HYDROXYTYROSOL FROM OLIVE EXTRACTS AND HEALTHY AGEING From antioxidant biomarker modulation to the Hydroxytyrosol–DOPAC metabolic axis

Hydroxytyrosol (HT; 3,4-dihydroxyphenylethanol, DOPET) is a characteristic olive phenol whose human biology is more complex than the conventional label ‘antioxidant’ suggests. A 2025 randomized, double-blind, placebo- controlled trial in adults aged 40–70 years with overweight and prediabetes reported that 15 mg/day for 16 weeks favourably modified oxidized LDL, protein carbonyls, 8-hydroxy-2′-deoxyguanosine and selected antioxidant/inflammatory variables, while conventional glycaemic indices, anthropometry and the standard lipid profile were not materially improved. A 2026 untargeted metabolomic analysis of the same cohort identified changes involving arachidonic-acid metabolism, purine catabolism and membrane-lipid classes. Together, these findings strengthen the biological plausibility of HT as a modulator of processes associated with cardiometabolic ageing, but they do not demonstrate prevention of diabetes, cardiovascular events, neurodegenerative disease or ageing itself. [1–3] A central translational issue is pharmacokinetics. Free HT appears rapidly in plasma and is extensively transformed by first-pass and systemic metabolism. Human studies repeatedly identify sulphated and glucuronidated HT, homovanillic acid and 3,4-dihydroxyphenylacetic acid (DOPAC) among the major products of exposure. After olive ingestion, plasma DOPAC can rise far more than free HT, supporting substantial conversion through the sequence HT → 3,4-dihydroxyphenylacetaldehyde (DOPAL) → DOPAC. This makes the ‘HT–DOPAC axis’ a scientifically useful model: oral HT should be understood as the entry point to a dynamic metabolite network rather than as a single circulating molecule. [4–7] The regulatory conclusion is equally important. In the European Union, the authorised claim concerns olive-oil polyphenols and protection of blood lipids from oxidative stress, under defined conditions requiring at least 5 mg of hydroxytyrosol and derivatives per 20 g olive oil. This is not a general authorisation for isolated HT supplements. Moreover, in 2025 EFSA concluded that a cause-and-effect relationship had not been established between phenolic compounds naturally present in olive oil and lowering LDL cholesterol or systolic blood pressure for a proposed coronary-heart-disease risk-reduction claim. [8,9]