Human Study of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
Condition: Healthy
Study type: Interventional

Summary: 
      Explore the detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme
      expression (leading to xenobiotics detoxification in the liver).
    

Detailed description: 
      Hydroxytyrosol is peculiar to olives (and, hence, to olive oil) and is being exploited as a
      potential supplement or preservative to be employed in the nutraceutical, cosmeceutical, and
      food industry. One of the properties described for the hydroxytyrosol is its high antioxidant
      activity. Also, hydroxytyrosol is able to modulate several enzymatic activities linked to
      cardiovascular disease. Animal experiments confirm hydroxytyrosol retains its antioxidant
      activity once ingested (though the human metabolic pathway has been elucidated and shows
      extensive glucuronidation and subsequent urinary excretion), protects from second hand
      smoke-induced oxidative damage, inhibits platelet aggregation, ameliorates lipid profile and
      decreases atherosclerosis development, increases brain cell resistance to oxidation and
      mitochondrial membrane potential Several mechanisms have been proposed to explain how
      biologically polyphenols protect against degenerative diseases. It is now thought more likely
      that some phytochemicals, including polyphenols, are processed by the body as xenobiotics.
      They stimulate stress- related cell signalling pathways that result in increased expression
      of genes encoding cytoprotective genes. Nrf2 (NF-E2-related factor 2) is a transcription
      factor which binds to the Antioxidant Response Element (ARE) in cells and thus regulates
      enzymes involved in antioxidant functions or detoxification (e.g. thioredoxin reductase-1 and
      glutathione peroxidases). Polyphenols might increase gene transcription of Nrf2 mediated by
      such response elements. This provides grounds for the theory of hormesis, i.e. when mild
      stress triggers defense mechanisms. In the case of polyphenols it indicates how they could
      have an indirect antioxidant action.

      That is why plans to carry this study to explore the detoxifying potential of hydroxytyrosol
      and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the
      liver). It´ll be a randomized crossover, pilot study examining the effects of two doses of
      hydroxytyrosol, in the form of a commercially-available raw mixture: 1) providing 5 mg/d; 2)
      25 mg/d, for one week with a one-week washout period in between, during 6 weeks.

      The investigators will recruit 20 healthy volunteers, from within those who participate in
      the Genyal Platform studies AT IMDEA-Food Institute.
    

Intervention name(s): hydroxytyrosol; placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Pilot study with 20 participants, each participant will alternately by the two arms of the study (hydroxytyrosol 5 mg and 20 mg) and control, during 6 weeks.
Intervention MeSH terms: 3,4-dihydroxyphenylethanol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: hydroxytyrosol; dietary supplement; gene expression regulation