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Rheumatoid Arthritis

Rheumatoid Arthritis

Description

Rheumatoid arthritis (RA) is a chronic inflammatory condition that affects the entire body, including the synovial membranes of the joints. The joints typically involved are the hands, feet, wrists, ankles and knees. Somewhere between 1% and 3% of the population are affected; female patients outnumber males almost 3:1. The usual age of onset is 20-40 years, although rheumatoid arthritis may begin at any age.

Standard medical treatment of RA involves the use of physical therapy along with drugs. Physical therapy includes exercise, heat, cold, massage and the use of special physical therapy equipment such as diathermy, lasers and paraffin baths.

The first drug generally employed is aspirin. It is often quite effective in relieving both the pain and inflammation. It is also relatively inexpensive. However, since the therapeutic dose required is relatively high, toxicity often occurs. Tinnitus (ringing in the ears) and gastric irritation are early manifestations of toxicity. Other NSAID (nonsteroidal anti-inflammatory drugs) are often used as well, especially when aspirin is ineffective or is intolerable. While more expensive, none of these drugs have demonstrated superior efficacy to aspirin. In addition, these drugs are also associated with side effects including gastrointestinal upset, headaches and dizziness.

If conservative therapy does not offer benefit, more aggressive and potentially more toxic treatments are available. Gold salt injection aids about 60% of patients but severe side effects occur in nearly one third of them. Other powerful drugs are used, including d-penicillamine and hydroxychloroquine, but benefit often does not substantiate toxicity. Corticosteroids are also used during acute worsenings of the disease but long-term use of them for RA is not advised due to the side effects. Joint surgery and joint replacement are reserved for the most severe cases.





Causes

There is abundant evidence that rheumatoid arthritis is an "autoimmune" reaction, where antibodies develop against components of joint tissues. Yet what triggers this autoimmune reaction remains largely unknown. Speculation and investigation is centered around genetic susceptibility, lifestyle factors, nutritional factors, food allergies and microorganisms.

An interesting association between rheumatoid arthritis and abnormal bowel function exists that may provide a unified theory as to the cause of RA. What is currently known is that individuals with RA have increased intestinal permeability to dietary and bacterial antigens as well as alterations in bacterial flora. This altered permeability and bacterial flora could result in the absorption of antigens that are very similar to antigens in joint tissues. Antibodies formed to bind these antigens would "cross-react" with the antigens in the joint tissues. Increasing evidence appears to support this concept.




Signs & Symptoms

The onset of rhematoid arthritis is usually gradual, but occasionally it is quite abrupt. The appearance of primary symptoms may precede the appearance of secondary symptoms by several weeks.

Early Symptoms

FatigueLow-grade fever
WeaknessJoint stiffness
Vague joint pain



Late Symptoms
Painful, warm, tender, swollen joints
Ruddy, purplish-blue color of skin over the affected joint(s)
Deformed joints

Several joints are usually involved in the onset, typically in a symmetrical fashion (i.e. both hands, both wrists, both ankles, etc.).

In about 1/3 of the cases of RA, initial involvement is confined to one or a few joints.

There are a variety of abnormal laboratory findings in RA, including elevated erythrocyte sedimentation rate (characteristic of inflammatory conditions), anemia, serum protein abnormalities, and antibodies to altered immunoglobulins. X-ray findings usually show soft tissue swelling, erosion of cartilage and joint space narrowing.









Nutritional Supplements

Structure & Function:
        Joint Support
        Immune System Support &
        Antioxidants


---------------------------------
General Supplements
---------------------------------

Betaine HCL400 mg. with meals
Copper1 mg./day
DHEA*
DLPA*
Fish oils1.8 grams/day
Glucosamine sulfate*
Manganese15 mg./day
Pantothenic acid*
Quercetin250 mg. between meals, t.i.d.
Selenium200 mcg./day
Vitamin C1-3 grams/day in divided doses
Vitamin E400 I.U./day
Zinc45 mg./day



* Please refer to the respective topic for specific nutrient amounts.

Betaine HCL

Many individuals with RA are deficient in stomach acid and other digestive factors. Supplementation with betaine HCL with meals will aid in protein digestion and possibly reduce food sensitivities through improved digestion.

Bromelain

The proteolytic enzyme of the pineapple, bromelain, has been demonstrated to be an effective anti-inflammatory agent in both clinical studies and experimental models. Its major effect is to reduce swelling. For best results, bromelain should be taken between meals.

Copper

Copper aspirinate (salicylate) is a form of aspirin that yields better results in reducing pain and inflammation than standard aspirin preparations. These copper containing substances may be indicated in patients with RA requiring aspirin.

The wearing of copper bracelets has been an old folk remedy which appears to have some scientific support as a double-blind study performed in Australia. Presumably, copper is absorbed through the skin and chelated to another compound which is able to exert anti-inflammatory action. Copper is a component, along with zinc, in copper-zinc SOD (one type of superoxide dismutase). Deficiency may result in significant susecptibility to free-radical damage as a result of decreased SOD levels. However, an excess intake of copper may be detrimental due to copper's ability to combine with peroxides and damage joint tissues.

DLPA

DLPA is a mixture of the natural form of phenylalanine (the L- form) with its mirror image (the D- form). The D-form has been shown to be an effective pain reliever against the chronic pain of osteoarthritis, RA, low back pain and migraine headaches. Its mode of action appears to be inhibiting the breakdown of endorphins, thereby increasing the effect of these components of the body's own pain relieving system. Endorphins are morphine-like compounds acting as mild mood elevators and potent pain relievers.


Fish oils / EPA

In a double-blind study of patients with rheumatoid arthritis, it was shown that a diet rich in polyunsaturated fats and low in saturated fat supplemented daily with 1.8 grams of eicosapentaenoic acid (EPA) brought about significant improvement. Prostaglandins and leukotrienes formed from EPA are significantly less inflammatory than those prostaglandins and leukotrienes formed from arachidonic acid. Supplementing the diet with EPA appears warranted in the treatment of RA and other inflammatory conditions.


Manganese

Manganese also functions in the antioxidant enzyme superoxide dismutase (manganese SOD), which is deficient in patients with RA. Manganese supplementation has been shown to increase SOD activity, indicating increased antioxidant activity. No trials have yet been done with manganese and RA, but supplementation appears to be indicated.


Quercetin

The bioflavonoid quercetin has demonstrated several effects in experimental studies indicating it may be beneficial to individuals with RA. Specifically, quercetin inhibits the release of histamine and the production of the potent inflammatory compounds, the leukotrienes. For best results, quercetin should be taken with bromelain between meals. Bromelain is believed to enhance the absorption of quercetin, as it does medications.


Selenium

Serum selenium levels are low in patients with RA. This may be a significant factor, as selenium plays a valuable role as an antioxidant and serves as the mineral cofactor in the free-radical scavenging enzyme glutathione peroxidase.

Selenium is also important in reducing the production of inflammatory prostaglandins and leukotrienes. Free radicals, oxidants, prostaglandins and leukotrienes cause much of the damage to tissues seen in RA. A deficiency of selenium would result in even more significant damage. Clinical studies have not yet clearly demonstrated that selenium supplementation alone improves the signs and symptoms of RA; however, one clinical study indicated that selenium, combined with vitamin E had a positive effect.

Supplementation appears to be appropriate due to increased demand for selenium in RA and selenium's synergistic effect with other antioxidant mechanisms.


Superoxide Dismutase

This antioxidant enzyme protects cells and tissues from free-radical damage. The injectable form of this enzyme (available in Europe) has been shown to be effective in the treatment of RA and osteoarthritis; however, it is not clear if any orally administered SOD can escape digestion in the intestinal tract and exert a therapeutic effect. In one study, oral SOD was not shown to affect tissue SOD levels.


Vitamin C

Vitamin C functions as an important antioxidant. Supplementation with Vitamin C increases SOD activity, decreases histamine levels and provides anti-inflammatory action.


Vitamin E

Vitamin E is an important antioxidant, working synergistically with glutathione peroxidase and other antioxidant enzymes (catalase, superoxide dismutase). Vitamin E also has slight anti-inflammatory action due to its effect on prostaglandin and leukotriene synthesis. Vitamin E combined with selenium supplementation has been shown to improve RA.


Zinc

Zinc is also an antioxidant and functions in the antioxidant enzyme superoxide dismutase (copper-zinc SOD). Zinc levels are typically reduced in patients with RA and several studies have been done using zinc sulfate in the treatment of RA, with some of the studies demonstrating a slight therapeutic effect. For these reasons, zinc supplementation appears to be indicated for individuals suffering from RA.


Note: All amounts are in addition to those supplements having a Recommended Dietary Allowance (RDA). Due to individual needs, one must always be aware of a possible undetermined effect when taking nutritional supplements. If any disturbances from the use of a particular supplement should occur, stop its use immediately and seek the care of a qualified health care professional.


Nutrient Depletion

Arthritis medications may rob your body of important nutrients, including:

Vitamin C NSAID drug therapy (including aspirin) can cause urinary excretion of vitamin C. This important vitamin is essential for maintaining connective tissue and synthesizing collagen, a protein and primary constituent of connective tissue. It also plays a role in the body's healing process by enhancing the immune system and aiding in the prevention of infections. Low levels of vitamin C are common in sufferers of rheumatoid arthritis (RA).

Calcium Corticosteroids can reduce dietary calcium, vital for nerve, muscle, and bone functioning. Reduced levels can increase the risk of osteoporosis. Low levels of calcium might cause aching joints, muscle cramps, extremity numbness, and is a common deficiency in R-A sufferers.

Vitamin E This antioxidant is essential in protecting the body's cellular membranes and aiding in the body's healing process.

Zinc Low serum levels of zinc are common in people taking corticosteroid medication and in those suffering from RA. This key mineral in the body is a constituent in the enzyme synthesis of collagen.

Arthritis medications may also affect the levels of Vitamin D, Folic Acid, & Selenium.

References:

Mahan, K. & Escott-Stump, S: Krause's Food, Nutrition and Diet Therapy. Saunders, 1996.

Drug Interactions

Drugs are the primary allopathic therapy to control the pain and inflammation associated with osteoarthritis and, more especially, rheumatoid Arthritis.

Most of the drugs diminish the production of prostaglandins, produced by the inflammatory process. [Vitamin E is a natural prostaglandin inhibitor.]

Today, the first line of attack comprises NSAIDs (Nonsteroidal anti-inflammatory drugs) including salicylates. More exotic drugs may also be resorted to in desperation: antimalarial agents, gold salts, penicillamine, steroids and immunosuppressive agents.

Side effects frequently include nutritional status.

Aspirin, for example, increases urinary excretion of vitamin C. Decreased vitamin status with respect to vitamin C as well as folate have been noted. There may also be extensive bleeding both with salicylates and other NSAIDs. An associated condition is anemia.

Methotrexate and Sulfasalazine (both used as NSAIDs) are associated with the greatest losses of folate and these drugs should be accompanied with daily supplements of folate.

Corticosteroids are the most potent drugs but are mostly reserved for the worst cases as the side-effects are so severe. Nutritionally, they can produce a negative nitrogen balance, so that protein is lost and muscle tissues waste away. There is also reduced calcium absorption, so that bones become soft and weak.

Penicillamine (like gold salts) may both cause proteinuria but with penicillamine there may also be depletion of minerals: zinc, copper and iron.

Dietary Considerations

Diet has been strongly implicated with many forms of arthritis for many years, both in regards to cause and cure. Various practitioners have recommended all sorts of specific diets for arthritis. In general, since rheumatoid arthritis is not found in societies that eat a more primitive diet and is found at a relatively high rate in societies consuming the so-called "Western" diet, a general healthful diet rich in whole foods, vegetables, fiber and low in sugar, meat, refined carbohydrates and saturated fat appears to be indicated in the prevention and possibly the treatment of RA. In addition, there appears to be strong, scientific support for the roles that food allergies and dietary fats play in the inflammatory process.

Food Allergies
Elimination of allergenic foods has been shown to offer significant benefit to some individuals with RA. An Elimination Diet or Hypoallergenic Diet followed by systematic reintroduction of possible allergenic foods is often an effective method of isolating offending foods. Virtually any food can result in aggravating RA, but the most common offending foods are wheat, corn, milk and other dairy products (see Allergy Free Cooking), beef and foods from the Nightshade Family (tomatoes, potatoes, eggplants, peppers and tobacco).

Dietary Fats
Fatty acids are important mediators of inflammation through their ability to form prostaglandins, thromboxanes and leukotrienes. Manipulation of dietary oil intake can significantly increase or decrease inflammation, depending on the type of oil being increased. Arachidonic acid is a fatty acid derived almost entirely from animal sources (meat, dairy products, etc.). It contributes greatly to the inflammatory process through its conversion to inflmmatory prostaglandins and leukotrienes. The Vegetarian Diet is often beneficial in the treatment of inflammatory conditions, presumably as a result of decreasing the availability of arachidonic acid for conversion to the products.

Another important way of decreasing the inflammatory response is the consumption of cold-water fish such as mackerel, herring, sardines and salmon. They are rich sources of eicosapentaenoic acid (EPA) which competes with arachidonic acid for prostaglandin and leukotriene production. The net effect of consumption of these fish is a significantly reduced inflammatory/allergic response.

In a double-blind study of patients with RA, it was shown a diet rich in polyunsaturated fats and low in saturated fats supplemented daily with 1.8 grams of eicosapentaenoic acid brought about significant improvement. Supplementation may not be necessary if a serving of one of these cold-water fish was consumed at least once daily.

In another study, individuals with arthritis who supplemented their diets with cod liver oil showed major clinical improvement. Cod liver oil may be a less expensive way of administering EPA.

Fasting
Patients with RA have benefitted from fasting, however it is not advised that an individual begin such a regimen without direct medical supervision. Fasting presumably decreases the absorption of allergenic food components.



Homeopathic Remedy

1.* Rhus Toxicodendron - 30C to 10M use chronically.
2.* Rhododendron - 6X to 15C.
3.* Elaterium - 15C especially gouty arthritis and arthritic nodules.
4. Arbutus andrachne - 3X to 15C better on larger joints.
5.* Bryonia alba tinct. - 12X to 15C especially with swelling, knees, feet.
6.**Apocynum androsaemifolium - 200X to 30C use when all joints hurt, swelling in feet, hot feet.

Rheumatism, chronic

1. Icthyolum - 15C
2. Rhododendron - 30C
3. Rhus Toxicodendron - 30C

Treatment Schedule

Doses cited are to be administered on a 3X daily schedule, unless otherwise indicated. Dose usually continued for 2 weeks. Liquid preparations usually use 8-10 drops per dose. Solid preps are usually 3 pellets per dose. Children use 1/2 dose.

Legend
X = 1 to 10 dilution - weak (triturition)
C = 1 to 100 dilution - weak (potency)
M = 1 to 1 million dilution (very strong)
X or C underlined means it is most useful potency

Asterisk (*) = Primary remedy. Means most necessary remedy. There may be more than one remedy - if so, use all of them.


References

Boericke, D.E., 1988. Homeopathic Materia Medica.

Coulter, C.R., 1986. Portraits of Homeopathic Medicines.

Kent, J.T., 1989. Repertory of the Homeopathic Materia Medica.

Koehler, G., 1989. Handbook of Homeopathy.

Shingale, J.N., 1992. Bedside Prescriber.

Smith, Trevor, 1989. Homeopathic Medicine.

Ullman, Dana, 1991. The One Minute (or so) Healer.

Tissue Salts

Calc. Fluor.enlarged joints;
Calc. Phos.stiff, numb joints, worse at night and in bad weather;
Mag. Phos.sharp pain, relieved by warmth;
Nat. Mur.joint pains, worse at night and in bad weather;
Nat. Phos.principal remedy: sour perspiration, acidosis;
Siliceashoulder pains, worse at night and from warm covering;


Herbal Approaches

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Herbs
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Blueberries (Bilberry), cherries and hawthorn berries
Curcumin
Devil's Claw
Feverfew
Ginger Plant
Licorice Root
White Willow Bark

German Commission E recommends a number of essential oils:

Cajeput essence
Camphor essence
Eucalyptus essence
Pine essence (external)
Terebinth essence

Note: The misdirected use of an herb can produce severely adverse effects, especially in combination with prescription drugs. This Herbal information is for educational purposes and is not intended as a replacement for medical advice.

Discussion:

Many herbs possess significant anti-inflammatory action and would be appropriate in the treatment of rhematoid arthritis. Some of the more effective herbs in the treatment of RA are discussed herein:

Blueberries, Cherries and Hawthorn Berries
These berries are rich sources of flavonoid molecules, particularly proanthocyanidins, the flavonoids giving them their deep red/blue color. These flavonoids exhibit membrane and collagen stabilizing, antioxidant, anti-inflammatory actions as well as many other actions very beneficial in the treatment of RA. These berries or extracts of them should be consumed.

Curcumin

Curcumin, the yellow pigment of Curcuma longa, and crude extracts of Curcuma longa have demonstrated significant anti-inflammatory activity in a variety of experimental models. Its effects in these models were comparable to cortisone and the drug phenylbutazone. It appears curcumin "sensitizes" or primes cortisol receptor sites, thereby potentiating cortisol action. Curcumin is more effective in acute inflammation, having little effect in chronic inflammation.

Devil's Claw

Devil's claw has been advocated in the treatment of a variety of diseases, including rheumatoid arthritis. Several pharmacological studies in animals and clinical trials in human beings have reported that devil's claw possesses an anti-inflammatory and analgesic effect comparable to the potent drug phenylbutazone. Other studies have indicated Devil's claw has little anti-inflammatory activity. In addition to relieving joint pain in the positive clinical trials, serum cholesterol and uric acid were reduced.

Feverfew

As feverfew has a long folk history in the treatment of fever, arthritis, and migraine, it would be only natural to assume that feverfew acts in a similar fashion as aspirin. Researchers have actually shown extracts of feverfew to have greater activity in inhibiting inflammation and fever than aspirin in experimental studies. They have specifically shown feverfew extracts to inhibit the synthesis of many pro-inflammatory compounds at their initial stage of synthesis. In addition, feverfew also decreases the secretion of inflammatory response. These experimental studies provide insight to the exact healing effect of feverfew in the treatment of arthritis.

Ginger

Common ginger exerts a greater effect on inhibiting the production of inflammatory compounds than the potent prescription drug indomethacin. Ginger has also been shown to possess pain-relieving and antioxidant activity. Including liberal amounts of ginger in the diet appears to offer some benefit to individuals with RA based on experimental evidence.

Licorice

Licorice has a long history of folk use in the treatment of many inflammatory conditions including RA. Much of its activity relates to its ability to increase the action of the adrenal hormone cortisol along with its direct effect on many key areas of inflammation.

Mistletoe is uniquely recommended by the German Commission E for use in degenrative joint inflammation.

White Willow Bark

The barks of trees in the willow and poplar families have been used since antiquity in the treatment of pain throughout the world. Their activity in relieving pain and inflammation is due to the high content of natural salicylates or aspirin-like molecules. The common white willow has a long folk history in the treatment of arthritis and also has a very high content of salicylates.

References:

Blumenthal, M (Ed.): The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. American Botanical Council. Austin, TX. 1998.

Aromatherapy - Essential Oils

Some oils that are beneficial for osteoarthritis are contraindicated for rheumatoid arthritis, which is an auto-immune disorder and some of the recommended oils actually stimulate the immune system.

Coriander Essence,Cypress Essence,
Ginger Essence,Juniper Essence,
Lavender Essence,Marjoram Essence,
Pine Essence.



Related Health Conditions

AcromegalyAging
AnemiaAnorexia
BursitisDiabetes mellitus
FatigueFever
GoutInfection
InjuryOchronosis
OsteoarthritisPain
Rheumatoid arthritis

Abstracts

References

Amella, M et. al., Inhibition of mast cell histamine release by flavonoids and bioflavonoids. Planta Medica 51:16-20, 185.

Arlington, LG et al., Placebo-controlled, blind study of dietary manipulation therapy in rheumatoid arthritis. Lancet i:236-8, 1986.

Arora, R., N. Basu, N. Kapoor & A. Jain: Anti-inflammatory studies on Curcuma longa (turmeric). Ind J Med Res 59: 1289-95, 1971.

Aruoma OI: Nutrition and health aspects of free radicals and antioxidants [published erratum appears in Food Chem Toxicol 1994 Dec;32(12):1185. Food Chem Toxicol, 1994 Jul, 32:7, 671-83.

Balogh, Z. et al: Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis. Ann. Rheum. Dis. 1980, 39(4): 329-332.

Barton-Wright, E.C. & Elliott, W.A.: The pantothenic acid metabolism of rheumatoid arthritis. Lancet, 1963, 2: 862-863.

Belch, J.J. et al: Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann. Rheum. Dis. 1986, 47(2): 96-104.

Bingham, R. et al: Yucca plant saponin in the management of arthritis. J. App. Nutr. 1975, 27: 45-50.

Blankenhorn, G.: Vitamin E: clinical research from Europe. Nutr. Dietary Consult. 1988 (June).

Bonica J., U. Lindblom & A. Iggo. eds. Advances in Pain Research and Therapy, volume 5. Raven Press, New York, NY 1983.

Bruch, C. A. & E. T. Johnson. A new dietary regimen for arthritis, value of cod liver oil on a fasting stomach. Journal of the National Medical Association 51: 266-70, 1959.

Capasso, F. The effect of an aqueous extract of Tanacetum parthenium L. on arachidonic acid metabolism by rat peritoneal leucocytes. Journal of Pharmacy and Pharmacology 38: 71-2, 1986.

Chung, M.H., L. Kessner & P.C. Chan. Degradation of articular cartilage by copper and hydrogen peroxide. Agents and Actions 15: 328-35, 1984.

Cleland, L.G. et al: Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J. Rheum. 1988, 15(10): 1,471-1,475.

Cohen, A. & J. Goldman. Bromelain's therapy in rheumatoid arthritis. Pennsylvania Medical Journal 67: 27-30, 1964.

Cotzias, G.C. et al: Slow turnover of manganese in active rheumatoid arthritis and acceleration by prednisone. J. Clin. Invest. 1968, 47: 992.

Cyong, J. A pharmacological study of the anti-inflammatory activity of chinese herbs. A review. Intnl J. of Acupuncture and Electro-Ther. Res. 7: 173-202, 1982.

De Witte, T.J., P.J. Geerdink, C.B. Lamers, et. al. Hypochlorhydria and hypergastrinemia in rheumatoid arthritis. Ann. Rheum. Dis. 38: 14-7, 1979.

Duke, J.A. Handbook of Medicinal Herbs. CRC Press, Boca Raton, FL, 1985.

Editorial: Fish oils in rheumatoid arthritis. Lancet, 1987, ii: 720-721.

Editorial: Gold therapy in rheumatoid arthritis. Lancet, 1991, 338: 19-20.

Gabor, M. Pharmacologic effects of flavonoids on blood vessels. Angiologica 9: 355-74, 1972.

Gerster H: The use of n-3 PUFAs (fish oil) in enteral nutrition. Int J Vitam Nutr Res, 1995, 65:1, 3-20.

Ghatak, N. & N. Basu. Sodium curcuminate as an effective anti-inflammatory agent. Ind J Exp Biol 10: 235-6, 1972.

Gibson, R.G. et al: Green-lipped mussel extract in arthritis. Lancet, 1981, i:439. (Letter)

Gilman, AG et al., The Pharmacological Basis of Therapeutics, 6th edition. Macmillan Publishing, New York, NY, 1980.

Giordano, N.: The Role of Iron, Vitamin B12, Folic Acid and Erythropoietin in the Anemia of Rheumatoid Arthritis. Clinical and Experimental Rheumatology, 1992;10:201-202.

Gordon, C.: Abnormal sulfur oxidation in systemic lupus eryhtematosus. Lancet, 1992, 339: 25-26.

Hansen, T.M. et al: Treatment of RA with prostaglandin E1 precursors cis-linoleic and gamma-linolenic acid. Scand. J. Rheum. 1983, 12: 85-88.

Hansen, T.M. & Hansen, N.E.: Serum ferritin as an indicator of iron responsive anemia in patients with rheumatoid arthritis. Ann. Rheum. Dis. 1986, 45:569.

Havsteen, B. Flavonoids, a class of natural products of high pharmacological potency. Biochemical Pharmacology 32: 1141-8, 1983.

Henricksson, KK et al., Gastrin, gastric acid secretion, and gastric microflora in patients with rheumatoid arthritis. Ann. Rheum. Dis. 45: 475-83, 1986.

Heptinstall S.et al., Extracts of feverfew inhibit granule secretion in blood platelets and polymorpho-nuclear leucocytes. Lancet I: 1071-4, 1985.

Hernandez-Beriain JA et al., Undernutrition in rheumatoid arthritis patients with disability. Scand J Rheumatol, 1996, 25:6, 383-7.

Hicklin, J.A., L.M. McEwenn & J.E. Morgan. The effect of diet in rheumatoid arthritis. Clinical allergy 10:463-7, 1980.

Hikino, H. Recent research on Oriental medicinal plants. Economic Medicinal Plant Research 1: 53-86, 1985.

Honkanen, V. et al: Vitamins A and E, retinol binding protein and zinc in rheumatoid arthritis. Clin. Exp. Rheumatol. 1989, 7: 465-469.

Honkanen, V. et al: Serum cholesterol and vitamins A and E in juvenile chronic arthritis. Clin. Exp. Rheum. 1990, 8: 187-191.

Honkanen, V. et al: Plasma zinc and copper concentrations in rheumatoid arthritis: Am. J. Clin. Nutr. 1991, 54: 1,082-1,086.

Jacobsson, I. et al: Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis. Ann. Rheum. Dis. 1990, 49: 901-905.

Kjeldsen-Kragh J et al., Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet [published erratum appears in Clin Rheumatol 1994 Dec;13(4):649]. Clin Rheumatol, 1994 Sep, 13:3, 475-82.

Kremer, J et al., Effects of manipulation of dietary fatty acids on clinical manifestation of rheumatoid arthritis. Lancet I:184-7, 1985.

Kroker, GP et al., Fasting and rheumatoid arthritis, a multicenter study. Clinical Ecology 2: 137-44, 1984.

Krupp, M.A. & M.J. Chatton. Current Medical Treatment and Diagnosis. Lange Medical Publications, 1982 pp 487-91.

Kuhnau, J. The flavonoids. A class of semi-essential food components: Their role in human nutrition. World Review Nutrition and Dietetics 24: 117-191, 1976.

Lee, T.H. & J.P. Arm. Prospects for modifying the allergic response by fish oil diets. Clinical Allergy 16: 89-100, 1986.

Leung, A.Y. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. John Wiley & Sons, New York, NY 1980.

Leuti, M. & M. Vignali. Influence of bromelain on penetration of antibiotics in uterus, slapinx and ovary. Drugs Under Experimental and Clinical Research.

Leventhal, L. J. et al. : Treatment of Rheumatoid Arthritis With Gamma-Linolenic Acid. Annals of Internal Medicine, November 1, 1993;119(9):867-873.

Levine, M. New concepts in the biology and biochemistry of ascorbic acid. New England Journal of Medicine 314: 892-902, 1986.

Lewis, A.J. The role of copper in inflammatory disorders. Agents and Actions 513-9, 1984.

Lindahl, O et al., Vegan diet regimen with reduced medication in the treatment of bronchial asthma. Journal of Asthma, 22: 45-55, 1985.

Lucas, P. & L. Power. Dietary fat aggravates active rheumatoid arthritis. Clinical Research 29: 754A, 1981.

Makheja, A. M. & J. M. Bailey. A platelet phospholipase inhibitor from the medicinal herb feverfew. Prost. Leuk. & Med. 8: 653-60, 1982.

Mattingly, P.C. & A.G. Mowat. Zinc sulphate in rheumatoid arthritis. Annals of the Rheumatic Diseases 41: 456-7, 1982.

McAdam, P.: Chicken Cartilage Assessed in Rheumatoid Arthritis. Medical Tribune, November 4, 1993;8.

McLeod, D.W et al., Investigations of Harpagophytum procumbens (Devil's claw) in the treatment of experimental inflammation and arthritis in the rat. British Journal of Pharmacology 66: 140P-141P, 1979.

Menander-Huber, K.B. Orgotein in the treatment of rheumatoid arthritis. European Journal of Rheumatology and Inflammation 4: 201-11, 1981.

Middleton, E. The flavonoids. Trends in Pharmaceutical Science 5: 335-8, 1984.

Morgan, S. L et al. : Folate Supplementation and Methotrexate. Annals of Rheumatic Diseases, 1993;52:315-316.

Mukhopadhyay, A et al., Gujral. Anti-inflammatory and irritant activities of curcumin analogues in rats. Agents Actions 12: 508-15, 1982.

Mullen, A. & Wilson, C.W.M.: The metabolism of ascorbic acid in rheumatoid arthritis. Proc. Nutr. Sci. 1976, 35: 8A-9A.

Newnham, R.E.: Boron beats arthritis. Proc. ANZAS. 1979.

Oldroyd, K.G. & Dawes,P.T.: Clinically significant vitamin C deficiency in rheumatoid arthritis. Br. J. Rheum. 1985, 24: 362-363.

Orange, LM: The High Cost of Managing NSAID-Induced Ulcers. Family Practice News, January 1, 1993;16.

Pandley, S.P et al., Zinc in rheumatoid arthritis. Indian Journal of Medical Research 81: 618-20, 1985.

Panganamala, R.V. & D.G. Cornwell. The effects of vitamin E on arachidonic acid metabolism. Annals of the New York Academy of Sciences 393: 376-91, 1982.

Panush, R.S. et al: Diet therapy for rheumatoid arthritis. Arthritis Rheum. 1984, 26: 462-471.

Panush, R.S. Delayed reactions to foods. Food allergy and rheumatic disease. Annals of Allergy 56: 500-3, 1986.

Pasquier, C et.al., Manganese-containing superoxide-dismutase deficiency in polymorphonuclear leukocytes of adults with RA. Inflammation 8: 27-32, 1984.

Peretz, A. et al., Zinc Distribution in Blood Components, Inflammatory Status, and Clinical Indexes of Disease Activity During Zinc Supplementation in Inflammatory in Rheumatic Diseases. Am. J. of Clinical Nutrition, 1993;57:690-4.

Pinals, R.S. et al: Treatment of rheumatoid arthritis with L-histadine: a randomized placebo controlled, double-blind trial. J. Rheum. 1977, 4(4): 414-419.

Prudden, J.F. & Balassa, L.L.: The biological activity of bovine cartilage preparations. Semin. Arth. Rheum. 1974, 3(4): 287-321.

Purdy KS et al., You are what you eat: healthy food choices, nutrition, and the child with juvenile rheumatoid arthritis. Pediatr Nurs, 1996 Sep-Oct, 22:5, 391-8.

Rall LC et al., The effect of progressive resistance training in rheumatoid arthritis. Increased strength without changes in energy balance or body composition. Arthritis Rheum, 1996 Mar, 39:3, 415-26.

Rall LC et al., Effects of progressive resistance training on immune response in aging and chronic inflammation. Med Sci Sports Exerc, 1996 Nov, 28:11, 1356-65.

Rawley, D.A. & Halliwell, B.: Formation of hydroxyl radicals from hydrogen peroxide and iron salts by superoxide and ascorbate dependent mechanisms: relevance to the pathology of rheumatoid arthritis. Clin. Sci. 1983, 64: 649-653.

Report (General Practitioner Research Group): Calcium pantothenate in arthritic conditions. Practitioner, 1980, 224: 208-211.

Roberts, P. et al: Vitamin C and inflammation. Med. Biol. 1984, 62:88.

Rosa, G.D., C.L. Keen, R.M. Leach & L.S. Hurley. Regulation of superoxide dismutase activity by dietary manganese. Jrnal of Nutrition 110: 795-804, 1980.

Rothwell, R.S. & Davis, P.: Relationship between serrum ferritin, anemia and disease activity in acute and chronic RA. Rheum. Int. 1981, 1(2): 65-67.

Roubenoff R et al., Abnormal homocysteine metabolism in rheumatoid arthritis. Arthritis Rheum, 1997 Apr, 40:4, 718-22.

Ryan S: Nutrition and the rheumatoid patient. Br J Nurs, 1995 Feb 9-22, 4:3, 132-6.

Sahud, M.A. & Cohen, R.J.: Effect of aspirin ingestion on ascorbic-acid levels in rheumatoid arthritis. Lancet, 1971, I: 937-938.

Segal, A.W et al., Preliminary evidence for gut involvement in the pathogenesis of rheumatoid arthritis. Br. J. of Rheum. 25:162-6, 1986.

Seltzer, S. et al., The effects of dietary tryptophan on chronic maxillofacial pain and experimental pain tolerance. Journal of Psychiatric Research 17: 181-6, 1982.

Seltzer, S. Pain relief by dietary manipulation and tryptophan supplements. Journal of Endodontics 11: 449-53, 1985.

Shiroky, J. B. et al. : Thyroid Dysfunction and Rheumatoid Arthritis: A Controlled Prospective Survey. Annals of Rheumatic Diseases, 1993;52:454-456.

Simkin, P. A. Treatment of rheumatoid arthritis with oral zinc sulfate. Agents and Actions (suppl)8: 587-95, 1981.

Skoldstam, L., L. Larsson & F.D. Lindstrom. Effects of fasting and lactovegetarian diet on rheumatoid arthritis. Scand. Jrnl of Rheumatology 8: 249-55, 1979.

Smith, MD et al., Abnormal Bowel Permeability in Ankylosing Spondylitis and Rheumatoid Arthritis. Journal of Rheumatology 12:299-305, 1985.

Sorenson, J.R.J. & W. Hangarter. Treatment of rheumatoid and degenerative disease with copper complexes. Inflammation 2: 217-38, 1977.

Srimal, R. & B. Dhawan. Pharmacology of diferuloyl methane (curcumin), a nonsteroidal anti-inflammatory agent. J. Pharm Pharmac 25: 447-52, 1973.

Subramanian, N. Histamine degradation potential of ascorbic acid. Agents and Actions 8: 484-7, 1978.

Tamura, Y., T. Nishikawa & K. Yamada. Effects of glycyrrhetinic acid and its dervatives on delta-4-5- alpha- and 5-beta -reductase in rat liver. Arzneim-Forsch 29: 647-9, 1979.

Tarp, U et al., Glutathione Redox Cycle Enzymes and Selenium in Severe Rheumatoid Arthritis: Ann. of the Rheumatic Diseases, 1992;51:1044-1049.

Tarp, U., K. Overvad, E.B. Thorling, et.al. Selenium treatment in rheumatoid arthritis. Scandinavian Journal of Rheumatology 53(suppl.) 103, 1984.

Taussig, S., M. Yokoyama, A. Chinen, et.al. Bromelain, a proteolytic enzyme and its clinical application. A review. Hiroshima Journal of Medical Hypothesis 6: 99-104, 1980.

Terano, T., J.A. Salmon, G.A. Higgs & S. Moncada. Eicosapentaenoic acid as a modulator of inflammation, effect on prostaglandin and leukotriene synthesis. Biochemical Pharmacology 35: 779-85, 1986.

Walji, Hasnain. 1994. Arthritis & Rheumatism - Orthodox & Complementary Approaches Hodder Headline Plc.London.

Walker, W.R. & D.M. Keats. An investigation of the therapeutic value of the "copper bracelet" - dermal assimilation of copper in arthritic - rheumatoid conditions. Agents and Actions 6: 454-8, 1976.

Warady BD et al., Effects of nutritional supplementation on bone mineral status of children with rheumatic diseases receiving corticosteroid therapy. J Rheumatol, 1994 Mar, 21:3, 530-5.

Watts, D.L. The nutritional relationships of copper. J. Orthomol. Med. 1989, 4(2): 99-108.

Whitehouse, LW et al., Devil's claw (Harpagophytum procumbens): no evidence for anti-inflammatory activity in the treatment of arthritic disease. Canadian Medical Association Journal 129: 249-51, 1983.

Woldenberg, S.C.: The treatment of arthritis with colloidal sulfur. J. South. Med. Assn. 1935, 28: 875-881.

Zaphiropoulos, G.C. Rheumatoid arthritis and the gut. British Journal of Rheumatology 25:138-40, 1986.

Zidenberg-Cherr, S., C.L. Keen, B. Lonnerdal & L.S. Hurley. Dietary superoxide dismutase does not affect tissue levels. Am. J of Clinical Nutrition 37: 5-7, 1983.

Ziff, M. Diet in the treatment of rheumatoid arthritis. Arthritis Rheumatism 26: 457-61, 1983.