Clinical trial NCT02273622: Human Study of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
Official title: Nutritional Intervention Study to Evaluate the Effect of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: hydroxytyrosol
dietary supplement
gene expression regulation
Lead sponsor: IMDEA Food
Sponsor class: OTHER
First posted: 2014-10-24
Enrollment: 20
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).
timeFrame: Change of Baseline and after one week hydroxytyrosol and placebo administration
Secondary outcomes:
measure: Number of participants with change in different anthropometrics parameters
timeFrame: Change of Baseline and after one week hydroxytyrosol and placebo administration
measure: Number of participants with change in different biochemical parameters
timeFrame: Change of Baseline and after one week hydroxytyrosol and placebo administration
measure: Concentration of hydroxytyrosol and metabolites in urine
timeFrame: Change of Baseline and after one week hydroxytyrosol and placebo administration
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: IMDEA-Food
Study officials:
affiliation: IMDEA Food
name: Francesco Visioli, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Visioli F, Galli C, Plasmati E, Viappiani S, Hernandez A, Colombo C, Sala A. Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress. Circulation. 2000 Oct 31;102(18):2169-71. doi: 10.1161/01.cir.102.18.2169.
citation: Visioli F, Galli C, Bornet F, Mattei A, Patelli R, Galli G, Caruso D. Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett. 2000 Feb 25;468(2-3):159-60. doi: 10.1016/s0014-5793(00)01216-3.
citation: Visioli F, Caruso D, Plasmati E, Patelli R, Mulinacci N, Romani A, Galli G, Galli C. Hydroxytyrosol, as a component of olive mill waste water, is dose- dependently absorbed and increases the antioxidant capacity of rat plasma. Free Radic Res. 2001 Mar;34(3):301-5. doi: 10.1080/10715760100300271.
citation: Visioli F, Bellosta S, Galli C. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci. 1998;62(6):541-6. doi: 10.1016/s0024-3205(97)01150-8.
citation: Crespo MC, Tome-Carneiro J, Burgos-Ramos E, Loria Kohen V, Espinosa MI, Herranz J, Visioli F. One-week administration of hydroxytyrosol to humans does not activate Phase II enzymes. Pharmacol Res. 2015 May-Jun;95-96:132-7. doi: 10.1016/j.phrs.2015.03.018. Epub 2015 Mar 30.