Olive juice dry extract containing hydroxytyrosol, as a nontoxic and safe substance: Results from pre-clinical studies and review of toxicological studies

Marie Liamin; Maria Pilar Lara; Olivier Michelet; Marie Rouault; Jose Carlos Quintela; Jérôme Le Bloch

doi:10.1016/j.toxrep.2023.02.003

Olive juice dry extract containing hydroxytyrosol, as a nontoxic and safe substance: Results from pre-clinical studies and review of toxicological studies

Toxicol Rep. 2023 Feb 12:10:245-260. doi: 10.1016/j.toxrep.2023.02.003. eCollection 2023.

Authors

Marie Liamin¹, Maria Pilar Lara², Olivier Michelet¹, Marie Rouault¹, Jose Carlos Quintela², Jérôme Le Bloch¹

Affiliations

¹ Nutraveris, A Food Chain ID Company, 6 rue de la gare, 22000 Saint-Brieuc, France.
² NATAC Biotech S.L., C/ Electrónica 7, 28923 Alcorcón, Madrid, Spain.

Abstract

Products derived from olives, such as the raw fruit and oils, are widely consumed due to their taste, and purported nutritional/health benefits. Phenolic compounds, especially hydroxytyrosol (HT), have been proposed as one of the key substances involved in these effects. An olive juice extract, standardized to contain 20% HT ("OE20HT"), was produced to investigate its health benefits. The aim of this study was to demonstrate the genotoxic safety of this ingredient based on in vitro Ames assay and in vitro micronucleus assay. Results indicated that OE20HT was not mutagenic at concentrations of up to 5000 µg/plate, with or without metabolic activation, and was neither aneugenic nor clastogenic after 3-hour exposure at concentrations of up to 60 µg/mL with or without metabolic activation, or after 24-hour exposure at concentrations of up to 40 µg/mL. To further substantiate the safety of OE20HT following ingestion without conducting additional animal studies, a comprehensive literature review was conducted. No safety concerns were identified based on acute or sub-chronic studies in animals, including reproductive and developmental studies. These results were supported by clinical studies demonstrating the absence of adverse effects after oral supplementation with olive extracts or HT. Based on in vitro data and the literature review, the OE20HT extract is therefore considered as safe for human consumption at doses up to 2.5 mg/kg body weight/day.

Keywords: 2AA, 2-aminoanthracene; 9AA, 9-aminoacridine; CBI, Centre for the Promotion of Imports from developing countries; CP, cyclophosphamide monohydrate; EFSA, European Food Safety Authority; Food product; Genotoxicity; HT, hydroxytyrosol; Hydroxytyrosol; MF, mutation factor; MMC, mitomycin C; MMS, methyl-methanesulfonate; Mutagenicity; NDP, 4-nitro-1,2-phenylene-diamine; NOAEL, no observed adverse effect level; OE20HT, olive juice dry extract titrated 20% hydroxytyrosol; OECD, Organization for Economic Co-operation and Development; Olive fruit extract; PD, population doubling; RICC, relative increase in cell count; RPD, relative population doubling; SAZ, sodium azide; Safety.