Human Study of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects

IMDEA Food

Status: Completed

Conditions: Healthy

Treatments: Dietary Supplement: placebo; Dietary Supplement: hydroxytyrosol

Study type: Interventional

Funder types: Other

Identifiers

NCT02273622

IMD PI011

Details and patient eligibility

About

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

Full 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.

Enrollment: 20 patients

Sex: Male

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Male gender with age range 20-40 years
• Signed patient informed consent

Exclusion criteria

• BMI < 19 and >26
• Subjects with a diagnosis of diabetes mellitus, dyslipidemia, hypertension and other cardiometabolic diseases.
• Subjects with dementia, mental illness or diminished cognitive function.
• Subjects with serious diseases (hepatic, renal, cardiovascular, etc.)
• Subjects who refuse to make the 24 hour urine collection and blood samples under study.
• Subjects with allergy or intolerance to olive and derivatives.
• Subjects with drug treatment of any kind.
• Current smoking.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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20 participants in 3 patient groups, including a placebo group

hydroxytyrosol 5 mg

Experimental group

Description:

each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo

Treatment:

Dietary Supplement: hydroxytyrosol

hydroxytyrosol 20 mg

Experimental group

Description:

each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo

Treatment:

Dietary Supplement: hydroxytyrosol

placebo

Placebo Comparator group

Description:

each participant will alternately by the three arms of the study (hydroxytyrosol 5 mg and 20 mg and placebo

Treatment:

Dietary Supplement: placebo