Abstract

The term "flavonoid" encompasses a group of plant compounds, predominantly flavonoids, present in fruits, vegetables, and other plant-based foods. These compounds deliver significant health benefits, including potent antioxidant properties that protect cells from free radicals, thereby mitigating aging and disease. We assessed study quality and bias using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. Inclusion criteria specified that the studies must examine a natural flavonoid from fruits, must involve animal or human trials, must be original studies, and must be English articles on the flavonoid's health and cancer-prevention effects, excluding conference abstracts and single-case studies. We conducted a comprehensive search of major databases including PubMed, Web of Science, Embase, SCOPUS, and Google Scholar, reviewing six clinical trials with total sample sizes of over 50 to 1500 participants. The results indicate that consuming flavonoid-rich fruits can aid in cancer prevention by targeting angiogenic and cancer-protective pathways. We specifically selected tomatoes, mulberries, Amazon grapes, apples, and citrus fruits due to their well-documented high levels of flavonoids and the robust clinical evidence supporting their physiological effects. In particular, citrus fruits contain additional beneficial phytochemicals that complement the action of flavonoids, enhancing their overall health effects. The anti-cancer mechanisms of flavonoids are not well-defined in the scientific literature, suggesting a gap that this study aims to address. Our study provides novel contributions by demonstrating how flavonoid supplementation induces anti-cancer effects through angiogenesis, anti-inflammatory actions, antioxidant-induced apoptosis, and modulation of pathways like PI3K/Akt and MAPK. These effects were particularly notable in the prevention and progression of breast, colon, liver, and lung cancers, with statistical significance (p < 0.05). By elucidating specific mechanisms and pathways, this study contributes to the understanding of flavonoids' role in cancer prevention and underscores the potential for developing natural anti-cancer therapeutics through the inclusion of flavonoid-rich fruits in the diet. Future research should focus on randomized controlled trials assessing long-term effects of flavonoid supplementation in diverse populations, exploring optimal dosages, and understanding interactions with conventional cancer therapies to provide comprehensive evidence for clinical applications.

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