Comparing the Effects of Docosahexaenoic and Eicosapentaenoic Acids on Inflammation Markers Using Pairwise and Network Meta-Analyses of Randomized Controlled Trials

Abstract

Recent data from randomized clinical trials (RCTs) suggest that DHA may have stronger anti-inflammatory effects than EPA. This body of evidence has not yet been quantitatively reviewed. The aim of this study was to compare the effect of DHA and EPA on several markers of systemic inflammation by pairwise and network meta-analyses of RCTs. MEDLINE, EMBASE, and The Cochrane Library were searched through to September 2019. We included RCTs of ≥7 d on adults regardless of health status that directly compared the effects of DHA with EPA and RCTs of indirect comparisons, in which the effects of DHA or EPA were compared individually to a control fatty acid. Differences in circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and adiponectin were the primary outcome measures. Data were pooled by pairwise and network meta-analysis and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic) in the pairwise meta-analysis. Inconsistency and transitivity were evaluated in the network meta-analysis. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Eligibility criteria were met by 5 RCTs (N = 411) for the pairwise meta-analysis and 20 RCTs (N = 1231) for the network meta-analysis. In the pairwise meta-analysis, DHA and EPA had similar effects on plasma CRP [MDDHA versus EPA = 0.14 mg/L (95% CI: -0.57, 0.85); I2 = 61%], IL-6 [MDDHA versus EPA = 0.10 pg/mL (-0.15, 0.34); I2 = 40%], and TNF-α [MDDHA versus EPA = -0.10 pg/mL (-0.37, 0.18); I2 = 40%]. In the network meta-analysis, the effects of DHA and EPA on plasma CRP [MDDHA versus EPA = -0.33 mg/L (-0.75, 0.10)], IL-6 [MDDHA versus EPA = 0.09 pg/mL (-0.12, 0.30)], and TNF-α [MDDHA versus EPA = -0.02 pg/mL (-0.25, 0.20)] were also similar. DHA and EPA had similar effects on plasma adiponectin in the network meta-analysis. Results from pairwise and network meta-analyses suggest that supplementation with either DHA or EPA does not differentially modify systemic markers of subclinical inflammation.

Keywords: C-reactive protein; DHA; EPA; cardiovascular disease; inflammation; interleukin; meta-analysis; omega-3; systematic review.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1

Summary of the search and selection process of the studies comparing the effect of DHA and EPA on inflammation markers in adults.

FIGURE 2

Network diagrams from network meta-analysis comparing the effect of DHA and EPA in adults on plasma CRP (Panel A), IL-6 (Panel B), TNF-α (Panel C), and adiponectin (Panel D). The size of the nodes is proportional to the number of participants and the thickness of the lines is proportional to the number of studies available for a particular comparison. CRP: C-reactive protein; oil mixture: mix of palm, olive, soy, canola, and coco butter oils.

FIGURE 3

Summary plot of pooled effect estimates from the pairwise and network meta-analyses comparing the effect of DHA and EPA on inflammation outcomes in adults. Pooled effect estimates from the pairwise meta-analysis are expressed as standardized mean differences, represented by diamonds and 95% CIs by the line through the diamond, and were estimated with the use of a generic inverse variance random-effect model. Interstudy heterogeneity was detected with the use of the Cochran's Q statistic and quantified with the use of the I2 statistic. Mean differences (MDs, 95% CI) for the inflammation outcomes as estimated from the network meta-analysis for the comparison of DHA compared with EPA are also presented. CRP: C-reactive protein; MD, mean difference; SMD, standardized mean difference.