{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T02:21:28Z","timestamp":1775874088190,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T00:00:00Z","timestamp":1589846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>A single-center, randomized, double-blind controlled trial was conducted to assess the efficacy of a food supplement based on a combination of grapefruit, bitter orange, and olive extracts administered for eight weeks (n = 51) versus placebo (n = 45) on reduction of cardiovascular risk in healthy volunteers. Study variables included flow-mediated vasodilation (FMD), blood pressure (BP), lipid profile, thrombotic status, oxidative stress biomarkers, inflammation-related biomarkers, anthropometric variables, quality of life, and physical activity. The per-protocol data set was analyzed. In the active product group, there were statistically significant within-group differences at eight weeks as compared with baseline in FMD, systolic and diastolic BP, total cholesterol, LDL-C, LDL-oxidase, oxidized\/reduced glutathione ratio, protein carbonyl, and IL-6. Significant between-group differences in these variables were also found. Significant changes in anthropometric variables and quality of life were not observed in the study groups. Changes in the level of physical activity were not recorded. Treatment with the active product was well tolerated. All these findings, taken together, support a beneficial effect of supplementation with a mixture of grapefruit, bitter orange fruits, and olive leaf extracts on underlying mechanisms that may interact each other to decrease the cardiovascular risk in healthy people.<\/jats:p>","DOI":"10.3390\/nu12051475","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T02:48:24Z","timestamp":1589942904000},"page":"1475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effect of a Combination of Citrus Flavones and Flavanones and Olive Polyphenols for the Reduction of Cardiovascular Disease Risk: An Exploratory Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7589-1344","authenticated-orcid":false,"given":"Maravillas","family":"S\u00e1nchez Macarro","sequence":"first","affiliation":[{"name":"Health Sciences Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"}]},{"given":"Juan Pablo","family":"Mart\u00ednez Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Health Sciences Ph.D. Program, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"},{"name":"Research and Development Department, Nutrafur iff-Health, E-30820 Murcia, Spain"}]},{"given":"Enrique","family":"Bernal Morell","sequence":"additional","affiliation":[{"name":"Unidad de Enfermedades Infecciosas, Hospital General Universitario Reina Sofia, E-30003 Murcia, Spain"}]},{"given":"Silvia","family":"P\u00e9rez-Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Health Sciences Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-9477","authenticated-orcid":false,"given":"Desir\u00e9e","family":"Victoria-Montesinos","sequence":"additional","affiliation":[{"name":"Health Sciences Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1021-5385","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Garc\u00eda-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Health Sciences Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8837-1927","authenticated-orcid":false,"given":"Fernando","family":"C\u00e1novas Garc\u00eda","sequence":"additional","affiliation":[{"name":"Health Sciences Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"}]},{"given":"Juli\u00e1n","family":"Castillo S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Research and Development Department, Nutrafur iff-Health, E-30820 Murcia, Spain"},{"name":"Food Technology & Nutrition Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), E-30107 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2841-5502","authenticated-orcid":false,"given":"Francisco Javier","family":"L\u00f3pez-Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Health Sciences Department, Universidad Cat\u00f3lica San Antonio de Murcia (UCAM), Campus de los Jer\u00f3nimos, E-30107 Murcia, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics\u20142019 Update: A Report From the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_2","unstructured":"European Heart Network (2019, October 22). European Cardiovascular Disease Statistics 2017. Available online: http:\/\/www.ehnheart.org\/cvd-statistics.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1093\/ije\/dyz143","article-title":"Is the long-term decline in cardiovascular-disease mortality in high-income countries over? Evidence from national vital statistics","volume":"48","author":"Lopez","year":"2019","journal-title":"Int. J. Epidemiol."},{"key":"ref_4","first-page":"1","article-title":"Cardiovascular disease as a leading cause of death: How are pharmacists getting involved?","volume":"8","author":"Alzubaidi","year":"2019","journal-title":"Integr. Pharm. Res. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"626205","DOI":"10.1155\/2014\/626205","article-title":"Contribution of Individual Risk Factor Changes to Reductions in Population Absolute Cardiovascular Risk","volume":"2014","author":"Cochrane","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1161\/CIRCULATIONAHA.115.008718","article-title":"Mbbs Worldwide Exposures to Cardiovascular Risk Factors and Associated Health Effects","volume":"133","author":"Tzoulaki","year":"2016","journal-title":"Circulation"},{"key":"ref_7","first-page":"293","article-title":"Emerging Modifiable Risk Factors for Cardiovascular Disease in Women","volume":"40","author":"Barnes","year":"2013","journal-title":"Tex. Heart Inst. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S0140-6736(19)32008-2","article-title":"Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): A prospective cohort study","volume":"395","author":"Yusuf","year":"2020","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/sj.jhh.1002212","article-title":"Increased consumption of fruit and vegetables is related to a reduced risk of coronary heart disease: Meta-analysis of cohort studies","volume":"21","author":"He","year":"2007","journal-title":"J. Hum. Hypertens."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0140-6736(06)68069-0","article-title":"Fruit and vegetable consumption and stroke: Meta-analysis of cohort studies","volume":"367","author":"He","year":"2006","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3945\/ajcn.113.076901","article-title":"Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: A systematic review and meta-analysis","volume":"100","author":"Afshin","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.numecd.2006.12.008","article-title":"Whole grain intake and cardiovascular disease: A meta-analysis","volume":"18","author":"Mellen","year":"2008","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1161\/CIRCULATIONAHA.109.924977","article-title":"Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: A systematic review and meta-analysis","volume":"121","author":"Micha","year":"2010","journal-title":"Circulation"},{"key":"ref_14","first-page":"h3978","article-title":"Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: Systematic review and meta-analysis of observational studies","volume":"351","author":"Mente","year":"2015","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"b4567","DOI":"10.1136\/bmj.b4567","article-title":"Salt intake, stroke, and cardiovascular disease: Meta-analysis of prospective studies","volume":"339","author":"Strazzullo","year":"2009","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.3390\/nu5093646","article-title":"Nutritional Recommendations for Cardiovascular Disease Prevention","volume":"5","author":"Sinai","year":"2013","journal-title":"Nutrients"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1017\/S0029665113001328","article-title":"Dietary strategies, policy and cardiovascular disease risk reduction in England","volume":"72","author":"Levy","year":"2013","journal-title":"Proc. Nutr. Soc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s11886-019-1176-y","article-title":"Effectiveness of Changes in Diet Composition on Reducing the Incidence of Cardiovascular Disease","volume":"21","author":"Calabrese","year":"2019","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_19","first-page":"e596","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"140","author":"Arnett","year":"2019","journal-title":"Circulation"},{"key":"ref_20","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA. Guideline on the management of blood cholesterol","volume":"139","author":"Grundy","year":"2019","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.atherosclerosis.2019.08.014","article-title":"2019 ESC\/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk","volume":"290","author":"Mach","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vogiatzoglou, A., Mulligan, A.A., Lentjes, M., Luben, R., Spencer, J.P.E., Schroeter, H., Khaw, K.-T., and Kuhnle, G.G. (2015). Flavonoid Intake in European Adults (18 to 64 Years). PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128132"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00394-013-0572-0","article-title":"Estimated dietary intakes and sources of flavanols in the German population (German National Nutrition Survey II)","volume":"53","author":"Vogiatzoglou","year":"2013","journal-title":"Eur. J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Peyrol, J., Riva, C., and Amiot, M.J. (2017). Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders. Nutrients, 9.","DOI":"10.3390\/nu9030306"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1080\/10942912.2016.1207188","article-title":"Health functionality of apigenin: A review","volume":"20","author":"Ali","year":"2016","journal-title":"Int. J. Food Prop."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Salehi, B., Venditti, A., Sharifi-Rad, J., Kregiel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E., and Novellino, E. (2019). The Therapeutic Potential of Apigenin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061305"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6185","DOI":"10.1021\/jf8006568","article-title":"Update on Uses and Properties of Citrus Flavonoids: New Findings in Anticancer, Cardiovascular, and Anti-inflammatory Activity","volume":"56","author":"Castillo","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"795","DOI":"10.2174\/156800907783220435","article-title":"Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways","volume":"7","author":"Castillo","year":"2007","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31450","DOI":"10.1038\/srep31450","article-title":"Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer\u2019s disease","volume":"6","author":"Balez","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Paredes, M.D., Romec\u00edn, P., Atucha, N.M., O\u2019Valle, F., Castillo, J., Ortiz-Ruiz, C., and Garcia-Esta\u00f1, J. (2018). Moderate Effect of Flavonoids on Vascular and Renal Function in Spontaneously Hypertensive Rats. Nutrients, 10.","DOI":"10.20944\/preprints201807.0384.v1"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Paredes, M.D., Romec\u00edn, P., Atucha, N.M., O\u2019Valle, F., Castillo, J., Ortiz-Ruiz, C., and Garcia-Esta\u00f1, J. (2018). Beneficial Effects of Different Flavonoids on Vascular and Renal Function in L-NAME Hypertensive Rats. Nutrients, 10.","DOI":"10.20944\/preprints201803.0060.v1"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Merola, N., Castillo, J., Benavente-Garc\u00eda, O., Ros-Berruezo, G., and Nieto, G. (2017). The Effect of Consumption of Citrus Fruit and Olive Leaf Extract on Lipid Metabolism. Nutrients, 9.","DOI":"10.3390\/nu9101062"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1538-7836.2004.01099.x","article-title":"Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor","volume":"3","author":"Guerrero","year":"2005","journal-title":"J. Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1021\/jf970373s","article-title":"Uses and Properties ofCitrusFlavonoids","volume":"45","author":"Castillo","year":"1997","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.foodres.2015.09.021","article-title":"Endothelium-dependent vascular relaxing effects of different citrus and olive extracts in aorta rings from spontaneously hypertensive rats","volume":"77","author":"Castillo","year":"2015","journal-title":"Food Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s00394-016-1188-y","article-title":"Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: A randomized controlled trial","volume":"56","author":"Lockyer","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s13063-017-2058-5","article-title":"A red yeast rice-olive extract supplement reduces biomarkers of oxidative stress, OxLDL and Lp-PLA2, in subjects with metabolic syndrome: A randomised, double-blind, placebo-controlled trial","volume":"18","author":"Hermans","year":"2017","journal-title":"Trials"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2473495","DOI":"10.1155\/2017\/2473495","article-title":"Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial","volume":"2017","author":"Colica","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s12967-015-0573-2","article-title":"Dietary flavonoid intake and cardiovascular risk: A population-based cohort study","volume":"13","author":"Ponzo","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1753-4887.2012.00508.x","article-title":"Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations","volume":"70","author":"Peterson","year":"2012","journal-title":"Nutr. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rees, A., Dodd, G.F., and Spencer, J.P. (2018). The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function. Nutrients, 10.","DOI":"10.3390\/nu10121852"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1001\/jama.2019.18102","article-title":"Implementation Strategies for Cardiovascular Polypills","volume":"322","author":"Huffman","year":"2019","journal-title":"JAMA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0735-1097(01)01746-6","article-title":"Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force","volume":"39","author":"Corretti","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/0140-6736(92)93147-F","article-title":"Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis","volume":"340","author":"Celermajer","year":"1992","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_47","first-page":"410","article-title":"Valores poblacionales de referencia de la versi\u00f3n espa\u00f1ola del Cuestionario de Salud SF-36","volume":"111","author":"Alonso","year":"1998","journal-title":"Med. Clin."},{"key":"ref_48","unstructured":"World Health Organization (2020, March 22). Global Physical Activity Questionnaire (GPAQ). Analysis Guide. Available online: https:\/\/www.who.int\/ncds\/surveillance\/steps\/resources\/GPAQ_Analysis_Guide.pdf."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.5339\/gcsp.2014.43","article-title":"Endothelial dysfunction and cardiovascular disease","volume":"2014","author":"Widmer","year":"2014","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1161\/01.CIR.0000028581.07992.56","article-title":"Endothelial function: A barometer for cardiovascular risk?","volume":"106","author":"Vita","year":"2002","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"351","DOI":"10.2217\/bmm.10.61","article-title":"Endothelial function as a functional expression of cardiovascular risk factors","volume":"4","author":"Reriani","year":"2010","journal-title":"Biomark. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1253\/circj.CJ-09-0692","article-title":"Green tea catechins improve human forearm endothelial dysfunction and have antiatherosclerotic effects in smokers","volume":"74","author":"Oyama","year":"2010","journal-title":"Circ. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1136\/heartjnl-2015-309218","article-title":"Beneficial effect of a polyphenol-rich diet on cardiovascular risk: A randomised control trial","volume":"102","author":"Noad","year":"2016","journal-title":"Heart"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.clnesp.2017.10.011","article-title":"The acute effect of black tea consumption on resistance artery endothelial function in healthy subjects. A randomized controlled trial","volume":"23","author":"Greyling","year":"2018","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/ajcn\/nqy066","article-title":"A nutritive dose of pure (\u2013)-epicatechin does not beneficially affect increased cardiometabolic risk factors in overweight-to-obese adults\u2014a randomized, placebo-controlled, double-blind crossover study","volume":"107","author":"Kirch","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1093\/ajcn\/nqy139","article-title":"Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: A randomized, placebo-controlled crossover trial","volume":"108","author":"Hollands","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1080\/10408398.2018.1470491","article-title":"The effect of high-polyphenol extra virgin olive oil on cardiovascular risk factors: A systematic review and meta-analysis","volume":"59","author":"George","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.numecd.2019.07.001","article-title":"Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis","volume":"29","author":"Schwingshackl","year":"2019","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_59","first-page":"CD009825","article-title":"Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease","volume":"3","author":"Rees","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/07315724.2015.1080108","article-title":"A Randomized Clinical Trial Evaluating the Efficacy of an Anthocyanin\u2013Maqui Berry Extract (Delphinol\u00ae) on Oxidative Stress Biomarkers","volume":"34","author":"Davinelli","year":"2015","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.phymed.2016.08.007","article-title":"Effects of low molecular weight procyanidin rich extract from french maritime pine bark on cardiovascular disease risk factors in stage-1 hypertensive subjects: Randomized, double-blind, crossover, placebo-controlled intervention trial","volume":"23","author":"Valls","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Verhoeven, V., Van Der Auwera, A., Van Gaal, L., Remmen, R., Apers, S., Stalpaert, M., Wens, J., and Hermans, N. (2015). Can red yeast rice and olive extract improve lipid profile and cardiovascular risk in metabolic syndrome? A double blind, placebo controlled randomized trial. BMC Complement Altern. Med., 15.","DOI":"10.1186\/s12906-015-0576-9"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00394-017-1572-2","article-title":"Measuring the impact of olive pomace enriched biscuits on the gut microbiota and its metabolic activity in mildly hypercholesterolaemic subjects","volume":"58","author":"Conterno","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jnutbio.2014.11.008","article-title":"Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing I\u039aB\u03b1\/NF-\u03baB signaling pathway","volume":"26","author":"Jia","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1253\/circj.CJ-10-0381","article-title":"Cardioprotective effects of luteolin during ischemia-reperfusion injury in rats","volume":"75","author":"Liao","year":"2010","journal-title":"Circ. J."},{"key":"ref_66","first-page":"3073","article-title":"Protective effect of luteolin on skin ischemia-reperfusion injury through an AKT-dependent mechanism","volume":"42","author":"Chen","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jdiacomp.2016.01.003","article-title":"The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk. A pilot double blind randomized placebo controlled trial","volume":"30","author":"Atkin","year":"2016","journal-title":"J. Diabetes Complicat."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/j.1464-5491.2009.02727.x","article-title":"Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: A double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity","volume":"26","author":"Kar","year":"2009","journal-title":"Diabet. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"005038","DOI":"10.1161\/JAHA.116.005038","article-title":"Interleukin 6 Inhibition and Coronary Artery Disease in a High-Risk Population: A Prospective Community-Based Clinical Study","volume":"6","author":"Bacchiega","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"IL6R Genetics Consortium Emerging Risk Factors Collaboration, Sarwar, N., Butterworth, A.S., Freitag, D.F., Gregson, J., Willeit, P., Gorman, N.N., Gao, P., Saleheen, D., and Rendon, A. (2012). Interleukin-6 receptor pathways in coronary heart disease: A collaborative meta-analysis of 82 studies. Lancet, 379, 1205\u20131213.","DOI":"10.1016\/S0140-6736(11)61931-4"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1161\/01.CIR.0000097109.90783.FC","article-title":"Inflammatory Markers and Onset of Cardiovascular Events: Results from the Health ABC Study","volume":"108","author":"Cesari","year":"2003","journal-title":"Circulation"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ginwala, R., Bhavsar, R., Chigbu, D.G.I., Khan, Z.K., and Khan, Z.K. (2019). Potential Role of Flavonoids in Treating Chronic Inflammatory Diseases with a Special Focus on the Anti-Inflammatory Activity of Apigenin. Antioxidants, 8.","DOI":"10.3390\/antiox8020035"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wang, G., Gurley, E.C., and Zhou, H. (2014). Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response through Multiple Mechanisms in Macrophages. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107072"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/5\/1475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:30:24Z","timestamp":1760175024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/5\/1475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,19]]},"references-count":73,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["nu12051475"],"URL":"https:\/\/doi.org\/10.3390\/nu12051475","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,19]]}}}