Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study

Angelo M Patti, Giuseppe Carruba, Arrigo F G Cicero, Maciej Banach, Dragana Nikolic, Rosaria V Giglio, Antonino Terranova, Maurizio Soresi, Lydia Giannitrapani, Giuseppe Montalto, Anca Pantea Stoian, Yajnavalka Banerjee, Ali A Rizvi, Peter P Toth, Manfredi Rizzo, Angelo M Patti, Giuseppe Carruba, Arrigo F G Cicero, Maciej Banach, Dragana Nikolic, Rosaria V Giglio, Antonino Terranova, Maurizio Soresi, Lydia Giannitrapani, Giuseppe Montalto, Anca Pantea Stoian, Yajnavalka Banerjee, Ali A Rizvi, Peter P Toth, Manfredi Rizzo

Abstract

Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 ± 11 years) for 2 months. Anthropometric data, metabolic parameters, hepatic steatosis (by fatty liver index, FLI), abdominal fat distribution (by ultrasound), and pro- and anti-inflammatory cytokines were assessed before and after the intervention. EVOO supplementation was associated with a reduction in body weight, waist circumference, body mass index (BMI), alanine transaminase and FLI, as well as interleukin (IL)-6, IL-17A, tumor necrosis factor-α and IL-1B, while IL-10 increased. Maximum subcutaneous fat thickness (SFT max) also increased, with a concomitant decrease in the ratio of visceral fat layer thickness/SFT max. Correlation analysis revealed positive associations between changes in body weight and BMI and those in SFT max, along with an inverse association between changes in IL-6 and those in SFT max. In conclusion, ingestion of EVOO with a high OC concentration had beneficial effects on metabolic parameters, inflammatory cytokines and abdominal fat distribution in MetS subjects with hepatic steatosis, a category of patients at high cardiometabolic risk.

Keywords: cytokines; metabolic syndrome; oleocanthal; olive oil; polyphenols.

Conflict of interest statement

The authors have given talks, attended conferences and participated in advisory boards and clinical trials sponsored by various pharmaceutical companies. Anca Pantea Stoian is currently Vice President of Romanian National Diabetes Committee. Manfredi Rizzo is currently Chief Medical and Scientific Advisor, Diabetes, Novo Nordisk South East Europe, Middle East and Africa (SEEMEA). The authors declare no conflict of interest, financial or otherwise.

References

    1. Rosato V., Temple N.J., La Vecchia C., Castellan G., Tavani A., Guercio V. Mediterranean diet and cardiovascular disease: A systematic review and meta-analysis of observational studies. Eur. J. Nutr. 2019;58:173–191. doi: 10.1007/s00394-017-1582-0.
    1. Cicero A.F.G., Colletti A., Bajraktari G., Descamps O., Djuric D.M., Ezhov M., Fras Z., Katsiki N., Langlois M., Latkovskis G., et al. Lipid lowering nutraceuticals in clinical practice: Position paper from an International Lipid Expert Panel. Arch. Med. Sci. 2017;13:965–1005. doi: 10.5114/aoms.2017.69326.
    1. Sahebkar A., Serban M.C., Gluba-Brzozka A., Mikhailidis D.P., Cicero A.F., Rysz J., Banach M. Lipid-modifying effects of nutraceuticals: An evidence-based approach. Nutrition. 2016;32:1179–1192. doi: 10.1016/j.nut.2016.04.007.
    1. Pan B., Wu Y., Yang Q., Ge L., Gao C., Xun Y., Tian J., Ding G. The impact of major dietary patterns on glycemic control, cardiovascular risk factors, and weight loss in patients with type 2 diabetes: A network meta-analysis. J. Evid. Based Med. 2019;12:29–39. doi: 10.1111/jebm.12312.
    1. Mancini J.G., Filion K.B., Atallah R., Eisenberg M.J. Systematic Review of the Mediterranean Diet for Long-Term Weight Loss. Am. J. Med. 2016;129:407–415.e4. doi: 10.1016/j.amjmed.2015.11.028.
    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. Jimenez-Lopez C., Carpena M., Lourenco-Lopes C., Gallardo-Gomez M., Lorenzo J.M., Barba F.J., Prieto M.A., Simal-Gandara J. Bioactive Compounds and Quality of Extra Virgin Olive Oil. Foods. 2020;9:1014. doi: 10.3390/foods9081014.
    1. Lozano-Castellon J., Lopez-Yerena A., Rinaldi de Alvarenga J.F., Romero Del Castillo-Alba J., Vallverdu-Queralt A., Escribano-Ferrer E., Lamuela-Raventos R.M. Health-promoting properties of oleocanthal and oleacein: Two secoiridoids from extra-virgin olive oil. Crit. Rev. Food Sci. Nutr. 2020;60:2532–2548. doi: 10.1080/10408398.2019.1650715.
    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. Francisco V., Ruiz-Fernandez C., Lahera V., Lago F., Pino J., Skaltsounis L., Gonzalez-Gay M.A., Mobasheri A., Gomez R., Scotece M., et al. Natural Molecules for Healthy Lifestyles: Oleocanthal from Extra Virgin Olive Oil. J. Agric. Food Chem. 2019;67:3845–3853. doi: 10.1021/acs.jafc.8b06723.
    1. Lozano-Sanchez J., Giambanelli E., Quirantes-Pine R., Cerretani L., Bendini A., Segura-Carretero A., Fernandez-Gutierrez A. Wastes generated during the storage of extra virgin olive oil as a natural source of phenolic compounds. J. Agric. Food Chem. 2011;59:11491–11500. doi: 10.1021/jf202596q.
    1. Beauchamp G.K., Keast R.S., Morel D., Lin J., Pika J., Han Q., Lee C.H., Smith A.B., Breslin P.A. Phytochemistry: Ibuprofen-like activity in extra-virgin olive oil. Nature. 2005;437:45–46. doi: 10.1038/437045a.
    1. Monti M.C., Margarucci L., Tosco A., Riccio R., Casapullo A. New insights on the interaction mechanism between tau protein and oleocanthal, an extra-virgin olive-oil bioactive component. Food Funct. 2011;2:423–428. doi: 10.1039/c1fo10064e.
    1. Segura Palacios J.M., Blazquez Sanchez N., Rivas Ruiz F., Aguilar Bernier M., Ramirez Lopez B., Sanchez M.E.F., de Troya Martin M. Topical treatment with oleocanthal extract in reducing inflammatory reactions after photodynamic therapy: A prospective quasi-experimental pilot study. Complement. Ther. Med. 2019;42:298–301. doi: 10.1016/j.ctim.2018.12.003.
    1. Pang K.L., Chin K.Y. The Biological Activities of Oleocanthal from a Molecular Perspective. Nutrients. 2018;10:570. doi: 10.3390/nu10050570.
    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. Cicerale S., Lucas L.J., Keast R.S. Antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil. Curr. Opin. Biotechnol. 2012;23:129–135. doi: 10.1016/j.copbio.2011.09.006.
    1. Booth J.N., 3rd, Colantonio L.D., Howard G., Safford M.M., Banach M., Reynolds K., Cushman M., Muntner P. Healthy lifestyle factors and incident heart disease and mortality in candidates for primary prevention with statin therapy. Int. J. Cardiol. 2016;207:196–202. doi: 10.1016/j.ijcard.2016.01.001.
    1. Khodarahmi M., Asghari-Jafarabadi M., Abbasalizad Farhangi M. A structural equation modeling approach for the association of a healthy eating index with metabolic syndrome and cardio-metabolic risk factors among obese individuals. PLoS ONE. 2019;14:e0219193. doi: 10.1371/journal.pone.0219193.
    1. Patti A.M., Al-Rasadi K., Giglio R.V., Nikolic D., Mannina C., Castellino G., Chianetta R., Banach M., Cicero A.F.G., Lippi G., et al. Natural approaches in metabolic syndrome management. Arch. Med. Sci. 2018;14:422–441. doi: 10.5114/aoms.2017.68717.
    1. Perez-Martinez P., Mikhailidis D.P., Athyros V.G., Bullo M., Couture P., Covas M.I., de Koning L., Delgado-Lista J., Diaz-Lopez A., Drevon C.A., et al. Lifestyle recommendations for the prevention and management of metabolic syndrome: An international panel recommendation. Nutr. Rev. 2017;75:307–326. doi: 10.1093/nutrit/nux014.
    1. Toth P.P., Patti A.M., Nikolic D., Giglio R.V., Castellino G., Biancucci T., Geraci F., David S., Montalto G., Rizvi A., et al. Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study. Front. Pharmacol. 2015;6:299. doi: 10.3389/fphar.2015.00299.
    1. Fogacci F., Grassi D., Rizzo M., Cicero A.F.G. Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials. Phytother. Res. 2019;33:862–870. doi: 10.1002/ptr.6282.
    1. Patti A.M., Al-Rasadi K., Katsiki N., Banerjee Y., Nikolic D., Vanella L., Giglio R.V., Giannone V.A., Montalto G., Rizzo M. Effect of a Natural Supplement Containing Curcuma Longa, Guggul, and Chlorogenic Acid in Patients With Metabolic Syndrome. Angiology. 2015;66:856–861. doi: 10.1177/0003319714568792.
    1. Cicero A.F.G., Fogacci F., Bove M., Veronesi M., Rizzo M., Giovannini M., Borghi C. Short-Term Effects of a Combined Nutraceutical on Lipid Level, Fatty Liver Biomarkers, Hemodynamic Parameters, and Estimated Cardiovascular Disease Risk: A Double-Blind, Placebo-Controlled Randomized Clinical Trial. Adv. Ther. 2017;34:1966–1975. doi: 10.1007/s12325-017-0580-1.
    1. Sonmez A., Nikolic D., Dogru T., Ercin C.N., Genc H., Cesur M., Tapan S., Karslioglu Y., Montalto G., Banach M., et al. Low- and high-density lipoprotein subclasses in subjects with nonalcoholic fatty liver disease. J. Clin. Lipidol. 2015;9:576–582. doi: 10.1016/j.jacl.2015.03.010.
    1. Magan-Fernandez A., Rizzo M., Montalto G., Marchesini G. Statins in liver disease: Not only prevention of cardiovascular events. Expert Rev. Gastroenterol. Hepatol. 2018;12:743–744. doi: 10.1080/17474124.2018.1477588.
    1. Rizvi A.A., Patti A.M., Giglio R.V., Nikolic D., Amato A., Al-Busaidi N., Al-Rasadi K., Soresi M., Banach M., Montalto G., et al. Liraglutide improves carotid intima-media thickness in patients with type 2 diabetes and non-alcoholic fatty liver disease: An 8-month prospective pilot study. Expert Opin. Biol. Ther. 2015;15:1391–1397. doi: 10.1517/14712598.2015.1067299.
    1. Targher G., Byrne C.D., Tilg H. NAFLD and increased risk of cardiovascular disease: Clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020;69:1691–1705. doi: 10.1136/gutjnl-2020-320622.
    1. Castellino G., Nikolic D., Magan-Fernandez A., Malfa G.A., Chianetta R., Patti A.M., Amato A., Montalto G., Toth P.P., Banach M., et al. Altilix((R)) Supplement Containing Chlorogenic Acid and Luteolin Improved Hepatic and Cardiometabolic Parameters in Subjects with Metabolic Syndrome: A 6 Month Randomized, Double-Blind, Placebo-Controlled Study. Nutrients. 2019;11:2580. doi: 10.3390/nu11112580.
    1. Ginter E., Simko V. Recent data on Mediterranean diet, cardiovascular disease, cancer, diabetes and life expectancy. Bratisl. Lek. Listy. 2015;116:346–348. doi: 10.4149/BLL_2015_065.
    1. Tosti V., Bertozzi B., Fontana L. Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms. J. Gerontol. A Biol. Sci. Med. Sci. 2018;73:318–326. doi: 10.1093/gerona/glx227.
    1. Banach M., Patti A.M., Giglio R.V., Cicero A.F.G., Atanasov A.G., Bajraktari G., Bruckert E., Descamps O., Djuric D.M., Ezhov M., et al. The Role of Nutraceuticals in Statin Intolerant Patients. J. Am. Coll. Cardiol. 2018;72:96–118. doi: 10.1016/j.jacc.2018.04.040.
    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. Martinez-Gonzalez M.A., Salas-Salvado J., Estruch R., Corella D., Fito M., Ros E., Predimed I. 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. Mazzocchi A., Leone L., Agostoni C., Pali-Scholl I. The Secrets of the Mediterranean Diet. Does [Only] Olive Oil Matter? Nutrients. 2019;11:2941. doi: 10.3390/nu11122941.
    1. Covas M.I., Konstantinidou V., Fito M. Olive oil and cardiovascular health. J. Cardiovasc. Pharmacol. 2009;54:477–482. doi: 10.1097/FJC.0b013e3181c5e7fd.
    1. Masala G., Bendinelli B., Versari D., Saieva C., Ceroti M., Santagiuliana F., Caini S., Salvini S., Sera F., Taddei S., et al. Anthropometric and dietary determinants of blood pressure in over 7000 Mediterranean women: The European Prospective Investigation into Cancer and Nutrition-Florence cohort. J. Hypertens. 2008;26:2112–2120. doi: 10.1097/HJH.0b013e32830ef75c.
    1. Pedret A., Fernandez-Castillejo S., Valls R.M., Catalan U., Rubio L., Romeu M., Macia A., Lopez de Las Hazas M.C., Farras M., Giralt M., et al. Cardiovascular Benefits of Phenol-Enriched Virgin Olive Oils: New Insights from the Virgin Olive Oil and HDL Functionality (VOHF) Study. Mol. Nutr. Food Res. 2018;62:e1800456. doi: 10.1002/mnfr.201800456.
    1. Luisi M.L.E., Lucarini L., Biffi B., Rafanelli E., Pietramellara G., Durante M., Vidali S., Provensi G., Madiai S., Gheri C.F., et al. Effect of Mediterranean Diet Enriched in High Quality Extra Virgin Olive Oil on Oxidative Stress, Inflammation and Gut Microbiota in Obese and Normal Weight Adult Subjects. Front. Pharmacol. 2019;10:1366. doi: 10.3389/fphar.2019.01366.
    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. Patti A.M., Toth P.P., Giglio R.V., Banach M., Noto M., Nikolic D., Montalto G., Rizzo M. Nutraceuticals as an Important Part of Combination Therapy in Dyslipidaemia. Curr. Pharm. Des. 2017;23:2496–2503. doi: 10.2174/1381612823666170317145851.
    1. Schwingshackl L., Krause M., Schmucker C., Hoffmann G., Rucker G., Meerpohl J.J. Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis. Nutr. Metab. Cardiovasc. Dis. 2019;29:1030–1039. doi: 10.1016/j.numecd.2019.07.001.
    1. Galvao Candido F., Xavier Valente F., da Silva L.E., Goncalves Leao Coelho O., Gouveia Peluzio M.D.C., Goncalves Alfenas R.C. Consumption of extra virgin olive oil improves body composition and blood pressure in women with excess body fat: A randomized, double-blinded, placebo-controlled clinical trial. Eur. J. Nutr. 2018;57:2445–2455. doi: 10.1007/s00394-017-1517-9.
    1. Sarapis K., Thomas C.J., Hoskin J., George E.S., Marx W., Mayr H.L., Kennedy G., Pipingas A., Willcox J.C., Prendergast L.A., et al. The Effect of High Polyphenol Extra Virgin Olive Oil on Blood Pressure and Arterial Stiffness in Healthy Australian Adults: A Randomized, Controlled, Cross-Over Study. Nutrients. 2020;12:2272. doi: 10.3390/nu12082272.
    1. Owen R.W., Giacosa A., Hull W.E., Haubner R., Wurtele G., Spiegelhalder B., Bartsch H. Olive-oil consumption and health: The possible role of antioxidants. Lancet Oncol. 2000;1:107–112. doi: 10.1016/S1470-2045(00)00015-2.
    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. Carnevale R., Pignatelli P., Nocella C., Loffredo L., Pastori D., Vicario T., Petruccioli A., Bartimoccia S., Violi F. Extra virgin olive oil blunt post-prandial oxidative stress via NOX2 down-regulation. Atherosclerosis. 2014;235:649–658. doi: 10.1016/j.atherosclerosis.2014.05.954.
    1. Basterra-Gortari F.J., Ruiz-Canela M., Martinez-Gonzalez M.A., Babio N., Sorli J.V., Fito M., Ros E., Gomez-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;42:1390–1397. doi: 10.2337/dc18-2475.
    1. Villani A., Sultana J., Doecke J., Mantzioris E. Differences in the interpretation of a modernized Mediterranean diet prescribed in intervention studies for the management of type 2 diabetes: How closely does this align with a traditional Mediterranean diet? Eur. J. Nutr. 2019;58:1369–1380. doi: 10.1007/s00394-018-1757-3.
    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. Primary prevention of cardiovascular disease with a Mediterranean diet. N. Engl. J. Med. 2013;368:1279–1290. doi: 10.1056/NEJMoa1200303.
    1. Rizzo M., Rizvi A.A., Rini G.B., Berneis K. The therapeutic modulation of atherogenic dyslipidemia and inflammatory markers in the metabolic syndrome: What is the clinical relevance? Acta Diabetol. 2009;46:1–11. doi: 10.1007/s00592-008-0057-4.
    1. Corrado E., Rizzo M., Coppola G., Fattouch K., Novo G., Marturana I., Ferrara F., Novo S. An update on the role of markers of inflammation in atherosclerosis. J. Atheroscler. Thromb. 2010;17:1–11. doi: 10.5551/jat.2600.
    1. Corrado E., Rizzo M., Tantillo R., Muratori I., Bonura F., Vitale G., Novo S. Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: A 5-year follow-up study. Stroke. 2006;37:482–486. doi: 10.1161/01.STR.0000198813.56398.14.
    1. Abate N., Sallam H.S., Rizzo M., Nikolic D., Obradovic M., Bjelogrlic P., Isenovic E.R. Resistin: An inflammatory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome. Curr. Pharm. Des. 2014;20:4961–4969. doi: 10.2174/1381612819666131206103102.
    1. Kirichenko T.V., Sobenin I.A., Nikolic D., Rizzo M., Orekhov A.N. Anti-cytokine therapy for prevention of atherosclerosis. Phytomedicine. 2016;23:1198–1210. doi: 10.1016/j.phymed.2015.12.002.
    1. Haidara M., Mikhailidis D.P., Yassin H.Z., Dobutovic B., Smiljanic K.T., Soskic S., Mousa S.A., Rizzo M., Isenovic E.R. Evaluation of the possible contribution of antioxidants administration in metabolic syndrome. Curr. Pharm. Des. 2011;17:3699–3712. doi: 10.2174/138161211798220882.
    1. Zhao Y., Evans M.A., Allison M.A., Bertoni A.G., Budoff M.J., Criqui M.H., Malik S., Ouyang P., Polak J.F., Wong N.D. Multisite atherosclerosis in subjects with metabolic syndrome and diabetes and relation to cardiovascular events: The Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2019;282:202–209. doi: 10.1016/j.atherosclerosis.2018.12.005.
    1. Piers L.S., Walker K.Z., Stoney R.M., Soares M.J., O’Dea K. The influence of the type of dietary fat on postprandial fat oxidation rates: Monounsaturated (olive oil) vs saturated fat (cream) Int. J. Obes. Relat. Metab. Disord. 2002;26:814–821. doi: 10.1038/sj.ijo.0801993.
    1. Alvarez-Perez J., Sanchez-Villegas A., Diaz-Benitez E.M., Ruano-Rodriguez C., Corella D., Martinez-Gonzalez M.A., Estruch R., Salas-Salvado J., Serra-Majem L., Investigators P.S. Influence of a Mediterranean Dietary Pattern on Body Fat Distribution: Results of the PREDIMED-Canarias Intervention Randomized Trial. J. Am. Coll. Nutr. 2016;35:568–580. doi: 10.1080/07315724.2015.1102102.
    1. Rozati M., Barnett J., Wu D., Handelman G., Saltzman E., Wilson T., Li L., Wang J., Marcos A., Ordovas J.M., et al. Cardio-metabolic and immunological impacts of extra virgin olive oil consumption in overweight and obese older adults: A randomized controlled trial. Nutr. Metab. 2015;12:28. doi: 10.1186/s12986-015-0022-5.
    1. Covas M.I., Nyyssonen K., Poulsen H.E., Kaikkonen J., Zunft H.J., Kiesewetter H., Gaddi A., de la Torre R., Mursu J., Baumler H., et al. The effect of polyphenols in olive oil on heart disease risk factors: A randomized trial. Ann. Intern. Med. 2006;145:333–341. doi: 10.7326/0003-4819-145-5-200609050-00006.
    1. Cruz M.A., Cruz J.F., Macena L.B., de Santana D.S., Oliveira C.C., Lima S.O., Franca A.V. Association of the Nonalcoholic Hepatic Steatosis and Its Degrees With the Values of Liver Enzymes and Homeostasis Model Assessment-Insulin Resistance Index. Gastroenterol. Res. 2015;8:260–264. doi: 10.14740/gr685w.
    1. Al-Seeni M.N., El Rabey H.A., Zamzami M.A., Alnefayee A.M. The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats. BMC Complement. Altern. Med. 2016;16:438. doi: 10.1186/s12906-016-1422-4.
    1. Szychlinska M.A., Castrogiovanni P., Trovato F.M., Nsir H., Zarrouk M., Lo Furno D., Di Rosa M., Imbesi R., Musumeci G. Physical activity and Mediterranean diet based on olive tree phenolic compounds from two different geographical areas have protective effects on early osteoarthritis, muscle atrophy and hepatic steatosis. Eur. J. Nutr. 2019;58:565–581. doi: 10.1007/s00394-018-1632-2.
    1. Pinto X., Fanlo-Maresma M., Corbella E., Corbella X., Mitjavila M.T., Moreno J.J., Casas R., Estruch R., Corella D., Bullo M., et al. A Mediterranean Diet Rich in Extra-Virgin Olive Oil Is Associated with a Reduced Prevalence of Nonalcoholic Fatty Liver Disease in Older Individuals at High Cardiovascular Risk. J. Nutr. 2019;149:1920–1929. doi: 10.1093/jn/nxz147.
    1. Bays H.E. Adiposopathy is "sick fat" a cardiovascular disease? J. Am. Coll. Cardiol. 2011;57:2461–2473. doi: 10.1016/j.jacc.2011.02.038.
    1. Despres J.P. Body fat distribution and risk of cardiovascular disease: An update. Circulation. 2012;126:1301–1313. doi: 10.1161/CIRCULATIONAHA.111.067264.
    1. Goedecke J.H., Utzschneider K., Faulenbach M.V., Rizzo M., Berneis K., Spinas G.A., Dave J.A., Levitt N.S., Lambert E.V., Olsson T., et al. Ethnic differences in serum lipoproteins and their determinants in South African women. Metabolism. 2010;59:1341–1350. doi: 10.1016/j.metabol.2009.12.018.
    1. Berneis K., Rizzo M., Evans J., Rini G.B., Spinas G.A., Goedecke J.H. Interleukin-18 levels are associated with low-density lipoproteins size. Eur. J. Clin. Investig. 2010;40:54–55. doi: 10.1111/j.1365-2362.2009.02228.x.
    1. Rizzo M., Berneis K. Who needs to care about small, dense low-density lipoproteins? Int. J. Clin. Pract. 2007;61:1949–1956. doi: 10.1111/j.1742-1241.2007.01596.x.
    1. Rizzo M., Berneis K., Zeljkovic A., Vekic J. Should we routinely measure low-density and high-density lipoprotein subclasses? Clin. Lab. 2009;55:421–429.
    1. Rizzo M., Kotur-Stevuljevic J., Berneis K., Spinas G., Rini G.B., Jelic-Ivanovic Z., Spasojevic-Kalimanovska V., Vekic J. Atherogenic dyslipidemia and oxidative stress: A new look. Transl. Res. 2009;153:217–223. doi: 10.1016/j.trsl.2009.01.008.
    1. Rizzo M., Berneis K. Small, dense low-density-lipoproteins and the metabolic syndrome. Diabetes Metab. Res. Rev. 2007;23:14–20. doi: 10.1002/dmrr.694.
    1. Rizzo M., Pernice V., Frasheri A., Di Lorenzo G., Rini G.B., Spinas G.A., Berneis K. Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome. Clin. Endocrinol. 2009;70:870–875. doi: 10.1111/j.1365-2265.2008.03407.x.
    1. Barylski M., Toth P.P., Nikolic D., Banach M., Rizzo M., Montalto G. Emerging therapies for raising high-density lipoprotein cholesterol (HDL-C) and augmenting HDL particle functionality. Best Pract. Res. Clin. Endocrinol. Metab. 2014;28:453–461. doi: 10.1016/j.beem.2013.11.001.
    1. Kinger M., Kumar S., Kumar V. Some Important Dietary Polyphenolic Compounds: An Anti-inflammatory and Immunoregulatory Perspective. Mini Rev. Med. Chem. 2018;18:1270–1282. doi: 10.2174/1389557517666170208143410.
    1. Parkinson L., Keast R. Oleocanthal, a phenolic derived from virgin olive oil: A review of the beneficial effects on inflammatory disease. Int. J. Mol. Sci. 2014;15:12323–12334. doi: 10.3390/ijms150712323.
    1. Carpi S., Scoditti E., Massaro M., Polini B., Manera C., Digiacomo M., Esposito Salsano J., Poli G., Tuccinardi T., Doccini S., et al. The Extra-Virgin Olive Oil Polyphenols Oleocanthal and Oleacein Counteract Inflammation-Related Gene and miRNA Expression in Adipocytes by Attenuating NF-kappaB Activation. Nutrients. 2019;11:2855. doi: 10.3390/nu11122855.
    1. Garcia-Bonilla L., Benakis C., Moore J., Iadecola C., Anrather J. Immune mechanisms in cerebral ischemic tolerance. Front. Neurosci. 2014;8:44. doi: 10.3389/fnins.2014.00044.
    1. Alberti K.G., Eckel R.H., Grundy S.M., Zimmet P.Z., Cleeman J.I., Donato K.A., Fruchart J.C., James W.P., Loria C.M., Smith S.C., Jr., et al. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644.
    1. Riboli E., Kaaks R. The EPIC Project: Rationale and study design. European Prospective Investigation into Cancer and Nutrition. Int. J. Epidemiol. 1997;26(Suppl. 1):S6–S14. doi: 10.1093/ije/26.suppl_1.S6.
    1. Victor R.G., Lynch K., Li N., Blyler C., Muhammad E., Handler J., Brettler J., Rashid M., Hsu B., Foxx-Drew D., et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. N. Engl. J. Med. 2018;378:1291–1301. doi: 10.1056/NEJMoa1717250.
    1. Bedogni G., Bellentani S., Miglioli L., Masutti F., Passalacqua M., Castiglione A., Tiribelli C. The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6:33. doi: 10.1186/1471-230X-6-33.
    1. Dinarello C.A. The IL-1 family and inflammatory diseases. Clin. Exp. Rheumatol. 2002;20:S1–S13.
    1. Kolls J.K., Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21:467–476. doi: 10.1016/j.immuni.2004.08.018.
    1. Popa C., Netea M.G., van Riel P.L., van der Meer J.W., Stalenhoef A.F. The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J. Lipid Res. 2007;48:751–762. doi: 10.1194/jlr.R600021-JLR200.
    1. Scheller J., Chalaris A., Schmidt-Arras D., Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta. 2011;1813:878–888. doi: 10.1016/j.bbamcr.2011.01.034.
    1. Mosser D.M., Zhang X. Interleukin-10: New perspectives on an old cytokine. Immunol. Rev. 2008;226:205–218. doi: 10.1111/j.1600-065X.2008.00706.x.
    1. Bio-Plex™Cytokine Assay. [(accessed on 19 August 2020)]; Available online: .
    1. Saverymuttu S.H., Joseph A.E., Maxwell J.D. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br. Med. J. (Clin. Res. Ed) 1986;292:13–15. doi: 10.1136/bmj.292.6512.13.
    1. Soresi M., Giannitrapani L., Florena A.M., La Spada E., Di Gesaro V., Rappa F., Alessandri A., Tripi S., Romano M., Montalto G. Reliability of the bright liver echo pattern in diagnosing steatosis in patients with cryptogenic and HCV-related hypertransaminasaemia. Clin. Radiol. 2009;64:1181–1187. doi: 10.1016/j.crad.2009.06.013.
    1. Armellini F., Zamboni M., Rigo L., Todesco T., Bergamo-Andreis I.A., Procacci C., Bosello O. The contribution of sonography to the measurement of intra-abdominal fat. J. Clin. Ultrasound. 1990;18:563–567. doi: 10.1002/jcu.1870180707.
    1. Suzuki R., Watanabe S., Hirai Y., Akiyama K., Nishide T., Matsushima Y., Murayama H., Ohshima H., Shinomiya M., Shirai K., et al. Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen. Am. J. Med. 1993;95:309–314. doi: 10.1016/0002-9343(93)90284-V.

Source: PubMed

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