First-of-a-kind study finds ratio of EPA to DHA in omega-3 supplements affect heart disease risk factors differently – Meta-analysis

By Guan Yu Lim

- Last updated on GMT

Meta-analysis reveals that ratio of EPA/DHA in omega-3 supplements matters ©Getty Images
Meta-analysis reveals that ratio of EPA/DHA in omega-3 supplements matters ©Getty Images

Related tags Epa Dha omega-3 supplementation

Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are commonly associated with a reduced risk of coronary heart disease (CHD), but new research highlights how the ratio of EPA to DHA matter in influencing different risk factors.

The risk factors of heart disease typically include higher blood pressure, inflammation markers such as C-reactive protein levels (CRP), lipid profile (total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol) and heart rate.

In a new meta-analysis, researchers from Jordan, UAE and Canada showed that the EPA to DHA ratio in omega-3 affects blood pressure and CRP, but not lipid profile and heart rate.

There are many studies on the intake of EPA and DHA combination in reducing the risk of CHD, however, they use a varied range of ratio and dose of EPA and DHA.

It is not known whether the ratio of EPA to DHA in omega-3 supplements affect their efficacy as modulators for cardiovascular risk factors​,” researchers wrote.

To the best of our knowledge, no trial has been designed to investigate the effect of EPA to DHA ratio on metabolic factors associated with CHD​.”

Study design

Published in the Complementary Therapies in Medicine​ journal, the meta-analysis studied 92 clinical trials from two databases (PubMed and Cochrane Library) on EPA and DHA intake and CHD risk.

The clinical trials selected were all randomised, placebo controlled, and double blind.

The dosage of EPA and DHA used ranged from 850 to 15,000 mg/day.

Most studies provided EPA and DHA in capsules and used olive oil as control. In most studies, participants did not make any significant changes to their daily diet.


Data from the analysis showed that the ratio of EPA to DHA influenced CRP levels and systolic blood pressure.

A higher EPA to DHA ratio saw a greater reduction in CRP, which meant a reduction in inflammation.

Researchers explained this may be related to EPA’s ability to produce eicosanoids which have lower-pro-inflammatory potential.

However, a higher EPA to DHA ratio was also associated to an undesired greater increase in systolic blood pressure.

EPA and DHA ratio was not associated with lipid profile, diastolic blood pressure, or heart rate.

Researchers said both EPA and DHA were crucial as cardio-metabolic modulators: “At the cellular level, both influence physiochemical properties of cell membranes, both can alter ion channel functions, both are ligands for nuclear receptors, and the metabolites of both are key drivers of inflammation resolution and return to tissue homeostasis​.”

First of its kind

Previous meta-analyses have analysed certain risk factors of CHD such as triglyceride reduction from EPA and DHA combination, or studied the effect of individual EPA and DHA, however none have explored the effect of EPA to DHA ratio.

There was one previous analysis on omega-3 fatty acids in people with type 2 diabetes. The study found that a higher EPA/DHA ratio of > 1.5 resulted in a higher reduction in triglycercides compared to a ratio of ≤ 1.5.

However, researchers said these results cannot be generalised to the general population as it was restricted to patients with diabetes.

There were also previous studies in animal models, although researchers cautioned against these, adding: “Drawing any conclusion from animal studies should be carried out with caution due to differences in fatty acid metabolism and the fed fatty acid doses​.”

They recommended future RCTs should study the most efficient ratio of EPA and DHA for cardio-metabolic effects, “Identification of the most efficacious EPA to DHA ratio could redefine current recommendations concerning the beneficial cardio-metabolic effects of omega-3 fatty acids​.”

In addition, the higher EPA/DHA ratio was associated to higher systolic blood pressure in this meta-analysis, and would be worth examining further.


Source: Complementary Therapies in Medicine

“The ratio of eicosapentaenoic acid to docosahexaenoic acid as a modulator for the cardio-metabolic effects of omega-3 supplements: a meta-regression of randomized clinical trials”

Authors: Suhad AbuMweis , et al​.

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