Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials

Abstract

Background Current evidence might support the use of omega-3 fatty acids (preferably docosahexaenoic acid and eicosapentaenoic acid) for lowering blood pressure (BP), but the strength and shape of the dose-response relationship remains unclear. Methods and Results This study included randomized controlled trials published before May 7, 2021, that involved participants aged ≥18 years, and examined an association between omega-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid, or both) and BP. A random-effects 1-stage cubic spline regression model was used to predict the average dose-response association between daily omega-3 fatty acid intake and changes in BP. We also conducted stratified analyses to examine differences by prespecified subgroups. Seventy-one trials were included, involving 4973 individuals with a combined docosahexaenoic acid+eicosapentaenoic acid dose of 2.8 g/d (interquartile range, 1.3 g/d to 3.6 g/d). A nonlinear association was found overall or in most subgroups, depicted as J-shaped dose-response curves. The optimal intake in both systolic BP and diastolic BP reductions (mm Hg) were obtained by moderate doses between 2 g/d (systolic BP, -2.61 [95% CI, -3.57 to -1.65]; diastolic BP, -1.64 [95% CI, -2.29 to -0.99]) and 3 g/d (systolic BP, -2.61 [95% CI, -3.52 to -1.69]; diastolic BP, -1.80 [95% CI, -2.38 to -1.23]). Subgroup studies revealed stronger and approximately linear dose-response relations among hypertensive, hyperlipidemic, and older populations. Conclusions This dose-response meta-analysis demonstrates that the optimal combined intake of omega-3 fatty acids for BP lowering is likely between 2 g/d and 3 g/d. Doses of omega-3 fatty acid intake above the recommended 3 g/d may be associated with additional benefits in lowering BP among groups at high risk for cardiovascular diseases.

Keywords: 1‐stage regression; docosahexaenoic acid; eicosapentaenoic acid; hypertension; long‐chain fatty acids.

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses flow diagram of systematic literature search and screening for randomized controlled trials published through May 2021 that met the study inclusion and exclusion criteria.

DHA indicates docosahexaenoic acid; and EPA, eicosapentaenoic acid.

Figure 2. Dose‐response relationship between changes in blood pressure and combined docosahexaenoic acid (DHA)+eicosapentaenoic acid (EPA) intake.

Marginal average dose‐response curve (solid line) with 95% point‐wise CIs (dashed lines) estimated by a 1‐stage random‐effects restricted cubic spline model, using 0 g/d as the referent. Studies included n=70 for systolic blood pressure (SBP) and n=69 for diastolic blood pressure (DBP).

Figure 3. Dose‐response relationship between changes in blood pressure and combined docosahexaenoic acid (DHA)+eicosapentaenoic acid (EPA) intake of the studies stratified by the baseline systolic blood pressure (SBP) level.

Marginal average dose‐response curve (solid line) with 95% point‐wise CIs (dashed lines) estimated by a 1‐stage random‐effects restricted cubic spline model, using 0 g/d as the referent, in participants with baseline SBP ≥130 mm Hg or <130 mm Hg. DBP indicates diastolic blood pressure; and n, number of the included study.

Figure 4. Dose‐response relationship between changes in blood pressure and combined docosahexaenoic acid (DHA)+eicosapentaenoic acid (EPA) intake of the studies stratified by the status of hyperlipidemia.

Marginal average dose‐response curve (solid line) with 95% point‐wise CIs (dashed lines) estimated by a 1‐stage random‐effects restricted cubic spline model, using 0 g/d as the referent, in participants with or without hyperlipidemia. n indicates the number of the included study.

Figure 5. Dose‐response relationship between changes in blood pressure and combined docosahexaenoic acid (DHA)+eicosapentaenoic acid (EPA) intake of the studies stratified by the mean of age.

Marginal average dose‐response curve (solid line) with 95% point‐wise CIs (dashed lines) estimated by a 1‐stage random‐effects restricted cubic spline model, using 0 g/d as the referent, among participants with a mean age ≥45 years or <45 years. n indicates the number of the included study.