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

A large number of studies have demonstrated the effects of omega- 3 supplements containing mixtures of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), known to favorably affect many modifiable risk factors of coronary heart disease (CHD). These studies have used diverse ratios and doses of EPA and DHA. However, it is not known whether the ratio of EPA to DHA in omega-3 supplements affect their efficacy as modulators for cardiovascular risk factors. This meta-regression aimed to investigate the effect of different ratios of EPA to DHA on risk factors associated with CHD including lipid profile, blood pressure, heart rate, and inflammation. A regression analysis was carried out on 92 clinical trials with acceptable quality (Jadad score ≥ 3) that were previously identified from two databases (PubMed and Cochrane Library). Data from studies that met the inclusion criteria for this analysis showed that the ratio of EPA to DHA was not associated with lipid profile, diastolic blood pressure, or heart rate. With all studies, the ratio of EPA to DHA was associated with C-reactive protein (CRP) (β = -1.3121 (95 % CI: -1.6610 to -0.9543), that is, the higher the EPA to DHA ratio, the greater the reduction. Using only studies that supplied EPA and DHA in the range of 2 g–6 g, the ratio of EPA to DHA was also associated with CRP (β = -2.10429 and 95 % CI: -3.89963 to -0.30895); that is, an even more pronounced reduction in CRP with a higher EPA to DHA ratio. Systolic blood pressure was only associated with an increasing EPA to DHA ratio in the 2 g–6 g range (β = 5.47129 and 95 % CI: 0.40677–10.53580), that is, a higher EPA to DHA ratio within this dose range, the greater the increase in SBP. Current data suggest that the EPA to DHA ratio only correlates to the modulation of CRP by omega-3 supplementation of EPA and DHA, and SBP in studies that supplemented EPA and DHA in the range of 2 g–6 g, shedding light on potential differential effects of EPA vs. DHA on inflammation and systolic blood pressure.