Effects of Phytochemicals from Fermented Food Sources in Alzheimer's Disease In Vivo Experimental Models: A Systematic Review

The socioeconomic burden of Alzheimer's Disease (AD) stems from its characteristic multifactorial etiology and, implicitly, the difficulties associated with its treatment. With the increase in life expectancy and health awareness, nutraceuticals and functional foods are filling in the gaps left by the limitation of classical medical treatment in chronic conditions associated with lifestyle factors, such as neurological disorders. Processes, such as fermentation that enhance food phytochemical content are garnering increased attention due to their functional and health-related properties. This systematic review aims to provide an overview of the evidence of phytochemicals from fermented food sources inducing therapeutic outcomes and cognitive benefits from in vivo experimental models of Alzheimer's Disease. The present systematic review was conducted in accordance with PRISMA guidelines. Searches were performed in the following databases: MEDLINE, Embase, Cochrane, Scopus, Google Scholar, and Science Citation Index Expanded (Web of Science) by two independent reviewers. Titles and abstracts yielded by the search were screened for eligibility against the inclusion criteria. The search strategy yielded 1899 titles, encompassing studies from 1948 to 2022. After the removal of duplicates, and screening of titles, abstracts, and full texts, thirty three studies obtained from the original search strategy and seven studies from references satisfied the inclusion criteria and were included in the present systematic review. Several studies have emphasized the potential of fermentation to yield small-molecule phytochemicals that are not present in raw products. When these phytochemicals are combined, their collective strength has demonstrated the ability to exceed the antioxidant, anti-inflammatory, and neuroprotective benefits of individual phytochemicals when given in their pure form. Among the various fermented foods that have been studied, soy isoflavones obtained through fermentation have shown the most substantial evidence of altering phytochemical content and improving outcomes in animal models of AD. While promising in initial results, other fermented foods and traditional medicines require more detailed research in order to establish their effectiveness and proper utilization. As is, many of the experimental designs lacked phytochemical analysis of the used fermented product or comparison with the non-fermented counterpart. This, coupled with proper reporting in animal studies, will significantly raise the quality of performed studies as well as the weight of obtained results.