Hydroxytyrosol supplementation improves antioxidant and anti-inflammatory status in individuals with overweight and prediabetes: A randomized, double-blind, placebo-controlled parallel trial.

Background & Aim: Hydroxytyrosol (HT), an olive-derived phenolic compound, possesses well-known antioxidant and anti-inflammatory properties. While its benefits in healthy individuals and as part of extra virgin olive oil are well studied, its preventive role as a dietary supplement in at-risk populations remains less explored. This study investigates the potential of HT supplementation in preventing aging-related diseases in overweight individuals with prediabetes.

Methods: A randomized, double-blind, placebo-controlled trial was conducted in adults with overweight and prediabetes (40-70 years). For 16 weeks, volunteers consumed either 15 mg of HT or a placebo daily. The primary outcome were oxidized LDL (oxLDL) levels, while secondary outcomes included biochemical and metabolic parameters, oxidative stress and inflammation biomarkers, and lifestyle assessments. Compliance was verified through urinary HT-3'-sulphate levels.

Results: A total of 52 participants were recruited and randomized, with 49 completing the study. They were then allocated to either the HT-treated group (n = 24) or the placebo group (n = 25). Compliance was confirmed, as the HT-supplemented group showed increased urinary HT-3'-sulphate levels, whereas the placebo group exhibited a significant decrease (p = 0.039). Compared with placebo, HT supplementation significantly reduced oxLDL levels (p = 0.045), protein carbonyls (p = 0.031), and 8-OHdG (p < 0.01). Additionally, it prevented a decline in total antioxidant status (p < 0.01) and GPx activity (p < 0.01). An anti-inflammatory effect was also observed, with reduced IL-6 levels (p = 0.05). No significant changes were found in lipid profile, anthropometric parameters, or lifestyle factors such as sleep, mental well-being, or physical capacity. No adverse events were observed throughout the intervention.

Conclusion: Chronic supplementation with 15 mg/day of HT for 16 weeks significantly improved antioxidant and anti-inflammatory status in individuals with overweight and prediabetes, suggesting a potential preventive role against aging-related diseases.

Registration Number Of Clinical Trial: NCT06295913 (https://clinicaltrials.gov/study/NCT06295913?intr=Hydroxytyrosol&page=2&rank=1).