What is the omega-3 (n-3) fatty acid pathway?

From the Guidelines

The omega-3 fatty acid pathway is crucial for optimal health, and consuming 1-2 grams of combined EPA/DHA daily is recommended for its anti-inflammatory effects and benefits on cardiovascular health, brain development, and inflammatory responses. The pathway begins with alpha-linolenic acid (ALA), which is converted through a series of enzymatic reactions into eicosapentaenoic acid (EPA) and then docosahexaenoic acid (DHA) 1. These conversions occur through desaturation and elongation processes in the endoplasmic reticulum and peroxisomes. EPA and DHA serve as precursors for anti-inflammatory mediators called resolvins, protectins, and maresins, which help resolve inflammation 1.

Key Points

• Omega-3 fatty acids compete with omega-6 fatty acids for the same enzymes, particularly cyclooxygenase (COX) and lipoxygenase (LOX), which convert them into different types of eicosanoids 1.
• Omega-3-derived eicosanoids tend to be anti-inflammatory, while omega-6-derived ones are generally pro-inflammatory 1.
• For optimal health, consuming omega-3 rich foods like fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts is recommended, or supplementing with 1-2 grams of combined EPA/DHA daily 1.
• The evidence supporting the clinical benefits of omega-3 fatty acids derive from population studies and randomized, controlled trials, and new information has emerged regarding the mechanisms of action of these nutrients 1.

Benefits of Omega-3 Fatty Acids

• Reduce the number of deaths from heart disease and all causes 1
• Help resolve inflammation and return to homeostasis 1
• Potentially counteract loss of muscle mass 1
• Enhance muscle protein synthesis and/or decrease the expression of factors regulating muscle protein breakdown 1

From the Research

Omega-3 Fatty Acid Pathway

• The omega-3 fatty acid pathway involves the metabolism of omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in oily fish and fish oil supplements 2, 3.
• EPA and DHA have been shown to have anti-inflammatory effects, including inhibiting the production of pro-inflammatory cytokines and eicosanoids, and promoting the production of anti-inflammatory resolvins, protectins, and maresins 2, 4.
• The mechanisms underlying the anti-inflammatory actions of EPA and DHA include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor κB, and activation of the anti-inflammatory transcription factor peroxisome proliferator-activated receptor γ 2.
• Omega-3 fatty acids have been linked to various health benefits, including reduced inflammation, improved cardiovascular function, and potential benefits in the management of inflammatory and autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, and ulcerative colitis 2, 3, 4.
• The conversion of alpha-linolenic acid (ALA) to EPA and DHA is inefficient, and therefore, it is necessary to obtain adequate amounts of EPA and DHA through fish and fish-oil products or enriched soy oil 5.
• Recent studies have suggested that increasing omega-3 intake may have little or no effect on mortality or cardiovascular health, although some evidence suggests that ALA may slightly reduce the risk of cardiovascular events and CHD mortality 6.

Key Findings

• EPA and DHA have anti-inflammatory effects and may be beneficial in the management of inflammatory and autoimmune diseases 2, 4.
• Omega-3 fatty acids have been linked to various health benefits, including reduced inflammation and improved cardiovascular function 2, 3.
• The conversion of ALA to EPA and DHA is inefficient, and therefore, it is necessary to obtain adequate amounts of EPA and DHA through fish and fish-oil products or enriched soy oil 5.
• Recent studies have suggested that increasing omega-3 intake may have little or no effect on mortality or cardiovascular health, although some evidence suggests that ALA may slightly reduce the risk of cardiovascular events and CHD mortality 6.

Omega-3 Fatty Acid Sources

• Oily fish and fish oil supplements are rich sources of EPA and DHA 2, 3.
• Enriched soy oil is a plant-based source of omega-3 fatty acids, including stearidonic acid (SDA), which can be converted to EPA more efficiently than ALA 5.
• ALA is found in plant-based sources, such as flaxseed and chia seeds, but its conversion to EPA and DHA is inefficient 5.