Elsevier

Atherosclerosis

Volume 221, Issue 2, April 2012, Pages 536-543
Atherosclerosis

Effect of omega-3 fatty acids supplementation on endothelial function: A meta-analysis of randomized controlled trials

https://doi.org/10.1016/j.atherosclerosis.2012.01.006Get rights and content

Abstract

Objective

Inverse association was reported between omega-3 fatty acids (FAs) supplementation and the risk of cardiovascular disease. Identifying the effect of omega-3 FAs on endothelial function may contribute to explain the association. We conducted a meta-analysis to assess the effect of omega-3 FAs supplementation on endothelial function, as measured by flow-mediated dilation (FMD) and endothelium-independent vasodilation (EIV).

Methods

Randomized placebo-controlled trials (RCTs) were identified from the databases of PubMed, EMBASE and Cochrane library by two investigators and the pooled effects were measured by weighted mean difference (WMD), together with 95% confidence intervals (CIs). Subgroup and meta-regression analyses were used to explore the source of between-study heterogeneity.

Results

Totally 16 eligible studies involving 901 participants were finally included in meta-analysis. Compared with placebo, omega-3 FAs supplementation significantly increased FMD by 2.30% (95% CI: 0.89–3.72%, P = 0.001), at a dose ranging from 0.45 to 4.5 g/d over a median of 56 days. Subgroup analyses suggested that the effect of omega-3 FAs on FMD might be modified by the health status of the participants or the dose of supplementation. Sensitivity analyses indicated that the protective effect of omega-3 on endothelial function was robust. No significant change in EIV was observed after omega-3 FAs supplementation (WMD: 0.57%; 95% CI: −0.88 to 2.01%; P = 0.442).

Conclusion

Supplementation of omega-3 fatty acids significantly improves the endothelial function without affecting endothelium-independent dilation.

Highlights

► We examine the effect of omega-3 FAs on endothelial function by a meta-analysis. ► Flow-mediated dilation was significantly improved by omega-3 FAs supplementation. ► No significant effect on endothelium-independent vasodilation was observed.

Introduction

Data from large-scale prospective studies and meta-analysis have provided evidences that dietary intake of omega-3 fatty acids (FAs), including alpha-linolenic acid (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA), has beneficial effects on various cardiac disorders, including cardiovascular diseases (CVD) and sudden death [1], [2]. Supplementation of omega-3 FAs has also been reported to improve the risk factors of CVD, such as blood pressure [3], [4], the plasma level of triglyceride [5], and heart rate [6]. Its cardioprotective effect might be partly explained by their antiatherosclerosis role in improving endothelial dysfunction. Endothelial dysfunction, characterized by a reduction of the bioavailability of vasodilators is a major contributor to atherosclerosis and supposed to be an independent predictor of subclinical CVD and recurrence of cardiovascular events [7], [8]. Growing evidence has linked the omega-3 intake with an improved endothelial function. The potential mechanisms for the enhanced endothelial function by omega-3 include reducing production of inflammatory cytokines [9], [10] and increasing endothelium-dependent vasodilation (EDV) through enhancing the release of nitric oxide (NO) [11].

Flow-mediated dilation (FMD) is a noninvasive surrogate for endothelial function and has been widely used to evaluate the EDV in humans. A smaller FMD indicates endothelial dysfunction and was predictive of increased incident cardiovascular events [12], [13] and corresponding endothelium-independent vasodilation (EIV) is performed by using sublingual nitroglycerin to clarify whether the dilation is indeed induced by endothelium.

An inverse relation between nonfried fish intake and baseline artery diameters in men and FMD in women has been suggested in a cross-sectional study conducted in participants from six US communities [14]. Furthermore, data from clinical trials also reported significant improvement in endothelial function after omega-3 supplementation [15], [16]. Recently, Egert and Stehle have systematically summarized the intervention studies investigating the effect of omega-3 FAs on endothelial function [10]. Although the study included other measurements of endothelial function, such as concentrations of soluble cell adhesion molecules (sCAMs) and levels of cytokines, the results were only descriptive and the vascular protective effects of omega-3 FAs have not been finally identified based on findings from recent large clinical trials [17], [18]. In addition, it would be of special interest at investigating whether any specific group benefits most from omega-3 FAs. We therefore systematically reviewed the published randomized controlled trials that measured endothelial function by FMD and EIV to analytically explore the explicit effect of omega-3 FAs on endothelial function.

Section snippets

Search strategy

We performed electronic searches of the English-language literatures on omega-3 FAs and endothelial function in PubMed, EMBASE, and Cochrane Library using the combined text words related to omega-3 fatty acids (e.g. “polyunsaturated fatty acid” or “omega-3 fatty acids” or “eicosapentaenoic acid” or EPA or “docosahexaenoic acid” or DHA or “n-3 fatty acids” or “fish oil”) and endothelial function (e.g. “endothelial function” or “endothelial” or “endothelium”) from 1955 to August 2011. We also

Search results and study characteristics

Totally 2890 articles were identified from electronic databases, of which 36 studies potentially related to our issue. Twenty of them were excluded for several reasons: endothelial function was not measured by FMD (10 studies); the outcome was short-term or postprandial FMD (9 studies) and one study [25] partially overlapped with another [26]. Finally, 16 randomized trials involving 901 participants [16], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40]

Discussion

Our systematic analyses of data from 16 trials showed that omega-3 FAs supplementation significantly improved endothelial function, at a dose ranging from 0.45 to 4.5 g/d over a median of 56 days. Significantly increased FMD by omega-3 were observed for individual with cardiovascular disease or its risk factor profiles at baseline, compared with health individuals. The results were robust in sensitivity analysis. No significant changes in EIV after omega-3 FAs supplementation were observed at a

Conflict of interest statement

No conflict of interest was declared.

Acknowledgements

This work was supported by National Basic Research Program of China (Grant No. 2011CB503901), National High Technology Research and Development Program of China (Grant No. 2006AA02Z170).

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