
2–10 medium-large joints
1–3 small joints
4–10 small joints
10+ small joints
Seronegative for RF and anti-CCP
Low-titer of RF and/or anti-CCP
High-titer of RF and/or anti-CCP (>3 times upper normal limit)
Duration of synovitis:
Less than 6 weeks
Acute phase reactants:
Normal ESR and CRP
Elevated CRP or ESR
Anti-CCP = anti-cyclic citrullinated peptide antibodies
CRP = C-reactive protein.
ESR = erythrocyte sedimentation rate
RF = rheumatoid factor
There is abundant evidence that RA is an autoimmune reaction, in which antibodies develop against components of joint tissues. Yet what triggers this autoimmune reaction remains largely unknown. Speculation and investigation have centered on genetic factors, abnormal bowel permeability, lifestyle and nutritional factors, food allergies, and microorganisms. RA is a classic example of a multifactorial disease, wherein assorted genetic, dietary, and environmental factors contribute to the disease process.
Other Autoimmune Diseases Affecting Connective Tissue
In addition to RA, there are several other autoimmune diseases that affect connective tissue (collagen structures that support internal organs as well as cartilage, tendons, muscles, and bone). These diseases include systemic lupus erythematosus (SLE or lupus; see that chapter), ankylosing spondylitis, scleroderma, polymyalgia rheumatica, and mixed connective tissue disease. There is tremendous overlap among these diseases in terms of underlying causes, symptoms, and treatment. They share many features with RA, but the autoimmune and inflammatory process is a bit different in each of these diseases. From a natural medicine perspective the treatment of any of these other autoimmune diseases should focus on the same treatment recommendations given here in this chapter for RA.
A positive family history is a risk factor for developing RA. Evidence of a genetic factor was first noted in studies of twins, yet in identical twins the chance that one twin will develop the disease if the other already has it is only 15%. If RA were purely a genetic disease, both twins would be affected every time. These results have led geneticists to focus on epigenetic factors—factors that can turn off or turn on the expression of the genetic code.2 The biggest determinants of epigenetic influence on the expression of DNA are nutrition and environmental toxins. Epigenetic factors are thought to be associated with more aggressive disease by affecting immune function, antioxidant pathways, detoxification mechanisms, and other processes. Interestingly, patients with RA also have changes in fecal flora that are thought to contribute to the disease process (see discussion below), and studies have shown that the flora of identical twins is more similar than that of fraternal twins, independent of other contributing factors, indicating that genetic factors influence the type of bacterial flora a person has.3
Genetic studies indicate that dietary and environmental factors are required for RA to be manifested. For example, toxins in cigarette smoke interact with epigenetic factors to enhance the inflammatory process and increase the risk of RA.4 The risk for smokers of developing RA is nearly 8-fold in genetically susceptible individuals and nearly 16-fold for identical twins. Smoking also increases RA risk in the general population, and quitting smoking results in decreased risk of RA.5 Other factors such as poor diet, drinking more than three cups of coffee per day, silicate exposure, and psychological factors may also play a role in the development of the disease and affect the levels of pain and physical disability experienced by RA patients,6 while oral contraceptives (birth control pills), tea (black or green) intake, and increased vitamin D consumption have been found to be protective. Other environmental factors such as low temperature, high atmospheric pressure, and high humidity have been correlated with increased RA pain.7
Several studies have shown that the risk of RA is highest in people with the lowest levels of nutrient antioxidants. Low antioxidant levels may be exacerbated by genetic factors.8 The resulting increase in oxidative stress could produce free radical damage to DNA and mutations that may contribute to the development of RA.9 Once disease is established, synovial concentrations of free radicals are elevated and concentrations of antioxidants are diminished, accelerating inflammation and joint destruction.
The serum of most individuals with RA contains an antibody called rheumatoid factor (RF) and cyclic citrullinated peptide autoantibodies (anti-CCP). The blood levels of these antibodies often reflect the severity of arthritis symptoms and prognosis, but not in every case, and the antibodies are not directly responsible for joint destruction. Autoantibodies have been detected as much as 10 years prior to the onset of clinical disease, and other inflammatory markers have been elevated for up to 12 years prior to diagnosis.10,11 This suggests a “multiple hit” model in which the disease progresses in distinct stages, perhaps explaining why autoantibodies are present for years before clinical symptoms.
Microbial Influences: Infection and Cross-Reactivity
Microorganisms may play a role in the disease process of RA. The onset of RA is preceded by a specific inciting event, such as an infection, in 8 to 15% of cases, and antimicrobials such as metronidazole, clotrimazole, acyclovir, roxithromycin, tetracycline, sulfasalazine, and minocycline have been associated with improvement in symptoms and, in some cases, complete remission.12–18 Many disease-causing organisms, such as Epstein-Barr virus, cytomegalovirus, parvovirus, rubella virus, mycoplasma, amebic organisms, E. coli, Proteus species, and influenza virus AH2N2, have been associated with RA. Yet no single microbial agent has been consistently isolated in patients with the disease, indicating that a multitude of organisms may directly or indirectly contribute to the disease process by the formation of cross-reacting antibodies that attack body cells instead of the infectious organism. It is well established that over a dozen different organisms can produce arthritis similar to RA after a gastrointestinal, urinary tract, or respiratory infection in genetically susceptible individuals and that the condition can become chronic in 15 to 60% of cases.
Dysbiosis and Small Intestinal Bacterial Overgrowth
Perhaps more important than specific disease-causing organisms is the subtler influence of the intestinal microflora on our internal gut environment. There are more microflora in our digestive tract than human cells in our bodies, and the composition of the hundreds of species of microorganisms is known to be affected by genetics, medical treatment, diet, and stress.19 The bacterial flora of our intestinal tract has a profound influence on immune function, nutritional status, and stress response and can contribute to many diseases.20,21 Many of these intestinal functions are thought to be involved in the disease process of RA.
It is well established that the fecal flora is significantly altered in RA, including significantly less bifidobacteria and bacteria of the Bacteroides, Porphyromonas, and Prevotella genera.22 This condition is called dysbiosis. Clinical studies have demonstrated improvement with changes in microbial flora.23,24 Likewise, many RA patients have small-intestine bacterial overgrowth (SIBO), 51% in one study, and the degree of SIBO was associated with the severity of symptoms and disease activity.25 Even bacteria from the periodontal tissue in the mouth may play a role. One study found identical periodontal bacterial DNA in 100% of joint fluid samples and 83.5% of blood samples of RA patients,26 and another study found a correlation between the severity of periodontitis and the severity of RA symptoms.27 Antibodies to periodontal bacteria are associated with elevated anti-CCP antibodies and promoting the autoimmune response in RA.28
Adverse Food Reactions
As much as 10% of the population has food allergies and, for patients who have tested positive for food allergies, consumption of those allergenic foods is associated with increases in inflammatory markers in the blood.29,30Outcomes of food allergy studies in RA have been conflicting. It is also important to point out that adverse food reactions such as food intolerance and sensitivity are not antibody-mediated and, therefore, not apparent with antibody testing.31 Yet these reactions may be contributory.
One group analyzed the studies that considered the quantitative exposure to allergenic foods and found that studies utilizing larger doses of food antigens tend to show a positive correlation between RA and food allergies in 20 to 40% of patients.32 These same authors examined jejunal and serum antibody secretions of RA patients and compared them with controls. While serum food antibodies were not correlated with RA, jejunal IgA, IgG, and especially IgM were significantly elevated against nearly all food antigens in RA patients compared with controls, and the antibodies were substantially cross-reactive with normal body proteins. These researchers conclude that RA patients may have multiple modest hypersensitivity reactions and that the additive effect could lead to widespread antibody-mediated tissue destruction.
Toxins and Autoantibody Production
Pesticides, herbicides, and other synthetic toxins are particularly problematic to both RA patients and people at risk for RA, owing to impaired detoxification processes.33 Slow detoxification also predicts the severity of RA.34
Other toxins also appear to induce similar autoimmune responses in genetically susceptible patients. Bacterial toxins can bind to the lining of the intestines and stimulate antibody production against peptides and normal tissue proteins.35 This same response was stimulated by gliadin peptides (from grains, especially wheat, rye, and barley), casein (a milk protein), and ethyl mercury (the vaccine adjuvant Thimerosal).36
Abnormal Gut Permeability
Individuals with RA have excessive intestinal permeability to dietary and bacterial antigens as well as alterations in the bacterial flora.37–39 Chronic inflammation in the gut can cause increased intestinal permeability and is associated with joint inflammation. Adverse food reactions and bacterial endotoxins40 may contribute greatly to chronic gut inflammation, and nonsteroidal anti-inflammatory drugs (NSAIDs) that are commonly prescribed for RA can worsen this situation as well.41 However, increased gut inflammation and permeability also occur in RA independent of NSAID use.42 This “leaky gut” facilitates the migration of dietary and gut-derived antigens and bacterial gut flora to blood, mesenteric lymph nodes, spleen, and kidneys.43 In conjunction with dysbiosis and bacterial overgrowth, increased gut permeability to bacterial endotoxins and food antigens can produce immune activation and circulating immune complexes, many of which have been recovered in synovial fluid and could contribute to joint inflammation and degeneration.
Decreased Androgen Levels
Low levels of androgens (male sex hormones) are linked to RA. Specifically, chronically low levels of testosterone and dehydroepiandrosterone (DHEA) have been found in early-stage and established RA.44–46 A small study showed that testosterone replacement therapy had positive effects in male RA patients, decreasing RF levels, the number of affected joints, and NSAID use.47
Abnormal Estrogen Levels
Unlike androgens, estrogens (female sex hormones) may be involved in sustaining the inflammatory activity of activated immune cells.48 Estradiol levels have been found to be higher in RA patients than controls and strongly and positively associated with markers of inflammation. A five-year study of 689 patients with similar disease duration and severity found that gender was a major predictor of remission in early RA. Women had a lower androgen-to-estrogen ratio and, at two and five years, had more severe disease and 16 to 22% fewer remissions than men. This effect could not be explained by any other differences between the groups, including disease duration, age, or treatments used.49
Standard medical therapy is limited by its overreliance on drugs designed to suppress the disease process and its symptoms, while failing to address the complex underlying causes of this disease.50 The effects and side effects of these drugs actually worsen many factors contributing to the disease process, and the drugs have significant morbidity and mortality risks of their own. Drug therapies generally fall into three categories: nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and biological therapies.
Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase Inhibitors
NSAIDs suppress of symptoms while accelerating factors that promote the disease process. While relieving symptoms by decreasing inflammation, NSAIDs can inhibit cartilage formation and actually promote joint destruction.51,52Furthermore, they promote several factors thought to contribute to the disease process of RA by increasing gastrointestinal tract hyperpermeability, dysbiosis (alteration in normal gut flora), free radicals in joint synovial fluid, and bacterial overgrowth.53,54 NSAIDs also cause serious gastrointestinal tract side effects, including ulcers, hemorrhage, and perforation, which according to one study led to 107,000 hospitalizations and 16,500 deaths in one year among arthritis patients alone.55
To mitigate GI toxicity, NSAIDs are sometimes given along with acid-blocking medications. These acid-blocking drugs help alleviate the upper GI damage but end up causing additional issues, including lower levels of hydrochloric acid in the stomach (resulting in impaired food digestion and hence more food allergies) and overgrowth of bacteria in the small intestine (still another factor contributing to the disease process of RA).56
Newer NSAIDs such as Celebrex, a cyclooxygenase inhibitor, are easier on the stomach, but they do not completely protect the lower GI tract from injury and are associated with adverse cardiovascular events.57,58 Because RA patients are already at increased risk for cardiovascular disease, these drugs may not be appropriate for general use with RA patients.59 Finally, all drugs in this class also have been connected to kidney toxicity, and chronic use of high doses in arthritis patients increases risk for kidney failure.60
Corticosteroid medications such as prednisone are generally reserved for patients who do not respond to NSAID therapy. By more completely blocking the inflammatory response, including the production and secretion of inflammatory mediators such as histamine, prostaglandins, and leukotrienes, they suppress not only inflammation but the normal immune response as well. These medications may be of great benefit in acute symptom management, but they become problematic with long-term use. Corticosteroids are associated with more frequent serious infections (those requiring hospitalization) and increased mortality. Even small doses (up to 7.5 mg prednisone or the equivalent) carry increased risk for infection and death when used over the long term. One study found the risk of mortality increased 14% after one year and 49% after more than 10 years of use when the subjects were compared with RA patients who had not been treated with low-dose corticosteroids.61
Common side effects of long-term use that negatively affect RA include severe cartilage damage, osteoporosis, increased intestinal permeability, and cardiovascular disease.61–65 Furthermore, the risk of peptic ulcers and GI bleeding in patients already using NSAIDs is greatly increased with simultaneous use of corticosteroids. Insomnia is also a side effect, and patients with RA are more susceptible to insomnia than the general population.66 In fact, one study concluded that the fatigue experienced by RA patients may be more a product of sleep fragmentation than a constitutional symptom of the disease itself.67 Finally, depression is a common side effect of prednisone and is also common among patients experiencing chronic pain from diseases such as RA. Patients with RA who experience depression have worse outcomes than those who are not depressed, further contraindicating the use of corticosteroids.68
Synthetic Disease-Modifying Antirheumatic Drugs
Once reserved for severe cases, disease-modifying antirheumatic drugs (DMARDs) are now used as first-line therapies in conventional treatment guidelines. Methotrexate is the most common drug used, with the best balance of efficacy and toxicity.69 Originally used as a chemotherapeutic agent, it exerts an immunosuppressive effect by decreasing white blood cell production. The more severe side effects of methotrexate include gastrointestinal ulceration, severe bone marrow suppression, frequent infections, elevated risk of cancer, and damage to lungs, liver, or kidneys. Other drugs in this class include hydroxychloroquine (Plaquenil), azathioprine, cyclophosphamide, and leflunomide and have similar and sometimes more severe side effects. Many patients may not actually continue long-term therapy with any DMARDs beyond the first few years owing to adverse effects or lack of efficacy. However, there is evidence that beginning a DMARD within the first three months of diagnosis is associated with decreased risk of joint erosion. Therefore, patients presenting with a diagnosis of RA will now most often be on DMARDs, individually or increasingly in combination, and perhaps additional drugs to manage their side effects.
Biological Disease-Modifying Antirheumatic Drugs
Newer biological agents include infliximab, etanercept, and adalimumab. Other members of this class include tocilizumab and abatacept. These medications are no more effective than methotrexate when used as a sole therapy. However, in an analysis of comparative trials, a combination of these drugs with methotrexate was more effective than methotrexate alone, especially in initially severe RA.70 Unfortunately, drug-free remission is still very rarely achieved and most patients experience higher disease activity upon discontinuation of therapy. Biological agents also carry significant health risks, including infections, anemia, and perhaps acceleration of atherosclerosis.71,72
Population studies have demonstrated that RA is found at higher rates in societies consuming a Western-style diet.73 A diet of organic whole foods, rich in vegetables and fiber and low in sugar, meat, refined carbohydrates, saturated fat, and additives, appears to offer some protection against the development of RA, as well as promise in its treatment.74–79
Adverse Food Reactions
Elimination of food allergens or reactive foods has been shown to offer significant benefit to some individuals with RA.79–82 The most common triggers in one study included corn (56%), wheat (54%), bacon/pork (39%), oranges (39%), milk or oats (37%), rye (34%), egg, beef, and coffee (32%), malt (27%), cheese or grapefruit (24%), tomato (22%), peanuts or cane sugar, (20%), and butter, lamb, soy, or lemon (17%). Of those participants who continued to avoid their reactive foods, 19% remained well without medications for follow-up periods of up to 5 years.83
Dietary elimination and challenge are methods of identifying triggering foods, which can be different for each patient. Some studies that fail to show benefit of dietary intervention provide the entire experimental group with the same hypoallergenic diet, not one customized to each participant’s particular sensitivity or sensitivities.
Patients with RA have historically benefited from fasting. Short-term fasts of three to five days’ duration are recommended during acute flare-ups to induce a substantial reduction of joint pain, swelling, morning stiffness, and other symptoms of RA.84 It is an obvious method for eliminating reactive foods but has effects that extend beyond allergen avoidance. Fasting increases serum DHEA, decreases serum inflammatory mediators,85 and favorably affects intestinal permeability.86 Juice, broth, and water fasts of longer duration, up to 10 days, have been shown to be effective as well.87 For more information on nutritional cleansing, see the chapter “Detoxification and Internal Cleansing.”
A predominantly vegetarian diet has considerable support in the medical literature in the treatment of RA. One 13-month controlled study began with a 7-to-10-day fast before transitioning to a vegetarian diet.88 The fast consisted of herbal teas, garlic, vegetable broth, decoction of potatoes and parsley, and the juice of carrots, beets, and celery. The diet was followed by a systematic reintroduction of a single food item every two days with elimination of foods that aggravated RA symptoms. The treatment group showed significant improvements compared with controls, and these improvements were maintained at one-year follow-ups in those patients still sticking to the diet. This study supported the positive results noted in prior studies of short-term fasting followed by a vegetarian diet, and the pooling of these data in a systematic review showed a statistically and clinically significant beneficial long-term effects.89–91 Beyond allergy elimination, vegetarian diets are also associated with higher fiber intake and improved gut flora, including decreased antibodies to suspected organisms linked to RA, less SIBO, and improvement in RA symptoms.92 Other changes include increased potassium intake (which may lead to improved biosynthesis and release of cortisol) and favorable fatty acid and antioxidant intake.
Patients with established RA in one study experienced a reduction in inflammatory activity, an increase in physical function, and improved vitality in 12 weeks on a Mediterranean-style diet.93,94 Rich in seasonally fresh plant-derived foods, the Mediterranean diet is similar to a vegetarian diet with the addition of fish and poultry, low to moderate amounts red meat, consumption of moderate amounts of dairy foods and red wine, and olive oil as the main source of lipids. Different types of dietary fats can either alleviate or aggravate RA by influencing eicosanoid metabolism.93,95 Both vegetarian and Mediterranean diets are inherently low in saturated fats and arachidonic acid, the precursor to the inflammatory series-2 prostaglandins and leukotrienes; and rich in gamma-linolenic and alpha-linolenic acids, the precursors to anti-inflammatory series-1 and series-3 prostaglandins. The consumption of cold-water fish such as anchovies, mackerel, herring, sardines, and salmon, which are rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), further promotes anti-inflammatory prostaglandins.
A population-based case-control study of women living in the Seattle area compared fish consumption in 324 cases of RA with 1,245 control cases.96 Consumption of broiled or baked fish was associated with a dose-dependent decreased risk of RA. This may explain some of the anti-inflammatory effects of the Mediterranean diet, which includes fish but relatively little meat. Excluding meats removes not only pro-inflammatory arachidonic acid from the diet but also a potential food allergen: several studies have found that RA patients are commonly allergic to meats, especially beef and pork.97,98 Furthermore, the inclusion of olive oil produces additional benefits in RA, including antioxidant and anti-inflammatory effects, competitive inhibition of omega-6 fatty acids, pain reduction, reduced morning stiffness, and improved patient evaluation of overall health.99 Additionally, these effects seem to be synergistic with fish oils.
The continuous production of free radicals within arthritic joints promotes joint degeneration, exhausts antioxidant systems, and may cause the low antioxidant levels commonly seen in RA patients.100 The importance of consuming a diet rich in fresh fruits and vegetables in the dietary treatment of RA cannot be overstated. These are the best sources of antioxidants such as vitamin C, carotenoids, vitamin E, selenium, and bioflavonoids, which promote healthy joints by neutralizing inflammation and supporting collagen structures. Antioxidants work synergistically in systems—for example, vitamin C is needed to regenerate vitamin E—and this may explain why systematic reviews have not found single antioxidant supplements to be effective, but have documented the benefit of antioxidant-rich diets. The antioxidant content of vegetarian and Mediterranean diets almost certainly contributes to their effectiveness in treating RA.
Blood and tissue samples from RA patients have been shown to be deficient in many nutrients, including magnesium, folate, vitamin B12, vitamin B6, zinc, and selenium.101–106 Many factors may contribute to this, including decreased dietary nutrient intake among RA patients, decreased absorption due to impaired gut function, increased utilization of antioxidant nutrients due to elevated oxidative stress, and increased excretion of nutrients due to stress and medications. Studies are few in number and have produced conflicting results, and systematic reviews have failed to demonstrate benefit from supplementation of individual nutrients, but it is almost certainly the case that a multifactorial condition such as RA requires a multifaceted approach to treatment rather than a nutrient monotherapy. It appears reasonable, safe, and at least hypothetically efficacious to address deficiencies of multiple nutrients simultaneously.
This is a key conceptual difference from conventional medicine, where typically a single drug is used to inhibit or poison an enzyme system to impair the production of inflammatory mediators or some other mechanism in the disease process. With natural medicine we are working to normalize the many dysfunctions that together result in the disease. Single natural therapies are rarely able to address all of a person’s physiological needs. A comprehensive approach that addresses all, or at least most, of the causes is always far more effective. Unfortunately, virtually all the research on nutrition is on single agents. Drawing on our decades of clinical experience, we can confidently tell you that the comprehensive natural medicine approach—combining diet, lifestyle, and supplementation—is far more effective than single agents. Nonetheless, since most of the research that is available addresses only single agents, we cover here specific nutrients that have been found to be deficient and/or beneficial in some clinical trials with RA.
Selenium and Vitamin E
These nutrients work together in reducing the production of inflammatory compounds and controlling free radical tissue damage. Clinical studies have not demonstrated improvement from selenium supplementation in RA; however, one clinical study did indicate that selenium combined with vitamin E had a positive effect.107,108 In another randomized, controlled trial, patients already diagnosed with RA who received 600 mg vitamin E twice a day showed significant pain reduction but no changes in clinical and biochemical indicators of inflammation.109 However, a review of five studies found no conclusive evidence of benefit from vitamin E or selenium supplementation alone.107 In order to be of benefit, both nutrients must be provided.
Zinc deficiency is common in RA patients, and it may predispose them to increased inflammation. Lower plasma zinc levels are associated with higher blood levels of inflammatory compounds.110 Zinc also has antioxidant effects and is a cofactor for the enzyme superoxide dismutase (SOD). Patients using corticosteroids may be at increased risk for zinc deficiency because these medications have been shown to decrease plasma zinc and increase loss of zinc in the urine.111 Several studies have demonstrated a slight therapeutic effect from zinc supplementation in RA patients.112–114
Manganese and Superoxide Dismutase
Manganese functions in the antioxidant enzyme superoxide dismutase (SOD), which prevents the damage caused by the toxic oxygen molecule known as superoxide. Manganese-containing SOD is deficient in patients with RA.115The injectable form of this enzyme has been shown to be effective in the treatment of RA;116 however, it has not been demonstrated that oral supplementation with SOD affects tissue SOD levels.117 What has been established is that oral manganese supplementation increases SOD activity.118 Although no clinical studies have been conducted to determine the effectiveness of manganese in the treatment of RA, it appears to be indicated on the basis of the low levels seen in patients with RA as well as its biochemical functions.
Vitamin C is an important antioxidant, but vitamin C concentrations in white blood cell and plasma are significantly decreased in patients with RA.119 Supplementation with vitamin C increases SOD activity, reduces histamine levels, and provides anti-inflammatory action.120,121 One intervention study with a Mediterranean diet showed a negative correlation between plasma vitamin C levels and RA disease activity,122 which was corroborated by another study that found higher vitamin C levels associated with lower markers of inflammation, such as CRP.123
Blood pantothenic acid levels have been reported to be lower in patients with RA than in normal controls and inversely correlated with disease activity.124 Correction of low pantothenic acid levels brings about some alleviation of RA symptoms. In one double-blind study, subjective improvement of RA symptoms was noted in patients receiving 2 g per day of calcium pantothenate.125 Patients noted improvements in duration of morning stiffness, degree of disability, and severity of pain.
Pyridoxine (Vitamin B6)
There is a clear relationship between low blood levels of vitamin B6 and inflammatory indicators of RA and more disability, pain, fatigue, and swollen joints.126 The low pyridoxine levels were attributed not to deficiency of intake but rather to ongoing chronic inflammatory processes using it up more quickly. Higher levels of homocysteine—a risk factor for heart disease—were also noted and correlated with low vitamin B6 status in RA patients.127
The wearing of copper bracelets has been a longtime folk remedy that appears to have some scientific support, as found in a double-blind study performed in Australia. Presumably, copper is absorbed through the skin and is chelated to another compound that is able to exert anti-inflammatory action.128 Copper is also utilized in SOD. Deficiency may result in significant susceptibility to free radical damage as a result of decreased SOD levels. However, an excessive intake of copper may be detrimental.129
Population-based studies indicate a significant association between vitamin D deficiency and an increased incidence of several autoimmune diseases, including RA.130 One study identified lower vitamin D levels and higher incidence of RA in northern European countries compared with southern European countries. In both northern and southern Europe, however, low 25(OH)-vitamin D levels were significantly correlated with worse RA symptoms.131
Pancreatic Enzymes and Hydrochloric Acid
Impaired digestion from inadequate secretion of pancreatic enzymes and/or of hydrochloric acid, which is common in RA patients, can be a major contributor to the disease process.132,133 In addition to poor assimilation of ingested nutrients, incompletely digested food molecules can be inappropriately absorbed, stimulating an immune response (i.e., food allergy). In one study, 80% of untreated RA patients had reduced gastric acid output.134 Gastric acid also plays a role in protecting against infection, and so individuals who produce insufficient hydrochloric acid may be predisposed to small-intestine bacterial overgrowth (SIBO). Half of RA patients who have inadequate hydrochloric acid secretion also have SIBO, and restoration of gastric pH can help resolve the overgrowth. For information on hydrochloric acid supplementation, see the chapter “Digestion and Elimination.”
Beyond their role in aiding digestion, pancreatic enzymes may offer additional benefits when taken between meals. Specifically, the protein-digesting enzymes (proteases) have been shown to reduce circulating levels of immune complexes in RA and other autoimmune diseases.135,136 Because clinical improvements usually correspond with decreases in immune complex levels, proteolytic enzyme supplementation is very important.
Probiotic supplementation can modulate the immune system in a positive manner, reduce inflammation, and reduce the growth of organisms linked to RA.137 One small-scale human trial of Lactobacillus rhamnosus GG did not show a clinical benefit; however, a recent study of Bacillus coagulans GBI-30, 6080 produced statistically significant improvement in pain scale compared with a placebo.138 Treatment also resulted in greater improvement in patient global assessment, self-assessed disability, CRP, ability to walk two miles, and participation in daily activities.139
Omega-3 Fatty Acids
Many published studies have documented the efficacy of fish oil supplementation in RA.140–147 Supplementation has been shown to be effective in decreasing long-term utilization of NSAIDs in these trials. A recent very detailed review concluded that there is convincing evidence of benefit in RA, including reduction of duration of morning stiffness, number of tender or swollen joints, joint pain, length of fatigue, and serum markers of inflammation.147Supplements may need to be consumed for at least 12 weeks at a minimum dose of 3 g per day combined EPA and DHA before effects are apparent. Furthermore, fish oil may further benefit RA patients by decreasing cardiovascular risk. It is important to select a product that has been rigorously tested for contaminants such as heavy metals, polychlorinated biphenyls (PCBs), dioxins, and lipid peroxides. Also, the benefits of omega-3 fatty acid supplementation are substantially enhanced when sources of arachidonic acid, including red meat and dairy products, are also significantly reduced.
Many botanicals possess significant anti-inflammatory action and are useful in the treatment of RA. The suggestions made here represent some of those with long historical use and stronger research support.
Curcumin, the yellow pigment of turmeric (Curcuma longa), exerts excellent anti-inflammatory and antioxidant effects and has been found to be as effective as cortisone or phenylbutazone in models of acute inflammation.148 In RA, one double-blind clinical trial compared curcumin (1,200 mg per day) with phenylbutazone (300 mg per day).149 The improvements in the duration of morning stiffness, walking time, and joint swelling were comparable in both groups. Furthermore, while phenylbutazone is associated with significant adverse effects, curcumin has not been shown to produce any side effects. It is noteworthy that curcumin has no direct pain-relieving effects, so the ability to reduce pain is the result of reducing the inflammatory factors that cause pain.
One concern regarding curcumin has been absorption, but there now exist a number of methods and products that enhance the absorption of curcumin. One of the first methods was using piperine, a compound found in black pepper.150 A more recent improved method is complexing the curcumin with soy phospholipids to produce a product sold under the name Meriva.151 Absorption studies of animals indicate that peak plasma levels of curcumin after administration of Meriva were five times higher than those after administration of regular curcumin. Studies with another advanced form of curcumin, Theracurmin, show even greater absorption (27 times greater than regular curcumin).152
Bromelain refers to a mixture of enzymes found in pineapple. Since 1957, more than 200 scientific papers have appeared in the research literature documenting a wide variety of beneficial effects, including reducing inflammation in RA.153,154 Much of its effect is due to activation of compounds that break down the inflammation-induced matrix of fibrin (a kind of internal scarring protein) that leads to inadequate tissue drainage and swelling. Bromelain also blocks the production of kinins, compounds produced during inflammation that increase swelling and cause pain. A protein-digesting enzyme product containing bromelain, papain (an enzyme from papaya), and trypsin and chymotrypsin (pancreatic enzymes from pigs) was shown to decrease excessive level of transforming growth factor (TGF),155 an inflammatory marker linked to the progression of joint destruction in RA.156
Ginger (Zingiber officinalis) contains antioxidants and exerts anti-inflammatory effects by inhibiting formation of a number of different inflammatory mediators. A preliminary clinical study was conducted with seven RA patients for whom conventional drugs had provided only temporary or partial relief.157 All patients were treated with ginger. One patient took 50 g per day of lightly cooked ginger, and the other six took either 5 g per day of fresh ginger or 0.1 to 1 g per day of powdered ginger. Despite the difference in dosage, all patients reported a substantial improvement, including pain relief, joint mobility, and a decrease in swelling and morning stiffness.
In the follow-up to this study, 28 patients with RA, 18 with osteoarthritis, and 10 with muscular discomfort who had been taking 500 to 4,000 mg powdered ginger for periods ranging from 3 to 30 months were evaluated.158 On the basis of clinical observations, it was reported that 75% of the patients with arthritis (either RA or osteoarthritis) and 100% of those with muscular discomfort experienced relief in pain or swelling and that the effects were dose-dependent.
Fresh ginger contains higher levels of gingerols and a protease that may have anti-inflammatory action similar to that of bromelain, and therefore may be more effective in the treatment of RA than dried preparations.159 Most studies have utilized 1 g powdered gingerroot, which is a relatively small dose compared with the average of 8 to 10 g consumed per day in India. A dose of 2 to 4 g powdered ginger per day is safe and may be effective in RA. This amount is roughly equivalent to 20 g fresh gingerroot, or a 1/2-inch slice. These amounts of ginger can easily be incorporated into the diet in fresh fruit and vegetable juices.
• Rheumatoid arthritis is an autoimmune reaction in which antibodies develop against components of joint tissues.
• RA is a classic example of a multifactorial disease, wherein an assortment of genetic, nutritional, and environmental factors contribute to the disease process.
• Standard medical therapy is of limited value in treating most cases of RA, as it fails to address the complex underlying causes of this disease.
• Diet has been strongly implicated in rheumatoid arthritis for many years, in regard to both cause and cure.
• Elimination of allergenic foods has been shown to offer significant benefit to some individuals with rheumatoid arthritis.
• Altered gastrointestinal tract flora have been linked to RA and other autoimmune diseases.
• A vegetarian diet has been shown to produce significant benefits in treating RA.
• In the dietary treatment of RA, the importance of consuming a diet rich in fresh fruits and vegetables cannot be overstated.
• Several natural anti-inflammatory compounds (e.g., curcumin, bromelain, and ginger) have shown positive effects in treating RA.
• Physical therapy (i.e., exercise, heat, cold, massage, diathermy, lasers, and paraffin baths) has a major role in the management of RA.
Exercise can improve strength and performance while maintaining range of motion in RA patients. Furthermore, it decreases cardiovascular risk, RA disease activity, and systemic inflammation.160 Patients with well-developed disease should begin with progressive, passive range-of-motion and isometric exercises, gradually introducing active range-of-motion and isotonic exercises as appropriate. One randomized, controlled trial studied the effects of high-intensity exercise in more than 300 patients with RA. Participants were given either standard physical therapy or a high-intensity exercise program for two years. While there was no X-ray evidence of increased damage to the large joints, except possibly in those patients who had considerable baseline damage, high-intensity exercise improved functionality and mood and provided a sense of well-being.161
Heat is typically used to help relieve stiffness and pain, relax muscles, and increase range of motion. Moist heat (e.g., moist packs, hot baths) is more effective than dry heat (e.g., a heating pad), and paraffin baths are used if skin irritation from regular water immersion develops. Cold packs are of value during acute inflammatory flare-ups or following hot applications.
Optimistic patients with RA report better psychosocial and physical functioning than pessimistic patients who adopt passive coping strategies such as staying in bed for many hours a day. Patients who believe they have a high ability to control and decrease pain by utilizing spiritual or religious coping methods tend to have less joint pain and fewer negative moods and are much more likely to have higher levels of general social support.162 Positive support from a spouse or family is inversely related to depression and can significantly enhance quality of life.163
Rheumatoid arthritis is often an aggressive disease that needs aggressive treatment. In mild to moderate RA, the measures below are extremely effective. Foremost is the use of diet to reduce the causes and ameliorate the symptoms of RA. Symptom relief can also be attained through the use of nutritional supplements, botanical medicines, and physical medicine techniques. In severe cases, drug therapy may be necessary, at least in the acute phase. However, do not abandon natural measures, because they will actually enhance the effectiveness of the drugs, allowing for lower dosages when drugs are necessary, while providing a foundation for healing by addressing the underlying causative factors and utilizing modalities that are both safe and beneficial in long-term use.
The first step is a therapeutic fast or elimination diet, followed by careful reintroduction of individual foods to detect those that trigger symptoms. Although any food can cause a reaction, the most common are wheat, corn, dairy products, beef, foods in the nightshade family (tomatoes, potatoes, eggplant, peppers), pork, citrus, oats, rye, egg, coffee, peanuts, cane sugar, lamb, and soy.
After all allergens have been isolated and eliminated, a vegetarian or Mediterranean-style diet rich in organic whole foods, vegetables, cold-water fish (mackerel, herring, sardines, and salmon), olive oil, and berries and low in sugar, meat, refined carbohydrates, and animal fats is indicated. The recommendations in the chapter “A Health-Promoting Diet” are appropriate in the long-term support of RA.
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Key individual nutrients:
Vitamin B6: 25 to 50 mg per day
Vitamin C: 500 to 1,000 mg per day
Vitamin E (mixed tocopherols): 200 to 400 IU per day
Vitamin D3: 2,000 to 4,000 IU per day
Selenium: 100 to 200 mcg per day
Zinc: 15 to 30 mg per day
Manganese: 1.5 to 2 mg per day
• Fish oils: 3,000 mg EPA + DHA per day
• One of the following:
Grape seed extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 100 to 300 mg per day
Some other flavonoid-rich extract with a similar flavonoid content, super greens formula, or another plant-based antioxidant that can provide an oxygen radical absorption capacity (ORAC) of 3,000 to 6,000 units or more per day
• Probiotic (Lactobacillus species and Bifidobacterium species): a minimum of 5 billion to 10 billion colony-forming units
• One of the following:
Pancreatin (10X USP): 350 to 750 mg between meals three times per day or
Bromelain: 250 to 750 mg (1,800 to 2,000 MCU) between meals three times per day
• One of the following:
Meriva: 500 to 1,000 mg twice daily
BCM95 Complex: 750 to 1,500 mg twice daily
Theracurmin: 300 mg one to three times daily
• Ginger: 8 to 10 g dried powdered ginger daily; or ginger extract (standardized to contain 20% gingerol and shogaol) 100 to 200 mg three times per day
Physical therapy (i.e., exercise, heat, cold, massage, diathermy, lasers, and paraffin baths) has a major role in the management of RA.
• Heat (moist packs, hot baths, etc.): 20 to 30 minutes one to three times per day
• Cold packs for acute flare-ups or following heat
Improving digestion with hydrochloric acid supplementation may be useful. Positive results from other tests may indicate that DHEA, testosterone, and treatment for intestinal permeability, dysbiosis, and environmental toxicity are advisable.