Dose‐response effect of marine‐derived omega‐3 fatty acids on erythrocyte membrane fatty acid content: double‐blind randomized controlled trial

Erythrocyte membrane content of EPA and DHA, the omega‐3 index (O3I), predicts cardiovascular disease mortality. Dietary intake of EPA+DHA is the main determinant of the O3I, yet the influence of other factors remains unclear. Our objective was to evaluate the dose‐response relationship of supplemental EPA+DHA intake on O3I, and by using a regression‐based approach, to identify predictors of treatment response that modulate the effects of supplementation. We conducted a placebo‐controlled, double blind, parallel study in healthy men and women with low EPA+DHA consumption. Subjects (n=125) were randomized to one of five doses (0, 300, 600, 900, 1,800 mg) of EPA+DHA given daily in fish oil supplements for approximately 5 months. A total of 116 subjects completed the study. There were no significant differences between groups at baseline. The O3I increased in a dose‐dependent manner (p<0.0001), with treatment alone predicting 67% of the variability in the O3I response with a quadratic fit. A multivariate model that included additional significant predictors: BMI, gender, age, and baseline O3I, explained 76.5% of the change in O3I. Thus, our results demonstrate the validity of the O3I as a biomarker of EPA+DHA supplementation and identify additional factors that may be used to tailor individual EPA + DHA recommendations in order to achieve an optimal O3I. Grant Funding Source : USDA