A B S T R A C T Background: The consumption of pomegranate juices and extracts has long been linked to many health benefits beyond nutrition, described mainly by innumerable preclinical studies. However, the European Food Safety Authority (EFSA) concluded in 2010 that a cause and effect relationship could not be established between the consumption of pomegranate-derived products and all the health claims presented. There are no additional EFSA opinions on health claims specifically addressed to

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... pomegranate in the last decade. Scope and approach: This review comprehensively compiles all human studies conducted on pomegranate. The aim is to discuss these studies critically to identify possible flaws and propose guidelines that might help establish a cause and effect relationship between pomegranate-derived product consumption and health. Key findings and conclusions: To date, 86 human studies have evaluated the health benefits of pomegranate juices and extracts. The most promising, albeit scarce, evidence is related to blood pressure improvement. Less evidence deals with inflammation, cancer, cognitive function, physical activity, and gut microbiota modulation (prebiotic effects). After a decade since EFSA's opinion, human evidence remains inconsistent, making it difficult to support most claimed health effects. The lack of effects and(or) data discrepancy might be attributable to design limitations, including insufficient product characterization and interindividual variability that influence pomegranate polyphenols' bioefficacy. New coordinated strategies between policy makers, research/academic institutions, and industry are needed to move forward. Therefore, this review presents a roadmap to conduct well-designed trials and cover existing gaps, which could establish a cause-effect relation between pomegranate consumption and health benefits beyond nutrition.