Metabolic disposition and biological significance of simple phenols of dietary origin: hydroxytyrosol and tyrosol

Abstract

Hydroxytyrosol and tyrosol are dietary phenolic compounds present in virgin olive oil and wine. Both compounds are also endogenously synthesized in our body as byproducts of dopamine and tyramine metabolisms, respectively. Over the last decades, research into hydroxytyrosol and tyrosol has experienced an increasing interest due to the role that these compounds may play in the prevention of certain pathologies (e.g. cardiovascular, metabolic, neurodegenerative diseases and cancer). The translation of promising in vitro and in vivo biological effects from preclinical studies to the context of human disease prevention initially depends on whether the dose ingested becomes available at the site of action. In this regard, information regarding the bioavailability and metabolic disposition of hydroxytyrosol and tyrosol is of most importance to evaluate the impact they may have on human health. In this review, we discuss and summarize the state of the art of the scientific evidence regarding the processes of absorption, distribution, metabolism and excretion of both hydroxytyrosol and tyrosol. We also examine the impact of these compounds and their metabolites on biological activity in terms of beneficial health effects. Finally, we evaluate the different analytical approaches that have been developed to measure the plasma and urinary levels of hydroxytyrosol, tyrosol and their metabolites.

Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells

“…Despite the promising anticancer activity of HT, there have been concerns about its poor bioavailability owing to its extensive metabolism (38). It has been suggested that the conjugated forms of HT should also be included in the cytotoxic assays, along with free HT, because this alone would be truly reflective for the HT in biological systems (38).…”

“…It has been suggested that the conjugated forms of HT should also be included in the cytotoxic assays, along with free HT, because this alone would be truly reflective for the HT in biological systems (38). On a positive note, it was noted that HT is a ‘safe’ compound and can be administered at higher doses without signs of any genotoxic or mutagenic effects (38; 39). Recently, there has been an interest in synthesis of HT-derivatives with a focus on improving the overall efficacy (40).…”

Understanding the link between antimicrobial properties of dietary olive phenolics and bacterial ATP synthase

“…A high concentration of tyrosol at about 25 mM caused the complete inhibition of ATP synthase. Tyrosol is primarily found in extra virgin olive oil, but it is also synthesized endogenously by humans [63]. Tyramine, which is derived from the amino acid tyrosine, can undergo a metabolic pathway in humans leading to the formation of tyrosol [64].…”

Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions

“…The beneficial effects of HT have been demonstrated in human, cellular and animal models, mainly consumed as EVOO [17,23] The HT from EVOO has also shown to increase insulin sensitivity and the secretory capacity of β-pancreatic cells, thus reducing the risk of developing metabolic syndrome. The phenolic content of olive oil depends on the place of cultivation, climate, variety of the olive, and its level of ripening at the time of harvest, reaching levels of 100–600 mg/kg, and approximately 50% of that phenolic content corresponds to HT and its derivatives [24,25]. HT is also present in wine, and it is considered a secondary metabolite of tyrosine formed by yeasts during alcoholic fermentation, having an approximate concentration up to 5 mg/L [26].…”

“…HT is also present in wine, and it is considered a secondary metabolite of tyrosine formed by yeasts during alcoholic fermentation, having an approximate concentration up to 5 mg/L [26]. In humans, there is an endogenous formation of HT from dopamine, which is favored in the presence of ethanol [24]. De la Torre et al, 2006 compared short-term and postprandial effects of moderate doses of EVOO (1.7 mg HT) and wine (0.35 mg HT), and found that the urinary recovery of HT was greater from wine intake than from EVOO consumption, despite having a lower HT content, which is explained by the endogenous formation from dopamine favored by the alcohol content of the wine [27].…”