Numerous clinical trials have investigated the effects of fish oil supplementation in several inflammatory and autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, lupus erythematosus and migraine headaches (Belluzzi 2002, Belluzzi et al 1996, Miura et al 1998, Simopoulos 2002). Although not all trials have produced positive results, many of the placebo-controlled trials reveal significant benefit in chronic disease, including decreased disease activity and sometimes, reduced requirement for anti-inflammatory medicines (Adam et al 2003). Rheumatoid arthritis Of the inflammatory diseases, the use of fish oil supplementation is most widely seen in RA. According to multiple randomised, controlled studies, fish oil supplements have been consistently shown to reduce symptoms in RA, such as the number of tender joints on physical examination and the amount of morning stiffness (Adam et al 2003, Cleland et al 2003, Kremer 2000, Ulbricht & Bäsch 2006, Volker et al 2000). Generally, supplements are taken daily as adjuncts to standard therapy with clinical effects appearing after 12 weeks. A dose ranging from 30 mg to 40 mg/kg of EPA and DHA daily has been used successfully, although some studies have found a minimum of 3 g/day is required.
Results from a double-blind crossover study suggest that the beneficial effects obtained from fish oil capsules is further enhanced when combined with an antiinflammatory diet providing less than 90 mg/day of AA (Adam et al 2003).
Although the anti-inflammatory activity of fish oil supplementation is thought to be chiefly responsible for symptom relieving effects, there is also evidence that n-3 fatty acids can modulate the expression and activity of degradation factors that cause cartilage destruction (Curtis et al 2000).
In spite of these positive findings, an evidence report conducted for the US Department of Health and Human Services in 2004 concludes that, upon metaanalysis of the trials to date, there is little evidence of statistically significant relief of
either objective or subjective features of RA, including swollen joint count and erythrocyte sedimentation rate, with the use of fish oils (MacLean et al 2004). While the studies incorporated met the strict methodological inclusion criteria of the review committee, it is important to note that the studies selected are all of reasonably small sample size and were conducted in the early 1990s, with more recent evidence failing to be incorporated.
A 2005 randomised study published after the above report was released has found that fish oil supplements (3 g/day), whether taken alone or in combination with olive oil (9.6 ml_) produced a statistically significant improvement (P < 0.05) compared to placebo on several clinical parameters in RA (Berbert et al 2005). Significant improvements were observed for joint pain intensity, right and left handgrip strength after 12 and 24 weeks, duration of morning stiffness, onset of fatigue, Ritchie's articular index for pain joints after 24 weeks, ability to bend down to pick up clothing from the floor, and getting in and out of a car after 24 weeks. The group using a combination of oils showed additional improvements with respect to duration of morning stiffness after 12 weeks, patient global assessment after 12 and 24 weeks, ability to turn taps on and off after 24 weeks, and rheumatoid factor after 24 weeks. In addition, this group showed a significant improvement in patient global assessment compared with fish oils alone after 12 weeks.
Based on these results, it appears that while fish oils will not improve all parameters of RA, overall they have demonstrated symptomatic relief in the majority and result in significantly reduced use of anti-inflammatory and corticosteroid use, a fact MacLean et al (2004) acknowledges and which is confirmed by a 2005 review by Stamp et al. There appears to be little evidence of sustained improvements following cessation of the supplements.
A large prospective cohort study (n = 57,053) investigating the association between dietary factors and risk of RA found that each increase in intake of 30 g fatty fish (>8 g fat/100 g fish) per day was associated with 49% reduction in the risk of RA (P = 0.06); however, a medium intake of fatty fish (3-7 g fat/100 g fish) was associated with significantly increased risk of RA (Pedersen et al 2005). No associations were found between risk of RA and intake of a range of other dietary factors, including long-chain fatty acids, olive oil, vitamins A, E, C and D, zinc, selenium, iron, and meat. The authors caution that due to the limited number of patients who developed RA during follow up, it is not yet possible to make firm conclusions.
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