Dihomo-γ-Linolenic Acid in Human Health and Disease

Polyunsaturated fatty acids (PUFAs) play pivotal roles in human physiology, acting as structural components of cell membranes and precursors to potent bioactive lipid mediators. While omega-6 (n-6) PUFAs have historically been viewed predominantly through the lens of pro-inflammatory processes, a more nuanced understanding has emerged regarding their complex metabolic pathways. This review focuses on gamma-linolenic acid (GLA, 18:3n-6) and its immediate elongation product, dihomo-γ-linolenic acid (DGLA, 20:3n-6). We synthesize current evidence regarding the biosynthesis of these fatty acids, heavily influenced by desaturase enzymes (FADS1 and FADS2) and dietary factors. The review highlights the dual nature of DGLA: its metabolites possess potent anti-inflammatory and vasodilatory properties, yet its circulating levels and the LA:DGLA ratio serve as critical biomarkers. Emerging literature points to the predictive value of these lipids in assessing zinc status, cardiovascular mortality, metabolic disorders, and adherence to dietary patterns. Furthermore, the therapeutic potential of GLA and DGLA supplementation – particularly in combination with omega-3 PUFAs – is explored across various clinical conditions, including inflammatory diseases, allergic symptoms, and neurodevelopmental disorders. By synthesizing data from recent prospective observational studies, randomized controlled trials, and mechanistic reviews, this article provides a comprehensive overview of the multifaceted roles of GLA and DGLA in human health.