Phenol‐enriched olive oils modify paraoxonase‐related variables: A randomized, crossover, controlled trial

Scope Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short‐ and long‐term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON‐related variables and the mechanisms involved. Methods and results Two randomized, controlled, double‐blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1‐associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and from thyme modulate mitogen‐activated protein kinases and peroxisome proliferator‐activated receptors regulating PON synthesis, while a combination of these PCs cancels such regulation. Conclusion This study reveals that the intake of phenol‐enriched FVOOs modulates oxidative balance by modifying PON‐related variables according to PC content and source, and this modulation can be perceived as beneficial. Two randomized, controlled, double‐blind, and crossover interventions were conducted: Acute study: intake of functional virgin olive oils (FVOO) differing in phenolic compounds (PC) content; Sustained study: intake of different FVOOs (same PC content but different source). Main outcomes include that the acute and sustained consumption of olive oil‐PC in humans modifies PON‐related variables towards a beneficial mode, increasing PON1 protein and decreasing its specific activities and PON3 protein. A combination of olive oil and thyme PC cancels such regulation.