Arthritis

Arthritis is the name given to problems that cause swelling, pain and stiffness in joints. It can mean anything from slight tightness to severe pain and disability. There are over 100 types of arthritis, including osteoarthritis, rheumatoid arthritis and gout. As many as one in seven Americans may suffer from arthritis, with women more commonly affected than men. Arthritis is the number one cause of disability in America, limiting everyday activities for about seven million people. As the population becomes older, this number is expected to increase.

 

Osteoarthritis

Symptoms of Osteoarthritis

Osteoarthritis is the most common joint disease. Initially, the onset is subtle and gradual, and usually involves one or only a few joints. Pain is the earliest symptom, usually made worse by exercise. Morning stiffness follows inactivity, but this only lasts around 15 to 30 minutes and improves with exercise.

Osteoarthritis occurs when degenerative changes take place in the cartilage in the joints, causing a roughening or loss of surface. There is increased bone formation in the area under the cartilage. This bone becomes stiffer and tiny fractures occur. Joints may lose their proper shape and become enlarged, or develop bony bumps that can limit movement. More women than men suffer from osteoarthritis, and symptoms usually start to show in middle age. As many as 75% of those aged over 70 show some evidence of the disease, with knees and hands being the most commonly affected sites. The cervical and lumbar spine is also commonly affected.

 

Causes of Osteoarthritis

There are many causes of osteoarthritis, including changes in bone and cartilage with aging and wear and tear on the joints from abnormal physical stresses such as obesity, injury, inflammatory processes and hormonal effects. There seems to be an imbalance in the processes that repair and maintain the joints. Genetic factors seem to play a role and long periods of weight-bearing exercise may increase the risk.1 Low estrogen levels seem to increase the risk of osteoarthritis and hormone replacement therapy appears to reduce it.2

Diagnosis of Osteoarthritis

In addition to symptom analysis, X-rays may be used to diagnose osteoarthritis as they show shrunken joints and bone abnormalities. Blood studies may also be used to rule out other disorders.

Treatment of Osteoarthritis

There is currently no way of stopping or reversing the changes which occur in osteoarthritis. Exercise is very important, as it maintains healthy cartilage and range of motion and develops the stress-absorbing tendons and muscles. Daily stretching exercises are particularly important as are periods of rest. Drugs such as aspirin are sometimes used to treat inflammation and for pain relief. Muscle relaxants may also be used. Knee and hip replacement surgery may be necessary in severe cases.

 

Vitamins, Minerals and Osteoarthritis

Vitamin D

Recent research suggests that older people whose knees are affected by osteoarthritis may run the risk of worsening their symptoms if they do not get enough vitamin D. Results from the Framingham Osteoarthritis Cohort Study published in 1996 showed that men and women with low dietary intakes and blood levels of vitamin D had three times the risk of their symptoms becoming worse than men and women with high intakes. However, they did not find a link between low vitamin D levels and the risk of developing osteoarthritis in a previously normal knee.3

Anti-arthritis drugs, including corticosteroids, and reduced activity and exposure to sunlight in those with the disease may contribute to low vitamin D levels. Vitamin D supplements may be beneficial in those already suffering from osteoarthritis who have low intakes. However, very high doses of vitamin D should be avoided as they may cause calcium to be deposited in the tissues causing irreversible damage.

Antioxidants

Other results from the Framingham Osteoarthritis Cohort Study suggest that high intakes of antioxidant nutrients may reduce the risk of cartilage loss and disease progression in people with osteoarthritis. A three-fold reduction in risk of progression was found for those with high vitamin C intakes. Those with high vitamin C intake also had a reduced risk of developing knee pain. A reduction in risk of disease progression was seen for beta carotene and vitamin E intake but was less consistent. Antioxidant nutrients did not seem to affect the initial appearance of the disease.4

B Vitamins

A controlled, double-blinded, crossover study done in 1994 found that patients taking vitamin B12 and folic acid supplements had less pain and stiffness than others not taking the supplements. The study involved 26 people diagnosed for an average of 5.7 years with osteoarthritis of the hands who had been medicated by prescribed NSAIDs. They were randomly given either 6400 mcg folate or 6400 mcg folate plus 20 mcg vitamin B12 or lactose placebo each for two months. The results showed that right and left hand grip values were higher and the number of tender hand joints was less in the supplements group. There were no side effects in the vitamin group.5

Other Nutrients

Epidemiological studies suggest that there may be a link between boron deficiency and osteoarthritis. In countries such as Mauritius and Jamaica, where boron intake is low, the incidence of osteoarthritis is around 50 to 70 per cent. In countries such as the USA, UK and Australia, where boron intake is relatively high, the incidence of osteoarthritis is around 20 per cent. Boron concentrations in bones next to osteoarthritic joints may be lower than in normal joints and supplements of 6 to 9 mg per day have been used to treat osteoarthritis with some improvement of symptoms. This may be because boron increases bone hardness.6

Glucosamine

Short-term studies in sufferers of osteoarthritis suggest that glucosamine sulfate may produce a gradual and progressive reduction in joint pain and tenderness, as well as improved range of motion and walking speed. Results of the trials have also shown that glucosamine has produced consistent benefits in patients with osteoarthritis and that, in some cases, it may be equal or superior to anti-inflammatory drugs in controlling symptoms.7

Rheumatoid Arthritis

Symptoms of Rheumatoid Arthritis

Rheumatoid arthritis occurs when the membrane linings around the joints become inflamed and the joint surfaces and tendons become distorted or even broken. The effects of rheumatoid arthritis differ from person to person and include fatigue, soreness, stiffness and aching. The hand and wrist joints on both sides of the body are often affected, and become warm, painful, swollen and tender, leading to difficulty with movement. Stiffness lasting at least 30 minutes after getting up in the morning or after prolonged inactivity is common; and early afternoon fatigue and malaise also occur. Deformities may develop rapidly. Osteoarthrtitis often develops in joints affected by rheumatoid arthritis, causing further destruction.

Rheumatoid arthritis occurs in around 1 per cent of people and female sufferers outnumber males by three to one. The disease usually starts around age 25 to 50, but it can occur at any age. When the disorder occurs in children under 16 years old, it is known as juvenile rheumatoid arthritis. The onset of rheumatoid arthritis is usually gradual, but in some cases it can be sudden. Stress may worsen the disease symptoms.

Causes of Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease, occurring when the immune system attacks joint tissue, releasing antibodies and other chemicals that cause pain, swelling and damage. The cause of the disease is unknown but genetic factors may play a role. However, not all patients with a high genetic susceptibility to the disease actually develop it. Researchers believe that even in patients who are genetically predisposed to rheumatoid arthritis, the disease must be initiated by an environmental agent. Possible triggers include viral infections, smoking, obesity, blood transfusions, food allergies and intolerances, and diets high in refined foods.

Diagnosis of Rheumatoid Arthritis

In addition to symptom analysis, blood tests are often used to confirm the presence of the disease. Most sufferers have antibodies known as rheumatoid factor in their blood.

Treatment of Rheumatoid Arthritis

As there is presently no cure for rheumatoid arthritis, treatment aims to relieve pain, reduce inflammation and slow joint damage. The disease may vary from person to person, and developing an individual treatment plan is important. Clinical evidence suggests that early diagnosis of arthritis and prompt treatment can alter the disease process, improve quality of life and extend longevity. Once the disease becomes more aggressive, it is more difficult to manage and treat.

Medications

Drugs which can be used to treat the symptoms of rheumatoid arthritis include aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) which cut down inflammation. Penicillamine, hydroxychloroquine, sulfasalazine, methotrexate and azathioprine may also be used. Gold is sometimes used to treat rheumatoid arthritis and recent research suggests that long-term wearing of gold rings slows progression of the disease in the joints near the rings.8 In severe cases, powerful corticosteroids may be given. These drugs are related to cortisone, a natural hormone produced by the human body. Unfortunately, their effectiveness declines over time and they have several undesirable side effects if they are used for long periods, including immune suppression and osteoporosis. New genetically engineered drugs which affect the inflammatory immune response may soon become available.

Lifestyle Measures

A balanced mixture of rest and exercise is important in the treatment of rheumatoid arthritis; rest being important during periods when the disease flares up and exercise when it is not so severe. Stretching and heat treatments can make exercises easier. In a study reported at the 1996 American College Of Rheumatology meeting, moderate exercise performed for a total of three hours over a six-week period substantially reduced joint stiffness in adults with rheumatoid arthritis. Obesity aggravates the symptoms of arthritis and weight loss can often bring improvement.

There are various devices such as joint splints, gloves and orthopedic shoes which can help to relieve symptoms and help patients to perform activities necessary for daily life. Stress relief and pain management techniques may also be valuable in the treatment of rheumatoid arthritis. A 1995 study involving 141 rheumatoid arthritis patients showed that those who underwent special stress management counseling had better coping skills, felt less helpless, reported less pain and had greater mobility several months later than patients who either attended an education program or had no counseling at all.9

Rheumatoid Arthritis and Diet

There is some evidence that a connection exists between diet and rheumatoid arthritis. However, no dietary therapy is widely accepted. Some experts believe that diets high in refined foods and food intolerances and allergies may lead to the development of the disease. Many sufferers find that eating meat and dairy products worsens symptoms while some people have benefited from avoiding foods of the nightshade family which contain a substance called solanine. These include potatoes, tomatoes, peppers, eggplant and tobacco. Avoiding caffeine, alcohol and food additives may also be helpful. Vegetable juices containing carrot, celery, beetroot and cucumber may also be beneficial in some patients.

Certain foods, such as oily fish, which contain anti-inflammatory omega-3 fatty acids may help reduce the pain of tender joints and morning stiffness of rheumatoid arthritis. In a 1996 population-based case-control study, researchers compared 324 women with rheumatoid arthritis cases and 1245 women without the disease. They used a food frequency questionnaire to ascertain diet during a one-year period five years before the women first visited their physicians because of joint symptoms. The results showed that women who ate broiled or baked fish more than twice a week had almost half the risk of rheumatoid arthritis.10

Recent research also suggests that a vegetarian diet may lessen the symptoms of arthritis in some people. It is unclear whether benefits come from eating more of certain foods or less of others. Fasting is also an effective treatment for rheumatoid arthritis, but most patients relapse when they start eating again. In a Norwegian randomized, single-blind controlled trial done in 1991, researchers assessed the effect on 27 patients of fasting followed by one year of a vegetarian diet. After a seven to ten day fast, patients were put on individually adjusted gluten-free vegan diets for three and a half months. They were then allowed to eat a lactovegetarian diet for the remainder of the study. A control group of 26 ate an ordinary diet throughout the whole study period. After four weeks, the diet group showed a significant improvement in both symptoms and laboratory measures of disease severity. In the control group, only pain score improved score. The benefits in the diet group were still present after one year.11 Follow-up studies done a year later found that those patients who had benefited from the vegetarian diet continued to show improvement in symptoms.12

Rheumatoid arthritis sufferers are often poorly nourished. Many people lose their appetite and tend to lose weight during the active phase of the disease. Drug treatment and the intestinal changes which can occur in the course of the disease may worsen malnutrition. Deficiencies of folic acid, vitamin C, vitamin D, vitamin B6, vitamin B12, iron, magnesium, selenium and zinc are often found in patients with rheumatoid arthritis but it is unclear whether nutrient deficiencies are a cause or a result of the disease.

 

Vitamins, Minerals and Rheumatoid Arthritis

Antioxidants

Research suggests that rheumatoid arthritis sufferers have low levels of antioxidant vitamins and minerals which may contribute to inflammation. Sufferers of the disease appear to have higher levels of free radicals in their blood and joint fluid.13 This may be due to increased activity of white blood cells known as macrophages. If these free radicals are not neutralized by antioxidants, they can cause inflammation and damage to tissues.

In a study published in 1997, researchers from the Training Center for Public Health Research in Maryland examined thousands of blood samples donated in 1974. They then specifically tested those from 21 people who were diagnosed with rheumatoid arthritis two to 15 years after donating their blood. The results showed that those with rheumatoid arthritis had 29 per cent lower beta carotene in their blood before they were diagnosed, 5 per cent less vitamin E and 7 per cent less vitamin A.14 Other studies have found low levels of vitamin C in rheumatoid arthritis sufferers.15

It is unclear from this study whether these lower levels of antioxidants are a cause or an effect of the disease. It is possible that the antioxidants in the blood are being used to combat free radical damage caused by the disease, or alternatively, that decreased intake, absorption or transport increases the risk of oxidative damage. Increasing intake of antioxidant nutrients is beneficial in reducing some of the inflammation caused by free radical damage to joint linings in rheumatoid arthritis sufferers.

In a study published in 1997, UK researchers investigated whether there was any additional anti-inflammatory or analgesic effects of vitamin E in rheumatoid arthritis patients who were already receiving anti-rheumatic drugs. The study involved 42 patients who were given 600 mg alpha TE (895 IU) twice a day or placebo for 12 weeks. The results showed that although laboratory measures of disease activity were unchanged, the patients reported less pain.16

B Vitamins

Folic acid levels are low in arthritis sufferers taking the anti-inflammatory drug, methotrexate, which interferes with the conversion of folic acid to its active form. Methotrexate reduces inflammation but can also have toxic side effects. Studies have shown that folic acid supplements do not interfere with the beneficial action of the drug but may be useful in protecting against the side effects.17

Riboflavin levels may be low in rheumatoid arthritis sufferers. In a 1996 study, UK researchers investigated this link in patients and in those without the disease. The results showed that biochemical riboflavin deficiency was more frequent in patients with active disease. Riboflavin is necessary for the action of an enzyme which has anti-inflammatory activity, and deficiency could reduce the activity and beneficial effect of that enzyme.18 Niacin, vitamin B6 and pantothenic acid have also been used to treat arthritis.

Vitamin D

Vitamin D may be useful in preventing the bone loss that occurs with severe rheumatoid arthritis. Researchers involved in a 1998 study investigated the links between disease activity and blood levels of vitamin D in 96 patients. They found that high disease activity was associated with alterations in vitamin D metabolism and increased bone breakdown. Low levels of vitamin D may also increase the proliferation of white blood cells, and may accelerate the arthritic process in rheumatoid arthritis.19

Calcium

Blood calcium levels are often lower than normal in those with rheumatoid arthritis. Corticosteroids used in the treatment of rheumatoid arthritis can cause bone loss, which may increase the risk of osteoporosis. Supplementation with calcium and vitamin D can help prevent this loss. In a recent two-year study, 96 patients with rheumatoid arthritis, 65 of whom were taking corticosteroid drugs, were given 1000 mg calcium and 500 IU vitamin D per day or placebo. The researchers analyzed the bone mineral density of the lumbar spine and femur once a year. In those patients taking corticosteroid drugs and placebo losses of bone mineral density were seen. In those taking the supplements gains were seen and in those not taking corticosteroids, the supplements did not appear to affect bone mineral density.20

Copper and Zinc

Copper and zinc metabolism may be altered in rheumatoid arthritis patients. They may have higher than normal urinary copper excretion rates, and serum copper and ceruloplasmin (copper protein complex) levels are also raised in arthritis sufferers while zinc levels are usually lower. Zinc and copper function in the antioxidant enzyme, superoxide dismutase; levels of which may be altered in arthritis sufferers.21 Some studies have shown beneficial effects of zinc and/or copper supplements in arthritis while others have not.

Iron

Some experts believe that high iron intake may aggravate joint inflammation in rheumatoid arthritis, possibly by increasing free radical damage. Some studies have found that the iron antidote, deferoxamine is useful in the treatment of rheumatoid arthritis. It may act by lowering iron levels in joint tissue and reducing the inflammation. Iron absorption, however, is decreased in rheumatoid arthritis and anemia is a relatively common complication of the disease.22

Manganese

Manganese supplements have been shown to have beneficial effects in the treatment of rheumatoid arthritis. Manganese is a component of the enzyme superoxide dismutase, which acts as an antioxidant and reduces inflammation. Manganese needs may be increased in rheumatoid arthritis sufferers.23

Selenium

Several studies indicate that selenium levels are low among patients with rheumatoid arthritis. Selenium is part of the enzyme glutathione peroxidase, which acts as an antioxidant and has anti-inflammatory effects. It acts by inhibiting certain hormone-like substances known as prostaglandins and leukotrienes which cause inflammation. Clinical studies have not clearly shown that selenium supplements bring improvements in the condition of rheumatoid arthritis sufferers. Vitamin E and selenium together may have beneficial effects.

In a 1997 German study, 70 patients with rheumatoid arthritis were randomly divided into two groups. One group was given 200 mcg per day of sodium selenite while the other group was given a placebo. Selenium concentrations in red blood cells of patients with rheumatoid arthritis were significantly lower than found in an average German population. At the end of the three-month experimental period, the selenium-supplemented group showed less tender or swollen joints, and morning stiffness. Selenium-supplemented patients needed less cortisone and other anti-inflammatory medications than the placebo group. Analysis also showed a decrease in laboratory indicators of inflammation.24

Other Nutrients and Rheumatoid Arthritis

Omega-3 fatty acids

Several research studies suggest that taking omega-3 fatty acids either in food or supplement form reduces the stiffness and pain of rheumatoid arthritis and may also reduce the need for anti-inflammatory medication. This may be due to effects on several parts of the inflammatory process.

Dietary fats are involved in the manufacture of hormone-like compounds known as prostaglandins, which can exert harmful or beneficial effects. Fats in vegetable oils lead to production of harmful inflammatory prostaglandins while fish oils contain fats such as omega-3 fatty acids which lead to the production of anti-inflammatory prostaglandins. Omega-3 fatty acids also seem to affect levels of other chemicals known as cytokines and leukotrienes which are produced by white blood cells and mediate the inflammatory processes involved in rheumatoid arthritis. Omega-3 fatty acids are found in fish oils and plant oils such as flaxseed oil.

In a study done in 1994 in Belgium, 90 patients were enrolled in a 12-month, double-blind, randomized study comparing daily supplementation with either 2.6 g of omega-3 fatty acids, or 1.3 g of omega-3 fatty acids plus 3 g of olive oil, or 6 g of olive oil. The researchers found significant improvement in both the patient's evaluation and in the physician's assessment of pain in those taking 2.6 g per day of omega 3 fatty acids. The number of patients who were able to reduce their anti-rheumatic medications was significantly greater in the group taking 2.6 g of omega 3 fatty acids.25

The omega-6 fatty acid, gamma-linoleic acid is found in evening primrose, blackcurrant, and borage seed oils. These supplements may also be effective in treating rheumatoid arthritis.26

Herbal Medicine and Arthritis

Herbal medicines that may be useful in the treatment of arthritis include Devil's claw (Harpagophytum procumbens), celery (Apium graveolens), ginger (Zingiber officinale), parsley (Petroselinum crispum), willow (Salix alba), cayenne (Capsicum annuum), dandelion (Taraxacum officinale), cranberry (Vaccinium macrocarpon), black cohosh (Cimicifuga racemosa), wild yam (Dioscorea villosa) and feverfew (Tanacetum parthenium).

 

 

1 Spector TD; Harris PA; Hart DJ; Cicuttini FM; Nandra D; Etherington J; Wolman RL; Doyle DV. Risk of osteoarthritis associated with long-term weight-bearing sports: a radiologic survey of the hips and knees in female ex-athletes and population controls. Arthritis Rheum, 1996 Jun, 39:6, 988-95

2 Spector TD; Nandra D; Hart DJ; Doyle DV. Is hormone replacement therapy protective for hand and knee osteoarthritis in women?: The Chingford Study. Ann Rheum Dis, 1997 Jul, 56: 432-44

3 McAlindon TE; Felson DT; Zhang Y; Hannan MT; Aliabadi P; Weissman B; Rush D; Wilson PW; Jacques P. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med, 1996 Sep, 125:5, 353-9

4 McAlindon TE; Jacques P; Zhang Y; Hannan MT; Aliabadi P; Weissman B; Rush D; Levy D; Felson DT Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum, 1996 Apr, 39:4, 648-56

5 Flynn MA; Irvin W; Krause G. The effect of folate and cobalamin on osteoarthritic hands. J Am Coll Nutr, 1994 Aug, 13:4, 351-6

6 12 Newnham RE Essentiality of boron for healthy bones and joints. Environ Health Perspect, 1994 Nov, 102 Suppl 7:, 83-5

7 da Camara CC; Dowless GV Glucosamine sulfate for osteoarthritis. Ann Pharmacother, 1998 May, 32:5, 580-7

8 Mulherin DM; Struthers GR; Situnayake RD Do gold rings protect against articular erosion in rheumatoid arthritis? Ann Rheum Dis, 1997 Aug, 56:8, 497-9

9 Parker JC; Smarr KL; Buckelew SP; Stucky Ropp RC; Hewett JE; Johnson JC; Wright GE; Irvin WS; Walker SE Effects of stress management on clinical outcomes in rheumatoid arthritis. Arthritis Rheum, 1995 Dec, 38:12, 1807-18

10 Shapiro JA; Koepsell TD; Voigt LF; Dugowson CE; Kestin M; Nelson JL. Diet and rheumatoid arthritis in women: a possible protective effect of fish consumption. Epidemiology, 1996 May, 7:3, 256-63

11 Kjeldsen-Kragh J; Haugen M; Borchgrevink CF; Laerum E; Eek M; Mowinkel P; Hovi K; Forre O. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet, 1991 Oct 12, 338:8772, 899-902

12 Kjeldsen-Kragh J; Haugen M; Borchgrevink CF; Forre O. Vegetarian diet for patients with rheumatoid arthritis - status: two years after the introduction of the diet. Clin Rheumatol, 1994 Sep, 13:3 475-82

13 Kaur H; Edmonds SE; Blake DR; Halliwell B Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid. Ann Rheum Dis, 1996 Dec, 55:12, 915-20

14 Comstock GW; Burke AE; Hoffman SC; Helzlsouer KJ; Bendich A; Masi AT; Norkus EP; Malamet RL; Gershwin ME. Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis, 1997 May, 56:5, 323-5

15 Oldroyd KG; Dawes PT. Clinically significant vitamin C deficiency in rheumatoid arthritis. Br J Rheumatol, 24: 4, 1985 Nov, 362-3

16 Edmonds SE et al. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann Rheum Dis, 1997 Nov, 56:11, 649-55

17 Morgan SL et al. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med, 1994 Dec, 121:11, 833-41

18 Mulherin DM; Thurnham DI; Situnayake RD Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis. Ann Rheum Dis, 1996 Nov, 55:11, 837-40

19 Oelzner P; Müller A; Deschner F; Hüller M; Abendroth K; Hein G; Stein G. Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int, 1998 Mar, 62:3, 193-8

20 Buckley LM; Leib ES; Cartularo KS; Vacek PM; Cooper SM. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med, 1996 Dec, 125:12, 961-8

21 Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis. Mazzetti I; Grigolo B; Borz´ RM; Meliconi R; Facchini A. Int J Clin Lab Res, 1996, 26:4, 245-9

22 Weber J. Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency. Ann Rheum Dis, 47: 5, 1988 May, 404-9

23 Pasquier C et al. Manganese containing superoxide dismutase deficiency in polymorphonuclear lymphocytes in rheumatoid arthritis. Inflammation. 1984;8:27-32

24 Heinle K; Adam A; Gradl M; Wiseman M; Adam O. Selenium concentration in erythrocytes of patients with rheumatoid arthritis. Clinical and laboratory chemistry infection markers during administration of selenium. Med Klin, 1997 Sep, 92 Suppl 3:, 29-31

25 Geusens P; Wouters C; Nijs J; Jiang Y; Dequeker J Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. A 12-month, double-blind, controlled study. Arthritis Rheum, 1994 Jun, 37:6, 824-9

26 Leventhal LJ; Boyce EG; Zurier RB Treatment of rheumatoid arthritis with blackcurrant seed oil. Br J Rheumatol, 1994 Sep, 33:9, 847-52