Microalgae have been increasingly considered as a sustainable “biofactory” with huge potentials to fill up the current and future shortages of food and nutrition. They have become an economically and technologically viable solution to produce a great diversity of high-value bioactive compounds, including n-3 polyunsaturated fatty acids (PUFA). The n-3 PUFA, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), possess an array of biological activities and positively affect a number of diseases, including cardiovascular and neurodegenerative disorders. As such, the global market of n-3 PUFA has been increasing at a fast pace in the past two decades. Nowadays, the supply of n-3 PUFA is facing serious challenges as a result of global warming and maximal/over marine fisheries catches. Although increasing rapidly in recent years, aquaculture as an alternative source of n-3 PUFA appears insufficient to meet the fast increase in consumption and market demand. Therefore, the cultivation of microalgae stands out as a potential solution to meet the shortages of the n-3 PUFA market and provides unique fatty acids for the special groups of the population. This review focuses on the biosynthesis pathways and recombinant engineering approaches that can be used to enhance the production of n-3 PUFA, the impact of environmental conditions in heterotrophic cultivation on n-3 PUFA production, and the technologies that have been applied in the food industry to extract and purify oil in microalgae and protect n-3 PUFA from oxidation.

Today’s consumers are increasingly aware of the beneficial effects of n-3 PUFA in preventing, delaying, and intervening various diseases, such as coronary artery disease, hypertension, diabetes, inflammatory and autoimmune disorders, neurodegenerative diseases, depression, and many other ailments. The role of n-3 PUFA on aging and cognitive function is also one of the hot topics in basic research, product development, and clinical applications. For decades, n-3 PUFA, especially EPA and DHA, have been supplied by fish oil and seafood. With the continuous increase of global population, awareness about the health benefits of n-3 PUFA, and socioeconomic improvement worldwide, the supply chain is facing increasing challenges of insufficient production. In this regard, microalgae have been well considered as promising sources of n-3 PUFA oil to mitigate the supply shortages. The use of microalgae to produce n-3 PUFA-rich oils has been explored for over two decades and some species have already been used commercially to produce n-3 PUFA, in particular EPA- and/or DHA-rich oils. In addition to n-3 PUFA, microalgae biomass contains many other high value biomolecules, which can be used in food, dietary supplement, pharmaceutical ingredient, and feedstock. The present review covers the health benefits of n-3 PUFA, EPA, and DHA, with particular attention given to the various approaches attempted in the nutritional interventions using EPA and DHA alone or combined with other nutrients and bioactive compounds towards improved health conditions in people with mild cognitive impairment and Alzheimer’s disease. It also covers the applications of microalgae n-3 PUFA in food and dietary supplement sectors and the economic and environmental sustainability of using microalgae as a platform for n-3 PUFA-rich oil production.

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