Background: Autoimmune diseases are chronic disorders in which the immune system does not recognize and attacks one self's healthy components. In this context, although natural remedies might represent a promising therapeutic strategy, evidence regarding Citrus flavonoids is still controversial. Objective: To summarize and critically discuss the clinical evidence on the effects of Citrus flavonoids for the management of autoimmune diseases. Method: A systematic review of articles has been carried out independently by two Authors using MEDLINE, Scopus and ISI Web of Science databases. Search terms comprised keywords related to Citrus flavonoids and autoimmune diseases. The last search was performed on March 16, 2021. No language restrictions were applied. Systematic review and study selection were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Before starting the review, Authors defined the types of articles to be included. Three reviewers independently carried out the extraction of papers. Results: Ten clinical studies fulfilled the eligibility criteria and were included in the final review. Conclusion: The studies discussed in this review are heterogeneous. Indeed, some studies suggest the use of Citrus flavonoids in the frame of autoimmune disorders, whereas others discourage it. Hence, this systematic review highlights the need of further large-scale clinical studies to define the exact role of Citrus flavonoids in the management of autoimmune diseases (PROSPERO number CRD42021234903).
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