Bioavailability of Hydroxytyrosol From Olive Watery Extract Supplements

NCT ID: NCT04876261

Last Updated: 2021-07-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-10

Study Completion Date

2021-07-02

Brief Summary

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The aim of this cross-over study is to assess the bioavailability of hydroxytyrosol in healthy males after the intake of two olive watery extract supplements and one olive oil. Blood and urine samples will be collected before and after intake of the investigational products. Sample will be analysed regarding the level of hydroxytyrosol and preventing lipid peroxidation.

Detailed Description

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Background:

Hydroxytyrosol is a phenolic phytochemical naturally occurring in olives with potential antioxidant, anti-inflammatory, and health benefits mainly related with cardiovascular diseases \[for review see Covas et al., 2015\]. OliPhenolia® bitter and OliPhenolia® are two food supplements resulting from the liquid by-product generated during olive oil production, that are rich in olive polyphenols, mainly hydroxytyrosol. Hydroxytyrosol and its derivatives (tyrosol and oleuropein) are present in higher levels in the watery extracts from olives when compared with the oil fraction.

Most studies on hydroxytyrosol bioavailability have been performed by consuming it with olive oil or as a highly purified molecule. In a study by D'Angelo and collaborators \[D'Angelo et al, 2001\] it was shown that hydroxytyrosol can be rapidly absorbed from the blood and distributed in the human body, metabolized and eliminated rapidly in urine mainly as a glucuronide. It has been estimated that the absorption process depends on the composition of the food matrix through which hydroxytyrosol is administered \[Visioli et al, 2003\], when consumed together with fats (e.g. olive oil) it is absorbed in a greater extent. By being a water-soluble molecule, hydroxytyrosol is only slightly soluble in fats, therefore naturally present in significantly higher concentrations in the olive fruit aqueous fractions than in the olive oil.

Overall, the human studies support the need to evaluate the bioavailability of hydroxytyrosol following its administration as a major component of the two aqueous food supplements, OliPhenolia® and OliPhenolia® bitter.

Study Procedure:

After detailed information and signed informed consent all males meeting the inclusion and exclusion criteria will be included into the study. During their study participation, participants are not allowed to consume any products with or made from olives or olive oil as well as alcohol and supplements with hydroxytyrosol, vitamins, minerals and antioxidants. Products high in polyphenols and antioxidants may only be consumed in moderate amounts. Three days prior to and at each intervention day, volunteers will be requested to avoid moderate or intense physical activity.

After a run-in period, participants will return in a fasted state to the site for the first intervention visit. Volunteers will be asked to empty their bladder at home 2h before IP intake. After arriving at the site, a baseline blood and urine sample (-5 min) will be collected and the participants receive according to the individual allocation determining the sequence of the IP intake either one of the olive watery extract supplements (OliPhenolia® bitter or OliPhenolia®) or the olive oil first. Further blood and urine samples will follow (+30 min, +60 min, +90 min, +120 min, +240 min, +12 h). Vital signs and AEs will be checked throughout the intervention visit. Participants will receive several snacks and water during their visit.

After a one-week washout phase each, participants will return to their second and third intervention visit. The same procedures as on intervention visit 1 will take place except the IP intake will vary according to the individual allocation.

At the end of the third intervention visit, participants will receive a study compensation.

Conditions

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Biological Availability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Three-armed study with a cross-over design. Participants will be randomly assigned to either group A, B or C. The group allocation will define the sequence of product intake:

* Group A: first OliPhenolia® bitter, second OliPhenolia®, third La Vialla Extra Virgin Olive Oil
* Group B: first OliPhenolia®, second La Vialla Extra Virgin Olive Oil, third OliPhenolia® bitter
* Group C: first La Vialla Extra Virgin Olive Oil, second OliPhenolia® bitter, third OliPhenolia®
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Participants and the laboratory will be blinded. Laboratory staff will be unblinded after samples are being analysed. Participants will be unblinded after study end.

Study Groups

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Group A

Group A will receive Oliphenolia® bitter on intervention visit 1 followed by Oliphenolia® on intervention visit 2 and followed by La Vialla Extra Virgin Olive Oil with 5 mg hydroxytyrosol on the third and final intervention visit

Group Type ACTIVE_COMPARATOR

Oliphenolia® bitter

Intervention Type DIETARY_SUPPLEMENT

* ingredients: concentrated watery extract of olives 94%, lemon juice 6%
* 35 mg hydroxytyrosol, 0,24 mg Oleuropein

Oliphenolia®

Intervention Type DIETARY_SUPPLEMENT

* ingredients: grape juice concentrate 70%, concentrated watery extract of olives 30%
* 38 mg hydroxytyrosol, 0,28 mg Oleuropein

La Vialla Extra Virgin Olive Oil containing 5 mg hydroxytyrosol

Intervention Type DIETARY_SUPPLEMENT

* extra virgin olive oil
* 5 mg hydroxytyrosol

Group B

Group B will receive Oliphenolia® on intervention visit 1 followed by La Vialla Extra Virgin Olive Oil with 5 mg hydroxytyrosol on intervention visit 2 and followed by Oliphenolia® bitter on the third and final intervention visit

Group Type ACTIVE_COMPARATOR

Oliphenolia® bitter

Intervention Type DIETARY_SUPPLEMENT

* ingredients: concentrated watery extract of olives 94%, lemon juice 6%
* 35 mg hydroxytyrosol, 0,24 mg Oleuropein

Oliphenolia®

Intervention Type DIETARY_SUPPLEMENT

* ingredients: grape juice concentrate 70%, concentrated watery extract of olives 30%
* 38 mg hydroxytyrosol, 0,28 mg Oleuropein

La Vialla Extra Virgin Olive Oil containing 5 mg hydroxytyrosol

Intervention Type DIETARY_SUPPLEMENT

* extra virgin olive oil
* 5 mg hydroxytyrosol

Group C

Group C will receive La Vialla Extra Virgin Olive Oil with 5 mg hydroxytyrosol on intervention visit 1 followed by Oliphenolia® bitter on intervention visit 2 and followed by Oliphenolia® on the third and final intervention visit

Group Type ACTIVE_COMPARATOR

Oliphenolia® bitter

Intervention Type DIETARY_SUPPLEMENT

* ingredients: concentrated watery extract of olives 94%, lemon juice 6%
* 35 mg hydroxytyrosol, 0,24 mg Oleuropein

Oliphenolia®

Intervention Type DIETARY_SUPPLEMENT

* ingredients: grape juice concentrate 70%, concentrated watery extract of olives 30%
* 38 mg hydroxytyrosol, 0,28 mg Oleuropein

La Vialla Extra Virgin Olive Oil containing 5 mg hydroxytyrosol

Intervention Type DIETARY_SUPPLEMENT

* extra virgin olive oil
* 5 mg hydroxytyrosol

Interventions

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Oliphenolia® bitter

* ingredients: concentrated watery extract of olives 94%, lemon juice 6%
* 35 mg hydroxytyrosol, 0,24 mg Oleuropein

Intervention Type DIETARY_SUPPLEMENT

Oliphenolia®

* ingredients: grape juice concentrate 70%, concentrated watery extract of olives 30%
* 38 mg hydroxytyrosol, 0,28 mg Oleuropein

Intervention Type DIETARY_SUPPLEMENT

La Vialla Extra Virgin Olive Oil containing 5 mg hydroxytyrosol

* extra virgin olive oil
* 5 mg hydroxytyrosol

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Self-reported healthy men aged 21-50,
* subject has an adequate understanding of the study and signs the informed consent to participate in the study,
* willingness to follow dietary and physical activity restrictions during study participation,
* body mass index range: \>18.5 and \<29.9 kg/m2.

Exclusion Criteria

* Any known allergies to IPs (olives and their derivates),
* any acute and chronic diseases (e.g. diagnosis of diabetes mellitus, hypertension, dyslipidemia or other cardiometabolic disorders, diagnosed hepatic, renal, or cardiovascular disease),
* any kind of eating disorders,
* not fluent in German,
* any previous (last 14 days prior to screening) and any ongoing pharmacological therapy (e.g. any medication, vaccination, infusion),
* any intake of nutritional supplements,
* any known addiction to drugs and/or alcohol,
* smoker,
* Investigator or physician doubts truthfulness of self-reported health information.
Minimum Eligible Age

21 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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ISTITUTO KURZ ITALIA S.R.L.

UNKNOWN

Sponsor Role collaborator

Institut Kurz GmbH

UNKNOWN

Sponsor Role collaborator

Fattoria La Vialla di Gianni, Antonio e Bandino Lo Franco Soc. Agr. Sempl.

UNKNOWN

Sponsor Role collaborator

Daacro

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Juliane Hellhammer, PhD

Role: PRINCIPAL_INVESTIGATOR

Daacro

Locations

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daacro GmbH & Co. KG

Trier, Rhineland-Palatinate, Germany

Site Status

Countries

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Germany

References

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D'Angelo S, Manna C, Migliardi V, Mazzoni O, Morrica P, Capasso G, Pontoni G, Galletti P, Zappia V. Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil. Drug Metab Dispos. 2001 Nov;29(11):1492-8.

Reference Type BACKGROUND
PMID: 11602527 (View on PubMed)

Caruso D, Visioli F, Patelli R, Galli C, Galli G. Urinary excretion of olive oil phenols and their metabolites in humans. Metabolism. 2001 Dec;50(12):1426-8. doi: 10.1053/meta.2001.28073.

Reference Type BACKGROUND
PMID: 11735087 (View on PubMed)

Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, Gaddi A, de la Torre R, Mursu J, Baumler H, Nascetti S, Salonen JT, Fito M, Virtanen J, Marrugat J; EUROLIVE Study Group. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006 Sep 5;145(5):333-41. doi: 10.7326/0003-4819-145-5-200609050-00006.

Reference Type BACKGROUND
PMID: 16954359 (View on PubMed)

Covas MI, de la Torre R, Fito M. Virgin olive oil: a key food for cardiovascular risk protection. Br J Nutr. 2015 Apr;113 Suppl 2:S19-28. doi: 10.1017/S0007114515000136.

Reference Type BACKGROUND
PMID: 26148918 (View on PubMed)

de Bock M, Thorstensen EB, Derraik JG, Henderson HV, Hofman PL, Cutfield WS. Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract. Mol Nutr Food Res. 2013 Nov;57(11):2079-85. doi: 10.1002/mnfr.201200795. Epub 2013 Jun 14.

Reference Type BACKGROUND
PMID: 23766098 (View on PubMed)

Hohmann CD, Cramer H, Michalsen A, Kessler C, Steckhan N, Choi K, Dobos G. Effects of high phenolic olive oil on cardiovascular risk factors: A systematic review and meta-analysis. Phytomedicine. 2015 Jun 1;22(6):631-40. doi: 10.1016/j.phymed.2015.03.019. Epub 2015 Apr 20.

Reference Type BACKGROUND
PMID: 26055128 (View on PubMed)

Karkovic Markovic A, Toric J, Barbaric M, Jakobusic Brala C. Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health. Molecules. 2019 May 24;24(10):2001. doi: 10.3390/molecules24102001.

Reference Type BACKGROUND
PMID: 31137753 (View on PubMed)

Mateos R, Martinez-Lopez S, Baeza Arevalo G, Amigo-Benavent M, Sarria B, Bravo-Clemente L. Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans. Food Chem. 2016 Aug 15;205:248-56. doi: 10.1016/j.foodchem.2016.03.011. Epub 2016 Mar 4.

Reference Type BACKGROUND
PMID: 27006237 (View on PubMed)

Miro-Casas E, Covas MI, Fito M, Farre-Albadalejo M, Marrugat J, de la Torre R. Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans. Eur J Clin Nutr. 2003 Jan;57(1):186-90. doi: 10.1038/sj.ejcn.1601532.

Reference Type BACKGROUND
PMID: 12548315 (View on PubMed)

Suarez M, Valls RM, Romero MP, Macia A, Fernandez S, Giralt M, Sola R, Motilva MJ. Bioavailability of phenols from a phenol-enriched olive oil. Br J Nutr. 2011 Dec;106(11):1691-701. doi: 10.1017/S0007114511002200. Epub 2011 Jun 21.

Reference Type BACKGROUND
PMID: 21736768 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10692578 (View on PubMed)

Visioli F, Galli C, Grande S, Colonnelli K, Patelli C, Galli G, Caruso D. Hydroxytyrosol excretion differs between rats and humans and depends on the vehicle of administration. J Nutr. 2003 Aug;133(8):2612-5. doi: 10.1093/jn/133.8.2612.

Reference Type BACKGROUND
PMID: 12888646 (View on PubMed)

Other Identifiers

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IK03-2020

Identifier Type: -

Identifier Source: org_study_id

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