Does hydroxytyrosol deserve a health claim? Effects of its supplementation on aging mechanism from preclinical to human intervention studies

The prevalence of non-communicable diseases with aging highlights the need for preventive strategies targeting mechanisms of degeneration. Hydroxytyrosol (HT), a phenolic compound from extra virgin olive oil (EVOO), has shown potential in preclinical research on its antioxidant, anti-inflammatory, metabolic, vascular, and microbiota-modulating effects; yet clinical evidence remains limited and inconclusive. While European Food Safety Authority (EFSA) has approved a health claim for the protective effect of HT on blood lipids against oxidative stress, this is limited to its naturally occurring form within EVOO, excluding supplements or fortified foods. This narrative review compiles evidence from preclinical and clinical studies, evaluating for the benefits on oxidative stress, inflammation, metabolic homeostasis, and vascular function of HT out of EVOO. Preliminary data also suggest roles in microbiota and epigenetic modulation. However, inconsistencies in human trials due to dose and population diversity limit firm conclusions. Future long-term, well-designed nutritional clinical trials incorporating omics approaches, especially metabolomic and metagenomic, and assessment of interindividual variability are essential to validate the health benefits of HT as stand-alone supplement.