The Examine.com page on fish oil cites 735 unique references, which speaks to the vast array of research investigating health effects of the two primary marine-based omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Much of fish oil’s health effects come from its incorporation into cell membranes, where it is used during times of stress to help reduce inflammation. The cellular membrane ratio of omega-3 to omega-6 fatty acids is important because the stress response will use either one without discrimination, and the omega-6 fatty acids are more likely to promote inflammation.
The standard Western diet has a very high omega-6 to omega-3 ratio (15:1), which is associated[1] with many inflammatory conditions including cardiovascular disease, cancer, and autoimmune diseases. By supplementing fish oil, the omega-6 to omega-3 ratio is reduced, which can reduce inflammation and hence lower susceptibility to various chronic diseases common among industrialized societies.
Omega-3 and omega-6 fatty acids do not just compete at the cell membrane level, however, as they also share a class of enzymes that are responsible for their bioconversion. For instance, both alpha-linolenic acid (ALA, a type of omega-3) and linoleic acid (a type of omega-6) compete for desaturase enzymes (as shown in Figure 1) that are responsible for converting them into EPA and arachidonic acid, respectively.

It is possible that supplementing fish oil containing preformed EPA and DHA may circumvent the problem of competition for these enzymes. However, it has been demonstrated[2] in rats that feeding fish oil in combination with saturated fatty acids (SFAs) increases the incorporation of EPA and DHA in cell membranes to a greater extent than feeding fish oil in combination with omega-6 fatty acids. Thus, it is important to understand how the background diet may influence the effect of fish oil supplementation in humans.
The study under review aimed to compare the degree of EPA and DHA incorporation into cell membranes and the effects on blood lipids in humans consuming a SFA-enriched diet or an omega-6-enriched diet.
The benefits of fish oil may come in part through balancing the body’s ratio of omega-3 to omega-6 fatty acids, which has downstream anti-inflammatory effects. Human studies have not yet investigated how fat composition in the background diet may influence the effect of fish oil supplementation. The current study aimed to fill this knowledge gap.