Virgin Olive Oil and Health: Summary of the III International Conference on Virgin Olive Oil and Health Consensus Report, JAEN (Spain) 2018

José J Gaforio, Francesco Visioli, Catalina Alarcón-de-la-Lastra, Olga Castañer, Miguel Delgado-Rodríguez, Monserrat Fitó, Antonio F Hernández, Jesús R Huertas, Miguel A Martínez-González, Javier A Menendez, Jesús de la Osada, Angeliki Papadaki, Tesifón Parrón, Jorge E Pereira, María A Rosillo, Cristina Sánchez-Quesada, Lukas Schwingshackl, Estefanía Toledo, Aristidis M Tsatsakis, José J Gaforio, Francesco Visioli, Catalina Alarcón-de-la-Lastra, Olga Castañer, Miguel Delgado-Rodríguez, Monserrat Fitó, Antonio F Hernández, Jesús R Huertas, Miguel A Martínez-González, Javier A Menendez, Jesús de la Osada, Angeliki Papadaki, Tesifón Parrón, Jorge E Pereira, María A Rosillo, Cristina Sánchez-Quesada, Lukas Schwingshackl, Estefanía Toledo, Aristidis M Tsatsakis

Abstract

The Mediterranean diet is considered as the foremost dietary regimen and its adoption is associated with the prevention of degenerative diseases and an extended longevity. The preeminent features of the Mediterranean diet have been agreed upon and the consumption of olive oil stands out as the most peculiar one. Indeed, the use of olive oil as the nearly exclusive dietary fat is what mostly characterizes the Mediterranean area. Plenty of epidemiological studies have correlated that the consumption of olive oil was associated with better overall health. Indeed, extra virgin olive oil contains (poly)phenolic compounds that are being actively investigated for their purported biological and pharma-nutritional properties. On 18 and 19 May 2018, several experts convened in Jaen (Spain) to discuss the most recent research on the benefits of olive oil and its components. We reported a summary of that meeting (reviewing several topics related to olive oil, not limited to health) and concluded that substantial evidence is accruing to support the widespread opinion that extra virgin olive oil should, indeed, be the fat of choice when it comes to human health and sustainable agronomy.

Keywords: Mediterranean diet; cancer; cardiovascular disease; hydroxytyrosol; neurodegeneration; olive oil; polyphenols; sustainable agriculture; sustainable diet.

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Trichopoulou A., Martinez-Gonzalez M.A., Tong T.Y., Forouhi N.G., Khandelwal S., Prabhakaran D., Mozaffarian D., de Lorgeril M. Definitions and Potential Health Benefits of the Mediterranean Diet: Views from Experts Around the World. BMC Med. 2014;12:112. doi: 10.1186/1741-7015-12-112.
    1. Trichopoulou A., Costacou T., Bamia C., Trichopoulos D. Adherence to a Mediterranean Diet and Survival in a Greek Population. N. Engl. J. Med. 2003;348:2599–2608. doi: 10.1056/NEJMoa025039.
    1. Martinez-Gonzalez M.A., Salas-Salvado J., Estruch R., Corella D., Fito M., Ros E., PREDIMED INVESTIGATORS Benefits of the Mediterranean Diet: Insights from the PREDIMED Study. Prog. Cardiovasc. Dis. 2015;58:50–60. doi: 10.1016/j.pcad.2015.04.003.
    1. Martinez-Gonzalez M.A., Hershey M.S., Zazpe I., Trichopoulou A. Transferability of the Mediterranean Diet to Non-Mediterranean Countries. what is and what is Not the Mediterranean Diet. Nutrients. 2017;9 doi: 10.3390/nu9111226.
    1. Dinu M., Pagliai G., Casini A., Sofi F. Mediterranean Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies and Randomised Trials. Eur. J. Clin. Nutr. 2018;72:30–43. doi: 10.1038/ejcn.2017.58.
    1. Martínez-González M.A., Gea A., Ruiz-Canela M. The Mediterranean Diet and Cardiovascular Health. Circ. Res. 2019;124:779–798. doi: 10.1161/CIRCRESAHA.118.313348.
    1. Serra-Majem L., Román-Viñas B., Sanchez-Villegas A., Guasch-Ferré M., Corella D., La Vecchia C. Benefits of the Mediterranean diet: Epidemiological and molecular aspects. Mol. Aspects. Med. 2019;67:1–55. doi: 10.1016/j.mam.2019.06.001.
    1. Carlos S., De La Fuente-Arrillaga C., Bes-Rastrollo M., Razquin C., Rico-Campa A., Martinez-Gonzalez M.A., Ruiz-Canela M. Mediterranean Diet and Health Outcomes in the SUN Cohort. Nutrients. 2018;10 doi: 10.3390/nu10040439.
    1. Alvarez-Alvarez I., Zazpe I., Perez de Rojas J., Bes-Rastrollo M., Ruiz-Canela M., Fernandez-Montero A., Hidalgo-Santamaria M., Martinez-Gonzalez M.A. Mediterranean Diet, Physical Activity and their Combined Effect on all-Cause Mortality: The Seguimiento Universidad De Navarra (SUN) Cohort. Prev. Med. 2018;106:45–52. doi: 10.1016/j.ypmed.2017.09.021.
    1. De Lorgeril M., Salen P., Martin J.L., Monjaud I., Delaye J., Mamelle N. Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction: Final Report of the Lyon Diet Heart Study. Circulation. 1999;99:779–785. doi: 10.1161/01.CIR.99.6.779.
    1. Martinez-Gonzalez M.A., Corella D., Salas-Salvado J., Ros E., Covas M.I., Fiol M., Warnberg J., Aros F., Ruiz-Gutierrez V., Lamuela-Raventos R.M., et al. Cohort Profile: Design and Methods of the PREDIMED Study. Int. J. Epidemiol. 2012;41:377–385. doi: 10.1093/ije/dyq250.
    1. Schwingshackl L., Missbach B., Konig J., Hoffmann G. Adherence to a Mediterranean Diet and Risk of Diabetes: A Systematic Review and Meta-Analysis. Public Health Nutr. 2015;18:1292–1299. doi: 10.1017/S1368980014001542.
    1. Wang H., Naghavi M., Allen C., Barber RM., Bhutta ZA., Carter A., Casey DC., Charlson FJ., Chen AZ., Coates M.M., et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1459–1544. doi: 10.1016/S0140-6736(16)31012-1.
    1. Lim S.S., Vos T., Flaxman A.D., Danaei G., Shibuya K., Adair-Rohani H., Amann M., Anderson H.R., Andrews K.G., Aryee M., et al. A Comparative Risk Assessment of Burden of Disease and Injury Attributable to 67 Risk Factors and Risk Factor Clusters in 21 Regions, 1990–2010: A Systematic Analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224–2260. doi: 10.1016/S0140-6736(12)61766-8.
    1. Danaei G., Finucane M.M., Lin J.K., Singh G.M., Paciorek C.J., Cowan M.J., Farzadfar F., Stevens G.A., Lim S.S., Riley L.M., et al. National, Regional, and Global Trends in Systolic Blood Pressure since 1980: Systematic Analysis of Health Examination Surveys and Epidemiological Studies with 786 Country-Years and 5.4 Million Participants. Lancet. 2011;377:568–577. doi: 10.1016/S0140-6736(10)62036-3.
    1. Alonso A., Ruiz-Gutierrez V., Martinez-Gonzalez M.A. Monounsaturated Fatty Acids, Olive Oil and Blood Pressure: Epidemiological, Clinical and Experimental Evidence. Public Health Nutr. 2006;9:251–257. doi: 10.1079/PHN2005836.
    1. Appel L.J., Sacks F.M., Carey V.J., Obarzanek E., Swain J.F., Miller E.R., 3rd, Conlin P.R., Erlinger T.P., Rosner B.A., Laranjo N.M., et al. Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood Pressure and Serum Lipids: Results of the OmniHeart Randomized Trial. JAMA. 2005;294:2455–2464. doi: 10.1001/jama.294.19.2455.
    1. Miura K., Stamler J., Brown I.J., Ueshima H., Nakagawa H., Sakurai M., Chan Q., Appel L.J., Okayama A., Okuda N., et al. Relationship of Dietary Monounsaturated Fatty Acids to Blood Pressure: The International Study of Macro/Micronutrients and Blood Pressure. J. Hypertens. 2013;31:1144–1150. doi: 10.1097/HJH.0b013e3283604016.
    1. Domenech M., Roman P., Lapetra J., Garcia de la Corte F.J., Sala-Vila A., de la Torre R., Corella D., Salas-Salvado J., Ruiz-Gutierrez V., Lamuela-Raventos R.M., et al. Mediterranean Diet Reduces 24-Hour Ambulatory Blood Pressure, Blood Glucose, and Lipids: One-Year Randomized, Clinical Trial. Hypertension. 2014;64:69–76. doi: 10.1161/HYPERTENSIONAHA.113.03353.
    1. Zamora-Zamora Z., Martínez-Galiano J.M., Gaforio J.J., Delgado-Rodríguez M. Effects of Olive Oil on Blood Pressure: A Systematic Review and Meta-Analysis. Grasas Y Aceites. 2018;69:e272. doi: 10.3989/gya.0105181.
    1. Eguaras S., Bes-Rastrollo M., Ruiz-Canela M., Carlos S., de la Rosa P., Martinez-Gonzalez M.A. May the Mediterranean Diet Attenuate the Risk of Type 2 Diabetes Associated with Obesity: The Seguimiento Universidad De Navarra (SUN) Cohort. Br. J. Nutr. 2017;117:1478–1485. doi: 10.1017/S0007114517001404.
    1. Finucane M.M., Stevens G.A., Cowan M.J., Danaei G., Lin J.K., Paciorek C.J., Singh G.M., Gutierrez H.R., Lu Y., Bahalim A.N., et al. National, Regional, and Global Trends in Body-Mass Index since 1980: Systematic Analysis of Health Examination Surveys and Epidemiological Studies with 960 Country-Years and 9.1 Million Participants. Lancet. 2011;377:557–567. doi: 10.1016/S0140-6736(10)62037-5.
    1. Arnold M., Pandeya N., Byrnes G., Renehan P.A.G., Stevens G.A., Ezzati P.M., Ferlay J., Miranda J.J., Romieu I., Dikshit R., et al. Global Burden of Cancer Attributable to High Body-Mass Index in 2012: A Population-Based Study. Lancet Oncol. 2015;16:36–46. doi: 10.1016/S1470-2045(14)71123-4.
    1. Aune D., Sen A., Norat T., Janszky I., Romundstad P., Tonstad S., Vatten L.J. Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies. Circulation. 2016;133:639–649. doi: 10.1161/CIRCULATIONAHA.115.016801.
    1. Romaguera D., Norat T., Vergnaud A.C., Mouw T., May A.M., Agudo A., Buckland G., Slimani N., Rinaldi S., Couto E., et al. Mediterranean Dietary Patterns and Prospective Weight Change in Participants of the EPIC-PANACEA Project. Am. J. Clin. Nutr. 2010;92:912–921. doi: 10.3945/ajcn.2010.29482.
    1. Trichopoulou A., Naska A., Orfanos P., Trichopoulos D. Mediterranean Diet in Relation to Body Mass Index and Waist-to-Hip Ratio: The Greek European Prospective Investigation into Cancer and Nutrition Study. Am. J. Clin. Nutr. 2005;82:935–940. doi: 10.1093/ajcn/82.5.935.
    1. Beunza J.J., Toledo E., Hu F.B., Bes-Rastrollo M., Serrano-Martinez M., Sanchez-Villegas A., Martinez J.A., Martinez-Gonzalez M.A. Adherence to the Mediterranean Diet, Long-Term Weight Change, and Incident Overweight Or Obesity: The Seguimiento Universidad De Navarra (SUN) Cohort. Am. J. Clin. Nutr. 2010;92:1484–1493. doi: 10.3945/ajcn.2010.29764.
    1. Buckland G., Bach A., Serra-Majem L. Obesity and the Mediterranean Diet: A Systematic Review of Observational and Intervention Studies. Obes. Rev. 2008;9:582–593. doi: 10.1111/j.1467-789X.2008.00503.x.
    1. Esposito K., Kastorini C.M., Panagiotakos D.B., Giugliano D. Mediterranean Diet and Weight Loss: Meta-Analysis of Randomized Controlled Trials. Metab. Syndr. Relat. Disord. 2011;9:1–12. doi: 10.1089/met.2010.0031.
    1. Estruch R., Martinez-Gonzalez M.A., Corella D., Salas-Salvado J., Fito M., Chiva-Blanch G., Fiol M., Gomez-Gracia E., Aros F., Lapetra J., et al. Effect of a High-Fat Mediterranean Diet on Bodyweight and Waist Circumference: A Prespecified Secondary Outcomes Analysis of the PREDIMED Randomised Controlled Trial. Lancet Diabetes Endocrinol. 2016;4:666–676. doi: 10.1016/S2213-8587(16)30085-7.
    1. Bes-Rastrollo M., Sanchez-Villegas A., de la Fuente C., de Irala J., Martinez J.A., Martinez-Gonzalez M.A. Olive Oil Consumption and Weight Change: The SUN Prospective Cohort Study. Lipids. 2006;41:249–256. doi: 10.1007/s11745-006-5094-6.
    1. Soriguer F., Almaraz M., Ruiz-de-Adana M.S., Esteva I., Linares F., Almeida J., Morcillo S., Garcia-Escobar E., Olveira G., Rojo-Martinez G. Incidence of Obesity is Lower in Persons Who Consume Olive Oil. Eur. J. Clin. Nutr. 2009;63:1371–1374. doi: 10.1038/ejcn.2009.65.
    1. Zamora-Zamora Z., Martínez-Galiano J.M., Gaforio J.J., Delgado-Rodríguez M., Aceite De Oliva Y. Peso Corporal. Revisión Sistemática Y Metaanálisis De Ensayos Controlados Aleatorizados. Rev. Esp. Salud Publ. 2018;92:e1–e15.
    1. World Health Organization . Globocan. Cancer Fact Sheets: Breast Cancer. World Health Organization; Geneva, Switzerland: 2012.
    1. Fitzmaurice C., Allen C., Barber R.M., Barregard L., Bhutta Z.A., Brenner H., Dicker D.J., Chimed-Orchir O., Dandona R., Danona L., et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2017;3:524–548.
    1. Trichopoulou A., Lagiou P., Kuper H., Trichopoulos D. Cancer and Mediterranean Dietary Traditions. Cancer Epidemiol. Biomarkers Prev. 2000;9:869–873.
    1. Van den Brandt P.A., Schulpen M. Mediterranean Diet Adherence and Risk of Postmenopausal Breast Cancer: Results of a Cohort Study and Meta-Analysis. Int. J. Cancer. 2017;140:2220–2231. doi: 10.1002/ijc.30654.
    1. World Cancer Research Fund & American Institute for Cancer Research . Diet, Nutrition, Physical Activity and Breast Cancer Risk. World Cancer Research Fund & American Institute for Cancer Research; London, UK: 2017. Revised 2018.
    1. Buckland G., Travier N., Cottet V., Gonzalez C.A., Lujan-Barroso L., Agudo A., Trichopoulou A., Lagiou P., Trichopoulos D., Peeters P.H., et al. Adherence to the Mediterranean Diet and Risk of Breast Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort Study. Int. J. Cancer. 2013;132:2918–2927. doi: 10.1002/ijc.27958.
    1. Buckland G., Mayen A.L., Agudo A., Travier N., Navarro C., Huerta J.M., Chirlaque M.D., Barricarte A., Ardanaz E., Moreno-Iribas C., et al. Olive Oil Intake and Mortality within the Spanish Population (EPIC-Spain) Am. J. Clin. Nutr. 2012;96:142–149. doi: 10.3945/ajcn.111.024216.
    1. Psaltopoulou T., Kosti R.I., Haidopoulos D., Dimopoulos M., Panagiotakos D.B. Olive Oil Intake is Inversely Related to Cancer Prevalence: A Systematic Review and a Meta-Analysis of 13,800 Patients and 23,340 Controls in 19 Observational Studies. Lipids Health. Dis. 2011;10:127. doi: 10.1186/1476-511X-10-127.
    1. Estruch R., Ros E., Salas-Salvado J., Covas M.I., Corella D., Aros F., Gomez-Gracia E., Ruiz-Gutierrez V., Fiol M., Lapetra J., et al. Retraction and Republication: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N. Engl. J. Med. 2018;378:2441–2442. doi: 10.1056/NEJMc1806491.
    1. Toledo E., Salas-Salvado J., Donat-Vargas C., Buil-Cosiales P., Estruch R., Ros E., Corella D., Fito M., Hu F.B., Aros F., et al. Mediterranean Diet and Invasive Breast Cancer Risk among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial. JAMA Intern. Med. 2015;175:1752–1760. doi: 10.1001/jamainternmed.2015.4838.
    1. Schwingshackl L., Schwedhelm C., Galbete C., Hoffmann G. Adherence to Mediterranean Diet and Risk of Cancer: An Updated Systematic Review and Meta-Analysis. Nutrients. 2017;9 doi: 10.3390/nu9101063.
    1. Machowetz A., Poulsen H.E., Gruendel S., Weimann A., Fito M., Marrugat J., de la Torre R., Salonen J.T., Nyyssonen K., Mursu J., et al. Effect of Olive Oils on Biomarkers of Oxidative DNA Stress in Northern and Southern Europeans. FASEB J. 2007;21:45–52. doi: 10.1096/fj.06-6328com.
    1. Salvini S., Sera F., Caruso D., Giovannelli L., Visioli F., Saieva C., Masala G., Ceroti M., Giovacchini V., Pitozzi V., et al. Daily Consumption of a High-Phenol Extra-Virgin Olive Oil Reduces Oxidative DNA Damage in Postmenopausal Women. Br. J. Nutr. 2006;95:742–751. doi: 10.1079/BJN20051674.
    1. Tunstall-Pedoe H., Kuulasmaa K., Mahonen M., Tolonen H., Ruokokoski E., Amouyel P. Contribution of Trends in Survival and Coronary-Event Rates to Changes in Coronary Heart Disease Mortality: 10-Year Results from 37 WHO MONICA Project Populations. Monitoring Trends and Determinants in Cardiovascular Disease. Lancet. 1999;353:1547–1557. doi: 10.1016/S0140-6736(99)04021-0.
    1. Degano I.R., Elosua R., Marrugat J. Epidemiology of Acute Coronary Syndromes in Spain: Estimation of the Number of Cases and Trends from 2005 to 2049. Rev. Esp. Cardiol. 2013;66:472–481. doi: 10.1016/j.rec.2013.01.018.
    1. Aravanis C., Corcondilas A., Dontas A.S., Lekos D., Keys A. Coronary Heart Disease in Seven Countries. IX. the Greek Islands of Crete and Corfu. Circulation. 1970;41:I88–I100. doi: 10.1161/01.CIR.41.4S1.I-88.
    1. McGovern P.G., Pankow J.S., Shahar E., Doliszny K.M., Folsom A.R., Blackburn H., Luepker R.V. Recent Trends in Acute Coronary Heart Disease—Mortality, Morbidity, Medical Care, and Risk Factors. the Minnesota Heart Survey Investigators. N. Engl. J. Med. 1996;334:884–890. doi: 10.1056/NEJM199604043341403.
    1. Bendinelli B., Masala G., Saieva C., Salvini S., Calonico C., Sacerdote C., Agnoli C., Grioni S., Frasca G., Mattiello A., et al. Fruit, Vegetables, and Olive Oil and Risk of Coronary Heart Disease in Italian Women: The EPICOR Study. Am. J. Clin. Nutr. 2011;93:275–283. doi: 10.3945/ajcn.110.000521.
    1. Samieri C., Feart C., Proust-Lima C., Peuchant E., Tzourio C., Stapf C., Berr C., Barberger-Gateau P. Olive Oil Consumption, Plasma Oleic Acid, and Stroke Incidence: The Three-City Study. Neurology. 2011;77:418–425. doi: 10.1212/WNL.0b013e318220abeb.
    1. Guasch-Ferre M., Hu F.B., Martinez-Gonzalez M.A., Fito M., Bullo M., Estruch R., Ros E., Corella D., Recondo J., Gomez-Gracia E., et al. Olive Oil Intake and Risk of Cardiovascular Disease and Mortality in the PREDIMED Study. BMC Med. 2014;12:78. doi: 10.1186/1741-7015-12-78.
    1. Schwingshackl L., Hoffmann G. Monounsaturated Fatty Acids, Olive Oil and Health Status: A Systematic Review and Meta-Analysis of Cohort Studies. Lipids Health. Dis. 2014;13:154. doi: 10.1186/1476-511X-13-154.
    1. Weinbrenner T., Fito M., de la Torre R., Saez G.T., Rijken P., Tormos C., Coolen S., Albaladejo M.F., Abanades S., Schroder H., et al. Olive Oils High in Phenolic Compounds Modulate Oxidative/Antioxidative Status in Men. J. Nutr. 2004;134:2314–2321. doi: 10.1093/jn/134.9.2314.
    1. Covas M.I., de la Torre K., Farre-Albaladejo M., Kaikkonen J., Fito M., Lopez-Sabater C., Pujadas-Bastardes M.A., Joglar J., Weinbrenner T., Lamuela-Raventos R.M., et al. Postprandial LDL Phenolic Content and LDL Oxidation are Modulated by Olive Oil Phenolic Compounds in Humans. Free Radic. Biol. Med. 2006;40:608–616. doi: 10.1016/j.freeradbiomed.2005.09.027.
    1. Estruch R., Martinez-Gonzalez M.A., Corella D., Salas-Salvado J., Ruiz-Gutierrez V., Covas M.I., Fiol M., Gomez-Gracia E., Lopez-Sabater M.C., Vinyoles E., et al. Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors: A Randomized Trial. Ann. Intern. Med. 2006;145:1–11. doi: 10.7326/0003-4819-145-1-200607040-00004.
    1. Storniolo C.E., Casillas R., Bullo M., Castaner O., Ros E., Saez G.T., Toledo E., Estruch R., Ruiz-Gutierrez V., Fito M., et al. A Mediterranean Diet Supplemented with Extra Virgin Olive Oil or Nuts Improves Endothelial Markers Involved in Blood Pressure Control in Hypertensive Women. Eur. J. Nutr. 2017;56:89–97. doi: 10.1007/s00394-015-1060-5.
    1. Toledo E., Hu F.B., Estruch R., Buil-Cosiales P., Corella D., Salas-Salvado J., Covas M.I., Aros F., Gomez-Gracia E., Fiol M., et al. Effect of the Mediterranean Diet on Blood Pressure in the PREDIMED Trial: Results from a Randomized Controlled Trial. BMC Med. 2013;11:207. doi: 10.1186/1741-7015-11-207.
    1. Shai I., Schwarzfuchs D., Henkin Y., Shahar D.R., Witkow S., Greenberg I., Golan R., Fraser D., Bolotin A., Vardi H., et al. Weight Loss with a Low-Carbohydrate, Mediterranean, Or Low-Fat Diet. N. Engl. J. Med. 2008;359:229–241. doi: 10.1056/NEJMoa0708681.
    1. Schwarzfuchs D., Golan R., Shai I. Four-Year Follow-Up After Two-Year Dietary Interventions. N. Engl. J. Med. 2012;367:1373–1374. doi: 10.1056/NEJMc1204792.
    1. Hohmann C.D., 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;22:631–640. doi: 10.1016/j.phymed.2015.03.019.
    1. Fito M., Cladellas M., de la Torre R., Marti J., Alcantara M., Pujadas-Bastardes M., Marrugat J., Bruguera J., Lopez-Sabater M.C., Vila J., et al. Antioxidant Effect of Virgin Olive Oil in Patients with Stable Coronary Heart Disease: A Randomized, Crossover, Controlled, Clinical Trial. Atherosclerosis. 2005;181:149–158. doi: 10.1016/j.atherosclerosis.2004.12.036.
    1. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Scientific Opinion on the Substantiation of Health Claims Related to Polyphenols in Olive and Protection of LDL Particles from Oxidative Damage (ID 1333, 1638, 1639, 1696, 2865), Maintenance of Normal Blood HDL-Cholesterol Concentrations (ID 1639), Maintenance of Normal Blood Pressure (ID 3781), “anti-Inflammatory Properties” (ID 1882), “contributes to the Upper Respiratory Tract Health” (ID 3468), “can Help to Maintain a Normal Function of Gastrointestinal Tract” (3779), and “contributes to Body Defences Against External Agents” (ID 3467) Pursuant to Article 13(1) of Regulation (EC) no 1924/2006. EFSA J. 2011;9:2033.
    1. EFSA Panel on Dietetic Products Nutrition and Allergy (NDA) Scientific Opinion on the Substantiation of Health Claims Related to Polyphenols in Olive Oil and Protection of LDL Particles from Oxidative Damage. EFSA J. 2011;9:2033.
    1. Holvoet P., Mertens A., Verhamme P., Bogaerts K., Beyens G., Verhaeghe R., Collen D., Muls E., Van de Werf F. Circulating Oxidized LDL is a Useful Marker for Identifying Patients with Coronary Artery Disease. Arterioscler. Thromb. Vasc. Biol. 2001;21:844–848. doi: 10.1161/01.ATV.21.5.844.
    1. Meisinger C., Baumert J., Khuseyinova N., Loewel H., Koenig W. Plasma Oxidized Low-Density Lipoprotein, a Strong Predictor for Acute Coronary Heart Disease Events in Apparently Healthy, Middle-Aged Men from the General Population. Circulation. 2005;112:651–657. doi: 10.1161/CIRCULATIONAHA.104.529297.
    1. Jenkins D.J.A., Spence J.D., Giovannucci E.L., Kim Y.I., Josse R., Vieth R., Blanco Mejia S., Viguiliouk E., Nishi S., Sahye-Pudaruth S., et al. Supplemental Vitamins and Minerals for CVD Prevention and Treatment. J. Am. Coll Cardiol. 2018;71:2570–2584. doi: 10.1016/j.jacc.2018.04.020.
    1. Svegliati Baroni S., Amelio M., Fiorito A., Gaddi A., Littarru G., Battino M. Monounsaturated Diet Lowers LDL Oxidisability in Type IIb and Type IV Dyslipidemia without Affecting Coenzyme Q10 and Vitamin E Contents. Biofactors. 1999;9:325–330. doi: 10.1002/biof.5520090231.
    1. Hernaez A., Fernandez-Castillejo S., Farras M., Catalan U., Subirana I., Montes R., Sola R., Munoz-Aguayo D., Gelabert-Gorgues A., Diaz-Gil O., et al. Olive Oil Polyphenols Enhance High-Density Lipoprotein Function in Humans: A Randomized Controlled Trial. Arterioscler. Thromb. Vasc. Biol. 2014;34:2115–2119. doi: 10.1161/ATVBAHA.114.303374.
    1. Rosenson R.S., Brewer H.B., Jr., Ansell B.J., Barter P., Chapman M.J., Heinecke J.W., Kontush A., Tall A.R., Webb N.R. Dysfunctional HDL and Atherosclerotic Cardiovascular Disease. Nat. Rev. Cardiol. 2016;13:48–60. doi: 10.1038/nrcardio.2015.124.
    1. Hernaez A., Castaner O., Elosua R., Pinto X., Estruch R., Salas-Salvado J., Corella D., Aros F., Serra-Majem L., Fiol M., et al. Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial. Circulation. 2017;135:633–643. doi: 10.1161/CIRCULATIONAHA.116.023712.
    1. Schwingshackl L., Krause M., Schmucker C., Hoffmann G., Rücker G., Meerpohl J.J. Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis. Nutr. Metabol. Cardiovasc. Dis. 2019 doi: 10.1016/j.numecd.2019.07.001. in Press.
    1. Ruano J., Lopez-Miranda J., de la Torre R., Delgado-Lista J., Fernandez J., Caballero J., Covas M.I., Jimenez Y., Perez-Martinez P., Marin C., et al. Intake of Phenol-Rich Virgin Olive Oil Improves the Postprandial Prothrombotic Profile in Hypercholesterolemic Patients. Am. J. Clin. Nutr. 2007;86:341–346. doi: 10.1093/ajcn/86.2.341.
    1. Fernandez de la Puebla R.A., Perez-Martinez P., Carmona J., Lopez-Miranda Carmen Marin J., Paniagua J.A., Fuentes F., Perez-Jimenez F. Factor VII Polymorphisms Influence the Plasma Response to Diets with Different Fat Content, in a Healthy Caucasian Population. Mol. Nutr. Food Res. 2007;51:618–624. doi: 10.1002/mnfr.200600298.
    1. Delgado-Lista J., Garcia-Rios A., Perez-Martinez P., Lopez-Miranda J., Perez-Jimenez F. Olive Oil and Haemostasis: Platelet Function, Thrombogenesis and Fibrinolysis. Curr. Pharm. Des. 2011;17:778–785. doi: 10.2174/138161211795428876.
    1. Capurso C., Massaro M., Scoditti E., Vendemiale G., Capurso A. Vascular Effects of the Mediterranean Diet Part I: Anti-Hypertensive and Anti-Thrombotic Effects. Vascul. Pharmacol. 2014;63:118–126. doi: 10.1016/j.vph.2014.10.001.
    1. Visioli F., Caruso D., Grande S., Bosisio R., Villa M., Galli G., Sirtori C., Galli C. Virgin Olive Oil Study (VOLOS): Vasoprotective potential of extra virgin olive oil in mildly dyslipidemic patients. Eur. J. Nutr. 2005;44:121–127. doi: 10.1007/s00394-004-0504-0.
    1. Visioli F., Franco M., Toledo E., Luchsinger J., Willett W.C., Hu F.B., Martinez-Gonzalez M.A. Olive oil and prevention of chronic diseases: Summary of an International conference. Nutr. Metab. Cardiovasc. Dis. 2018;28:649–656. doi: 10.1016/j.numecd.2018.04.004.
    1. Pacheco Y., López S., Bermúdez B., Abia R., Muriana F. Extra-Virgin Vs. Refined Olive Oil on Postprandial Hemostatic Markers in Healthy Subjects. J. Thromb. Haemost. 2006;4:1421–1422. doi: 10.1111/j.1538-7836.2006.01963.x.
    1. Oosthuizen W., Vorster H.H., Jerling J.C., Barnard H.C., Smuts C.M., Silvis N., Kruger A., Venter C.S. Both Fish Oil and Olive Oil Lowered Plasma Fibrinogen in Women with High Baseline Fibrinogen Levels. Thromb. Haemost. 1994;72:557–562. doi: 10.1055/s-0038-1648914.
    1. WHO Diabetes-Fact Sheet. [(accessed on 23 May 2019)];2017 Available online: .
    1. Panagiotakos D.B., Tzima N., Pitsavos C., Chrysohoou C., Zampelas A., Toussoulis D., Stefanadis C. The Association between Adherence to the Mediterranean Diet and Fasting Indices of Glucose Homoeostasis: The ATTICA Study. J. Am. Coll. Nutr. 2007;26:32–38. doi: 10.1080/07315724.2007.10719583.
    1. Salas-Salvado J., Bullo M., Estruch R., Ros E., Covas M.I., Ibarrola-Jurado N., Corella D., Aros F., Gomez-Gracia E., Ruiz-Gutierrez V., et al. Prevention of Diabetes with Mediterranean Diets: A Subgroup Analysis of a Randomized Trial. Ann. Intern. Med. 2014;160:1–10. doi: 10.7326/M13-1725.
    1. Koloverou E., Esposito K., Giugliano D., Panagiotakos D. The Effect of Mediterranean Diet on the Development of Type 2 Diabetes Mellitus: A Meta-Analysis of 10 Prospective Studies and 136,846 Participants. Metabolism. 2014;63:903–911. doi: 10.1016/j.metabol.2014.04.010.
    1. Esposito K., Maiorino M.I., Bellastella G., Chiodini P., Panagiotakos D., Giugliano D. A Journey into a Mediterranean Diet and Type 2 Diabetes: A Systematic Review with Meta-Analyses. BMJ Open. 2015;5:e008222. doi: 10.1136/bmjopen-2015-008222.
    1. Esposito K., Chiodini P., Maiorino M.I., Bellastella G., Panagiotakos D., Giugliano D. Which Diet for Prevention of Type 2 Diabetes? A Meta-Analysis of Prospective Studies. Endocrine. 2014;47:107–116. doi: 10.1007/s12020-014-0264-4.
    1. Carnevale R., Loffredo L., Del Ben M., Angelico F., Nocella C., Petruccioli A., Bartimoccia S., Monticolo R., Cava E., Visioli F. Extra virgin olive oil improves post-prandial glycemic and lipid profile in patients with impaired fasting glucose. Clinical Nutrition. 2017;36:782–787. doi: 10.1016/j.clnu.2016.05.016.
    1. Soriguer F., Esteva I., Rojo-Martinez G., Ruiz de Adana M.S., Dobarganes M.C., Garcia-Almeida J.M., Tinahones F., Beltran M., Gonzalez-Romero S., Olveira G., et al. Oleic Acid from Cooking Oils is Associated with Lower Insulin Resistance in the General Population (Pizarra Study) Eur. J. Endocrinol. 2004;150:33–39. doi: 10.1530/eje.0.1500033.
    1. Santangelo C., Filesi C., Vari R., Scazzocchio B., Filardi T., Fogliano V., D’Archivio M., Giovannini C., Lenzi A., Morano S., et al. Consumption of Extra-Virgin Olive Oil Rich in Phenolic Compounds Improves Metabolic Control in Patients with Type 2 Diabetes Mellitus: A Possible Involvement of Reduced Levels of Circulating Visfatin. J. Endocrinol. Invest. 2016;39:1295–1301. doi: 10.1007/s40618-016-0506-9.
    1. Basterra-Gortari FJ., Ruiz-Canela M., Martínez-González MA., Babio N., Sorlí JV., Fito M., Ros E., Gómez-Gracia E., Fiol M., Lapetra J., et al. Effects of a Mediterranean Eating Plan on the Need for Glucose-Lowering Medications in Participants With Type 2 Diabetes: A Subgroup Analysis of the PREDIMED Trial. Diabetes Care. 2019 doi: 10.2337/dc18-2475.
    1. Jones D.P., Sies H. The Redox Code. Antioxid. Redox Signal. 2015;23:734–746. doi: 10.1089/ars.2015.6247.
    1. Yazulla S. Neurochemistry. is GABA the Neurotransmitter for some Photoreceptors? Nature. 1986;320:685–686. doi: 10.1038/320685a0.
    1. Iliakis G., Kurtzman S. Mechanism of Radiosensitization by Halogenated Pyrimidines: Bromodeoxyuridine and Beta-Arabinofuranosyladenine Affect Similar Subsets of Radiation-Induced Potentially Lethal Lesions in Plateau-Phase Chinese Hamster Ovary Cells. Radiat. Res. 1991;127:45–51. doi: 10.2307/3578087.
    1. Femia A.P., Dolara P., Servili M., Esposto S., Taticchi A., Urbani S., Giannini A., Salvadori M., Caderni G. No Effects of Olive Oils with Different Phenolic Content Compared to Corn Oil on 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats. Eur. J. Nutr. 2008;47:329–334. doi: 10.1007/s00394-008-0731-x.
    1. Corona G., Deiana M., Incani A., Vauzour D., Dessi M.A., Spencer J.P. Hydroxytyrosol Inhibits the Proliferation of Human Colon Adenocarcinoma Cells through Inhibition of ERK1/2 and Cyclin D1. Mol. Nutr. Food Res. 2009;53:897–903. doi: 10.1002/mnfr.200800269.
    1. Pampaloni B., Mavilia C., Fabbri S., Romani A., Ieri F., Tanini A., Tonelli F., Brandi M.L. In Vitro Effects of Extracts of Extra Virgin Olive Oil on Human Colon Cancer Cells. Nutr. Cancer. 2014;66:1228–1236. doi: 10.1080/01635581.2014.951727.
    1. Hashim Y.Z., Worthington J., Allsopp P., Ternan N.G., Brown E.M., McCann M.J., Rowland I.R., Esposito S., Servili M., Gill C.I. Virgin Olive Oil Phenolics Extract Inhibit Invasion of HT115 Human Colon Cancer Cells in Vitro and in Vivo. Food Funct. 2014;5:1513–1519. doi: 10.1039/c4fo00090k.
    1. Coccia A., Bastianelli D., Mosca L., Monticolo R., Panuccio I., Carbone A., Calogero A., Lendaro E. Extra Virgin Olive Oil Phenols Suppress Migration and Invasion of T24 Human Bladder Cancer Cells through Modulation of Matrix Metalloproteinase-2. Nutr. Cancer. 2014;66:946–954. doi: 10.1080/01635581.2014.922204.
    1. Coccia A., Mosca L., Puca R., Mangino G., Rossi A., Lendaro E. Extra-Virgin Olive Oil Phenols Block Cell Cycle Progression and Modulate Chemotherapeutic Toxicity in Bladder Cancer Cells. Oncol. Rep. 2016;36:3095–3104. doi: 10.3892/or.2016.5150.
    1. Khanal P., Oh W.K., Yun H.J., Namgoong G.M., Ahn S.G., Kwon S.M., Choi H.K., Choi H.S. P-HPEA-EDA, a Phenolic Compound of Virgin Olive Oil, Activates AMP-Activated Protein Kinase to Inhibit Carcinogenesis. Carcinogenesis. 2011;32:545–553. doi: 10.1093/carcin/bgr001.
    1. Fogli S., Arena C., Carpi S., Polini B., Bertini S., Digiacomo M., Gado F., Saba A., Saccomanni G., Breschi M.C., et al. Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells. Nutr. Cancer. 2016;68:873–877. doi: 10.1080/01635581.2016.1180407.
    1. Cusimano A., Balasus D., Azzolina A., Augello G., Emma M.R., Di Sano C., Gramignoli R., Strom S.C., McCubrey J.A., Montalto G., et al. Oleocanthal Exerts Antitumor Effects on Human Liver and Colon Cancer Cells through ROS Generation. Int. J. Oncol. 2017;51:533–544. doi: 10.3892/ijo.2017.4049.
    1. Ayoub N.M., Siddique A.B., Ebrahim H.Y., Mohyeldin M.M., El Sayed K.A. The Olive Oil Phenolic (-)-Oleocanthal Modulates Estrogen Receptor Expression in Luminal Breast Cancer in Vitro and in Vivo and Synergizes with Tamoxifen Treatment. Eur. J. Pharmacol. 2017;810:100–111. doi: 10.1016/j.ejphar.2017.06.019.
    1. Yan C.M., Chai E.Q., Cai H.Y., Miao G.Y., Ma W. Oleuropein Induces Apoptosis Via Activation of Caspases and Suppression of Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway in HepG2 Human Hepatoma Cell Line. Mol. Med. Rep. 2015;11:4617–4624. doi: 10.3892/mmr.2015.3266.
    1. Rosignoli P., Fuccelli R., Sepporta M.V., Fabiani R. In Vitro Chemo-Preventive Activities of Hydroxytyrosol: The Main Phenolic Compound Present in Extra-Virgin Olive Oil. Food Funct. 2016;7:301–307. doi: 10.1039/C5FO00932D.
    1. Toteda G., Lupinacci S., Vizza D., Bonofiglio R., Perri E., Bonofiglio M., Lofaro D., La Russa A., Leone F., Gigliotti P., et al. High Doses of Hydroxytyrosol Induce Apoptosis in Papillary and Follicular Thyroid Cancer Cells. J. Endocrinol. Invest. 2017;40:153–162. doi: 10.1007/s40618-016-0537-2.
    1. Lopez de Las Hazas M.C., Pinol C., Macia A., Motilva M.J. Hydroxytyrosol and the Colonic Metabolites Derived from Virgin Olive Oil Intake Induce Cell Cycle Arrest and Apoptosis in Colon Cancer Cells. J. Agric. Food Chem. 2017;65:6467–6476. doi: 10.1021/acs.jafc.6b04933.
    1. Corominas-Faja B., Cuyàs E., Lozano-Sánchez J., Cufí S., Verdura S., Fernández-Arroyo S., Borrás-Linares I., Martin-Castillo B., Martin Á.G., Lupu R., et al. Extra-virgin olive oil contains a metabolo-epigenetic inhibitor of cancer stem cells. Carcinogenesis. 2018;39:601–613. doi: 10.1093/carcin/bgy023.
    1. Verdura S., Cuyàs E., Lozano-Sánchez J., Bastidas-Velez C., Llorach-Parés L., Fernández-Arroyo S., Hernández-Aguilera A., Joven J., Nonell-Canals A., Bosch-Barrera J. An olive oil phenolic is a new chemotype of mutant isocitrate dehydrogenase 1 (IDH1) inhibitors. Carcinogenesis. 2019;40:27–40. doi: 10.1093/carcin/bgy159.
    1. Cuyàs E., Castillo D., Llorach-Parés L., Lozano-Sánchez J., Verdura S., Nonell-Canals A., Brunet J., Bosch-Barrera J., Joven J., Valdés R., et al. Computational de-orphanization of the olive oil biophenol oleacein: Discovery of new metabolic and epigenetic targets. Food Chem. Toxicol. 2019;131:110529. doi: 10.1016/j.fct.2019.05.037.
    1. Childs B.G., Durik M., Baker D.J., van Deursen J.M. Cellular Senescence in Aging and Age-Related Disease: From Mechanisms to Therapy. Nat. Med. 2015;21:1424–1435. doi: 10.1038/nm.4000.
    1. Menicacci B., Cipriani C., Margheri F., Mocali A., Giovannelli L. Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols. Int. J. Mol. Sci. 2017;18 doi: 10.3390/ijms18112275.
    1. Cheng Y.T., Yang C.C., Shyur L.F. Phytomedicine-Modulating Oxidative Stress and the Tumor Microenvironment for Cancer Therapy. Pharmacol. Res. 2016;114:128–143. doi: 10.1016/j.phrs.2016.10.022.
    1. D’Ignazio L., Batie M., Rocha S. Hypoxia and Inflammation in Cancer, Focus on HIF and NF-kappaB. Biomedicines. 2017;5 doi: 10.3390/biomedicines5020021.
    1. Nocella C., Cammisotto V., Fianchini L., D’Amico A., Novo M., Castellani V., Stefanini L., Violi F., Carnevale R. Extra Virgin Olive Oil and Cardiovascular Diseases: Benefits for Human Health. Endocr Metab. Immune Disord. Drug Targets. 2018;18:4–13. doi: 10.2174/1871530317666171114121533.
    1. Crespo M.C., Tomé-Carneiro J., Dávalos A., Visioli F. Pharma-Nutritional Properties of Olive Oil Phenols. Transfer of New Findings to Human Nutrition. Foods. 2018;7:90. doi: 10.3390/foods7060090.
    1. Buil-Cosiales P., Irimia P., Berrade N., Garcia-Arellano A., Riverol M., Murie-Fernández M., Martínez-Vila E., Martínez-González M.A., Serrano-Martínez M. Carotid intima-media thickness is inversely associated with olive oil consumption. Atherosclerosis. 2008;196:742–748. doi: 10.1016/j.atherosclerosis.2006.12.028.
    1. Casas R., Sacanella E., Urpí-Sardà M., Chiva-Blanch G., Ros E., Martínez-González M.A., Covas M.I., Rosa M.A., Lamuela R., Salas-Salvadó J., et al. The effects of the mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial. PLoS ONE. 2014;9:e100084. doi: 10.1371/journal.pone.0100084.
    1. Bullon P., Quiles J.L., Morillo J.M., Rubini C., Goteri G., Granados-Principal S., Battino M., Ramirez-Tortosa M. Gingival Vascular Damage in Atherosclerotic Rabbits: Hydroxytyrosol and Squalene Benefits. Food Chem. Toxicol. 2009;47:2327–2331. doi: 10.1016/j.fct.2009.06.026.
    1. Rosenblat M., Volkova N., Coleman R., Almagor Y., Aviram M. Antiatherogenicity of Extra Virgin Olive Oil and its Enrichment with Green Tea Polyphenols in the Atherosclerotic Apolipoprotein-E-Deficient Mice: Enhanced Macrophage Cholesterol Efflux. J. Nutr. Biochem. 2008;19:514–523. doi: 10.1016/j.jnutbio.2007.06.007.
    1. Lou-Bonafonte J.M., Arnal C., Navarro M.A., Osada J. Efficacy of Bioactive Compounds from Extra Virgin Olive Oil to Modulate Atherosclerosis Development. Mol. Nutr. Food Res. 2012;56:1043–1057. doi: 10.1002/mnfr.201100668.
    1. Filipek A., Czerwinska M.E., Kiss A.K., Polanski J.A., Naruszewicz M. Oleacein may Inhibit Destabilization of Carotid Plaques from Hypertensive Patients. Impact on High Mobility Group Protein-1. Phytomedicine. 2017;32:68–73. doi: 10.1016/j.phymed.2017.06.004.
    1. Torres-Pena J.D., Garcia-Rios A., Delgado-Casado N., Gomez-Luna P., Alcala-Diaz J.F., Yubero-Serrano E.M., Gomez-Delgado F., Leon-Acuna A., Lopez-Moreno J., Camargo A., et al. Mediterranean Diet Improves Endothelial Function in Patients with Diabetes and Prediabetes: A Report from the CORDIOPREV Study. Atherosclerosis. 2018;269:50–56. doi: 10.1016/j.atherosclerosis.2017.12.012.
    1. Davis C.R., Hodgson J.M., Woodman R., Bryan J., Wilson C., Murphy K.J. A Mediterranean Diet Lowers Blood Pressure and Improves Endothelial Function: Results from the MedLey Randomized Intervention Trial. Am. J. Clin. Nutr. 2017;105:1305–1313. doi: 10.3945/ajcn.116.146803.
    1. Villarejo A.B., Ramirez-Sanchez M., Segarra A.B., Martinez-Canamero M., Prieto I. Influence of Extra Virgin Olive Oil on Blood Pressure and Kidney Angiotensinase Activities in Spontaneously Hypertensive Rats. Planta Med. 2015;81:664–669. doi: 10.1055/s-0034-1383263.
    1. Storniolo C.E., Rosello-Catafau J., Pinto X., Mitjavila M.T., Moreno J.J. Polyphenol Fraction of Extra Virgin Olive Oil Protects Against Endothelial Dysfunction Induced by High Glucose and Free Fatty Acids through Modulation of Nitric Oxide and Endothelin-1. Redox Biol. 2014;2:971–977. doi: 10.1016/j.redox.2014.07.001.
    1. Katsarou A.I., Kaliora A.C., Papalois A., Chiou A., Kalogeropoulos N., Agrogiannis G., Andrikopoulos N.K. Serum Lipid Profile and Inflammatory Markers in the Aorta of Cholesterol-Fed Rats Supplemented with Extra Virgin Olive Oil, Sunflower Oils and Oil-Products. Int. J. Food Sci. Nutr. 2015;66:766–773. doi: 10.3109/09637486.2015.1088936.
    1. D’Amore S., Vacca M., Cariello M., Graziano G., D’Orazio A., Salvia R., Sasso R.C., Sabba C., Palasciano G., Moschetta A. Genes and miRNA Expression Signatures in Peripheral Blood Mononuclear Cells in Healthy Subjects and Patients with Metabolic Syndrome After Acute Intake of Extra Virgin Olive Oil. Biochim. Biophys. Acta. 2016;1861:1671–1680. doi: 10.1016/j.bbalip.2016.07.003.
    1. Casas R., Estruch R., Sacanella E. The Protective Effects of Extra Virgin Olive Oil on Immune-Mediated Inflammatory Responses. Endocr Metab. Immune Disord. Drug Targets. 2018;18:23–35. doi: 10.2174/1871530317666171114115632.
    1. Khaw K.T., Sharp S.J., Finikarides L., Afzal I., Lentjes M., Luben R., Forouhi N.G. Randomised Trial of Coconut Oil, Olive Oil Or Butter on Blood Lipids and Other Cardiovascular Risk Factors in Healthy Men and Women. BMJ Open. 2018;8:e020167. doi: 10.1136/bmjopen-2017-020167.
    1. Anderson-Vasquez H.E., Perez-Martinez P., Ortega Fernandez P., Wanden-Berghe C. Impact of the Consumption of a Rich Diet in Butter and it Replacement for a Rich Diet in Extra Virgin Olive Oil on Anthropometric, Metabolic and Lipid Profile in Postmenopausal Women. Nutr. Hosp. 2015;31:2561–2570.
    1. Maki K.C., Lawless A.L., Kelley K.M., Kaden V.N., Geiger C.J., Palacios O.M., Dicklin M.R. Corn Oil Intake Favorably Impacts Lipoprotein Cholesterol, Apolipoprotein and Lipoprotein Particle Levels Compared with Extra-Virgin Olive Oil. Eur. J. Clin. Nutr. 2017;71:33–38. doi: 10.1038/ejcn.2016.169.
    1. Violi F., Loffredo L., Pignatelli P., Angelico F., Bartimoccia S., Nocella C., Cangemi R., Petruccioli A., Monticolo R., Pastori D., et al. Extra Virgin Olive Oil use is Associated with Improved Post-Prandial Blood Glucose and LDL Cholesterol in Healthy Subjects. Nutr. Diabetes. 2015;5:e172. doi: 10.1038/nutd.2015.23.
    1. Hernaez A., Castaner O., Goday A., Ros E., Pinto X., Estruch R., Salas-Salvado J., Corella D., Aros F., Serra-Majem L., et al. The Mediterranean Diet Decreases LDL Atherogenicity in High Cardiovascular Risk Individuals: A Randomized Controlled Trial. Mol. Nutr. Food Res. 2017;61:10. doi: 10.1002/mnfr.201601015.
    1. Wang D.D., Toledo E., Hruby A., Rosner B.A., Willett W.C., Sun Q., Razquin C., Zheng Y., Ruiz-Canela M., Guasch-Ferre M., et al. Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevencion Con Dieta Mediterranea) Circulation. 2017;135:2028–2040. doi: 10.1161/CIRCULATIONAHA.116.024261.
    1. Toledo E., Wang D.D., Ruiz-Canela M., Clish C.B., Razquin C., Zheng Y., Guasch-Ferre M., Hruby A., Corella D., Gomez-Gracia E., et al. Plasma Lipidomic Profiles and Cardiovascular Events in a Randomized Intervention Trial with the Mediterranean Diet. Am. J. Clin. Nutr. 2017;106:973–983.
    1. Hao J., Shen W., Yu G., Jia H., Li X., Feng Z., Wang Y., Weber P., Wertz K., Sharman E., et al. Hydroxytyrosol Promotes Mitochondrial Biogenesis and Mitochondrial Function in 3T3-L1 Adipocytes. J. Nutr. Biochem. 2010;21:634–644. doi: 10.1016/j.jnutbio.2009.03.012.
    1. Giordano E., Davalos A., Visioli F. Chronic Hydroxytyrosol Feeding Modulates Glutathione-Mediated Oxido-Reduction Pathways in Adipose Tissue: A Nutrigenomic Study. Nutr. Metab. Cardiovasc. Dis. 2014;24:1144–1150. doi: 10.1016/j.numecd.2014.05.003.
    1. Ricordi C., Garcia-Contreras M., Farnetti S. Diet and Inflammation: Possible Effects on Immunity, Chronic Diseases, and Life Span. J. Am. Coll. Nutr. 2015;34:10–13. doi: 10.1080/07315724.2015.1080101.
    1. Puertollano M.A., Puertollano E., Alvarez de Cienfuegos G., de Pablo Martinez M.A. Olive Oil, Immune System and Infection. Nutricion Hospit. 2010;25:1–8.
    1. Montserrat-de la Paz S., Naranjo M.C., Lopez S., Abia R., Muriana F.J., Bermudez B. Niacin and Olive Oil Promote Skewing to the M2 Phenotype in Bone Marrow-Derived Macrophages of Mice with Metabolic Syndrome. Food Funct. 2016;7:2233–2238. doi: 10.1039/C6FO00381H.
    1. Magdalon J., Vinolo M.A., Rodrigues H.G., Paschoal V.A., Torres R.P., Mancini-Filho J., Calder P.C., Hatanaka E., Curi R. Oral Administration of Oleic Or Linoleic Acids Modulates the Production of Inflammatory Mediators by Rat Macrophages. Lipids. 2012;47:803–812. doi: 10.1007/s11745-012-3687-9.
    1. De La Puerta Vazquez R., Martinez-Dominguez E., Sanchez Perona J., Ruiz-Gutierrez V. Effects of Different Dietary Oils on Inflammatory Mediator Generation and Fatty Acid Composition in Rat Neutrophils. Metabol. Clin. Exp. 2004;53:59–65. doi: 10.1016/j.metabol.2003.08.010.
    1. Hatanaka E., Levada-Pires A.C., Pithon-Curi T.C., Curi R. Systematic Study on ROS Production Induced by Oleic, Linoleic, and Gamma-Linolenic Acids in Human and Rat Neutrophils. Free Radic. Biol. Med. 2006;41:1124–1132. doi: 10.1016/j.freeradbiomed.2006.06.014.
    1. Cury-Boaventura M.F., Gorjao R., de Lima T.M., Fiamoncini J., Torres R.P., Mancini-Filho J., Soriano F.G., Curi R. Effect of Olive Oil-Based Emulsion on Human Lymphocyte and Neutrophil Death. JPEN. 2008;32:81–87. doi: 10.1177/014860710803200181.
    1. Aparicio-Soto M., Sanchez-Hidalgo M., Cardeno A., Rosillo M.A., Sanchez-Fidalgo S., Utrilla J., Martin-Lacave I., Alarcon-de-la-Lastra C. Dietary Extra Virgin Olive Oil Attenuates Kidney Injury in Pristane-Induced SLE Model Via Activation of HO-1/Nrf-2 Antioxidant Pathway and Suppression of JAK/STAT, NF-kappaB and MAPK Activation. J. Nutr. Biochem. 2016;27:278–288. doi: 10.1016/j.jnutbio.2015.09.017.
    1. Tontini G.E., Vecchi M., Pastorelli L., Neurath M.F., Neumann H. Differential Diagnosis in Inflammatory Bowel Disease Colitis: State of the Art and Future Perspectives. World J. Gastroenterol. 2015;21:21–46. doi: 10.3748/wjg.v21.i1.21.
    1. Orel R., Kamhi Trop T. Intestinal Microbiota, Probiotics and Prebiotics in Inflammatory Bowel Disease. World J. Gastroenterol. 2014;20:11505–11524. doi: 10.3748/wjg.v20.i33.11505.
    1. Durchschein F., Petritsch W., Hammer H.F. Diet Therapy for Inflammatory Bowel Diseases: The Established and the New. World J. Gastroenterol. 2016;22:2179–2194. doi: 10.3748/wjg.v22.i7.2179.
    1. Limketkai B.N., Wolf A., Parian A.M. Nutritional Interventions in the Patient with Inflammatory Bowel Disease. Gastroenterol. Clin. North. Am. 2018;47:155–177. doi: 10.1016/j.gtc.2017.09.007.
    1. Cabre E., Domenech E. Impact of Environmental and Dietary Factors on the Course of Inflammatory Bowel Disease. World J. Gastroenterol. 2012;18:3814–3822. doi: 10.3748/wjg.v18.i29.3814.
    1. Sanchez-Fidalgo S., Sanchez de Ibarguen L., Cardeno A., Alarcon de la Lastra C. Influence of Extra Virgin Olive Oil Diet Enriched with Hydroxytyrosol in a Chronic DSS Colitis Model. Eur. J. Nutr. 2012;51:497–506. doi: 10.1007/s00394-011-0235-y.
    1. Sanchez-Fidalgo S., Cardeno A., Sanchez-Hidalgo M., Aparicio-Soto M., Villegas I., Rosillo M.A., de la Lastra C.A. Dietary Unsaponifiable Fraction from Extra Virgin Olive Oil Supplementation Attenuates Acute Ulcerative Colitis in Mice. Eur. J. Pharm. Sci. 2013;48:572–581. doi: 10.1016/j.ejps.2012.12.004.
    1. Sanchez-Fidalgo S., Cardeno A., Sanchez-Hidalgo M., Aparicio-Soto M., de la Lastra C.A. Dietary Extra Virgin Olive Oil Polyphenols Supplementation Modulates DSS-Induced Chronic Colitis in Mice. J. Nutr. Biochem. 2013;24:1401–1413. doi: 10.1016/j.jnutbio.2012.11.008.
    1. Sanchez-Fidalgo S., Villegas I., Rosillo M.A., Aparicio-Soto M., de la Lastra C.A. Dietary Squalene Supplementation Improves DSS-Induced Acute Colitis by Downregulating p38 MAPK and NFkB Signaling Pathways. Mol. Nutr. Food Res. 2015;59:284–292. doi: 10.1002/mnfr.201400518.
    1. Cardeno A., Magnusson M.K., Strid H., Alarcon de La Lastra C., Sanchez-Hidalgo M., Ohman L. The Unsaponifiable Fraction of Extra Virgin Olive Oil Promotes Apoptosis and Attenuates Activation and Homing Properties of T Cells from Patients with Inflammatory Bowel Disease. Food Chem. 2014;161:353–360. doi: 10.1016/j.foodchem.2014.04.016.
    1. Sanchez-Fidalgo S., Villegas I., Cardeno A., Talero E., Sanchez-Hidalgo M., Motilva V., Alarcon de la Lastra C. Extra-Virgin Olive Oil-Enriched Diet Modulates DSS-Colitis-Associated Colon Carcinogenesis in Mice. Clin. Nutr. 2010;29:663–673. doi: 10.1016/j.clnu.2010.03.003.
    1. Brooks P.M. The Burden of Musculoskeletal Disease—A Global Perspective. Clin. Rheumatol. 2006;25:778–781. doi: 10.1007/s10067-006-0240-3.
    1. Zvaifler N.J. A Speculation on the Pathogenesis of Joint Inflammation in Rheumatoid Arthritis. Arthritis Rheum. 1965;8:289–293. doi: 10.1002/art.1780080212.
    1. Boissier M.C., Semerano L., Challal S., Saidenberg-Kermanac’h N., Falgarone G. Rheumatoid Arthritis: From Autoimmunity to Synovitis and Joint Destruction. J. Autoimmun. 2012;39:222–228. doi: 10.1016/j.jaut.2012.05.021.
    1. Rosillo M.A., Alarcon-de-la-Lastra C., Sanchez-Hidalgo M. An Update on Dietary Phenolic Compounds in the Prevention and Management of Rheumatoid Arthritis. Food Funct. 2016;7:2943–2969. doi: 10.1039/C6FO00485G.
    1. Rosillo M.A., Sanchez-Hidalgo M., Sanchez-Fidalgo S., Aparicio-Soto M., Villegas I., Alarcon-de-la-Lastra C. Dietary Extra-Virgin Olive Oil Prevents Inflammatory Response and Cartilage Matrix Degradation in Murine Collagen-Induced Arthritis. Eur. J. Nutr. 2016;55:315–325. doi: 10.1007/s00394-015-0850-0.
    1. Rosillo M.A., Alcaraz M.J., Sanchez-Hidalgo M., Fernandez-Bolanos J.G., Alarcon-de-la-Lastra C., Ferrandiz M.L. Anti-Inflammatory and Joint Protective Effects of Extra-Virgin Olive-Oil Polyphenol Extract in Experimental Arthritis. J. Nutr. Biochem. 2014;25:1275–1281. doi: 10.1016/j.jnutbio.2014.07.006.
    1. Scotece M., Gomez R., Conde J., Lopez V., Gomez-Reino J.J., Lago F., Smith A.B., 3rd, Gualillo O. Further Evidence for the Anti-Inflammatory Activity of Oleocanthal: Inhibition of MIP-1alpha and IL-6 in J774 Macrophages and in ATDC5 Chondrocytes. Life Sci. 2012;91:1229–1235. doi: 10.1016/j.lfs.2012.09.012.
    1. Iacono A., Gomez R., Sperry J., Conde J., Bianco G., Meli R., Gomez-Reino J.J., Smith A.B., 3rd, Gualillo O. Effect of Oleocanthal and its Derivatives on Inflammatory Response Induced by Lipopolysaccharide in a Murine Chondrocyte Cell Line. Arthritis Rheum. 2010;62:1675–1682. doi: 10.1002/art.27437.
    1. Impellizzeri D., Esposito E., Mazzon E., Paterniti I., Di Paola R., Morittu V.M., Procopio A., Britti D., Cuzzocrea S. Oleuropein Aglycone, an Olive Oil Compound, Ameliorates Development of Arthritis Caused by Injection of Collagen Type II in Mice. J. Pharmacol. Exp. Ther. 2011;339:859–869. doi: 10.1124/jpet.111.182808.
    1. Castejon M.L., Rosillo M.A., Montoya T., Gonzalez-Benjumea A., Fernandez-Bolanos J.G., Alarcon-de-la-Lastra C. Oleuropein Down-Regulated IL-1beta-Induced Inflammation and Oxidative Stress in Human Synovial Fibroblast Cell Line SW982. Food Funct. 2017;8:1890–1898. doi: 10.1039/C7FO00210F.
    1. Silva S., Sepodes B., Rocha J., Direito R., Fernandes A., Brites D., Freitas M., Fernandes E., Bronze M.R., Figueira M.E. Protective Effects of Hydroxytyrosol-Supplemented Refined Olive Oil in Animal Models of Acute Inflammation and Rheumatoid Arthritis. J. Nutr. Biochem. 2015;26:360–368. doi: 10.1016/j.jnutbio.2014.11.011.
    1. Rosillo M.A., Sanchez-Hidalgo M., Gonzalez-Benjumea A., Fernandez-Bolanos J.G., Lubberts E., Alarcon-de-la-Lastra C. Preventive Effects of Dietary Hydroxytyrosol Acetate, an Extra Virgin Olive Oil Polyphenol in Murine Collagen-Induced Arthritis. Mol. Nutr. Food Res. 2015;59:2537–2546. doi: 10.1002/mnfr.201500304.
    1. Mateos R., Trujillo M., Pereira-Caro G., Madrona A., Cert A., Espartero J.L. New Lipophilic Tyrosyl Esters. Comparative Antioxidant Evaluation with Hydroxytyrosyl Esters. J. Agric. Food Chem. 2008;56:10960–10966. doi: 10.1021/jf8020267.
    1. Mateos R., Pereira-Caro G., Saha S., Cert R., Redondo-Horcajo M., Bravo L., Kroon P.A. Acetylation of Hydroxytyrosol Enhances its Transport Across Differentiated Caco-2 Cell Monolayers. Food Chem. 2011;125:865–872. doi: 10.1016/j.foodchem.2010.09.054.
    1. Rubio L., Macia A., Valls R.M., Pedret A., Romero M.P., Sola R., Motilva M.J. A New Hydroxytyrosol Metabolite Identified in Human Plasma: Hydroxytyrosol Acetate Sulphate. Food Chem. 2012;134:1132–1136. doi: 10.1016/j.foodchem.2012.02.192.
    1. Rosillo M.A., Sanchez-Hidalgo M., Castejon M.L., Montoya T., Gonzalez-Benjumea A., Fernandez-Bolanos J.G., Alarcon de la Lastra C. Extra-Virgin Olive Oil Phenols Hydroxytyrosol and Hydroxytyrosol Acetate, Down-Regulate the Production of Mediators Involved in Joint Erosion in Human Synovial Cells. J. Funct. Foods. 2017;36:27–33. doi: 10.1016/j.jff.2017.06.041.
    1. Petri M., Orbai A.M., Alarcon G.S., Gordon C., Merrill J.T., Fortin P.R., Bruce I.N., Isenberg D., Wallace D.J., Nived O., et al. Derivation and Validation of the Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheum. 2012;64:2677–2686. doi: 10.1002/art.34473.
    1. Long H., Yin H., Wang L., Gershwin M.E., Lu Q. The Critical Role of Epigenetics in Systemic Lupus Erythematosus and Autoimmunity. J. Autoimmun. 2016;74:118–138. doi: 10.1016/j.jaut.2016.06.020.
    1. Chun H.Y., Chung J.W., Kim H.A., Yun J.M., Jeon J.Y., Ye Y.M., Kim S.H., Park H.S., Suh C.H. Cytokine IL-6 and IL-10 as Biomarkers in Systemic Lupus Erythematosus. J. Clin. Immunol. 2007;27:461–466. doi: 10.1007/s10875-007-9104-0.
    1. Paley M.A., Strand V., Kim A.H. From Mechanism to Therapies in Systemic Lupus Erythematosus. Curr. Opin. Rheumatol. 2017;29:178–186. doi: 10.1097/BOR.0000000000000369.
    1. Su D.L., Lu Z.M., Shen M.N., Li X., Sun L.Y. Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE. J. Biomed. Biotechnol. 2012;2012:347141. doi: 10.1155/2012/347141.
    1. Leng R.X., Pan H.F., Chen G.M., Wang C., Qin W.Z., Chen L.L., Tao J.H., Ye D.Q. IL-23: A Promising Therapeutic Target for Systemic Lupus Erythematosus. Arch. Med. Res. 2010;41:221–225. doi: 10.1016/j.arcmed.2010.02.011.
    1. Pan H.F., Tao J.H., Ye D.Q. Therapeutic Potential of IL-27 in Systemic Lupus Erythematosus. Expert Opin. Ther. Targets. 2010;14:479–484. doi: 10.1517/14728221003769911.
    1. Cai Z., Wong C.K., Dong J., Chu M., Jiao D., Kam N.W., Lam C.W., Tam L.S. Remission of Systemic Lupus Erythematosus Disease Activity with Regulatory Cytokine Interleukin (IL)-35 in Murphy Roths Large (MRL)/Lpr Mice. Clin. Exp. Immunol. 2015;181:253–266. doi: 10.1111/cei.12639.
    1. Greco C.M., Nakajima C., Manzi S. Updated Review of Complementary and Alternative Medicine Treatments for Systemic Lupus Erythematosus. Curr. Rheumatol. Rep. 2013;15:378. doi: 10.1007/s11926-013-0378-3.
    1. Aparicio-Soto M., Sanchez-Hidalgo M., Cárdeno A., Gonzalez-Benjumea A., Fernandez-Bolanos J.G., Alarcon de la Lastra C. Dietary Hydroxytyrosol and Hydroxytyrosyl Acetate Supplementation Prevent Pristane-Induced Systemic Lupus Erythematous in Mice. J. Funct. Foods. 2017;29:84–92. doi: 10.1016/j.jff.2016.12.001.
    1. McCombe P.A., Henderson R.D. The Role of Immune and Inflammatory Mechanisms in ALS. Curr. Mol. Med. 2011;11:246–254. doi: 10.2174/156652411795243450.
    1. Olivan S., Martinez-Beamonte R., Calvo A.C., Surra J.C., Manzano R., Arnal C., Osta R., Osada J. Extra Virgin Olive Oil Intake Delays the Development of Amyotrophic Lateral Sclerosis Associated with Reduced Reticulum Stress and Autophagy in Muscle of SOD1G93A Mice. J. Nutr. Biochem. 2014;25:885–892. doi: 10.1016/j.jnutbio.2014.04.005.
    1. De Paola M., Sestito S.E., Mariani A., Memo C., Fanelli R., Freschi M., Bendotti C., Calabrese V., Peri F. Synthetic and Natural Small Molecule TLR4 Antagonists Inhibit Motoneuron Death in Cultures from ALS Mouse Model. Pharmacol. Res. 2016;103:180–187. doi: 10.1016/j.phrs.2015.11.020.
    1. Milo R., Miller A. Revised Diagnostic Criteria of Multiple Sclerosis. Autoimmun. Rev. 2014;13:518–524. doi: 10.1016/j.autrev.2014.01.012.
    1. Sospedra M., Martin R. Immunology of Multiple Sclerosis. Annu. Rev. Immunol. 2005;23:683–747. doi: 10.1146/annurev.immunol.23.021704.115707.
    1. Steinman L. Assessment of Animal Models for MS and Demyelinating Disease in the Design of Rational Therapy. Neuron. 1999;24:511–514. doi: 10.1016/S0896-6273(00)81107-1.
    1. Martin R., Carvalho-Tavares J., Hernandez M., Arnes M., Ruiz-Gutierrez V., Nieto M.L. Beneficial Actions of Oleanolic Acid in an Experimental Model of Multiple Sclerosis: A Potential Therapeutic Role. Biochem. Pharmacol. 2010;79:198–208. doi: 10.1016/j.bcp.2009.08.002.
    1. Martin R., Hernandez M., Cordova C., Nieto M.L. Natural Triterpenes Modulate Immune-Inflammatory Markers of Experimental Autoimmune Encephalomyelitis: Therapeutic Implications for Multiple Sclerosis. Br. J. Pharmacol. 2012;166:1708–1723. doi: 10.1111/j.1476-5381.2012.01869.x.
    1. Belanger M., Magistretti P.J. The Role of Astroglia in Neuroprotection. Dialogues Clin. Neurosci. 2009;11:281–295.
    1. Liuzzi G.M., Latronico T., Brana M.T., Gramegna P., Coniglio M.G., Rossano R., Larocca M., Riccio P. Structure-Dependent Inhibition of Gelatinases by Dietary Antioxidants in Rat Astrocytes and Sera of Multiple Sclerosis Patients. Neurochem. Res. 2011;36:518–527. doi: 10.1007/s11064-010-0373-2.
    1. Rossi R. The Eu Olive and Olive Oil Sector Main Features, Challenges and Prospects. [(accessed on 17 September 2017)];PE 608.690. Briefing September 2017. European Parliamentary Research Service (EPRS). Members’ Research Service. Available online: .
    1. Feng Y., Zhang A. A Floral Fragrance, Methyl Benzoate, is an Efficient Green Pesticide. Sci. Rep. 2017;7:42168. doi: 10.1038/srep42168.
    1. Pretty J., Bharucha Z. Integrated Pest Management for Sustainable Intensification of Agriculture in Asia and Africa. Insects. 2015;6:152–182. doi: 10.3390/insects6010152.
    1. European Commission . Short-Term Outlook for EU Agricultural Markets in 2017 and 2018. Directorate-General for Agriculture and Rural Development–Shortterm Outlook–N°17; Brussels, Belgium: 2017. p. 9.
    1. Gianessi L., Williams A. Herbicide use in Spanish Olive Groves Conserves Soil and Water, International Pesticide Benefits case Study No. 38. [(accessed on 30 August 2019)]; Available online:
    1. EEA (European Environment Agency) Pesticide Sales. Annual Indicator Report Series (AIRS) PO3.7, 2017. [(accessed on 30 August 2019)]; Available online:
    1. Sporleder M., Lacey L. Biopesticides. In: Insect Pests of Potato. In: Giordanengo P., Vincent C., Alyokhin A., editors. Global Perspectives on Biology and Managemen. Elsevier; Amsterdam, The Netherlands: 2013. pp. 463–497.
    1. Damalas C.A., Eleftherohorinos I.G. Pesticide Exposure, Safety Issues, and Risk Assessment Indicators. Int. J. Environ. Res. Public. Health. 2011;8:1402–1419. doi: 10.3390/ijerph8051402.
    1. Kesavachandran C.N., Fareed M., Pathak M.K., Bihari V., Mathur N., Srivastava A.K. Adverse Health Effects of Pesticides in Agrarian Populations of Developing Countries. Rev. Environ. Contam. Toxicol. 2009;200:33–52.
    1. Ntzani E., Chondrogiorgi M., Ntritsos G., Evangelou E., Tzoulaki I. Literature Review on Epidemiological Studies Linking Exposure to Pesticides and Health Effects. Volume 497. EFSA Supporting Publication; Parma, Italy: 2013. [(accessed on 30 August 2019)]. p. 159. Available online: .
    1. Miller G.T. Sustaining the Earth: An integrated Approach. 6th ed. Thompson Learning Inc.; Pacific Grove, CA, USA: 2004. pp. 211–216.
    1. Safa M., Watts M. Energy Inputs in Pest Control using Pesticides in New Zealand. In: Pimentel D.P., editor. Integrated Pest Management. Springer; Dordrecht, The Netherlands: 2014. pp. 99–126.
    1. Randall C., Hock W., Crow E., Hudak-Wise C., Kasai J. Pesticides in the environment. In: Maryland Pesticide applicators core manual, National Association of State Departments of Agriculture Research Foundation Ed.; Arlington, VA, USA, 2008. [(accessed on 30 August 2019)];:105–122. Available online: .
    1. Beketov M.A., Kefford B.J., Schafer R.B., Liess M. Pesticides Reduce Regional Biodiversity of Stream Invertebrates. Proc. Natl. Acad. Sci. USA. 2013;110:11039–11043. doi: 10.1073/pnas.1305618110.
    1. Sadegh-Zadeh F., Abd-Wahid S., Jalili B. Sorption, Degradation and Leaching of Pesticides in Soils Amended with Organic Matter: A Review. Adv. Environ. Tech. 2017;2:119–132.
    1. Aktar M.W., Sengupta D., Chowdhury A. Impact of Pesticides use in Agriculture: Their Benefits and Hazards. Interdiscip. Toxicol. 2009;2:1–12. doi: 10.2478/v10102-009-0001-7.
    1. Palmer W., Bromley P., Brandenburg R. Wildlife & Pesticides-Peanuts. North Carolina Cooperative Extension Service; Raleigh, NC, USA: 2007.
    1. Cornell University . Pesticide Fact Sheets and Tutorial, Module. 6th ed. Pesticide Safety Education Program; Urbana, IL, USA: 2007. Pesticides in the Environment.
    1. Kohler H.R., Triebskorn R. Wildlife Ecotoxicology of Pesticides: Can we Track Effects to the Population Level and Beyond? Science. 2013;341:759–765. doi: 10.1126/science.1237591.
    1. Hanazato T. Pesticide Effects on Freshwater Zooplankton: An Ecological Perspective. Environ. Pollut. 2001;112:1–10. doi: 10.1016/S0269-7491(00)00110-X.
    1. Helfrich L., Weigmann D., Hipkins P., Stinson E. Pesticides and Aquatic Animals: A Guide to Reducing Impacts on Aquatic Systems. Virginia Cooperative Extension Publication; Blacksburg, VA, USA: 1996.
    1. EFSA (European Food Safety Authority) The 2015 Annual EU Monitoring Programme for Pesticide Residues in Food. [(accessed on 22 May 2018)];EFSA J. 2017 15:4791. Available online: .
    1. Beaufoy G. The Environmental Impact of Olive Oil Production in the European Union: Practical Options for Improving the Environmental Impact. [(accessed on 30 May 2018)];2001 Available online: .
    1. Grovermann C., Schreinemachers P., Berger T. Quantifying Pesticide Overuse from Farmer and Societal Points of View: An Application to Thailand. Crop. Prot. 2013;53:161–168. doi: 10.1016/j.cropro.2013.07.013.
    1. Yubero-Serrano E.M., Lopez-Moreno J., Gomez-Delgado F., Lopez-Miranda J. Extra virgin olive oil: More than a healthy fat. Eur J. Clin. Nutr. 2019;72:8–17. doi: 10.1038/s41430-018-0304-x.
    1. Foscolou A., Critselis E., Panagiotakos D. Olive oil consumption and human health: A narrative review. Maturitas. 2018;118:60–66. doi: 10.1016/j.maturitas.2018.10.013.
    1. Bazal P., Gea A., de la Fuente-Arrillaga C., Barrio-López M.T., Martinez-González M.A., Ruiz-Canela M. Olive oil intake and risk of atrial fibrillation in the SUN cohort. Nutr. Metab. Cardiovasc. Dis. 2019;29:450–457. doi: 10.1016/j.numecd.2019.02.002.
    1. Gavahian M., Khaneghah A., Lorenzo J.M., Munekata P., Garcia-Mantrana I., Collado M.C., Meléndez-Martínez A.J., Barba F.J. Health benefits of olive oil and its components: Impacts on gut microbiota antioxidant activities, and prevention of noncommunicable diseases. Trends Food Sci. Technol. 2019;88:220–227. doi: 10.1016/j.tifs.2019.03.008.
    1. Fernandes J., Fialho M., Santos R., Peixoto-Plácido C., Madeira T., Sousa-Santos N., Virgolino A., Santos O., Vaz Carneiro A. Is olive oil good for you? A systematic review and meta-analysis on anti-inflammatory benefits from regular dietary intake. Nutrition. 2019:110559. doi: 10.1016/j.nut.2019.110559.
    1. Romani A., Ieri F., Urciuoli S., Noce A., Marrone G., Nediani C., Bernini R. Health Effects of Phenolic Compounds Found in Extra-Virgin Olive Oil, By-Products, and Leaf of Olea europaea L. Nutrients. 2019;11:1776. doi: 10.3390/nu11081776.
    1. Cory H., Passarelli S., Szeto J., Tamez M., Mattei J. The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front. Nutr. 2018;5:87. doi: 10.3389/fnut.2018.00087.
    1. Gorzynik-Debicka M., Przychodzen P., Cappello F., Kuban-Jankowska A., Marino Gammazza A., Knap N., Wozniak M., Gorska-Ponikowska M. Potential Health Benefits of Olive Oil and Plant Polyphenols. Int. J. Mol. Sci. 2018;19:686. doi: 10.3390/ijms19030686.
    1. López-Miranda J., Pérez-Jiménez F., Ros E., De Caterina R., Badimón L., Covas M.I., Escrich E., Ordovás J.M., Soriguer F., Abiá R., 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;20:284–294. doi: 10.1016/j.numecd.2009.12.007.
    1. Farr S.A., Price T.O., Dominguez L.J., Motisi A., Saiano F., Niehoff M.L., Morley J.E., Banks W.A., Ercal N., Barbagallo M. Extra virgin olive oil improves learning and memory in SAMP8 mice. J. Alzheimers Dis. 2012;28:81–92. doi: 10.3233/JAD-2011-110662.
    1. Dominguez L.J., Barbagallo M. The relevance of nutrition for the concept of cognitive frailty. Curr. Opin. Clin. Nut.r Metab. Care. 2017;20:61–68. doi: 10.1097/MCO.0000000000000337.
    1. Omar S.H. Mediterranean and MIND Diets Containing Olive Biophenols Reduces the Prevalence of Alzheimer’s Disease. Int. J. Mol. Sci. 2019;20:2797. doi: 10.3390/ijms20112797.

Source: PubMed

3
Tilaa