Abstract
Hydroxytyrosol (HXT), a phenolic compound from olive, shows great potential as a neuroprotective agent and a translational target for claim-ready nutrition and food products. Human studies increasingly report benefits for vascular function, inflammatory tone, and early cognitive/psychomotor outcomes, consistent with engagement of redox and signalling pathways (Keap1-Nrf2-ARE, PI3K/Akt-ERK, and AMPK-SIRT1-PGC-1α). HXT is rapidly absorbed and likely reaches the brain, acting on endothelial and microglial targets. On the neurovascular axis, it reduces oxidative stress, preserves nitric-oxide bioavailability, lower inflammatory markers, and favourable intrinsic connectivity. For product development, bitterness from oleuropein-rich inputs can be mitigated by hydrolysis, followed by structure-guided delivery to balance sensory quality with exposure. Viable formats include cyclodextrin inclusion, microencapsulation, and (micro)emulsions in lipid matrices, plus stability engineering for aqueous systems (acidification, chelation, low-oxygen handling, or barrier packaging). Matrix effects are consequential; some proteins and fibers may decrease HXT bioaccessibility, whereas lipid phases and microstructured carriers often enhance it. Clinically, recommended doses are ~7-15 mg/day chronically and ~30-60 mg acutely. As conclusions of this review, future work should prioritize harmonized pharmacokinetics-pharmacodynamics readouts, cognition anchored to a compact neurovascular/blood-brain barrier biomarker core, and head-to-head comparisons of manufacturable delivery formats.