Nutritional Intervention With Table Olives in Healthy Volunteers

NCT03886597 | Completed Phase 1

• 1 other identifier: IIBSP-OLI-2016-23
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Olives and olive oil are typical components of the Mediterranean diet being part of its cultural and gastronomic heritage. Since ancient times, olives have been used either for both, oil extraction or whole fruit consumption as table olives. Olive oil stands out from both the nutritional and the health point of view. However, the effect of table olives consumption remains almost unknown. The beneficial properties of olive oil have been initially ascribed to the high concentration of oleic acid. Nowadays, these positive effects have been attributed also to minor compounds such as polyphenols or pentacyclic triterpenes. Table olives contain a higher amount of both polyphenols and pentacyclic triterpenes than their oil, with the same healthy fatty acid profile. Therefore, the present intervention aims at investigating the pharmacokinetic of polyphenols and pentacyclic triterpenes after a single olive intake as well as the assessment of the effect of the consumption of olives during 30 days on the overall health status playing particular attention to the anti-inflammatory, antioxidant and cardiovascular biomarkers.

Conditions

Healthy; Biological Availability; Nutritional Intervention; Functional Food; Nutrition Physiology

Keywords

Polyphenols; Triterpenes; Olea europaea; Table Olives; Pharmacokinetics; Functional Food; Antioxidant; Cardiovascular Disease; Anti-inflammatory

Outcome Measures

Primary Outcomes (33)

• Stage 1: Maximum plasma concentration (Cmax)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Concentration at the end of the dosing interval (Ct)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Time until Cmax is reached (Tmax)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Area under the curve from administration to last observed concentration at time (AUC (0-t)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: AUC extrapolated to infinite time (AUC (0-∞)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Percentage of AUC extrapolated (AUC%)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Terminal elimination rate constant (Kel)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Plasma concentration half-life (t ½)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Volume of distribution (Vd/ F)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Clearance (Cl/F)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Peak trough fluctuation over one dosing interval at steady state (PTF)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Cmax dose normalized (Cmax/Dose)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: AUC (0-t) dose normalized (AUC (0-t)/Dose)

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Urine polyphenols concentration

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 1: Urine triterpenes concentration

  24 hour dosing period; 2 dosing periods each separated by 7 days washout

  24 hours

• Stage 2: Plasma polyphenols concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Plasma triterpenes concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Urine polyphenols concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Urine triterpenes concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Malondialdehyde concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Catalase concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Glutathione peroxidase concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Superoxide dismutase concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: F2A isoprostane concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: 8 isoprostane concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Oxidized low-density lipoprotein concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: C-Reactive Protein concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Lipoprotein-associated phospholipase A2 concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Apolipoprotein A1 concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Apolipoprotein B100 concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Tumor necrosis factor alpha concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Interleukin 6 concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Interleukin 1 concentration

  30 days

  30 days dosing period or 30 days as control group separated by 15 days washout

Secondary Outcomes (18)

• Stage 1 and 2: Number of participants with treatment-related adverse events

  30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 1 and 2: Systolic and diastolic blood pressure

  Stage 1: 24 hour dosing period; 2 dosing periods each separated by 7 days washout, Stage 2: 30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 1 and 2: Heart rate

  Stage 1: 24 hour dosing period; 2 dosing periods each separated by 7 days washout, Stage 2: 30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 1 and 2: Respiratory rate

  Stage 1: 24 hour dosing period; 2 dosing periods each separated by 7 days washout, Stage 2: 30 days dosing period or 30 days as control group separated by 15 days washout

• Stage 2: Body weight

  30 days dosing period or 30 days as control group separated by 15 days washout

Study Arms (4)

60 Arbequina Table Olives

EXPERIMENTAL

Pharmacokinetics Study

Other: Table Olives

120 Arbequina Table Olives

EXPERIMENTAL

Pharmacokinetics Study

Other: Table Olives

60 Table Olives

EXPERIMENTAL

Table Olives Nutritional Intervention

Other: Table Olives

Control

NO INTERVENTION

Control of Table Olives Nutritional Intervention

Interventions

Table Olives OTHER

At early morning (08:00 h e.g.) and after 10 hours of fasting conditions, the olives of the Arbequina variety will be administered to each subject. The 60 olives will be weighted before the ingestion and the remaining stones will be subsequently weighted to keep a record of the amount of olive pulp that has been consumed. The subjects will have a period of 5 minutes to ingest 60 olives with 240 mL of water. Blood samples will be collected from 1 hour prior to administration until 24 hours after dosing. Urine samples will also be collected and blood pressure will be measured.

60 Arbequina Table Olives

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body Mass Index between 19 and 30 kg/m2.
• Healthy on the basis of physical examination and routine biochemical and hematological laboratory determinations.
• Free acceptance to participate in the study by obtains signed informed consent.

You may not qualify if:

• Smoking.
• Alcohol or drug abuse.
• Heavy consumer of stimulating beverages (\>5 coffees, teas, chocolate or cola drinks per day) and grapefruit juice.
• Background of allergy, idiosyncrasy or hypersensitivity to drugs.
• Intake of any medication within 2 weeks prior taking the study intervention (except for use of paracetamol in short-term symptomatic treatments), including over-the-counter products (including natural food supplements, vitamins and medicinal plants products), or any enzymatic inductor or inhibitor within 3 months before the drug administration.
• Positive serology for hepatitis B, C or HIV.
• Background or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, hematological or neurological disease or other chronic diseases.
• Having undergone major surgery during the previous 6 months.
• Pregnancy or lactation status (if applied).
• Participation in another clinical trial during the 3 months preceding the drug administration.
• Donation of blood during the 4 weeks preceding the drug administration.
• Acute illness four weeks before drug administration.

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead
• Ministerio de Economía y Competitividad (Spain) AGL 2013-41188R: collaborator
• University of Barcelona: collaborator

Study Sites (1)

Institut de Recerca Hospital de la Santa Creu i Sant Pau - CIM Sant Pau

Barcelona, 08041, Spain

Location

Related Publications (20)

• Bachhav SS, Bhutada MS, Patil SP, Sharma KS, Patil SD. Oleanolic Acid Prevents Increase in Blood Pressure and Nephrotoxicity in Nitric Oxide Dependent Type of Hypertension in Rats. Pharmacognosy Res. 2014 Oct-Dec;7(4):385-92. doi: 10.4103/0974-8490.159575.

  PMID: 26692754 BACKGROUND

• Cicerale S, Conlan XA, Sinclair AJ, Keast RS. Chemistry and health of olive oil phenolics. Crit Rev Food Sci Nutr. 2009 Mar;49(3):218-36. doi: 10.1080/10408390701856223.

  PMID: 19093267 BACKGROUND

• 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.

  PMID: 16954359 BACKGROUND

• de la Torre-Carbot K, Chavez-Servin JL, Jauregui O, Castellote AI, Lamuela-Raventos RM, Fito M, Covas MI, Munoz-Aguayo D, Lopez-Sabater MC. Presence of virgin olive oil phenolic metabolites in human low density lipoprotein fraction: determination by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Anal Chim Acta. 2007 Feb 5;583(2):402-10. doi: 10.1016/j.aca.2006.10.029. Epub 2006 Nov 2.

  PMID: 17386573 BACKGROUND

• Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D, Markova L, Urban M, Sarek J. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep. 2006 Jun;23(3):394-411. doi: 10.1039/b515312n. Epub 2006 May 3. No abstract available.

  PMID: 16741586 BACKGROUND

• Ghanbari R, Anwar F, Alkharfy KM, Gilani AH, Saari N. Valuable nutrients and functional bioactives in different parts of olive (Olea europaea L.)-a review. Int J Mol Sci. 2012;13(3):3291-3340. doi: 10.3390/ijms13033291. Epub 2012 Mar 12.

  PMID: 22489153 BACKGROUND

• Juan ME, Planas JM, Ruiz-Gutierrez V, Daniel H, Wenzel U. Antiproliferative and apoptosis-inducing effects of maslinic and oleanolic acids, two pentacyclic triterpenes from olives, on HT-29 colon cancer cells. Br J Nutr. 2008 Jul;100(1):36-43. doi: 10.1017/S0007114508882979. Epub 2008 Feb 26.

  PMID: 18298868 BACKGROUND

• Kountouri AM, Mylona A, Kaliora AC, Andrikopoulos NK. Bioavailability of the phenolic compounds of the fruits (drupes) of Olea europaea (olives): impact on plasma antioxidant status in humans. Phytomedicine. 2007 Oct;14(10):659-67. doi: 10.1016/j.phymed.2007.06.001. Epub 2007 Sep 17.

  PMID: 17870451 BACKGROUND

• Liu J, Sun H, Duan W, Mu D, Zhang L. Maslinic acid reduces blood glucose in KK-Ay mice. Biol Pharm Bull. 2007 Nov;30(11):2075-8. doi: 10.1248/bpb.30.2075.

  PMID: 17978478 BACKGROUND

• Lou-Bonafonte JM, Arnal C, Navarro MA, Osada J. Efficacy of bioactive compounds from extra virgin olive oil to modulate atherosclerosis development. Mol Nutr Food Res. 2012 Jul;56(7):1043-57. doi: 10.1002/mnfr.201100668.

  PMID: 22760979 BACKGROUND

• Lozano-Mena G, Sanchez-Gonzalez M, Juan ME, Planas JM. Maslinic acid, a natural phytoalexin-type triterpene from olives--a promising nutraceutical? Molecules. 2014 Aug 4;19(8):11538-59. doi: 10.3390/molecules190811538.

  PMID: 25093990 BACKGROUND

• Madlala HP, Van Heerden FR, Mubagwa K, Musabayane CT. Changes in Renal Function and Oxidative Status Associated with the Hypotensive Effects of Oleanolic Acid and Related Synthetic Derivatives in Experimental Animals. PLoS One. 2015 Jun 5;10(6):e0128192. doi: 10.1371/journal.pone.0128192. eCollection 2015.

  PMID: 26046776 BACKGROUND

• Marrugat J, Covas MI, Fito M, Schroder H, Miro-Casas E, Gimeno E, Lopez-Sabater MC, de la Torre R, Farre M; SOLOS Investigators. Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation--a randomized controlled trial. Eur J Nutr. 2004 Jun;43(3):140-7. doi: 10.1007/s00394-004-0452-8. Epub 2004 Jan 6.

  PMID: 15168036 BACKGROUND

• Martin-Pelaez S, Covas MI, Fito M, Kusar A, Pravst I. Health effects of olive oil polyphenols: recent advances and possibilities for the use of health claims. Mol Nutr Food Res. 2013 May;57(5):760-71. doi: 10.1002/mnfr.201200421. Epub 2013 Mar 1.

  PMID: 23450515 BACKGROUND

• Melliou E, Zweigenbaum JA, Mitchell AE. Ultrahigh-pressure liquid chromatography triple-quadrupole tandem mass spectrometry quantitation of polyphenols and secoiridoids in california-style black ripe olives and dry salt-cured olives. J Agric Food Chem. 2015 Mar 11;63(9):2400-5. doi: 10.1021/jf506367e. Epub 2015 Feb 26.

  PMID: 25668132 BACKGROUND

• Poudyal H, Campbell F, Brown L. Olive leaf extract attenuates cardiac, hepatic, and metabolic changes in high carbohydrate-, high fat-fed rats. J Nutr. 2010 May;140(5):946-53. doi: 10.3945/jn.109.117812. Epub 2010 Mar 24.

  PMID: 20335636 BACKGROUND

• Rodriguez-Rodriguez R, Perona JS, Herrera MD, Ruiz-Gutierrez V. Triterpenic compounds from "orujo" olive oil elicit vasorelaxation in aorta from spontaneously hypertensive rats. J Agric Food Chem. 2006 Mar 22;54(6):2096-102. doi: 10.1021/jf0528512.

  PMID: 16536581 BACKGROUND

• Sanchez-Quesada C, Lopez-Biedma A, Warleta F, Campos M, Beltran G, Gaforio JJ. Bioactive properties of the main triterpenes found in olives, virgin olive oil, and leaves of Olea europaea. J Agric Food Chem. 2013 Dec 18;61(50):12173-82. doi: 10.1021/jf403154e. Epub 2013 Nov 22.

  PMID: 24279741 BACKGROUND

• Uylaser V, Yildiz G. The historical development and nutritional importance of olive and olive oil constituted an important part of the Mediterranean diet. Crit Rev Food Sci Nutr. 2014;54(8):1092-101. doi: 10.1080/10408398.2011.626874.

  PMID: 24499124 BACKGROUND

• Weinbrenner T, Fito M, de la Torre R, Saez GT, Rijken P, Tormos C, Coolen S, Albaladejo MF, Abanades S, Schroder H, Marrugat J, Covas MI. Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J Nutr. 2004 Sep;134(9):2314-21. doi: 10.1093/jn/134.9.2314.

  PMID: 15333722 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Joana M Planas, PhD Prof.

  Departament de Bioquímica i Fisiologia. Facultat de Farmàcia i Ciències de l´Alimentació. Universitat de Barcelona

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study involve two stages, the first one corresponding to the pharmacokinetic study of the single administration of table olives in healthy male volunteers and the second one corresponding to the study of a nutritional intervention with 30 table olives during 30 days.

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: March 22, 2019
• Study Start: March 25, 2019
• Primary Completion: May 25, 2019
• Study Completion: June 15, 2019
• Last Updated: August 8, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)