Finding "Sweet Spot" for Omega-3 Fatty Acid Consumption Could Help Lower Blood Pressure

A systematic review and meta-analysis of more than 70 RCTs details a J-shape dose-response relationship between omega-3 fatty acid consumption and blood pressure, with 2-3 grams per day considered the optimal dose for blood pressure lowering.

A new study is adding to the debate surrounding the potential cardiovascular benefits, or lack thereof, associated with fish oil supplements, suggesting consumption of 3 grams per day could provide some relief in those with hypertension.

A systematic review and meta-analysis of randomized clinical trials examining the effects of omega-3 fatty acids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or a combination of both, results depict a J-shaped dose-response curve, with consumption of 3 grams per day, which was determined to be an optimal dose, associated with a mean decrease of in systolic blood pressure of 4.5 mmHg among those with hypertension and about 2 mmHg for those without.

“Our study supports the FDA guidance that EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease by lowering high blood pressure, especially among people already diagnosed with hypertension,” said lead investigator Xinzhi Li, MD, PhD, assistant professor and program director of the School of Pharmacy at Macau University of Science and Technology in Macau, China, in a statement. “However, while our study may add a layer of credible evidence, it does not meet the threshold to make an authorized health claim for omega-3 fatty acids in compliance with FDA regulations.”

Apart from vitamin D, few topics have garnered as much attention from medical professionals and mainstream outlets for their potential benefits as fish oil. In recent decades, dozens of trials have examined the effects of consumption of various omega-3 fatty acid consumptions, including EPA- and DHA-based agents as well as combination agents. Although some might expect a firm conclusion on the matter with such a wide breadth of clinical trials launched to explore the potential associations, debate still exists surrounding the risks and benefits of omega-3 fatty acids.

With this in mind, Li and a team of colleagues sought to assess the current evidence base detailing use of omega-3 fatty acids for lowering blood pressure and determine the strength and shape of the dose-response relationship. To do so, investigators designed their study as a systematic review and meta-analysis of randomized controlled trials published in the PubMed and Embase databases from inception of the database through May 7, 2021.

Studies of interest for the systematic review and meta-analysis required trials to enroll patients aged 18 years and older and to have examined an association between DHA, EPA, or both and blood pressure. Studies were excluded if they lacked concurrent inactive placebo controls, the intervention duration was less than 4 weeks, if the washout period between treatments in crossover trials was greater than 4 weeks, if patients with hypertension received concurrent antihypertensive agents, and if studies were conducted in pregnant or nursing women, or individuals with preexisting cardiovascular events, renal disease, or secondary hypertension.

From their initial search, investigators identified 3066 relevant articles. After a title and abstract review, a full-text examination was perfumed on 169 articles. Of these, 71 randomized controlled trials were identified for inclusion in their analyses. These studies included a total study population of 4973 individuals.

Investigators noted a random-effects 1-stage cubic spline regression model was used to predict the average dose-response association between daily intake and changes in blood pressure. Investigators also noted that stratified analyses were conducted to determine differences among prespecified subgroups, which included hypertensive, hyperlipidemic, and older populations.

Upon analysis, investigators observed a nonlinear association overall or in most subgroups, which was depicted as a J-shaped dose-response curve. Based on results, the optimal intake of omega-3 fatty acids in both systolic and diastolic blood pressure reductions were between 2 grams per day (systolic: −2.61 [95% CI, −3.57 to −1.65]; diastolic: −1.64 [95% CI, −2.29 to −0.99]) and 3 grams per day (systolic: −2.61 [95% CI, −3.52 to −1.69]; diastolic: −1.80 [95% CI, −2.38 to −1.23]). In subgroup analyses, results pointed to stronger and approximately linear dose-response relationships among patient subgroups defined by hypertension status, presence of hyperlipidemia, and age.

In a related editorial, Marc George, MRCP, PhD, of University College London Hospitals, and Ajay Gupta, MD, PhD, of Queen Mary University of London, highlight the need for further study regarding the potential risk-benefit ratio of EPA- and DHA-based agents as well as combination therapies across a range of cardiovascular conditions.

“Further RCTs and postmarketing studies are required to resolve the remaining questions, particularly one that was raised by the disparity between REDUCE-IT and STRENGTH of EPA monotherapy versus the combination of EPA and DHA. Therefore, omega-3 PUFAs are still not fully ready for prime time, and physicians should keep an open mind on these compounds with acute awareness toward of the mixed evidence base and the potential risks of increased atrial fibrillation and bleeding when prescribing,” George and Gupta wrote.

This study, “Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials,” was published in the Journal of the American Heart Association.