Omega-3 fatty acids — specifically the EPA (eicosapentaenoic acid) and the DHA (docosahexaenoic acid) — are the polyunsaturated fatty acids that are the essential precursors of the anti-inflammatory eicosanoids, resolvins, and protectins. The omega-3 fatty acids are unique among the fatty acids in that they are not the precursors of the pro-inflammatory eicosanoids (the prostaglandins, the thromboxanes, and the leukotrienes that are synthesised from the arachidonic acid, the omega-6 fatty acid that is abundant in the Western diet). Instead, the EPA and the DHA are the precursors of the resolvins (the resolution-phase interaction proteins), of the protectins (the neuroprotectins), and of the maresins (the macrophage-derived mediators of the resolution) — the lipid mediators that actively promote the resolution of the inflammation and that are deficient in the chronic inflammatory conditions. The omega-3 fatty acids also modulate the membrane fluidity, the signal transduction, and the gene expression through the activation of the PPAR (peroxisome proliferator-activated receptor) nuclear receptors and through the inhibition of the NF-kappaB signalling pathway. Without adequate omega-3 fatty acids and their anti-inflammatory mediators, the chronic inflammation develops, the autoimmune diseases progress, and the cardiovascular disease accelerates — the hallmark of the omega-3 deficiency and of the high omega-6-to-omega-3 ratio that is characteristic of the Western diet. The typical dietary omega-3 intake in the developed world is 100-200mg daily (from the fish, the shellfish, and the algae), which is well below the recommended intake of 1000-2000mg daily of the combined EPA and DHA — making the omega-3 deficiency one of the most common and most consequential nutritional deficiencies in the modern world.
Omega-3 and the Inflammatory Resolution
The inflammation has two phases — the initiation phase (which is characterised by the recruitment of the neutrophils and the macrophages to the site of the injury or the infection, and which is mediated by the pro-inflammatory eicosanoids that are synthesised from the arachidonic acid) and the resolution phase (which is characterised by the switch from the pro-inflammatory to the anti-inflammatory lipid mediators, the cessation of the neutrophil recruitment, the induction of the macrophage clearance of the cellular debris, and the restoration of the tissue homeostasis). The resolution phase is mediated by the specialised pro-resolving mediators (SPMs) — the resolvins, the protectins, and the maresins — which are synthesised from the EPA and the DHA by the lipoxygenase and the cyclooxygenase enzymes. Without adequate omega-3 fatty acids, the resolution phase is impaired, the inflammation becomes chronic, and the tissue damage accumulates — which is the primary mechanism of the chronic inflammatory diseases, including the rheumatoid arthritis, the inflammatory bowel disease, the asthma, the atherosclerosis, and the metabolic syndrome.
The clinical importance of the omega-3 fatty acids for the inflammatory resolution is underscored by the observation that the omega-3 supplementation reduces the inflammatory markers and improves the symptoms in people with the chronic inflammatory conditions. A meta-analysis of 68 RCTs in over 4600 participants found that the omega-3 supplementation at 1000-4000mg daily significantly reduced the CRP (by 20-30%), reduced the IL-6 (by 15-25%), and improved the DAS28 score (by 0.3-0.5 points) in people with the rheumatoid arthritis — demonstrating the potent anti-inflammatory effect of the omega-3 fatty acids in the chronic inflammatory conditions.
Practical Application
For general omega-3 supplementation for the anti-inflammatory and cardiovascular support, the evidence-based approach is to supplement with 1000-2000mg of combined EPA and DHA daily (from the fish oil or from the algae oil — the latter is the vegan source of the DHA and the EPA). The omega-3 supplements should be standardised to the EPA and DHA content per capsule (not just the total fish oil weight), and they should be taken with the meals (to enhance the absorption and to reduce the gastrointestinal side effects). The balanced ratio of the omega-3 to the omega-6 fatty acids is as important as the absolute omega-3 intake — the typical Western diet has an omega-6-to-omega-3 ratio of 15:1 to 20:1, whereas the optimal ratio for the inflammatory balance is approximately 4:1 or lower. For comprehensive anti-inflammatory and cardiovascular support, omega-3 pairs well with the vitamin D (which has complementary immunomodulatory effects and which is increasingly recognised as an important determinant of the inflammatory status), with the vitamin K2 (which works synergistically with the omega-3 for the cardiovascular health and for the bone health), with the curcumin (which has complementary anti-inflammatory effects through the NF-kappaB inhibition), and with the magnesium (which is a cofactor for many of the enzymes of the fatty acid metabolism and which has complementary effects on the cardiovascular health).
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