Intake of ω-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: A systematic review and meta-analysis

Highlights

• Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease that puts the patient at high risk for developing cardiovascular diseases.

• Oral intake of ω-3 polyunsaturated fatty acids played a role in RA in some clinical trials.

• In this meta-analysis of 20 randomized controlled trials, disease activity–related markers and leukotriene B4 were reduced with oral intake of ω-3 fatty acids.

• An additional positive effect on blood lipid profile of patients with RA was evident for the first time.

Abstract

Objectives

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease of multiple joints that puts the patient at high risk for developing cardiovascular diseases (CVDs). The aim of the present study was to conduct an up-to-date systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess potential changes in RA disease activity, inflammation, and CVD risk after oral intake of ω-3 polyunsaturated fatty acids.

Methods

Publications up to July 31, 2016 were examined using the PubMed, SCOPUS, and EMBASE databases. Inclusion criteria: English language; human subjects; both sexes; RCTs; oral intake of ω-3 fatty acids; minimum duration of 3 mo; and no medication change throughout intervention. The Cochrane Risk of Bias tool was used to assess quality of trials. We included 20 RCTs, involving 717 patients with RA in the intervention group and 535 RA patients in the control group.

Results

Despite the evidence of overall low quality of trials, consumption of ω-3 fatty acids was found to significantly improve eight disease-activity–related markers. Regarding inflammation, only leukotriene B4 was reduced (five trials, standardized mean difference [SMD], –0.440; 95% confidence interval [CI], −0.676 to −0.205; I² = 46.5%; P < 0.001). A significant amelioration was found for blood triacylglycerol levels (three trials, SMD, −0.316; 95% CI, −0.561 to −0.070; I² = 0.0%; P = 0.012).

Conclusion

The beneficial properties of ω-3 polyunsaturated fatty acids on RA disease activity confirm the results of previous meta-analyses. Among five proinflammatory markers evaluated, only leukotriene B4 was found to be reduced. However, a positive effect on blood lipid profile of patients with RA was evident, perhaps for the first time.

Introduction

Rheumatoid arthritis (RA) is the most common of the autoimmune rheumatic diseases, primarily affecting the synovium and leading to joint destruction, functional disability, various systemic complications, and sometimes death. Prevalence of RA is 0.5% to 1% of the population worldwide and is more common in women than men [1], [2].

RA pathogenesis is still unknown. Hyperplasia of the synovium is accompanied by inflammatory cell infiltration, angiogenesis, and bone and cartilage erosion [3], [4]. T-cell imbalance with subsequent deregulation of cytokine production is central in RA pathogenesis. Among cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6 have been extensively studied.

The clinical diagnosis of RA is based on criteria developed by the European and American rheumatology associations [5], although different tools of assessing disease activity have been developed [6]. Treatment usually involves disease-modifying antirheumatic drugs (DMARDs) that target remission of the disease. It is now well documented that initiation of aggressive treatment with DMARDs at the early stages of RA, in the so-called “window of opportunity,” has been associated with a beneficial change in the course of the disease, leading to protection against joint destruction [7], [8]. The introduction of biologic agents gives an extra advantage in the progress of RA treatment strategy [9], [10]. However, the heterogeneity of RA pathophysiology does not allow clinical remission for many patients, resulting in reduced mobility, disability, and low quality of life. Additionally, patients with RA have a heightened risk for developing cardiovascular diseases (CVDs), which is associated with the degree of inflammation, contributing to overall RA mortality [8], [11].

Data from large observational studies support the efficacy of ω-3 polyunsaturated fatty acids (PUFAs), mainly 20:5 (ω-3) eicosapentaenoic acid (EPA) and 22:6 (ω-3), docosahexaenoic acid (DHA), to prevent inflammation by lowering the blood levels of inflammatory biomarkers such as, IL-6, TNF-α, C-reactive protein (CRP), serum amyloid A, and white blood cell counts [12], [13], [14], [15]. ω-3 Fatty acids seem to interfere with arachidonic acid metabolism, thus decreasing synthesis of the inflammatory eicosanoids [16].

The effects of consumption of ω-3 fatty acids on RA symptomatology have been studied since the 1980s, but the results of clinical trials on disease activity remain equivocal. Additionally, data of previous meta-analyses on inflammatory- and CVD-related biomarkers are limited. Thus, the purpose of the present study was to conduct an up-to-date systematic review and meta-analysis of all relevant published randomized controlled trials (RCTs) that examine the effects of ω-3 PUFA consumption on RA progression regarding disease activity, inflammation, and risk for CVD, while maintaining conventional treatment throughout trial intervention.