Omega-3 Fatty Acids Linked to BP Reductions, Meta-analysis Hints

Consuming up to 3 grams per day of omega-3 polyunsaturated fatty acids (PUFAs) in food and/or through dietary supplements is associated with significant reductions in blood pressure, a meta-analysis suggests.

At the 3 g/day dose, individuals saw an average decrease of 4.5 mm Hg in systolic blood pressure (SBP) if they had established hypertension and a reduction of about 2 mm Hg on average if they did not.

“These findings were slightly stronger in studies where the average participant age was ≥ 45 years for systolic BP,” write Xin Zhang, PhD (Macau University of Science and Technology, China), and colleagues. “We also found evidence of a stronger, approximately linear dose-response relationship among hyperlipidemic and hypertensive populations, suggesting that this is a population that could be more responsive to the beneficial impacts of omega-3 PUFA intake on reductions in BP.” The study was published June 1, 2022, in the Journal of the American Heart Association.

As part of a heart-healthy diet, the American Heart Association recommends consuming seafood high in omega-3 PUFAs by eating one to two meals per week of cooked, but not fried, fatty fish like salmon and tuna. However, they do not recommend supplementation for the primary prevention of CAD.

Recent high-profile trials looking at the efficacy of prescription-strength omega-3 fatty acid formulations have turned up mixed results. For example, STRENGTH failed to show a reduction in CV events in patients with elevated triglycerides and low HDL cholesterol, while REDUCE-IT demonstrated a reduction in CV events in statin-treated patients with high triglyceride levels and either established CV disease or diabetes plus additional risk factors. In another trial, diabetic patients who lacked established CV disease saw no reduction in serious vascular events with daily supplementation of 1 g of fish oil in the form of 460 mg of eicosapentaenoic acid (EPA) and 380 mg of docosahexaenoic acid (DHA).

Andrew Freeman, MD (National Jewish Health, Denver, CO), who was not involved in the new meta-analysis, noted that DHA and EPA supplements are “notoriously unequal,” which is why the vast majority of medical associations don’t recommend over-the-counter fish oil supplements. Then there is the issue of trying to glean dosing information from meta-analyses.

“I’m leery of meta-analyses like these because these studies are using different supplements, different doses, different approaches, different formulations. It’s not clear what the dietary sources were, so there's just a lot of confounders,” Freeman said. “They were able to find a potential signal in the noise, but I guess I would argue that this is somewhat noisy. If this was a study that actually did a randomized controlled trial and gave people some set amount of DHA and EPA in whatever ratios, and then followed them, that would be much more convincing.”

Senior study author Xinzhi Li, MD, PhD (Macau University of Science and Technology), said in an email that while it’s true that there were many variations among the studies, the researchers “tried to tear out these influential factors by subgrouping the included trials to account for these differences in our analyses.”

Li added that in many of these subgroup analyses, they were able to obtain the optimal doses that fell between 2-3 g/day using 1-stage regression models.

“Of course, it would be more convincing if we use stricter clinical selection criteria, such as the absorbed fatty acid (as a more accurate exposure level) and standardized blood pressure methods,” Li said. “Due to the limited number of studies that met these criteria, we could not obtain a conclusive result using the 1-stage regression method, which needs a reasonable sample size to estimate the dose-response relationship.”

Benefits in High-risk Populations

For their meta-analysis, Zhang and colleagues examined 71 RCTs published between 1987 and 2020 that included parallel or crossover designs tracking intake of DHA/EPA (through diet or supplements) and systolic and/or diastolic BP in adults aged 18 years and older. The average intake was 2.8 g/day for 10 weeks in the 4,973 individuals, who ranged in age from 22 to 86 years.

Compared with those not consuming DHA/EPA, people who consumed between 2 and 3 g daily saw  systolic reductions of 2.6 mm Hg in systolic BP and 1.8 mm Hg in diastolic BP. At levels above 3 g/day, the reductions were greatest in hypertensive patients, with a nearly 4-mm Hg reduction in systolic BP at a 5 g/day dose. For those without hypertension however, the higher dose resulted in no additional decrease. In subgroup analyses, patients with versus without hyperlipidemia had greater reductions in diastolic BP at doses of 2-3 g/day. Zhang and colleagues say that information may be important given the increasing prevalence of metabolic syndromes.

“It could be that high-risk population, such as those with hypertension and hyperlipidemia, could benefit differently from omega-3 PUFA intake supplementation in comparison to younger and healthier populations, particularly since omega-3 PUFA is hypothesized to interact with many pathways, such as triglycerides, inflammation, and heart rate,” they write.

“If this was a study that actually did a randomized controlled trial and gave people some set amount of DHA and EPA in whatever ratios, and then followed them, that would be much more convincing.” Andrew Freeman

In an accompanying editorial, Marc George, MRCP, PhD (University College London Hospitals NHS Foundation Trust, England), and Ajay Gupta, MD, PhD (Royal London Hospital, England), say that on a population level a 2.6-mm Hg reduction in BP has the potential to reduce deaths from stroke and ischemic heart disease. In the United States, they add, such a reduction could translate to a decrease of more than 30,000 CV events per year among middle-aged adults.

However, George and Gupta note that the meta-analysis fails to shed light on the role of omega-3 PUFAs in people already on BP-lowering medications. “This is important for understanding these apparently greater reductions, because previous reports suggest that the BP reduction may be attenuated if they also included participants who were on treatment,” they add.

As for the discordant findings of STRENGTH and REDUCE-IT, George and Gupta say the BP-lowering impact of omega-3 PUFAs together with other pleiotropic effects may be “the missing link” that explains the CV risk reduction seen in REDUCE-IT, since “there was a reduction in new-onset hypertension in those on active treatment, alluding to a BP-lowering effect.”

Freeman told TCTMD that while he does prescribe icosapent ethyl (Vascepa; Amarin) for some patients, he tells those who don’t need a prescription supplement that they are better off getting EPA and DHA from the many types of readily-available edible algae. Still, he said, studies are needed to better clarify the uncertainties around omega-3 PUFAs and CV risk reduction.

“Before people start adding supplements or really going up on whatever fish oil type supplement or prescription they're taking, they really should do it in concert with good quality data and a discussion with their care team,” he added.