Omega-3 Polyunsaturated Fatty Acids (EPA and DHA)

Mechanism

🐟 Eicosapentaenoic Acid (EPA)

• Structure: 20 carbons with five double bonds.
• Function: Precursor of eicosanoids of the series with lower proinflammatory potential (Prostaglandins of series 3 and Leukotrienes of series 5).
• It plays a preferential role in the systemic reduction of cardiovascular risk.

🧠 Docosahexaenoic Acid (DHA)

• Structure: 22 carbons with six double bonds.
• Function: Main structural lipid constituent of the membranes of the retina and the cerebral cortex.
• Essential for fetal neurological development during the third trimester of pregnancy.

Mechanism of anti-inflammatory and lipid action

Omega-3 fatty acids regulate the inflammatory cellular response and serum lipid profile through three metabolic pathways:

1. Competitive Displacement in the Membrane

EPA and DHA are competitively incorporated into the phospholipids of cell membranes at the expense of omega-6 fatty acids (such as arachidonic acid). When a cellular inflammatory stimulus is triggered, phospholipases release EPA and DHA from the membrane. These compete with arachidonic acid for the enzymes cyclooxygenase (COX) and lipoxygenase (LOX), producing substantially less potent inflammatory mediators that decrease platelet aggregation and leukocyte chemotaxis.

2. Biosynthesis of Specialized Pro-Resolving Mediators (SPMs)

EPA and DHA are converted enzymatically locally into highly active lipid metabolites called resolvins (series E and D), protecins and maresins. These compounds act on specific cellular receptors to actively stop the migration of neutrophils, promote the clearance of cellular debris by macrophages and accelerate the resolution of the tissue inflammatory process.

3. Lipid Regulation via PPAR-α

At the liver level, omega-3 fatty acids act as high-affinity ligands for the nuclear receptors PPAR-α (Peroxisome Proliferator-Activated Receptor Alpha). This activation significantly increases the transcription of enzymes involved in the β-oxidation of mitochondrial fatty acids, reduces the synthesis of apolipoprotein C-III and inhibits diacylglycerol acyltransferase, which results in a drastic decrease in the hepatic production and secretion of triglycerides in the form of VLDL.

Indicators and dose

Clinical Indications and Dosage

Indicated for complementary treatment in Severe hypertriglyceridemia (> 500 mg/dL) to prevent acute pancreatitis, and for the secondary prevention of cardiovascular events in high-risk patients.

2 to 4 g of purified omega-3 ethyl esters are prescribed orally together with fatty foods daily to optimize their intestinal micellar absorption.

Security

Risk of Atrial Fibrillation and Prolonged Hemorrhage

Large-scale controlled clinical trials have revealed that supplementation with high doses of purified omega-3 (> 4 g/day) is associated with an increased relative risk of developing atrial fibrillation in patients with pre-existing cardiovascular risk factors. Likewise, due to its antiplatelet effect mediated by the reduction of thromboxane A2, high doses may slightly prolong bleeding time, requiring monitoring in combination with antiplatelets or anticoagulants.