Human Study of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects

Healthy Clinical Trial

Official title:

Nutritional Intervention Study to Evaluate the Effect of Hydroxytyrosol on Phase II Enzymes in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02273622
• Other study ID #: IMD PI011
• Status: Completed
• Phase: N/A
• First received: October 15, 2014
• Last updated: March 23, 2015
• Start date: October 2014
• Est. completion date: January 2015

Study information

• Verified date: October 2014
• Source: IMDEA Food
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• hydroxytyrosol
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.
• placebo

Locations

Country	Name	City	State
Spain	IMDEA-Food	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
IMDEA Food

Country where clinical trial is conducted

Spain, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detoxifying potential of hydroxytyrosol and its effects on Phase II enzyme expression (leading to xenobiotics detoxification in the liver).	The analyses of gene expression will be carried out at the ad-hoc platform in use at IMDEA-Food (see www.food.imdea.org for details). Total RNA will be extracted from mononuclear cells with TRI Reagent (Sigma-Aldrich, Inc., St. Louis, MO, USA) and purified with RNeasy MiniElute Cleanup Kit (Qiagen, Hilden, Germany). Recovered RNA will be quantified using a Nanodrop ND-1000 v3.5.2 spectrophotometer (Nanodrop TechnologyR, Cambridge, UK). RNA integrity will be assessed using 1.6% agarose gel, 1× TBE. RNA will be judged suitable for array hybridization only if samples exhibited intact bands corresponding to 18S and 28S ribosomal RNAs. During the study blood samples will be obtained from venous puncture and blood samples will be collected in tubes containing EDTA, maintained on ice and rapidly centrifuged to obtain plasma. Plasma will be immediately distributed in aliquots for the different determinations and stored at -70 °C until analysis.	Change of Baseline and after one week hydroxytyrosol and placebo administration	No
Secondary	Number of participants with change in different anthropometrics parameters	The different anthropometrics parameters are: weight, height, body mass index, fat mass, lean mass	Change of Baseline and after one week hydroxytyrosol and placebo administration	No
Secondary	Number of participants with change in different biochemical parameters	The different biochemical parameters are: Lipid profile (TG, CT, LDL-C, HDL-C), oxidation (LDL-ox, 8-iso PGF2a), inflammatory (PCRu, TNFa, IL1ß, VCAM1, ICAM; TXB2).	Change of Baseline and after one week hydroxytyrosol and placebo administration	No
Secondary	Concentration of hydroxytyrosol and metabolites in urine	Urine sampling will be performed before administration of the substance (t=0) and after 24 h post dose. Urinary HT and metabolites will be measured by mass spectrometry	Change of Baseline and after one week hydroxytyrosol and placebo administration	No