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Studies:

Berbert et al, 2005: Supplementation of fish oil and olive oil in patients with rheumatoid arthritis.

• Objective:

  • Evaluate whether supplementation with olive oil could improve disease activity in rheumatoid patients using fish oil supplements.

• Parallel randomized design

• 43 patients (34 female, 9 male)

• Placebo (soy oil) (G1) vs. fish oil omega-3 fatty acids (G2) vs. fish oil Ω-3 FA + olive oil (G3)

• Results:

  • Statistically significant improvement in G2 and G3 vs. G1 with respect to joint pain intensity, right and left handgrip strength (12 and 24 wk), duration of morning stiffness, onset of fatigue, Ritchie’s articular index for pain joints (24 wk), ability to bend down to pick up clothing from the floor, and getting in and out of a car (24 wk).

  • G3, but not G2, in relation to G1 showed additional improvements with respect to duration of morning stiffness (12 wk), patient global assessment (12 and 24 wk), ability to turn faucets on and off (24 wk), and rheumatoid factor (24 wk).

• Conclusions:

  • Fish oil Ω-3 FA relieves several clinical parameters.  However, patients showed greater improvement when fish oil was used in combination with olive oil.

Sundrarjun et al, 2004: Effects of n-3 fatty acids on serum interleukin-6 tumor necrosis factor-α, and soluble tumor necrosis factor receptor p55 in active rheumatoid arthritis.

•  Objective:

  • Effects of a low n-6 FA diet supplemented with fish oil on serum pro-inflammatory cytokine concentrations and clinical variables in patient with active RA.

• 60 patients

• Diet low in n-6 FAs and n-3 FAs supplement (fish oil) vs. diet low in n-6 FAs and placebo vs. no special diet (control)

• Results:

  • Week 18, the fish oil group had significant reduction in n-6, CRP and sTNF-F p55 compared with baseline. 

  • No significant differences in clinical variables existed between groups.

  • Week 24, there were significant reductions in IL-6 and TNF-α in the fish oil and placebo groups.

• Conclusions:

  • Supplementation with n-3 FA and a low n-6 FA intake decreased serum sTNF-R, p55, and CRP levels in RA patients

Medizinische et al, 2003: Anti-inflammatory effects of a low arachadonic acid diet and fish oil in patients with rheumatoid arthritis.

• Objective:

  • Investigate the effects of dietary measures on inflammation, fatty acid composition of erythrocyte lipids, eicosanoids, and cytokine biosynthesis in RA patients.

• Double-blind crossover study

• 68 patients (2 groups of 34 pts. Each)

• Normal western diet (WD) vs. anti-inflammatory diet (AID) with AA intake < 90 mg/day. 

• Patients in both groups received placebo or fish oil capsules.

• Results:

  • In AID patients, but not WD patients, the numbers of swollen joints decreased by 14% during placebo treatment. 

  • In AID, compared to WD patients, fish led to significant reduction in the number of tender and swollen joints.

  • Higher levels of EPA in erythrocyte lipids, and lower LTB4 and prostaglandin metabolites were found in AID patients, especially when fish oil was given.

• Conclusions:

  • A diet low in AA ameliorates clinical signs of inflammation in patients with RA and augments beneficial effects of fish oil supplementation.

Volker D et al, 2000: Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis.

•  Objective:

  • Determine the efficacy of Ω-3 FA supplementation in FA subjects when FA intake in the background diet was < 10 g/day, compared to olive/corn oil supplement.

• Placebo controlled, double blind, randomized study

• 50 subjects

• RA patients whose diet was naturally low in n-6 FA was supplemented with n-3 FA at a rate of 40 mg/kg body weight.

• Results:

  • Analysis of 9 variables indicated significant difference between control and treatment groups.

• Conclusions:

  • Fish oil supplementation that delivers n-3 FA at 40 mg/kg/day, with dietary n-6 FA intake < 10 g/day in the background diet, results in improvement in clinical status in patients with RA.

Navarro E et al, 2000: Abnormal fatty acid pattern in rheumatoid arthritis.  A rationale for treatment with marine and botanical lipids.

• Objective:

  • Assess the FA pattern in plasma and synovial fluid (SF) in RA and determine clinical factors related to possible abnormalities.

• 39 patients with RA

• SF samples were obtained from 9 patients

• Results:

  • Decreased levels of EPA and n-3 PUFA were obtained from plasma and joint fluid, respectively. 

  • Patients with active disease showed mild decrease of n-3 and n-6 PUFA.

  • No changes in FA profile were found in relation to use of steroids, NSAIDs, gold salts, or malnutrition.

• Conclusions:

  • The FA pattern found in RA may explain the beneficial effect of fish oil.

Saso L et al, 1999: Inhibition of Protein Denaturation by Fatty Acids, Bile Salts and other Natural Substances: A New Hypothesis for the Mechanism of Action of Fish Oil in Rheumatic Diseases.

•  Results:

  • Fish oil rich in n-3 PUFA, such as EPA and DHA, administered in a rat protected ex vivo serum against  heat-induced denaturation more than bendazac, which is a known anti-denaturant drug.

• Conclusions:

  • The antidenaturant activity of fish oil may be partially responsible for its beneficial effects in RA.

Ariza-Ariza R, Mestanza-Peralta M, Cardiel MH, 1998: Omega-3 fatty acids in rheumatoid arthritis: an overview.

•  Objectives:

  • Review background, pharmacological properties, mechanisms of action, and published clinical experience using Ω-3 FA in RA.

• English language publications were identified through a computerized search between 1979 and 1995 using the terms “omega-3 fatty acids” and “fish oil.”

• Results:

  • Omega-3 FA are superior to placebo in improving some outcome measures and decrease the long term need for NSAIDs.  Clinical significance remains to be established.

• Conclusions:

  • Treatment with Ω-3 FA has been shown to improve some outcome measures in RA.  Studies are needed to determine if they may represent an alternative is NSAIDs.

   

James MJ, Cleland LJ, 1997: Dietary n-3 fatty acids and therapy for rheumatoid arthritis.

•  Objectives:

  • Examine the potential for dietary n-3 fats as supplemental therapy for RA.

• Results:

  • Evidence from double blind, placebo-controlled trials have shown that dietary n-3 FA can be beneficial in treatment of RA.  Mechanisms include their ability to suppress production of inflammatory mediators and proinflammatory cytokines. 

• Conclusions:

  • There may be a potential for complementarity between drug therapy and dietary choices that increase n-3 fats and decrease n-6 fats.  This may include drug sparing effects.

Kremer JM et al, 1995: Effects of high dose oil on rheumatoid arthritis after stopping nonsteroidal anti-inflammatory drugs.  Clinical and immune correlates.

•  Objectives:

  • Determine: 1) whether dietary supplementation with fish oil will allow discontinuation of NSAIDs in RA; 2) efficacy of high-dose Ω-3 FA fish oil supplementation in RA; 3) effect of fish oil supplements on the production of multiple cytokines.

• Double-blind, placebo-controlled, prospective study

• 66 RA patients

• Ω-3 FA + diclofenac vs. corn oil + diclofenac

• Placebo diclofenac was substituted halfway through the study

• Results:

  • Patients taking fish oil demonstrated decrease in the number of tender joints, duration of morning stiffness, physician’s and patient evaluation of global arthritis activity, and physician’s evaluation of pain. 

  • Patients taking corn oil showed no improvement over baseline.

• Conclusions:

  • Some patients who take fish oil are able to discontinue NSAID use without experiencing disease flare.

Fortin PR et al, 1995: Validation of a meta-analysis: the effects of fish oil in rheumatoid arthritis.

•  Objectives:

  • Many small studies have concluded that fish oil supplementation lead to a reduction in RA symptoms, but because these studies have been small, their publication has not impacted medical management.

  • Determine 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, ESR, and overall global assessment of disease severity.

• Meta Analysis: 10 double blind, randomized, placebo controlled studies

• 368 participants

• Results:

  • Significant improvement in the number of tender joints and shortening in the duration of morning stiffness.

Lau CS, Morley KD, Belch JJ, 1993: Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis—a double-blind placebo controlled study.

•  Objectives:

  • Maxepa contains EPA and DHA and therefore should be expected to reduce the requirements for NSAIDs in patients with RA.

• 64 patients with stable RA, requiring only NSAID therapy

•  10 Maxepa vs. air-filled placebo

• Results:

  • Significant reduction in NSAID dosage for patients using Maxepa compared to placebo.

  • This effect persisted for 3 months after therapy was discontinued.

• Conclusions:

  • RA patients may be able to reduce their NSAID requirement without experiencing deterioration in RA status.

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