The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils

Sara Biel, Maria-Dolores Mesa, Rafael de la Torre, Juan-Antonio Espejo, Jose-Ramón Fernández-Navarro, Montserrat Fitó, Estefanía Sánchez-Rodriguez, Carmen Rosa, Rosa Marchal, Juan de Dios Alche, Manuela Expósito, Manuel Brenes, Beatriz Gandul, Miguel Angel Calleja, María-Isabel Covas, Sara Biel, Maria-Dolores Mesa, Rafael de la Torre, Juan-Antonio Espejo, Jose-Ramón Fernández-Navarro, Montserrat Fitó, Estefanía Sánchez-Rodriguez, Carmen Rosa, Rosa Marchal, Juan de Dios Alche, Manuela Expósito, Manuel Brenes, Beatriz Gandul, Miguel Angel Calleja, María-Isabel Covas

Abstract

Background: Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO).

Methods/design: A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion.

Discussion: For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition.

Trial registration: The Trial has been registered in ClinicalTrials.gov ID: NCT02520739 .

Keywords: Functional olive oil; Maslinic acid; Oleanolic acid; Olive oil; Olive oil polyphenols; Virgin olive oil.

Figures

Fig. 1
Fig. 1
Flow chart of the study. Sequence 1: a, b, and c olive oils; Sequence 2 :b,c, and a olive oils; Sequence 3: c, a, and b olive oils

References

    1. Covas MI, de la Torre R, Fitó M. Virgin olive oil: a key food for cardiovascular protection. Br J Nutr. 2015;113:S19–S28. doi: 10.1017/S0007114515000136.
    1. EFSA General guidance for stakeholders on the evaluation of Article 13.1, 13.5 and 14 health claims. EFSA Journal. 2011;9(4):2135 [24 pp.].
    1. Commission Regulation (EU).N° 432/2012 of 16 May 2012. Oficial Journal of the European Union, L136/1. 25, 5, 2012
    1. Perona JS, Cabello-Moruno R, Ruiz-Gutierrez V. The role of virgin olive oil components in the modulation of endothelial function. J Nutr Biochem. 2006;17(7):429–45. doi: 10.1016/j.jnutbio.2005.11.007.
    1. Lozano-Mena G, Sánchez-González M, Juan MJ, Planas JM. Maslinic acid, a natural phytoalexin-type triterpene from olives--a promising nutraceutical. Molecules. 2014;19(8):11538–59. doi: 10.3390/molecules190811538.
    1. Zhang W, Men X, Lei P. Review on anti-tumour effect of triterpene acid compounds. J Cancer Res Ther. 2014;10(Suppl 1):14–9.
    1. Woolf SM, Battista RN, Anderson GM, Logan AG, Wang E. Assessing the clinical effectiveness of preventive manoeuvres: analytic principals and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination. J Clin Epidemiol. 1990;43(9):891–905. doi: 10.1016/0895-4356(90)90073-X.
    1. Vijayananthan A, Nawawi O. The importance of Good Clinical Practice guidelines and its role in clinical trials. Biomed Imaging Interv J. 2008;4:e5.
    1. Cooke MS, Olinski R, Evans MD. Does measurement of oxidative damage to DNA have clinical significance? Clin Chim Acta. 2006;365(1-2):30–49. doi: 10.1016/j.cca.2005.09.009.
    1. Di Minno A, Turnu L, Porro B, Squellerio I, Cavalca V, Tremoli E, Di Minno MN. 8-Hydroxy-2-Deoxyguanosine Levels and Cardiovascular Disease: A Systematic Review and Meta-Analysis of the Literature. Antioxid Redox Signal. 2016;24(10):548–55. doi: 10.1089/ars.2015.6508.
    1. Evans MD, Saparbaev M, Cooke MS. DNA repair and the origins of urinary oxidized 2′-deoxyribonucleoside. Mutagenesis. 2010;25(5):433–42. doi: 10.1093/mutage/geq031.
    1. Wu Q, Ni X. ROS-Mediated DNA Methylation Pattern Alterations in Carcinogenesis. Curr Drug Targ. 2015;16(1):13–19. doi: 10.2174/1389450116666150113121054.
    1. Machowetz A, Poulsen HE, Gruendel S, Weimann A, Fitó M, Marrugat J, de la Torre R, et al. Effect of olive oils on biomarkers of oxidative DNA stress in Northern and Southern Europeans. FASEB J. 2007;21(1):45–52. doi: 10.1096/fj.06-6328com.
    1. Mitjavila MT, Fandos M, Salas-Salvadó J, Covas MI, Borrego S, Estruch R, et al. The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial. Clin Nutr. 2013;32(2):172–8. doi: 10.1016/j.clnu.2012.08.002.
    1. Rangel-Huerta OD, Aguilera CM, Martin MV, Soto MJ, Rico MC, Vallejo F, Mesa MD. Normal or High Polyphenol Concentration in Orange Juice Affects Antioxidant Activity, Blood Pressure, and Body Weight in Obese or Overweight Adults. J Nutr. 2015;145(8):1808–16. doi: 10.3945/jn.115.213660.
    1. García-Flores LA, Medina S, Cejuela-Anta R, Martínez-Sanz JM, Abellán Á, Genieser HG, et al. DNA catabolites in triathletes: effects of supplementation with an aronia-citrus juice (polyphenols-rich juice) Food Funct. 2016;7(4):2084–93. doi: 10.1039/C6FO00252H.
    1. Elosua R, Marrugat J, Molina L, Pons S, Pujol E. Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish men. The MARATHOM Investigators. Am J Epidemiol. 1994;139(12):1197–209.
    1. Elosua R, García M, Aguilar A, Molina L, Covas MI, Marrugat J. Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish Women. The MARATDON Investigators. Med Sci Sports Exerc. 2000;32(8):1431–7. doi: 10.1097/00005768-200008000-00011.
    1. Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes. 2000;24:38–48. doi: 10.1038/sj.ijo.0801083.
    1. Miró-Casas E, Farré Albaladejo M, Covas MI, Rodriguez JO, Menoyo Colomer E, Lamuela Raventós RM, et al. Capillary gas chromatography-mass spectrometry quantitative determination of hydroxytyrosol and tyrosol in human urine after olive oil intake. Annal Biochem. 2001;294:63–72. doi: 10.1006/abio.2001.5160.
    1. Martínez-González MA, Toledo E, Arós F, Fiol M, Corella D, Salas-Salvadó J, et al. Extra-virgin olive oil consumption reduces the risk of atrial fibrillation. The PREDIMED (Prevención con Dieta Mediterránea) Trial. Circulation. 2014;130(1):18–26. doi: 10.1161/CIRCULATIONAHA.113.006921.
    1. Covas MI, Nyyssönen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, et al. The EUROLIVE Study group. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006;145(5):333–41. doi: 10.7326/0003-4819-145-5-200609050-00006.
    1. Gómez M, Vila J, Elosua R, Molina L, Bruguera J, Sala J, et al. Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population. Atherosclerosis. 2014;232(1):134–40. doi: 10.1016/j.atherosclerosis.2013.10.026.
    1. Hernáez A, Fernández-Castillero S, Farràs M, Catalán Ú, Subirana I, Montes R, et al. Olive oil polyphenols enhance high density lipoprotein function in humans. A randomized controlled trial. Arterioscler Thromb Vasc Biol. 2014;34(9):2115–9. doi: 10.1161/ATVBAHA.114.303374.
    1. Hernáez A, Remaley AT, Farràs M, Fernández-Castillejo S, Subirana I, Schröder H, et al. Olive Oil polyphenols decrease LDL concentrations and LDL atherogenicity in men in a randomized controlled trial. J Nutr. 2015;145(8):1692–7. doi: 10.3945/jn.115.211557.
    1. Cole TG, Contois JH, Csako G, McConnell JP, Remaley AT, Devaraj S, et al. Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices. Clin Chem. 2013;59(5):752–70. doi: 10.1373/clinchem.2012.196733.
    1. López-Miranda J, Pérez-Jiménez F, Ros E, De Caterina R, Badimón L, Covas MI, et al. Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008. Nutr Metab Cardiovasc Dis. 2010;20(4):284–4. doi: 10.1016/j.numecd.2009.12.007.
    1. Rangel-Zúñiga OA, Haro C, Pérez-Martinez P, Delgado-Lista J, Marín C. Quintana- Navarro GM, et al. Effect of frying oils on the postprandial endoplasmic reticulum stress in obese people. Mol Nutr Food Res. 2014;58(11):2239–42. doi: 10.1002/mnfr.201400401.
    1. Valls RN, Farrás M, Suárez M, Fernández-Castillejo S, Fitó M, Konstantinidou V, et al. Effects of functional olive oil enriched with its own phenolic compounds on endothelial function in hypertensive patients. A randomised controlled trial. Food Chem. 2015;167:30–35. doi: 10.1016/j.foodchem.2014.06.107.
    1. Farràs M, Valls RM, Fernández-Castillejo S, Giralt M, Solà R, Subirana I, et al. Olive oil polyphenols enhance the expression of cholesterol efflux related genes in vivo in humans. A randomized controlled trial. J Nutr Biochem. 2013;24(7):1334–9. doi: 10.1016/j.jnutbio.2012.10.008.
    1. Farràs M, Castañer O, Martín-Peláez S, Hernáez Á, Schröder H, Subirana I, et al. Complementary phenol-enriched olive oil improves HDL characteristics in hypercholesterolemic subjects. A randomized, double-blind, crossover, controlled trial. The VOHF study. Mol Nutr Food Res. 2015;59(9):1758–70. doi: 10.1002/mnfr.201500030.
    1. Fernández-Castillero S, Valls RM, Castañer O, Rubio L, Catalán U, Pedret A, et al. Polyphenol Rich Olive Oils improve Lipoprotein Particle Atherogenic Ratios and Subclasses Profile: A Randomized, Crossover, Controlled Trial. Mol Nutr Food Res. 2016 (in press).

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe