Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

Clinic of Obstetrics and Gynecology Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Department of Applied Ecology Faculty of Environmental Sciences Czech University of Life Sciences Prague Kamýcká 129 165 00 Prague Czech Republic

Department of Histology and Embryology Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Department of Medical Biology Jessenius Faculty of Medicine Comenius University in Bratislava 036 01 Martin Slovakia

Department of Physiology and Biophysics Weill Cornell Medicine in Qatar Education City Qatar Foundation Doha 24144 Qatar

Department of Physiology and Pharmacology Vittorio Erspamer Faculty of Pharmacy and Medicine Sapienza University 00185 Rome Italy

Department of Radiation Oncology University Hospital Bonn Rheinische Friedrich Wilhelms Universität Bonn 53127 Bonn Germany

European Association for Predictive Preventive and Personalised Medicine EPMA 1150 Brussels Belgium

Lambda Life JSC 851 01 Bratislava Slovakia

Museum of Literature in Moravia Klášter 1 664 61 Rajhrad Czech Republic

Predictive Preventive Personalised Medicine Department of Radiation Oncology University Hospital Bonn Rheinische Friedrich Wilhelms Universität Bonn 53127 Bonn Germany

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