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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    ABSTRACT: Rheumatoid arthritis (RA) develops through a series of stages. In the seropositive subset of classified RA patients, a preclinical stage is present for years before the onset of clinically apparent disease. Relevant preclinical biomarkers include autoantibodies, alterations of lymphoid populations, elevated cytokines/chemokines, genetic/genomic factors, imaging studies, clinical findings, dietary and environmental biomarkers, cardiovascular disease risk assessment, microbiome analyses, and metabolomic changes. Identifying the population of asymptomatic subjects at sufficiently high risk for disease to be informative and representative of "preclinical patients" is a challenge. This article reviews the results of analyses that have been undertaken in these "at-risk" subjects. Copyright © 2014 Elsevier Inc. All rights reserved.
    Rheumatic Disease Clinics of North America 09/2014; 40(4). DOI:10.1016/j.rdc.2014.07.003 · 1.74 Impact Factor
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    ABSTRACT: Randomised controlled trials (RCT) examining the effects of fish oil supplementation on cardiac outcomes have yielded varying results over time. Although RCT are placed at the top of the evidence hierarchy, this methodology arose in the framework of pharmaceutical development. RCT with pharmaceuticals differ in important ways from RCT involving fish oil interventions. In particular, in pharmaceutical RCT, the test agent is present only in the intervention group and not in the control group, whereas in fish oil RCT, n-3 fats are present in the diet and in the tissues of both groups. Also, early phase studies with pharmaceuticals determine pharmacokinetics and pharmacodynamics to design the dose of the RCT intervention so that it is in a predicted linear dose-response range. None of this happens in fish oil RCT, and there is evidence that both baseline n-3 intake and tissue levels may be sufficiently high in the dose-response range that it is not possible to demonstrate a clinical effect with a RCT. When these issues are considered, it is possible that the changing pattern of fish consumption and fish oil use over time, especially in cardiac patients, can explain the disparity where benefit was observed in the early fish oil trials but not in the more recent trials.
    British Journal Of Nutrition 06/2014; 112(05):1-9. DOI:10.1017/S0007114514001408 · 3.34 Impact Factor
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    ABSTRACT: Objectives: Family history of RA is one of the strongest risk factors for developing RA, and is therefore routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history might diminish. We aimed to test how much of the RA familial risk could be explained by established genetic and non-genetic risk factors.Methods: RA disease history in first degree relatives of individuals in the EIRA case-control study was assessed through linkage to the Swedish Multi-Generation and Patient registers. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of non-genetic (smoking, alcohol intake, parity, silica exposure, BMI, fatty fish consumption, socio-economic status) and genetic (shared epitope (SE) and 76 SNPs) risk factors.Results: Established non-genetic risk factors did not explain any significant part of the familial risk in either seropositive or -negative RA. Genetic risk factors explained a limited proportion of the familial risk for seropositive RA (Family history ORCrude=4.10, ORAdjustedforSE=3.72, ORAdjustedfor76SNPs=3.46, ORAdjustedforboth=3.35).Conclusion: Established risk factors only explained a minor part of the familial risk of RA, suggesting that many (and familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA thus remains an important clinical risk factor for RA that currently cannot be substituted with other information. There is thus a need for further etiologic studies in both seropositive and seronegative RA. © 2014 American College of Rheumatology.
    01/2015; 67(2):352-362. DOI:10.1002/art.38927

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