Table 2.
Selected meta-analyses of the effect of marine n-3 fatty acids on cardiovascular risk factors.
| Study | Cardiovascular Risk Factors Assessed | Study Design | Form and Dosage of n-3 Fatty Acids | Duration of n-3 Fatty Acid Treatment | Pooled Effects of n-3 Fatty Acids Versus Placebo |
|---|---|---|---|---|---|
| AbuMweis et al., 2018 [26] | Blood lipids, heart rate, blood pressure, inflammatory markers, platelet function and flow-mediated dilatation | Meta-analysis of 171 RCTs (up to Feb 2013) in participants in various states of health (note: the number of studies used for the analysis of different outcomes varied from 110 for triglycerides and HDL-cholesterol to 9 for flow-mediated dilatation) | Oral marine n-3 fatty acid supplements providing 0.18–15 g/d EPA+DHA | 4–240 weeks | Significant dose-dependent decrease in triglycerides |
| (MD = −0.368 mmol/L; 95% CI: −0.427–−0.309) | |||||
| Significant decrease in systolic blood pressure | |||||
| (MD = −2.195 mmHg; 95% CI: −3.171–−1.217) | |||||
| Significant decrease in diastolic blood pressure | |||||
| (MD = −1.37 mmHg; 95% CI: −2.415–−0.325) | |||||
| Significant decrease in heart rate (MD = −1.37 bpm; 95% CI: −2.41–−0.325) | |||||
| Significant decrease in CRP (MD = −0.343 mg/L; 95% CI: −0.454–−0.232) | |||||
| Significant increase in LDL-cholesterol (MD = 0.150 mmol/L; 95% CI: 0.058–0.243) and HDL-cholesterol (MD = 0.039 mmol/L; 95% CI: 0.024–0.054) | |||||
| No significant effect on total cholesterol, TNF-α, fibrinogen, platelet count, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1 or flow-mediated dilatation | |||||
| Gao et al., 2013 [31] | Platelet aggregation | Meta-analysis of 15 RCTs (up to Jul 2011) including 742 participants in various states of health | Oral marine n-3 fatty acid supplements providing 0.84–6.8 g/d EPA+DHA | 2–16 weeks | Significant decrease in adenosine diphosphate-induced platelet aggregation (SMD = −1.23; 95% CI: −2.24–−0.23; p = 0.02) |
| Significant decrease in platelet aggregation units (SMD = −6.78; 95% CI: −12.58–−0.98; p = 0.02) | |||||
| Non-significant trend towards decreased collagen-induced and arachidonic acid-induced platelet aggregation | |||||
| Greater effect observed in non-healthy participants | |||||
| Hidayat et al., 2017 [30] | Heart rate | Meta-analysis of 51 RCTs (up to May 2017) including ~3000 participants in various states of health | Oral marine n-3 fatty acid supplements providing 0.5–15.0 g/d EPA+DHA | 2–52 weeks | Significant decrease in heart rate (WMD = −2.23 bpm; 95% CI: −3.07–−1.40); observed to be due to DHA, not EPA |
| Jiang et al., 2016 [36] | Pro-inflammatory eicosanoids | Meta-analysis of 18 RCTS (up to November 2015) including 826 subjects in various states of health | Oral marine n-3 fatty acid supplements providing 0.18–4.05 g/d EPA+DHA or EPA alone | 4–24 weeks | Significant decrease in serum/plasma thromboxane B2 in participants with high risk of CVD (SMD = −1.26; 95% CI: −1.65–−0.86) |
| Significant decrease in neutrophil leukotriene B4 in unhealthy subjects (SMD = −0.59; 95% CI: −1.02–−0.16) | |||||
| Li et al., 2014 [35] | Pro-inflammatory cytokines | Meta-analysis of 68 RCTs (up to 2013) including 4601 participants in various states of health | Oral marine n-3 fatty acid supplements or dietary intake providing 0.3–6.6 g/d EPA+DHA | 4–12 months | Participants with chronic disease: |
| Significant decrease in CRP (WMD = −0.20 mg/L; 95% CI: −0.28–−0.12) and IL-6 (WMD = −0.22 pg/mL; 95%CI: −0.38–−0.06) | |||||
| No significant effect on TNF-α | |||||
| Healthy participants: Significant decrease in CRP (WMD = −0.18 mg/L; 95% CI: −0.28–−0.08) and TNF-α (WMD = −0.12 pg/mL; 95% CI: −0.16–−0.07) | |||||
| No significant effect on IL-6 | |||||
| Miller et al., 2014 [27] | Blood pressure | Meta-analysis of 70 RCTs (up to February 2013) in normotensive and hypertensive subjects | Oral marine n-3 fatty acids from seafood, fortified foods, fish oil, algal oil and purified ethyl esters; mean EPA+DHA dose: 3.8 g/d | >3 weeks (mean study duration: 69 days) | Significant decrease in systolic blood pressure (WMD = −1.52 mmHg; 95% CI: −2.25–−0.79) |
| Significant decrease in diastolic blood pressure (WMD = −0.99 mmHg; 95% CI: −1.54–−0.44) | |||||
| Significant decrease in systolic blood pressure (WMD = −4.51 mmHg; 95% CI: −6.12–−2.83) and diastolic blood pressure (WMD = −3.05 mmHg; 95% CI: −4.35–−1.74) in hypertensive individuals | |||||
| Mozaffarian et al., 2005 [28] | Heart rate | Meta-analysis of 30 RCTs (up to January 2005) including 1678 healthy participants | Oral marine n-3 fatty acid supplements; median EPA+DHA intake: 3.5 g/d | >2 weeks (median study duration: 8 weeks) | Significant decrease in heart rate (WMD = −1.6 bpm; 95% CI: 0.6–2.5) |
| In those with baseline heart rate ≥ 69 bpm, heart rate decreased by 2.5 bpm (95% CI: 1.4–3.5) | |||||
| Pase et al., 2011 [34] | Arterial stiffness | Meta-analysis of 10 RCTs (up to September 2010) including 550 participants in various states of health | Oral marine n-3 fatty acid supplements providing 0.64–3 g/d EPA+DHA | 6–105 weeks | Significant improvement in pulse wave velocity (SMD = 0.33; 95% CI: 0.12–0.56) |
| Significant improvement in arterial compliance (SMD = 0.48; 95% CI: 0.24–0.72) | |||||
| Wang et al., 2012 [33] | Vascular endothelial function | Meta-analysis of 16 RCTs (up to August 2011) including 901 participants in various states of health | Oral marine n-3 fatty acid supplements and dietary intake providing 0.45–4.7 g/d EPA+DHA | 2 weeks to 12 months (median: 56 days) | Significant increase in flow-mediated dilatation (WMD = 2.3%; 95% CI: 0.89–3.72) |
| No significant change in endothelium-independent vasodilation | |||||
| Xin et al., 2012 [32] | Vascular endothelial function | Meta-analysis of 16 RCTs (up to February 2012) including 1385 participants in various states of health | Oral marine n-3 fatty acid supplements providing 0.45–4.53 g/d EPA+DHA | 2-52 weeks | Significant increase in flow-mediated dilatation (WMD = 1.49%; 95% CI: 0.48–2.5) |
| Xin et al., 2013 [29] | Heart rate variability | Meta-analysis of 15 RCTS including 692 participants in various states of health | Oral marine n-3 fatty acid supplements providing 0.64–5.9 g/d EPA+DHA | 6-24 weeks | Significant increase in high frequency power value of heart rate variability (SMD = 0.30). A sensitivity analysis demonstrated a significant reduction in low frequency power/high frequency power ratio with >1 g/d EPA+DHA |
Abbreviations: CI, confidence interval; CVD, cardiovascular disease; CRP, C-reactive protein; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HDL, high-density lipoprotein; IL-6, interleukin-6; LDL, low-density lipoprotein; MD, mean difference; RCT, randomized controlled trial; SMD, standard mean difference; TNF-α, tumour necrosis factor-α; WMD, weighted mean difference.