Conversion of α-linolenic acid into n-3 long-chain polyunsaturated fatty acids: bioavailability and dietary regulation.

N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are essential for physiological requirements and disease prevention throughout life but are not adequately consumed worldwide. Dietary supplementation with plant-derived α-linolenic acid (ALA) has the potential to rebalance the fatty acid profile and enhance health benefits but faces challenges such as high β-oxidation consumption, low hepatic conversion efficiency, and high oxidative susceptibility under stress. This review focuses on the metabolic fate and potential regulatory targets of ALA-containing lipids in vivo, specifically the pathway from the gastrointestinal tract to the lymph, blood circulation, and liver. We propose a hypothesis that positively regulates the conversion of ALA into n-3 LCPUFAs based on the model of "fast" or "slow" absorption, transport, and hepatic metabolic fate. Furthermore, the potential effects of dietary nutrients on the metabolic conversion of ALA into n-3 LCPUFAs are discussed. The conversion of ALA is differentially regulated by structured lipids, phospholipids, other lipids, carbohydrates, specific proteins, amino acids, polyphenols, vitamins, and minerals. Future research should focus on designing a steady-state and precise delivery system for ALA, coupled with specific nutrients or phytochemicals, to effectively improve its metabolic conversion and ultimately achieve synergistic regulation of nutrition and health effects.