Bioavailability of Oleanolic Acid Formulated as Functional Olive Oil

NCT05529953 | Completed

• 1 other identifier: PID2019-107837RB-100
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The oral bioavailability of Oleanolic acid (OA) when formulated as functional olive oil, and its mechanisms of systemic transport, will be approached by mean of randomized and controlled trial with 20 healthy volunteers. Ten individuals randomly selected will receive 55 mL of the functional OA-enriched olive oil (equivalent dose 30 mg OA) as part of an experimental breakfast. The other ten participants will receive within this experimental meal the same amount of the control olive oil. Immediately before and after eating the respective breakfasts, aliquots of cubital blood will be drawn every hour, over a postprandial period of 7 hours. Since in this trial design, each participant is his/her own control, a four-week washout period is established, after which a new series of tests that cross the type of olive oil consumed will be carried out. From the aliquots of cubital blood, sera will be obtained by centrifugation. The extraction and quantification of serum OA will be realized by gas chromatography (GC) using flame ionization (FID) and mass spectrometry (MS) detectors. In the pharmacokinetic analysis of data, a mono-compartmental model will be assumed. It will be determined: 1) absorption parameters such as the maximum concentration achieved and the timing for it, the constant of absorption and the area under the curve; 2) distribution parameters such as the constant and volume of distribution; 3) metabolism parameters, such as the OA fraction associated with albumin; and 4) elimination parameters such as the elimination constant, the half-life and the clearance. To demonstrate the presence of OA in postprandial TRL, chylomicron and VLDL fractions will be prepared by plasma ultrafiltration in normal saline, and hydrolysed with pancreatic enzyme. The possible presence of OA among the TRL-derived lipids will be evaluated. The content of apo B48 and B100, as markers of the presence of chylomicrons and VLDL, respectively, will be determined by ELISA. Other parameters related to glycemic control, such as serum insulin, C-peptide and GLP-1 will be analyzed by ELISA.

Conditions

Healthy Subjects; Bioavailability

Keywords

Oleanolic acid; bioavailability; triglyceride-rich lipoproteins; postprandial dietary intervention; pharmacokinetic; randomized and controlled trial; crossover design

Outcome Measures

Primary Outcomes (2)

• Area Under the Plasma Concentration Versus Time Curve (AUC) of Oleanolic acid

  Quantification of the Oleanolic acid plasma concentration every 60 minutes

  postpradial 6-hours period

• Identification and quantification of the Oleanolic acid presence in triglyceride-rich lipoproteins

  isolation and analysis of Oleanolic acid in postprandial chylomicrons and VLDL

  postpradial 6-hours period

Secondary Outcomes (3)

• Fraction of the Oleanolic acid associated to serum albumin

  postpradial 6-hours period

• Influence of the Oleanolic acid-based intervention on the postprandial glycemic control

  postpradial 6-hours period

• Influence of the Oleanolic acid-based intervention on plasma lipids

  postpradial 6-hours period

Study Arms (2)

Oleanolic acid-enriched functional olive oil

EXPERIMENTAL

functional olive oil elaborated enriching the control olive oil with Oleanolic acid up to 600 mg OA/kg oil. Single oral intake of 55 mL of functional olive oil (dose equivalent to 30 mg OA).

Dietary Supplement: Oleanolic acid (CAS no. 598-02-1; PubChem CID 10494)

Control olive oil

ACTIVE COMPARATOR

commercial olive oil (blend of virgin and refined olive oils) chosen by its very low content of bioactive minor components. Single oral intake of 55 mL of commercial olive oil

Dietary Supplement: Control commercial olive oil

Interventions

Oleanolic acid (CAS no. 598-02-1; PubChem CID 10494) DIETARY_SUPPLEMENT

Postprandial study of bioavailability of Oleanolic acid, formulated as functional olive oil, in healthy subjects

Also known as: Oleanolic acid-enriched functional olive oil

Oleanolic acid-enriched functional olive oil

Control commercial olive oil DIETARY_SUPPLEMENT

Postprandial study of Oleanolic acid bioavailability in healthy subjects

Control olive oil

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy women and men
• aged 18-30 years
• BMI in the range 18.5-29.9 kg/m2
• complete biochemical and hematological analysis yield results within normal limits
• grant the written consent to the protocols approved by the Institutional Committees for Human Research of the CSIC and HUVR, after being conveniently informed both orally and documentally.

You may not qualify if:

• suffering from digestive, metabolic or oncologic disorders or any other pathology that, in opinion of the clinical investigators, could prevent them from participating in the trial (checked in their electronic medical histories).

Sponsors & Collaborators

• Spanish National Research Council: lead
• Andalusian Health Service: collaborator
• Universidad Pablo de Olavide: collaborator

Study Sites (1)

Universitary Hospitals Virgen del Rocío

Seville, Sevilla, 41013, Spain

Location

Related Publications (8)

• Guinda A, Rada M, Delgado T, Gutierrez-Adanez P, Castellano JM. Pentacyclic triterpenoids from olive fruit and leaf. J Agric Food Chem. 2010 Sep 8;58(17):9685-91. doi: 10.1021/jf102039t.

  PMID: 20712364 BACKGROUND

• Castellano JM, Guinda A, Delgado T, Rada M, Cayuela JA. Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes. Diabetes. 2013 Jun;62(6):1791-9. doi: 10.2337/db12-1215.

  PMID: 23704520 BACKGROUND

• Castellano JM, Ramos-Romero S, Perona JS. Oleanolic Acid: Extraction, Characterization and Biological Activity. Nutrients. 2022 Jan 31;14(3):623. doi: 10.3390/nu14030623.

  PMID: 35276982 BACKGROUND

• Fernandez-Aparicio A, Correa-Rodriguez M, Castellano JM, Schmidt-RioValle J, Perona JS, Gonzalez-Jimenez E. Potential Molecular Targets of Oleanolic Acid in Insulin Resistance and Underlying Oxidative Stress: A Systematic Review. Antioxidants (Basel). 2022 Aug 3;11(8):1517. doi: 10.3390/antiox11081517.

  PMID: 36009236 BACKGROUND

• Santos-Lozano JM, Rada M, Lapetra J, Guinda A, Jimenez-Rodriguez MC, Cayuela JA, Angel-Lugo A, Vilches-Arenas A, Gomez-Martin AM, Ortega-Calvo M, Castellano JM. Prevention of type 2 diabetes in prediabetic patients by using functional olive oil enriched in oleanolic acid: The PREDIABOLE study, a randomized controlled trial. Diabetes Obes Metab. 2019 Nov;21(11):2526-2534. doi: 10.1111/dom.13838. Epub 2019 Aug 28.

  PMID: 31364228 BACKGROUND

• Jimenez-Sanchez A, Martinez-Ortega AJ, Remon-Ruiz PJ, Pinar-Gutierrez A, Pereira-Cunill JL, Garcia-Luna PP. Therapeutic Properties and Use of Extra Virgin Olive Oil in Clinical Nutrition: A Narrative Review and Literature Update. Nutrients. 2022 Mar 31;14(7):1440. doi: 10.3390/nu14071440.

  PMID: 35406067 BACKGROUND

• Rada M, Castellano JM, Perona JS, Guinda A. GC-FID determination and pharmacokinetic studies of oleanolic acid in human serum. Biomed Chromatogr. 2015 Nov;29(11):1687-92. doi: 10.1002/bmc.3480. Epub 2015 May 5.

  PMID: 25943913 BACKGROUND

• Karpe F, Tornvall P, Olivecrona T, Steiner G, Carlson LA, Hamsten A. Composition of human low density lipoprotein: effects of postprandial triglyceride-rich lipoproteins, lipoprotein lipase, hepatic lipase and cholesteryl ester transfer protein. Atherosclerosis. 1993 Jan 4;98(1):33-49. doi: 10.1016/0021-9150(93)90221-f.

  PMID: 8457249 BACKGROUND

MeSH Terms

Interventions

Oleanolic Acid

Intervention Hierarchy (Ancestors)

Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Organic Chemicals; Sapogenins

Study Officials

• José M. Castellano, PhD

  Instituto de la Grasa-Spanish National Research Council (CSIC)

  PRINCIPAL INVESTIGATOR

• Pedro P. García-Luna

  Andalusian Public Foundation for Health Research Management in Seville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Double-blind trial. Each recruited participant is assigned a random alphanumeric ID code. Assignment of participants to study groups is done by randomization of their ID. The olive oils (functional and control) used in the postprandial trial are labeled with alphanumeric codes known only to the principal investigator of the project.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 2, 2022
• First Posted: September 7, 2022
• Study Start: March 15, 2021
• Primary Completion: June 30, 2021
• Study Completion: July 15, 2021
• Last Updated: October 31, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)