FATTY ACIDS IN PHYSIOLOGY AND PATHOLOGY: FOCUS ON ALPHA-LINOLENIC ACID (ALA) AND PUFAS

This thesis investigates the clinical and pathophysiological roles of polyunsaturated fatty acids (PUFAs), focusing on alpha-linolenic acid (ALA), and linoleic acid (LA), within a broad range of human biological processes. PUFAs are essential nutrients involved in modulating cell membrane fluidity, intracellular signaling, and gene regulation, as well as serving as precursors to bioactive lipid mediators such as eicosanoids and prostaglandins. Following a general overview of fatty acid classification, structure, metabolism, and biochemistry, the thesis explores the relevance of ALA and LA in emerging clinical domains including assisted reproduction, pregnancy, sarcopenia, and neuropsychiatric disorders like ADHD and depression, while identifying key factors influecing long-chain PUFA conversion efficiency and the impact of individual variables (sex, age, diet, genetics). The methodoloy comprises a narrative analysis of clinical, epidemiological, and experimental evidence published from 2005 to 2023, prioritizing studies on diverse human populations across various life stages, including children, older adults, and pregnant or lactating women. Results indicate that appropriate PUFA intake, especially from plant-based sources rich in ALA, is associated with positive effects on fertility, cognitive development, inflammation regulation, and the prevention of chronic diseases (cardiovascular, neurodegenerative, affective). Nevertheless, the literature reveals considerable heterogeneity in results, attributable to interindivdual differences in lipid metabolism and varying nutritional strategies across studies. Special attention is given to sensitive populations, such as children, the elderly, pregnant women, and those with neuropsychiatric conditions, where the omega-6/omeha-3 balance proves particularly crucial. The conclusion highlight the need for additional randomized clinical and interventional studies to clarify the efficacy of PUFA-based nutritional support in chronic disease prevention and management, and to define personalized protocols based on individual characteristics. The thesis provides new perspectives for the implementation of innovative, targeted dietary strategies, emphasizing the potential of PUFAs as adjuvants in conventional therapies and as key factors in public health promotion.