Crespo · Pharmacological research 2015 · randomized, double-blind, placebo-controlled crossover trial · n=?

One-week administration of hydroxytyrosol to humans does not activate Phase II enzymes.

Cited 64 times in the scientific literature.

Level 2 - randomized trial

Individual double-blind randomized placebo-controlled crossover trial

PubMed 25836918 · doi:10.1016/j.phrs.2015.03.018 · record verified 2026-08-29

What was done

A double-blind, randomized, placebo-controlled crossover trial using a Latin square design evaluated the effects of oral hydroxytyrosol (HT) in humans. Participants received HT at doses of 5 mg/day and 25 mg/day versus placebo for one week. Outcomes measured included Phase II enzyme expression in peripheral blood mononuclear cells (PBMCs) and surrogate cardiovascular markers (lipid profile, inflammation, and oxidation markers).

What was found

The abstract reports no numerical values, confidence intervals, or p-values. The authors report that HT was well tolerated but resulted in no significant modifications in PBMC Phase II enzyme expression at either dose compared to placebo. No significant changes were detected across lipid profiles, inflammation markers, or oxidation markers.

Why it matters

These findings challenge the popular hormesis hypothesis that dietary polyphenols exert physiological benefits primarily via Keap1/Nrf2/ARE-mediated Phase II enzyme induction in humans.

Limits

The abstract does not disclose the sample size, participant demographics, baseline health status, or quantitative data. The intervention duration was very short (one week), and enzyme expression was assessed only in circulating blood mononuclear cells rather than solid metabolic tissues (such as liver or vascular endothelium).

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