Fish oil and arthritis

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

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Omega-3 fatty acids appear to benefit patients with cardiovascular disease and arthritis, although the mechanism for this is not yet fully understood.

Researchers at the Brigham and Women's Hospital and Harvard Medical School have identified a new class of aspirin-triggered bioactive lipids in humans, called resolvins, that could partly explain fish oils’ anti-inflammatory effects on joints and blood flow.

Resolvins are made from omega-3 fatty acids by cellular enzymes and can reduce inflammation in mice. The main bioactive component of this class of lipids, identified in mice, has been named resolvin E1. The researchers have now identified this lipid in plasma taken from volunteers given omega-3 fatty acids and aspirin.

In the 7 March issue of The Journal of Experimental Medicine (vol 201, no 5, 713-722), the authors write that human resolvin E1 inhibits both the migration of inflammatory cells to sites of inflammation and the turning on of other inflammatory cells.

Drugs. 2003;63(9):845-53.

The role of fish oils in the treatment of rheumatoid arthritis.

Cleland LG, James MJ, Proudman SM.

Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Fish oils are a rich source of omega-3 long chain polyunsaturated fatty acids (n-3 LC PUFA). The specific fatty acids, eicosapentaenoic acid and docosahexaenoic acid, are homologues of the n-6 fatty acid, arachidonic acid (AA). This chemistry provides for antagonism by n-3 LC PUFA of AA metabolism to pro-inflammatory and pro-thrombotic n-6 eicosanoids, as well as production of less active n-3 eicosanoids. In addition, n-3 LC PUFA can suppress production of pro-inflammatory cytokines and cartilage degradative enzymes.In accordance with the biochemical effects, beneficial anti-inflammatory effects of dietary fish oils have been demonstrated in randomised, double-blind, placebo-controlled trials in rheumatoid arthritis (RA). Also, fish oils have protective clinical effects in occlusive cardiovascular disease, for which patients with RA are at increased risk. Implementation of the clinical use of anti-inflammatory fish oil doses has been poor.

Research has shown that supplementation with fish oils (eicosapentaenoic acid and docosahexaenoic acid) can markedly reduce interleukin-1beta production and results in a significant reduction in morning stiffness and the number of painful joints in RA patients. Omega-6 polyunsaturated fatty acids (found in cooking oils and margarine), on the other hand, have been found to exacerbate RA symptoms. Fish oils have also been found useful in the management of systemic lupus erythematosus.

Investigators point out that long-term supplementation with fish oils may affect immune function and caution against daily intakes of more than 750 mg of EPA. They also point out that fish oil supplements should contain at least 3 mg of vitamin E per gram of fish oil in order to avoid excessive peroxidation.

Darlington, L. Gail and Stone, Trevor W. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. British Journal of Nutrition, Vol. 85, March 2001, pp. 251-69

At least 13 published randomized, controlled clinical trials have reported significant benefits of fish oil supplementation in rheumatoid arthritis patients. Researchers at the University of Newcastle have provided additional evidence to support these earlier findings. Their 15- week study involved 50 patients who had been diagnosed with rheumatoid arthritis. The patients were all consuming a diet which contained less than 10 grams/day of omega-6 fatty acids. These fats are known to promote inflammation through their eicosanoid metabolites. Half the patients were given fish oil capsules to provide a daily intake of 40 mg/kg body weight (about 2.8 grams for a 70 kg person); the other half received placebo capsules containing 50/50 corn/olive oil. All subjects continued with their regular diet and medications. About half the patients dropped out during the experiment, mainly due to changes in their medications. Complete clinical evaluations were carried out at baseline, 4, 8 and 15 weeks.

There were no significant changes after 4 or 8 weeks, but at the 15-week evaluation major improvements were noted in the group receiving fish oil. Particularly impressive were the improvements in the duration of morning stiffness and the overall assessment of disease activity (by both patients and physicians). Significant improvements were noted in 6 of the 9 evaluation parameters in the fish oil group; no improvements were noted in the control group. Only the total number of joints affected, the erythrocyte sedimentation rate (ESR), and the C-reactive protein level were unaffected by supplementation.

In an editorial Drs. Cleland and James of the Royal Adelaide Hospital emphasize the importance of maintaining a low intake of omega-6 fatty acids in order to keep the ratio of omega-6 to omega-3 as low as possible. They conclude that “dietary fish oil supplements should now be regarded as part of standard therapy for rheumatoid arthritis”.

Volker, Dianne, et al. Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. Journal of Rheumatology, Vol. 27, October 2000, pp. 2343-46Cleland, Leslie G. and James, Michael J. Fish oil and rheumatoid arthritis: antiinflammatory and collateral health benefits. Journal of Rheumatology, Vol. 27, October 2000, pp. 2305-06 (editorial)

Several studies have shown that supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish oils is beneficial for rheumatoid arthritis (RA) patients. Spanish medical researchers now report that RA patients tend to have decreased levels of n-3 PUFAs in their blood and synovial (joint) fluid. Their study involved 24 female and 15 male RA patients (median age of 64 years). Blood and joint fluid samples were collected from the patients and from a control group consisting of 28 healthy volunteers (17 male and 11 female with a median age of 61 years). All samples were analyzed to determine their fatty acid profile. RA patients were found to have significantly lower levels of eicosapentaenoic acid (the main component of fish tissue oil) in both their blood plasma and synovial fluid. The level of alpha-linolenic acid was lower in the synovial fluid of RA patients, but not in their blood plasma. The level of docosahexaenoic acid (a major component of fish tissue oil) also tended to be lower in synovial fluids of RA patients, but not in their blood plasma.

The researchers conclude that RA patients have an abnormal fatty acid profile and a significant deficiency in certain essential fatty acids. They believe this finding may explain why supplements such as fish oils and gamma-linolenic acid (from evening primrose and borage) have been found to be beneficial in the treatment of rheumatoid arthritis.

Navarro, Elisabet, et al. Abnormal fatty acid pattern in rheumatoid arthritis - A rationale for treatment with marine and botanical lipids. Journal of Rheumatology, Vol. 27, February 2000, pp. 298-303

Dr. Joel Kremer of the Albany Medical College has summarized the current knowledge concerning fish oils and rheumatoid arthritis and concludes that taking 3-6 grams daily of fish oils (n-3 dietary fatty acids) for 12 weeks or more will significantly diminish joint pain and morning stiffness in RA patients. Several studies have shown that the improvement in some patients is significant enough to allow them to materially reduce or completely discontinue their use of non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac and naproxen. Dr. Kremer also points out that fish oil supplementation has been found to benefit patients with inflammatory bowel disease.

Kremer, Joel M. n-3 fatty acid supplements in rheumatoid arthritis. American Journal of Clinical Nutrition, Vol. 71 (suppl), January 2000, pp. 349S-51S

Many small studies have concluded that fish oil supplementation leads to a marked improvement in rheumatoid arthritis symptoms. A team of researchers from the Harvard Medical School has combined and analyzed the results of these smaller studies. Their meta-analysis covered 10 double-blind, randomized, placebo-controlled studies aimed at determining the effect of fish oil supplementation on 8 measures of arthritis severity including the number of tender joints, number of swollen joints, extent of morning stiffness, grip strength, erythrocyte sedimentation rates, and overall global assessment of disease severity. The studies involved a total of 368 participants who took fish oil supplements for at least three months. The meta-analysis revealed a highly significant decrease in the number of tender joints and a significant shortening in the duration of morning stiffness among patients supplementing with fish oils. No statistically significant changes were observed for the other measured indicators of disease severity.

Fortin, Paul R., et al. Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis. Journal of Clinical Epidemiology, Vol. 48, 1995, pp. 1379-90

There is considerable evidence that fish oil supplementation can alleviate the symptoms of rheumatoid arthritis (RA). What is less clear is how much is required and whether fish oils are effective enough to eliminate the need for non-steroidal anti-inflammatory drugs (NSAIDs). Researchers at the Albany Medical College have released the results of a study which throws light on both of these questions.

The double-blind, placebo-controlled study involved 66 patients with active RA as indicated by the presence of at least 3 of the following symptoms:

• 6 or more tender joints;
• 3 or more swollen joints;
• 30 minutes or more of morning stiffness;
• a sedimentation rate of 28 mm/hour or higher.

The patients were weaned off their current anti-inflammatory medications and were then started on the NSAID diclofenac (75 mg twice a day). After 2 weeks they were randomized into 2 groups receiving 130 mg/kg per day of either fish oil (EPA+DHA ethyl esters) or corn oil (an omega-6 fatty acid). The daily dose of fish oil corresponds to about 9 grams/day for a person weighing 70 kg. After 18 or 22 weeks the diclofenac was replaced by a placebo and the fish and corn oil supplementation continued for another 8 weeks after which all patients were switched to the corn oil plus diclofenac placebo until the end of the study at week 48.

The researchers found that the fish oil group achieved a significant lessening of their symptoms from the start of supplementation and until the replacement of diclofenac with the placebo. No statistically significant benefits were observed in the corn oil group. Several patients in the fish oil group maintained their improved status even after diclofenac withdrawal. The researchers conclude that some RA patients using fish oil supplementation may be able to discontinue NSAIDs without experiencing a flare-up of their disease. They also noted that the benefits achieved from supplementing with 9 grams/day of fish oil were no greater than those observed in other studies using only 3 to 6 grams/day.

Kremer, Joel M., et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis & Rheumatism, Vol. 38, August 1995, pp. 1107-14

Belgian researchers have released the results of a major study aimed at determining the long-term effects of fish oil supplementation in rheumatoid arthritis patients. Sixty patients completed the year-long, double-blind, randomized study. The participants were divided into 3 groups with 1 group receiving a daily supplement of 6 capsules containing 1 gram of olive oil each (placebo); another group receiving 3 olive oil capsules plus 3 fish oil capsules (containing 1 gram of fish oil each); and the third group receiving 6 fish oil capsules daily (corresponding to 2.6 grams/day of omega-3 fatty acid). All patients continued on their regular arthritis medications.

Three months into the study it became clear that the patients on fish oil alone had improved considerably when compared to the other 2 groups and this improvement became even more pronounced after 12 months of supplementation. Fifty-three per cent of the patients in the fish oil group showed significant overall (global) improvement as compared to 10% in the placebo group and 33% in the fish oil plus olive oil group. Forty-seven per cent of the patients in the fish oil group were also able to reduce their intake of NSAIDs and disease-modifying anti-rheumatic drugs as compared to 15% in the placebo group and 29% in the olive oil plus fish oil group. The researchers conclude that long-term supplementation with fish oils benefits rheumatoid arthritis patients significantly and may lessen their need for NSAIDs and other RA medications.

Geusens, Piet, et al. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis. Arthritis & Rheumatism, Vol. 37, June 1994, pp. 824-29

Fish oil supplements containing EPA (eicosapentaenoic acid) have an anti- inflammatory effect and may benefit people suffering from rheumatoid arthritis and psoriasis. This beneficial effect is significantly reduced when the diet is high in linoleic acid. A seven week controlled experiment involving 30 male volunteers was recently completed in Australia. The participants were given 1.6 gram EPA and 0.32 gram DHA (docosahexaenoic acid) daily. Half the volunteers were kept on a diet high in linoleic acid by using margarine as a spread and polyunsaturated oils for cooking. The other half used butter and olive oil which are low in linoleic acid. The experiment clearly showed that the incorporation of fish oil is enhanced by a diet containing butter and fish oil. Margarine and polyunsaturated oils had an inhibiting effect and should therefore be excluded from the diet in order to obtain maximum benefit from fish oil.

Cleland, Leslie G., et al. Linoleate inhibits EPA incorporation from dietary fish-oil supplements in human subjects. American Journal of Clinical Nutrition, Vol. 55, February 1992, pp. 395-99

Rheumatoid arthritis is believed to involve an overactivity of certain inflammatory agents derived from arachidonic acid. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main components of fish oils, are known to inhibit the formation of these inflammatory agents. Research has shown that fish oil supplementation is beneficial in alleviating the symptoms of several inflammatory diseases.

Researchers at the Albany Medical College and the State University of New York now report that fish oils are quite effective in relieving the symptoms of rheumatoid arthritis. Their study involved 33 arthritis patients (25 women and 8 men) aged between 23 and 74 years who had suffered from arthritis for more than 3 years. Half the patients were assigned to supplement daily with 15 fish oil capsules (containing a total of 2.7 grams EPA and 1.8 grams DHA) while the other half received 15 placebo capsules every day (containing olive oil). After 14 weeks of supplementation and a 4-week wash-out period during which everyone took placebo capsules the group on fish oil switched to placebos and vice versa for a further 14 weeks. After 14 weeks on fish oil there was a very noticeable decrease in the average number of tender joints among the patients (from 9 to 5.5) and a 2.5-hour increase in the time to the first onset of fatigue after getting up in the morning. Although not statistically significant a trend to a shorter duration of morning stiffness and fewer swollen joints were also observed.

The researchers conclude that fish oil supplementation relieves arthritis symptoms, but point out that at least 12 weeks of fish oil ingestion is required before the benefits are felt.

Kremer, Joel M., et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis: A double-blinded, controlled, crossover study. Annals of Internal Medicine, Vol. 106, April 1987, pp. 497-503

Nutrition. 2005 Feb;21(2):131-6.

Supplementation of fish oil and olive oil in patients with rheumatoid arthritis.

Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I.

Department of Department of Pathology, Londrina State University, Parana, Brazil.

OBJECTIVE: This study evaluated whether supplementation with olive oil could improve clinical and laboratory parameters of disease activity in patients who had rheumatoid arthritis and were using fish oil supplements. METHODS: Forty-three patients (34 female, 9 male; mean age = 49 +/- 19y) were investigated in a parallel randomized design. Patients were assigned to one of three groups. In addition to their usual medication, the first group (G1) received placebo (soy oil), the second group (G2) received fish oil omega-3 fatty acids (3 g/d), and the third group (G3) received fish oil omega-3 fatty acids (3 g/d) and 9.6 mL of olive oil. Disease activity was measured by clinical and laboratory indicators at the beginning of the study and after 12 and 24 wk. Patients' satisfaction in activities of daily living was also measured. RESULTS: There was a statistically significant improvement (P < 0.05) in G2 and G3 in relation to G1 with respect to joint pain intensity, right and left handgrip strength after 12 and 24 wk, duration of morning stiffness, onset of fatigue, Ritchie's articular index for pain joints after 24 wk, ability to bend down to pick up clothing from the floor, and getting in and out of a car after 24 wk. G3, but not G2, in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 wk, patient global assessment after 12 and 24 wk, ability to turn faucets on and off after 24 wk, and rheumatoid factor after 24 wk. In addition, G3 showed a significant improvement in patient global assessment in relation to G2 after 12 wk. CONCLUSIONS: Ingestion of fish oil omega-3 fatty acids relieved several clinical parameters used in the present study. However, patients showed a more precocious and accentuated improvement when fish oil supplements were used in combination with olive oil.

Fish oil comes as a liquid and in softgel capsules. The usual dose is about three grams, or 3,000 milligrams (mg), total of EPA/DHA (the key ingredient in fish oil) per day. Be sure to check the labels: the capsules may say "1,000 mg of fish oil," but will have varying percentages of EPA and DHA. If they contain 300 mg, you’ll need to take 10 capsules a day. Look for high potency capsules so you don’t have to take so many. A month’s supply costs about $45.

The type of fish oil taken should be pure and high in Omega-3 content. Check out "Sea Gold", our propriety highly potent fish oil supplement for arthritis. You can get it at our online store at Arthritis Treatment Center

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