Nutritional Intervention With Table Olives in Healthy Volunteers

Healthy Clinical Trial

— BIOLIVA  

Official title:

Table Olives Nutritional Intervention: Pharmacokinetics of Polyphenols and Pentacyclic Triterpenes and Assessment of Antioxidant, Cardiovascular and Anti-inflammatory Biomarkers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03886597
• Other study ID #: IIBSP-OLI-2016-23
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 25, 2019
• Est. completion date: June 15, 2019

Study information

• Verified date: August 2019
• Source: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: June 15, 2019
• Est. primary completion date: May 25, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

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

Intervention

Other:
• Table Olives
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.
• Table Olives
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 120 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 10 minutes to ingest 120 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.
• Table Olives
All the subjects will perform two experimental sessions of 30 days with 15 days of washout periods within experimental periods. In one experimental session subjects will ingest table olives and in the other session they will act as their own controls following their normal dietary habits. During all the experiment participants will avoid the consumption of products rich in phenolic and triterpenic compounds. Subjects will include the dose of 60 table olives within their normal dietary habits. Consequently, the olives will be consumed two times daily within each main meal; 30 olives before lunch and 30 olives before dinner. Blood samples will be collected at baseline and 15 and 30 days of each experimental session. Tolerability variables and blood pressure will also be measured.

Locations

Country	Name	City	State
Spain	Institut de Recerca Hospital de la Santa Creu i Sant Pau - CIM Sant Pau	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau	Ministerio de Economía y Competitividad (Spain) AGL 2013-41188R, University of Barcelona

Country where clinical trial is conducted

Spain, 

References & 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. — View Citation

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. Review. — View Citation

Covas MI, Nyyssönen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, Gaddi A, de la Torre R, Mursu J, Bäumler H, Nascetti S, Salonen JT, Fitó 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. — View Citation

de la Torre-Carbot K, Chávez-Servín JL, Jaúregui O, Castellote AI, Lamuela-Raventós RM, Fitó M, Covas MI, Muñoz-Aguayo D, López-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. Epub 2006 Nov 2. — View Citation

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. Epub 2006 May 3. Review. — View Citation

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):3291-340. doi: 10.3390/ijms13033291. Epub 2012 Mar 12. Review. — View Citation

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. — View Citation

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. Epub 2007 Sep 17. — View Citation

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. — View Citation

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. Review. — View Citation

Lozano-Mena G, Sánchez-González 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. Review. — View Citation

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. — View Citation

Marrugat J, Covas MI, Fitó M, Schröder H, Miró-Casas E, Gimeno E, López-Sabater MC, de la Torre R, Farré 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. Epub 2004 Jan 6. — View Citation

Martín-Peláez S, Covas MI, Fitó M, Kušar 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Sánchez-Quesada C, López-Biedma A, Warleta F, Campos M, Beltrán 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. Review. — View Citation

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. — View Citation

Weinbrenner T, Fitó 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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Maximum plasma concentration (Cmax)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	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
Primary	Stage 1: Time until Cmax is reached (Tmax)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	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
Primary	Stage 1: AUC extrapolated to infinite time (AUC (0-8)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 1: Percentage of AUC extrapolated (AUC%)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 1: Terminal elimination rate constant (Kel)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 1: Plasma concentration half-life (t ½)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 1: Volume of distribution (Vd/ F)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 1: Clearance (Cl/F)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	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
Primary	Stage 1: Cmax dose normalized (Cmax/Dose)	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	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
Primary	Stage 1: Urine polyphenols concentration	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 1: Urine triterpenes concentration	24 hour dosing period; 2 dosing periods each separated by 7 days washout	24 hours
Primary	Stage 2: Plasma polyphenols concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Plasma triterpenes concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Urine polyphenols concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Urine triterpenes concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Malondialdehyde concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Catalase concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Glutathione peroxidase concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Superoxide dismutase concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: F2A isoprostane concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: 8 isoprostane concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Oxidized low-density lipoprotein concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: C-Reactive Protein concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Lipoprotein-associated phospholipase A2 concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Apolipoprotein A1 concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Apolipoprotein B100 concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Tumor necrosis factor alpha concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Interleukin 6 concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Primary	Stage 2: Interleukin 1 concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 1 and 2: Number of participants with treatment-related adverse events	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 1 and 2: Systolic and diastolic blood pressure	Stage 1: 24 hours, Stage 2: 30 days	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
Secondary	Stage 1 and 2: Heart rate	Stage 1: 24 hours, Stage 2: 30 days	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
Secondary	Stage 1 and 2: Respiratory rate	Stage 1: 24 hours, Stage 2: 30 days	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
Secondary	Stage 2: Body weight	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: High-density lipoprotein cholesterol concentration (HDL-C)	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Low-density lipoprotein cholesterol concentration (LDL-C)	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Very low-density lipoprotein cholesterol concentration (VLDL-C)	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Triglyceride concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Total cholesterol concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Sodium concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Glucose concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Urea concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Creatinine concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Aspartate aminotransferase concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Alanine aminotransferase concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Alkaline phosphatase concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout
Secondary	Stage 2: Total proteins concentration	30 days	30 days dosing period or 30 days as control group separated by 15 days washout