Creative Touch Permanent Makeup and Aesthetics

Dihomo-gamma-linolenic acid (DGLA) is a 20-carbon omega-6 polyunsaturated fatty acid (PUFA) produced when gamma-linolenic acid (GLA) is elongated by the enzyme ELOVL5. It sits at the most consequential branch point in the omega-6 pathway: from DGLA, metabolism can proceed in two quite different directions depending on which enzymes are most active. Delta-5 desaturase converts DGLA to arachidonic acid (AA), feeding the pro-inflammatory COX and LOX eicosanoid cascades. Alternatively, COX-1 converts DGLA to prostaglandin E1 (PGE1), and 15-lipoxygenase generates 15-HETrE, both anti-inflammatory mediators. DGLA is therefore neither straightforwardly pro- nor anti-inflammatory; its net effect depends on the metabolic environment in which it operates. ^[2]

The Branch Point and What Controls It

Delta-5 desaturase activity is the key variable. When delta-5 desaturase is highly active, DGLA is efficiently converted to AA and the pro-inflammatory branch dominates. When delta-5 desaturase activity is lower, or when it is competitively inhibited, DGLA accumulates and flows preferentially toward PGE1 and 15-HETrE production. EPA, the omega-3 fatty acid, is a direct competitive inhibitor of delta-5 desaturase; its presence in membrane phospholipids slows the DGLA-to-AA conversion and shifts the balance toward the anti-inflammatory branch. This is one of the mechanisms through which combined GLA and EPA supplementation produces a more pronounced anti-inflammatory effect than either alone; GLA increases the DGLA pool whilst EPA reduces its conversion to AA. ^[1]

Relevance to Inflammatory Skin Conditions

In the context of atopic dermatitis, where the delta-6 desaturase step converting LA to GLA is often impaired, DGLA is the proximate mediator whose deficit explains much of the inflammatory picture. Reduced GLA production means a reduced DGLA pool, which means less PGE1 and 15-HETrE available to suppress leukotriene B4 (LTB4) activity. GLA supplementation is clinically relevant precisely because it restores DGLA availability directly, bypassing the impaired enzymatic step upstream. The anti-inflammatory benefit attributed to GLA in atopic presentations is mechanistically a DGLA effect. ^[2]