Long-term intake of hydroxytyrosol

As a natural polyphenolic compound widely present in plants like olive oil, the long-term intake safety of hydroxytyrosol is a key research direction in the field of food and health. Substantial data has been accumulated from evaluations of its subchronic toxicity and genotoxicity, which are analyzed in detail below from two major dimensions:

I. Subchronic Toxicity Studies: Dosage and Health Effects of Long-Term Intake

Subchronic toxicity studies typically examine the effects of long-term exposure (3-6 months) to compounds through animal experiments (e.g., rats, mice), focusing on indicators such as organ damage and metabolic disorders:

Toxicity Thresholds at Different Dosages

Low to moderate dosages (50-500 mg/kg bw/day): Multiple studies show that hydroxytyrosol within this range exerts no significant adverse effects on experimental animals' body weight, blood biochemical indices (e.g., liver and kidney function markers ALT, AST, creatinine, etc.), or histopathology (liver, kidney, heart, and other organs). For example, a study administering hydroxytyrosol to rats via gavage for 90 consecutive days (up to 500 mg/kg bw/day) found normal appetite and activity, with no organic damage in various organs, indicating high safety for long-term intake at this dosage.

High dosages (1000 mg/kg bw/day and above): Some studies have found that extremely high doses of hydroxytyrosol may cause mild gastrointestinal reactions (such as diarrhea) or slight hepatic steatosis, but these effects are mostly reversible and not accompanied by functional abnormalities. However, such dosages are generally far higher than human daily dietary intakes (humans typically ingest 1-50 mg of hydroxytyrosol daily through foods like olive oil), so their reference significance for actual dietary scenarios is limited.

Potential Effects on Special Populations

Studies on pregnant or lactating animals show that hydroxytyrosol at conventional dosages does not adversely affect fetal development, offspring growth, or reproductive capacity, suggesting potential safety during special physiological stages, though more clinical data is still needed for support.

II. Genotoxicity Assessment: Induction of DNA Damage or Mutations

Genotoxicity assessment aims to determine whether a compound can cause gene mutations, chromosomal aberrations, etc., serving as a key indicator of long-term safety. Related research is mainly carried out through the following experiments:

In Vitro Genotoxicity Tests

Ames test (bacterial reverse mutation test): Hydroxytyrosol at different concentrations (typically up to 5000 μg/dish) did not induce gene mutations in Salmonella typhimurium or E. coli, indicating it does not possess direct mutagenicity.

Chromosome aberration test (cell culture): In human peripheral blood lymphocytes or mammalian cell lines (such as CHO cells), hydroxytyrosol did not cause abnormalities in chromosome structure or number, nor did it increase the micronucleus rate, suggesting no obvious damage to cellular genetic material.

In Vivo Genotoxicity Tests

Mouse bone marrow micronucleus test: After gavage administration of hydroxytyrosol to mice (up to 2000 mg/kg bw), the micronucleus rate in bone marrow cells showed no significant difference from the control group, indicating no induction of chromosome breakage or non-disjunction in vivo.

Comet assay (DNA strand break detection): No obvious DNA strand breaks were detected in either animal tissues (e.g., liver, kidney) or peripheral blood cells after hydroxytyrosol treatment, further supporting the conclusion of no genotoxicity.

III. Safety Conclusions and Practical Application References

Comprehensive subchronic toxicity and genotoxicity studies show that hydroxytyrosol has good safety at conventional dietary dosages (far lower than the high doses in experiments), with no detected toxic risks from long-term intake. Currently, institutions such as the European Food Safety Authority (EFSA) also recognize its safety as a food component, and multiple clinical studies have shown that long-term intake of olive oil extracts rich in hydroxytyrosol is associated with benefits such as cardiovascular health and antioxidant stress. It should be noted that existing research is mainly based on animal experiments and in vitro models, and safety data for long-term high-dose intake in humans still needs further accumulation. However, from the existing evidence, the safety of hydroxytyrosol as a natural active ingredient is worthy of affirmation.