Overconsumption of Omega-6 Polyunsaturated Fatty Acids (PUFAs) versus Deficiency of Omega-3 PUFAs in Modern-Day Diets: The Disturbing Factor for Their "Balanced Antagonistic Metabolic Functions" in the Human Body

Abstract

Polyunsaturated fatty acids (PUFAs) contain ≥2 double-bond desaturations within the acyl chain. Omega-3 (n-3) and Omega-6 (n-6) PUFAs are the two known important families in human health and nutrition. In both Omega families, many forms of PUFAs exist: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) from the n-3 family and linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA) from the n-6 family are the important PUFAs for human health. Omega-3 and Omega-6 PUFAs are competitively metabolized by the same set of desaturation, elongation, and oxygenase enzymes. The lipid mediators produced from their oxidative metabolism perform opposing (antagonistic) functions in the human body. Except for DGLA, n-6 PUFA-derived lipid mediators enhance inflammation, platelet aggregation, and vasoconstriction, while those of n-3 inhibit inflammation and platelet aggregation and enhance vasodilation. Overconsumption of n-6 PUFAs with low intake of n-3 PUFAs is highly associated with the pathogenesis of many modern diet-related chronic diseases. The volume of n-6 PUFAs is largely exceeding the volume of n-3PUFAs. The current n-6/n-3 ratio is 20-50/1. Due to higher ratios of n-6/n-3 in modern diets, larger quantities of LA- and AA-derived lipid mediators are produced, becoming the main causes of the formation of thrombus and atheroma, the allergic and inflammatory disorders, and the proliferation of cells, as well as the hyperactive endocannabinoid system. Therefore, in order to reduce all of these risks which are due to overconsumption of n-6 PUFAs, individuals are required to take both PUFAs in the highly recommended n-6/n-3 ratio which is 4-5/1.

Figure 1

The most nutritionally important n-3 and n-6 PUFAs and their chemical structure. (a) n-3 PUFAs. (b) n-6 PUFAs. Adapted from Saini and Keum [12].

Figure 2

The chemical structure of linoleic acid (LA, 18:2n-6 or 18:2^Δ9,12) and its two alternative systematic nomenclature. LA contains 2 double bonds, or desaturations, at the Δ9 and Δ12 carbon positions from the carboxyl (Δ terminus) or at the n-6 and n-9 carbon positions counted from the methyl (-n) end [27].

Figure 3

Biosynthesis of Omega-3 and Omega-6 PUFAs is shown at the center. The oxidative metabolism of LA, DGLA, AA, EPA, and DHA into their respective lipid mediators through oxygenase enzymes is also shown in the right and left sides. COX: cyclooxygenase; LOX: lipoxygenase; MPO: myeloperoxidase [19, 33, 48, 60].