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Fish oil and rheumatoid arthritis: Past, present and future

Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Proceedings of The Nutrition Society (Impact Factor: 4.94). 08/2010; 69(3):316-23. DOI: 10.1017/S0029665110001564
Source: PubMed

ABSTRACT Meta- and mega-analysis of randomised controlled trials indicate reduction in tender joint counts and decreased use of non-steroidal anti-inflammatory drugs with fish-oil supplementation in long-standing rheumatoid arthritis (RA). Since non-steroidal anti-inflammatory drugs confer cardiovascular risk and there is increased cardiovascular mortality in RA, an additional benefit of fish oil in RA may be reduced cardiovascular risk via direct mechanisms and decreased non-steroidal anti-inflammatory drug use. Potential mechanisms for anti-inflammatory effects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), and provision of substrates for synthesis of lipid suppressors of inflammation (resolvins). Future studies need progress in clinical trial design and need to shift from long-standing disease to examination of recent-onset RA. We are addressing these issues in a current randomised controlled trial of fish oil in recent-onset RA, where the aim is to intervene before joint damage has occurred. Unlike previous studies, the trial occurs on a background of drug regimens determined by an algorithm that is responsive to disease activity and drug intolerance. This allows drug use to be an outcome measure whereas in previous trial designs, clinical need to alter drug use was a 'problem'. Despite evidence for efficacy and plausible biological mechanisms, the limited clinical use of fish oil indicates there are barriers to its use. These probably include the pharmaceutical dominance of RA therapies and the perception that fish oil has relatively modest effects. However, when collateral benefits of fish oil are included within efficacy, the argument for its adjunctive use in RA is strong.

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    • "Recent studies have reported that resolvins and protectins, which are a new class of lipid mediators, are associated with the resolution of renal inflammation [33]. í µí¼”-3 PUFAs are used as an additional treatment for inflammatory diseases, such as rheumatoid arthritis [34]. However, some studies have reported that í µí¼”-3 PUFAs intake does not have anti-inflammatory benefits in CKD patients [35]. "
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    ABSTRACT: The prevalence rate of chronic kidney disease (CKD) is increasing worldwide, and cardiovascular disease (CVD) is a main cause of death in patients with CKD. The high incidence of CVD in CKD patients is related to chronic inflammation, dyslipidemia, malnutrition, atherosclerosis, and vascular calcification. Omega-3 polyunsaturated fatty acids ( ω -3 PUFAs) have been shown to reduce the risk of CVD. In this paper, we review the beneficial effects of ω -3 PUFAs on CVD and the possible cardioprotective mechanisms of ω -3 PUFAs in CKD patients by determining the effect of ω -3 PUFAs in the general population. ω -3 PUFAs have several cardioprotective benefits, such as reducing inflammation, decreasing oxidative stress, inhibiting platelet activity, exerting antiarrhythmic effects, and improving triglyceride levels, in the general population and patients with CKD. Modifications of erythrocyte membrane fatty acid content, including an increased ω -3 index and decreased oleic acid, after ω -3 PUFAs supplementation are important changes related to CVD risk reduction in the general population and patients with CKD. Further basic and clinical studies are essential to confirm the effects of ω -3 PUFAs on vitamin D activation, vascular calcification prevention, cardiovascular events, and mortality in CKD patients.
    04/2013; 2013:712949. DOI:10.1155/2013/712949
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    • "This problem is made all the more urgent by the EU directive, with a potential for an " epidemic " of broken bones in free range and furnished cage systems post 2012. Current interest in omega-3 (n3) polyunsaturated fatty acid (PUFA) supplementation in human diets results from evidence that a number of conditions prevalent in Western societies, such as heart disease [3], arthritis [4] [5], colitis [6] and osteoporosis [7], are due to 10 to 20-fold deficit in n3 PUFAs compared with n6, whereas natural human diets are thought to have approximately equal levels [8]. Similarly, it is thought that the natural foraging diet of hens would provide a relatively high level of n3 through consumption of green leaves, and therefore farmed laying hens, fed a grain rich diet, are also exposed to unnaturally low levels of n3. "
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    ABSTRACT: INTRODUCTION: The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the immediate precursors to a number of important mediators of immunity, inflammation and bone function, with products of omega-6 generally thought to promote inflammation and favour bone resorption. Western diets generally provide a 10 to 20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to have contributed to the marked rise in incidence of disorders of modern human societies, such as heart disease, colitis and perhaps osteoporosis. Many of our food production animals, fed on grains rich in omega-6, are also exposed to a dietary deficit in omega-3, with perhaps similar health consequences. Bone fragility due to osteoporotic changes in laying hens is a major economic and welfare problem, with our recent estimates of breakage rates indicating up to 95% of free range hens suffer breaks during lay. METHODS: Free range hens housed in full scale commercial systems were provided diets supplemented with omega-3 alpha linolenic acid, and the skeletal benefits were investigated by comparison to standard diets rich in omega-6. RESULTS: There was a significant 40-60% reduction in keel bone breakage rate, and a corresponding reduction in breakage severity in the omega-3 supplemented hens. There was significantly greater bone density and bone mineral content, alongside increases in total bone and trabecular volumes. The mechanical properties of the omega-3 supplemented hens were improved, with strength, energy to break and stiffness demonstrating significant increases. Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid phosphatase (an osteoclast marker) both showed significant increases with the omega-3 diets, indicating enhanced bone turnover. This was corroborated by the significantly lower levels of the mature collagen crosslinks, hydroxylysyl pyridinoline, lysyl pyridinoline and Histidinohydroxy-lysinonorleucine, with a corresponding significant shift in the mature:immature crosslink ratio. CONCLUSIONS: The improved skeletal health in laying hens corresponds to as many as 68 million fewer hens suffering keel fractures in the EU each year. The biomechanical and biochemical evidence suggests that increased bone turnover has enhanced the bone mechanical properties, and that this may suggest potential benefits for human osteoporosis.
    Bone 11/2012; 52(2). DOI:10.1016/j.bone.2012.11.003 · 4.46 Impact Factor
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    • "Although CVD is the leading cause of mortality in RA patients, morbidity as a result of progressive joint destruction and functional disability always requires medical treatment. The effects of n-3 LCP on clinical outcomes in RA have been tested in a number of RCTs, have been the subject of 3 metaanalyses and have been extensively reviewed elsewhere [165] [166] [167] [168]. "
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    ABSTRACT: Rheumatoid arthritis (RA), the most common chronic systemic inflammatory disease leading to joint destruction and disability, is associated with increased cardiovascular mortality. Systemic inflammation and increased burden of traditional cardiovascular risk factors present in RA are currently considered responsible for the accelerated atherosclerosis in these patients. Herein, we highlight a potential double effect of dietary intake of the n-3 long-chain polyunsaturated fatty acids (LCP) eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) on cardiovascular risk reduction and disease control in patients with RA. Large studies in non-RA populations provide strong evidence for the beneficial effect of n-3 LCP supplementation in primary and secondary cardiovascular prevention. Cardiovascular risk reduction is at least partly explained by n-3 LCP effects on blood pressure, dyslipidemia, thrombosis and inflammation, all important factors also in RA, whereas abnormalities in vascular function and in vascular morphology similar to those observed in RA patients may even be moderately reversed. On the other hand, there is evidence from 6 of 14 randomized controlled trials supporting a favorable effect of n-3 LCP supplementation in decreasing joint inflammation in RA. Although specific studies in RA patients are currently lacking, a double beneficial effect of n-3 LCP seems likely. The size of any such effect and how it compares with other interventions such as lifestyle changes, biologic therapies, and statin therapy, needs to be investigated prospectively in carefully designed studies.
    Current pharmaceutical design 02/2012; 18(11):1531-42. DOI:10.2174/138161212799504722 · 3.29 Impact Factor
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