Impact of Extra Virgin Olive Oil (EVOO) With Health Properties in Metabolic Syndrome

Metabolic Syndrome Clinical Trial

Official title:

Impact of Extra Virgin Olive Oil (EVOO) With Health Properties in Improving the Overall Health Status and Preventing Cardiovascular Risk in Metabolic Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05282316
• Other study ID #: ASMS01
• Status: Recruiting
• Phase: N/A
• Start date: March 9, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: University of Palermo
• Contact: Aurelio Seidita, MD
• Phone: +390916554710
• Email: aurelio.seidita[@]unipa.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Metabolic syndrome (MS), defined according to the revised Adult Treatment Panel III - National Cholesterol Education Program (ATP III - NCEP) criteria, represents a widespread condition in Western populations (prevalence ranging from 22% to about 33%) and with a trend that increases with time and age. MS, not differently from each of the components that characterize it, is a known risk factor for cardiovascular and metabolic diseases. To date, national and international panels indicate lifestyle modification as the only indication for treating MS and reducing the risk of cardiovascular and metabolic diseases. The increase in daily physical activity and the modification of the diet are therefore the cornerstones of the treatment.

The Mediterranean Diet (MD) represents a traditional value of the Italian population which has shown in several studies a protective effect on mortality and survival free from cardiovascular events. The added value of MD is the presence of extra virgin olive oil (EVOO), a healthy food with high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations (range 50-800 mg/kg) of phenols (oleuropein, ligstroside, and oleocanthal, and their derivatives phenolic alcohols, such as hydroxytyrosol and tyrosol). Olive oil is defined as healthy according to EC Reg. 432/2012. A good EVOO contains about 75% of oleic acid although a variability between 55% and 83% of all fatty acids is expected according to the World Health Organization. The polyphenols content plays a key role in the choice of the type and quantity of oil with health objectives, with particular reference to the unsaturated and polyunsaturated component (oleic acid, linoleic acid, alpha linolenic acid). Phenolic compounds not only determine EVOO main organoleptic qualities (oxidative stability and specific flavor and taste features) but, theoretically, make it a substance with antioxidant, antiinflammatory, insulin-sensitizing, cardioprotective, antiatherogenic, neuroprotective, immunomodulatory and anticancer activity.

The study aims to use a polyphenols enriched EVOO with health properties, derived from different cultivation variants of olives (cultivars), chosen on the basis of preliminary research, coming from Sicilian harvesting campaigns, to evaluate its potential to modify 'in vivo', in subjects with MS, some clinical and laboratory parameters inferring cardiovascular risk, metabolism and inflammation.

Description:

Metabolic syndrome (MS), defined according to the to the revised Adult Treatment Panel III - National Cholesterol Education Program (ATP III - NCEP) criteria,, represents a widespread condition in Western populations (absolute prevalence ranging from 22% to about 33%) and with a trend that increases with time and age (it is expected that its prevalence will increase by about 53% by 2035). MS, not differently from each of the components that characterize it, is a known risk factor for cardiovascular diseases (relative risk (RR) 1.53-2.18) and type 2 diabetes mellitus (RR 3.53-5.17). To date, national and international panels indicate lifestyle modification as the only indication for treating MS and reducing the risk of cardiovascular and metabolic diseases. The increase in daily physical activity and the modification of the diet are therefore the cornerstones of the treatment.

The Mediterranean Diet (MD) represents a traditional value of the Italian population which has shown in several studies a protective effect on mortality and survival free from cardiovascular events. The added value of MD is the presence of extra virgin olive oil (EVOO), a healthy food with high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations (range 50-800 mg/kg) of phenols (oleuropein, ligstroside, and oleocanthal, and their derivatives phenolic alcohols, such as hydroxytyrosol and tyrosol). Olive oil is defined as healthy according to European Commission (EC) Reg. 432/2012. A good EVOO contains about 75% of oleic acid although a variability between 55% and 83% of all fatty acids is expected according to the World Health Organization. The polyphenols content plays a key role in the choice of the type and quantity of oil with health objectives, with particular reference to the unsaturated and polyunsaturated component (oleic acid, linoleic acid, alpha linolenic acid). Phenolic compounds not only determine EVOO main organoleptic qualities (oxidative stability and specific flavor and taste features) but, theoretically, make it a substance with antioxidant, antiinflammatory, insulin-sensitizing, cardioprotective, antiatherogenic, neuroprotective, immunomodulatory and anticancer activity.

Any beneficial substance, including olive oil, goes through a series of biochemical processes before reaching the target organ, by the digestive enzymes and bacteria of the gut microbiota, or the eventual formation of active metabolites after the first liver passage; thus, an exclusively 'in vitro' evaluation of a substance on target cells does not always represent the physiological model of the interaction of these substances with the organism.

The study aims to use a polyphenols enriched EVOO with health properties, derived from different cultivation variants of olives (cultivars), chosen on the basis of preliminary research, coming from Sicilian harvesting campaigns, to evaluate its potential to modify 'in vivo', in subjects with MS, some clinical and laboratory parameters inferring cardiovascular risk, metabolism and inflammation.

Preliminarily, in the phase of the olive harvesting campaigns (three different harvesting periods carried out between November and December: green, mature and advanced ripening), the different indigenous cultivars coming from the same area of Western Sicily (precisely from Val di Mazara, Valle del Belice, Trapani valleys and called Biancolilla, Nocellara, Cerasuolo) will be subjected to biochemical analyses which will aim to identify those with the highest oleic acid and polyphenols content, which will contribute to the enhancement of the specific territory and to the maintenance of biodiversity.

The general objective of the study is to strengthen and enhance the research chain in the nutraceutical and health food sector and the cooperation between the research system and local companies, to support the maximum diffusion and use of new therapeutic substances and advanced technologies for treatment and prevention, and, at the same time, contributing to competitiveness and economic growth by raising the level of scientific-technical skills and knowledge in the production system and in Institutions.

The main objectives of the research, therefore, will be the following:

1. Identification and selection of specific autochthonous cultivar able to provide a high quality and polyphenols enriched EVOO.

2. Establish potential benefits of a polyphenols enriched EVOO-MD assessing the improvement over metabolic (lipidic and glycemic status), inflammatory (cytokines) and cardiovascular (cIMT and endothelial dysfunction) parameters.

3. Establish potential benefits of a polyphenols enriched EVOO-MD assessing the improvement over liver steatosis.

4. Analysis of polyphenols enriched EVOO effects on peripheral blood mononuclear cells (PBMC) gene expression exploring their potential use as diagnostic and therapeutic response tool.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 31, 2024
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• diagnosis of metabolic syndrome according the revised NCEP ATP III criteria; three or more of the following five criteria are met: waist circumference over 102 cm/40 inches (men) or 88 cm/35 inches (women), blood pressure over 130/85 mmHg, fasting triglyceride level over 150 mg/dl, fasting high-density lipoprotein cholesterol level less than 40 mg/dl (men) or 50 mg/dl (women) and fasting blood sugar over 100 mg/dl.

• Hepatitis B virus (HBV) and hepatitis C virus (HCV) negativity.

Exclusion Criteria:

• alcohol intake (>30 g/day for men and >20 g/day for women);

• acute or chronic hepatic and/or cardiac failure;

• acute or chronic kidney disease (stage G4 Kidney Disease: Improving Global Outcomes (KDIGO) revised classification, glomerular filtration rate <30 mL/min/1.73 m2);

• neoplasms;

• autoimmune or acute and chronic inflammatory diseases;

• acute or chronic infective diseases;

• pregnancy and/or breastfeeding.

Related Conditions & MeSH terms

• Metabolic Syndrome
• Syndrome

Intervention

Dietary Supplement:
• EVOO polyphenols enriched
Addition of 40 ml daily of healthy polyphenols enriched EVOO to mediterranean diet for 6 months
• EVOO standard
Addition of 40 ml daily of standard EVOO to mediterranean diet for 6 months

Locations

Country	Name	City	State
Italy	Department of Internal Medicine, University Hospital of Palermo	Palermo

Sponsors (1)

Lead Sponsor	Collaborator
University of Palermo

Country where clinical trial is conducted

Italy, 

References & Publications (14)

Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. 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 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644. Epub 2009 Oct 5. — View Citation

Gaforio JJ, Visioli F, Alarcon-de-la-Lastra C, Castaner O, Delgado-Rodriguez M, Fito M, Hernandez AF, Huertas JR, Martinez-Gonzalez MA, Menendez JA, Osada J, Papadaki A, Parron T, Pereira JE, Rosillo MA, Sanchez-Quesada C, Schwingshackl L, Toledo E, Tsatsakis AM. Virgin Olive Oil and Health: Summary of the III International Conference on Virgin Olive Oil and Health Consensus Report, JAEN (Spain) 2018. Nutrients. 2019 Sep 1;11(9):2039. doi: 10.3390/nu11092039. — View Citation

George ES, Marshall S, Mayr HL, Trakman GL, Tatucu-Babet OA, Lassemillante AM, Bramley A, Reddy AJ, Forsyth A, Tierney AC, Thomas CJ, Itsiopoulos C, Marx W. The effect of high-polyphenol extra virgin olive oil on cardiovascular risk factors: A systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2019;59(17):2772-2795. doi: 10.1080/10408398.2018.1470491. Epub 2018 Nov 13. — View Citation

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005 Oct 25;112(17):2735-52. doi: 10.1161/CIRCULATIONAHA.105.169404. Epub 2005 Sep 12. No abstract available. Erratum In: Circulation. 2005 Oct 25;112(17):e297. Circulation. 2005 Oct 25;112(17):e298. — View Citation

Jimenez-Torres J, Alcala-Diaz JF, Torres-Pena JD, Gutierrez-Mariscal FM, Leon-Acuna A, Gomez-Luna P, Fernandez-Gandara C, Quintana-Navarro GM, Fernandez-Garcia JC, Perez-Martinez P, Ordovas JM, Delgado-Lista J, Yubero-Serrano EM, Lopez-Miranda J. Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial. Stroke. 2021 Nov;52(11):3440-3449. doi: 10.1161/STROKEAHA.120.033214. Epub 2021 Aug 10. Erratum In: Stroke. 2021 Nov;52(11):e754. — View Citation

Jurado-Ruiz E, Varela LM, Luque A, Berna G, Cahuana G, Martinez-Force E, Gallego-Duran R, Soria B, de Roos B, Romero Gomez M, Martin F. An extra virgin olive oil rich diet intervention ameliorates the nonalcoholic steatohepatitis induced by a high-fat "Western-type" diet in mice. Mol Nutr Food Res. 2017 Mar;61(3). doi: 10.1002/mnfr.201600549. Epub 2016 Dec 13. — View Citation

Mirabelli M, Chiefari E, Arcidiacono B, Corigliano DM, Brunetti FS, Maggisano V, Russo D, Foti DP, Brunetti A. Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases. Nutrients. 2020 Apr 12;12(4):1066. doi: 10.3390/nu12041066. — View Citation

Pastor R, Bouzas C, Tur JA. Beneficial effects of dietary supplementation with olive oil, oleic acid, or hydroxytyrosol in metabolic syndrome: Systematic review and meta-analysis. Free Radic Biol Med. 2021 Aug 20;172:372-385. doi: 10.1016/j.freeradbiomed.2021.06.017. Epub 2021 Jun 18. — View Citation

Patti AM, Carruba G, Cicero AFG, Banach M, Nikolic D, Giglio RV, Terranova A, Soresi M, Giannitrapani L, Montalto G, Stoian AP, Banerjee Y, Rizvi AA, Toth PP, Rizzo M. 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. Metabolites. 2020 Oct 2;10(10):392. doi: 10.3390/metabo10100392. — View Citation

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:S6-14. doi: 10.1093/ije/26.suppl_1.s6. — View Citation

Saibandith B, Spencer JPE, Rowland IR, Commane DM. Olive Polyphenols and the Metabolic Syndrome. Molecules. 2017 Jun 29;22(7):1082. doi: 10.3390/molecules22071082. — View Citation

Sayon-Orea C, Razquin C, Bullo M, Corella D, Fito M, Romaguera D, Vioque J, Alonso-Gomez AM, Warnberg J, Martinez JA, Serra-Majem L, Estruch R, Tinahones FJ, Lapetra J, Pinto X, Tur JA, Lopez-Miranda J, Bueno-Cavanillas A, Delgado-Rodriguez M, Matia-Martin P, Daimiel L, Sanchez VM, Vidal J, Vazquez C, Ros E, Ruiz-Canela M, Sorli JV, Castaner O, Fiol M, Navarrete-Munoz EM, Aros F, Gomez-Gracia E, Zulet MA, Sanchez-Villegas A, Casas R, Bernal-Lopez R, Santos-Lozano JM, Corbella E, Bouzas C, Garcia-Arellano A, Basora J, Asensio EM, Schroder H, Monino M, Garcia de la Hera M, Tojal-Sierra L, Toledo E, Diaz-Lopez A, Goday A, Salas-Salvado J, Martinez-Gonzalez MA. Effect of a Nutritional and Behavioral Intervention on Energy-Reduced Mediterranean Diet Adherence Among Patients With Metabolic Syndrome: Interim Analysis of the PREDIMED-Plus Randomized Clinical Trial. JAMA. 2019 Oct 15;322(15):1486-1499. doi: 10.1001/jama.2019.14630. — View Citation

Schwingshackl L, Christoph M, Hoffmann G. Effects of Olive Oil on Markers of Inflammation and Endothelial Function-A Systematic Review and Meta-Analysis. Nutrients. 2015 Sep 11;7(9):7651-75. doi: 10.3390/nu7095356. — View Citation

Yubero-Serrano EM, Lopez-Moreno J, Gomez-Delgado F, Lopez-Miranda J. Extra virgin olive oil: More than a healthy fat. Eur J Clin Nutr. 2019 Jul;72(Suppl 1):8-17. doi: 10.1038/s41430-018-0304-x. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of glycemic control induced by polyphenols enriched EVOO-MD.	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of glycated hemoglobin levels.	From baseline to end of intervention (6 months)
Primary	Change of insulin resistance induced by polyphenols enriched EVOO-MD.	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of (HOMA-IR) index.	From baseline to end of intervention (6 months)
Primary	Change of high density lipoproteins levels induced by polyphenols enriched EVOO-MD.	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of high density lipoproteins (HDL) levels.	From baseline to end of intervention (6 months)
Primary	Change of triglycerides levels induced by polyphenols enriched	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of triglycerides levels.	From baseline to end of intervention (6 months)
Primary	Change of inflammatory parameter tumor necrosis factor (TNF)-a induced by polyphenols enriched EVOO-MD.	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of TNF-a levels.	From baseline to end of intervention (6 months)
Primary	Change of inflammatory parameter interleukine (IL)-6, induced by polyphenols enriched EVOO-MD.	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of tumor necrosis factor IL-6 levels.	From baseline to end of intervention (6 months)
Secondary	Change in liver steatosis ultrasound pattern induced by polyphenols enriched EVOO-MD.	Statistically significant change from baseline (T0) to end of intervention (T1) of liver ultrasound steatosis pattern by ultrasonography.	From baseline to end of intervention (6 months)
Secondary	Change in visceral fat thickness induced by polyphenols enriched EVOO-MD.	Statistically significant change (p<0.05) from baseline (T0) to end of intervention (T1) of visceral fat thickness by ultrasonography.	From baseline to end of intervention (6 months)
Secondary	Change in carotid intima-media thickness (cIMT) induced by polyphenols enriched EVOO-MD.	Statistically significant change (p <0.05) from baseline (T0) to end of intervention (T1) of cIMT by ultrasonography.	From baseline to end of intervention (6 months)
Secondary	Change in endothelial disfunction induced by polyphenols enriched EVOO-MD.	Statistically significant change (p <0.05) from baseline (T0) to end of intervention (T1) in endothelial dysfunction, by flow-mediated dilatation technique of the brachial artery.	From baseline to end of intervention (6 months)
Secondary	EVOO effects on PBMC stress response gene expression	Statistically significant change (p <0.05) from baseline (T0) to end of intervention (T1) of expression of nuclear protein 1 (NUPR1)	From baseline to end of intervention (6 months)
Secondary	EVOO effects on PBMC lipid metabolism gene expression	Statistically significant change (p <0.05) from baseline (T0) to end of intervention (T1) of expression of Acetyl-Coenzyme A Carboxylase 1 (ACC1).	From baseline to end of intervention (6 months)