{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:01:00Z","timestamp":1776675660362,"version":"3.51.2"},"reference-count":112,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Mediterranean Diet (MD) is recognized for promoting longevity and reducing the risk of chronic disease, yet the mechanisms underlying these benefits remain uncharacterized. This review highlights the diverse nutritional and phytoactive constituents of the MD and research exploring its complex network of polyphenols. It discusses data evaluating MD-derived constituents formulated into a dietary supplement capsule developed using a systems and network biology framework. Component selection was based on their actions on enzyme systems involved in senescence-related pathways and health preservation. This review highlights how MD components synergistically modulate pathways central to antioxidant activity, cognitive health, and aging. Liquid chromatography\u2013mass spectrometry identified phytochemically diverse constituents in capsules (supplied by DailyColors\u2122, Warwickshire, UK and Sebastopol, CA, USA) derived from primary color groups in sixteen Mediterranean plants. These constituents were mapped to bioactive networks targeting enzymes linked to inflammation, metabolic regulation, and cellular senescence. Preclinical studies demonstrated the modulation of mitochondrial and metabolic health markers, with complementary effects on cytokine inhibition and glucose sensitivity. Two clinical studies confirmed broad proteomic and epigenetic effects on pathways governing immunity, skeletal muscle, cognition, and inflammation. Therefore, this review advances a novel perspective that MD polyphenols act through synergistic, multi-pathway interactions that link dietary patterns to coordinated regulation of longevity and healthy aging.<\/jats:p>","DOI":"10.3390\/ijms27083634","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding the Longevity Networks of the Mediterranean Diet: Systems Biology and Multi-Pathway Mechanisms Shaping Healthspan"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2698-7224","authenticated-orcid":false,"given":"Sandra K.","family":"Szlapinski","sequence":"first","affiliation":[{"name":"Division of Client Services, Department of Regulatory Affairs, KGK Science Inc., London, ON N6B 3L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryana","family":"Hallam","sequence":"additional","affiliation":[{"name":"Division of Client Services, Department of Regulatory Affairs, KGK Science Inc., London, ON N6B 3L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Charrette","sequence":"additional","affiliation":[{"name":"Division of Client Services, Department of Regulatory Affairs, KGK Science Inc., London, ON N6B 3L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najla","family":"Guthrie","sequence":"additional","affiliation":[{"name":"Division of Client Services, Department of Regulatory Affairs, KGK Science Inc., London, ON N6B 3L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corey J.","family":"Hilmas","sequence":"additional","affiliation":[{"name":"Division of Client Services, Department of Regulatory Affairs, KGK Science Inc., London, ON N6B 3L1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8947","DOI":"10.18632\/oncotarget.13553","article-title":"Impact of Mediterranean Diet on Metabolic Syndrome, Cancer and Longevity","volume":"8","author":"Noce","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.numecd.2014.03.003","article-title":"Mediterranean Dietary Pattern, Inflammation and Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Trials","volume":"24","author":"Schwingshackl","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pcad.2015.04.003","article-title":"Benefits of the Mediterranean Diet: Insights From the PREDIMED Study","volume":"58","author":"Estruch","year":"2015","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.3945\/ajcn.2008.26528","article-title":"Association between Adherence to the Mediterranean Diet and Oxidative Stress","volume":"88","author":"Dai","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/bcp.12986","article-title":"Polyphenol Intake from a Mediterranean Diet Decreases Inflammatory Biomarkers Related to Atherosclerosis: A Substudy of the PREDIMED Trial","volume":"83","author":"Casas","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative Stress, Aging, and Diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and Aging-Related Diseases: From Molecular Mechanisms to Interventions and Treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.psyneuen.2005.08.011","article-title":"Cell Aging in Relation to Stress Arousal and Cardiovascular Disease Risk Factors","volume":"31","author":"Epel","year":"2006","journal-title":"Psychoneuroendocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Boccardi, V., Esposito, A., Rizzo, M.R., Marfella, R., Barbieri, M., and Paolisso, G. (2013). Mediterranean Diet, Telomere Maintenance and Health Status among Elderly. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062781"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41430-017-0005-x","article-title":"Fruit and Vegetable Intake and Cognitive Impairment: A Systematic Review and Meta-Analysis of Observational Studies","volume":"72","author":"Mottaghi","year":"2018","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"g5472","DOI":"10.1136\/bmj.g4490","article-title":"BMJ Fruit and Vegetable Consumption and Mortality from All Causes, Cardiovascular Disease, and Cancer: Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies","volume":"349","author":"Wang","year":"2014","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1039\/D4FO06259K","article-title":"Effects of the DailyColorsTM Polyphenol Supplement on Serum Proteome, Cognitive Function, and Health in Older Adults at Risk of Cognitive and Functional Decline","volume":"16","author":"Bowtell","year":"2025","journal-title":"Food Funct."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1002\/ptr.8219","article-title":"Pomegranate Polyphenol Punicalin Ameliorates Lipopolysaccharide-Induced Memory Impairment, Behavioral Disorders, Oxidative Stress, and Neuroinflammation via Inhibition of TLR4-NF-\u043aB Pathway","volume":"38","author":"Chen","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1016\/j.tjnut.2024.05.005","article-title":"Higher Dietary Polyphenol Intake Is Associated With Lower Blood Inflammatory Markers","volume":"154","author":"Griffin","year":"2024","journal-title":"J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109154","DOI":"10.1016\/j.jnutbio.2022.109154","article-title":"Blueberries and Their Bioactives in the Modulation of Oxidative Stress, Inflammation and Cardio\/Vascular Function Markers: A Systematic Review of Human Intervention Studies","volume":"111","author":"Martini","year":"2023","journal-title":"J. Nutr. Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3945\/jn.111.144428","article-title":"Total and Specific Polyphenol Intakes in Midlife Are Associated with Cognitive Function Measured 13 Years Later","volume":"142","author":"Fezeu","year":"2012","journal-title":"J. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/09637486.2016.1146235","article-title":"Anti-Obesity Effects of Artificial Planting Blueberry (Vaccinium Ashei) Anthocyanin in High-Fat Diet-Treated Mice","volume":"67","author":"Wu","year":"2016","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.fct.2010.10.002","article-title":"Anthocyanins from Purple Sweet Potato Attenuate Dimethylnitrosamine-Induced Liver Injury in Rats by Inducing Nrf2-Mediated Antioxidant Enzymes and Reducing COX-2 and iNOS Expression","volume":"49","author":"Hwang","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1093\/nutrit\/nuab106","article-title":"Dietary Modulation of Large Extracellular Vesicles: The Good and the Bad for Human Health","volume":"80","author":"Monfoulet","year":"2022","journal-title":"Nutr. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3945\/ajcn.110.006866","article-title":"Mediterranean Diet Reduces Endothelial Damage and Improves the Regenerative Capacity of Endothelium","volume":"93","author":"Marin","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1016\/j.clnu.2020.02.027","article-title":"The Mediterranean Diet Decreases Prothrombotic Microvesicle Release in Asymptomatic Individuals at High Cardiovascular Risk","volume":"39","author":"Crespo","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aac4854","article-title":"NAD+ in Aging, Metabolism, and Neurodegeneration","volume":"350","author":"Verdin","year":"2015","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41580-020-00313-x","article-title":"NAD+ Metabolism and Its Roles in Cellular Processes during Ageing","volume":"22","author":"Covarrubias","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.cell.2013.11.037","article-title":"Declining NAD(+) Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging","volume":"155","author":"Gomes","year":"2013","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev.pathol.4.110807.092250","article-title":"Mammalian Sirtuins: Biological Insights and Disease Relevance","volume":"5","author":"Haigis","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tcb.2014.04.002","article-title":"NAD+ and Sirtuins in Aging and Disease","volume":"24","author":"Imai","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1126\/science.1202723","article-title":"SIRT6 Promotes DNA Repair under Stress by Activating PARP1","volume":"332","author":"Mao","year":"2011","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.cell.2008.10.025","article-title":"SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging","volume":"135","author":"Oberdoerffer","year":"2008","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.1111\/j.1742-4658.2005.04864.x","article-title":"Poly(ADP-Ribose). The Most Elaborate Metabolite of NAD+","volume":"272","year":"2005","journal-title":"FEBS J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.cmet.2016.05.006","article-title":"CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism","volume":"23","author":"Chini","year":"2016","journal-title":"Cell Metab."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tsofliou, F., Vlachos, D., Hughes, C., and Appleton, K.M. (2022). Barriers and Facilitators Associated with the Adoption of and Adherence to a Mediterranean Style Diet in Adults: A Systematic Review of Published Observational and Qualitative Studies. Nutrients, 14.","DOI":"10.3390\/nu14204314"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Trajkovska Petkoska, A., Ognenoska, V., and Trajkovska-Broach, A. (2025). Mediterranean Diet: From Ancient Traditions to Modern Science\u2014A Sustainable Way Towards Better Health, Wellness, Longevity, and Personalized Nutrition. Sustainability, 17.","DOI":"10.3390\/su17094187"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"149590","DOI":"10.1016\/j.bbrc.2024.149590","article-title":"The Therapeutic Perspective of NAD+ Precursors in Age-Related Diseases","volume":"702","author":"Iqbal","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","unstructured":"Pond, H. (2025, October 30). Composition and Methods for Nutritional Supplements 2021. Available online: https:\/\/patents.justia.com\/patent\/11065295."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhang, S., Li, F., Zhou, T., Wang, G., and Li, Z. (2020). Caenorhabditis Elegans as a Useful Model for Studying Aging Mutations. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.554994"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chong, J.R., de Lucia, C., Tovar-Rios, D.A., Castellanos-Perilla, N., Collins, C., Kvernberg, S.M., Ballard, C., Siow, R.C., and Aarsland, D. (2024). A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing. Antioxidants, 13.","DOI":"10.3390\/antiox13080995"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Piedra-Quintero, Z.L., Wilson, Z., Nava, P., and Guerau-de-Arellano, M. (2020). CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.597959"},{"key":"ref_38","first-page":"2233906","article-title":"Oxidative Stress and 4-Hydroxy-2-Nonenal (4-HNE): Implications in the Pathogenesis and Treatment of Aging-Related Diseases","volume":"2022","author":"Li","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0022-2275(20)37268-0","article-title":"Altered Properties of High Density Lipoprotein Subfractions in Obese Subjects","volume":"38","author":"Sasahara","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Grao-Cruces, E., Varela, L.M., Martin, M.E., Bermudez, B., and Montserrat-de la Paz, S. (2021). High-Density Lipoproteins and Mediterranean Diet: A Systematic Review. Nutrients, 13.","DOI":"10.3390\/nu13030955"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bakaloudi, D.R., Chrysoula, L., Kotzakioulafi, E., Theodoridis, X., and Chourdakis, M. (2021). Impact of the Level of Adherence to Mediterranean Diet on the Parameters of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Observational Studies. Nutrients, 13.","DOI":"10.3390\/nu13051514"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e2421976","DOI":"10.1001\/jamanetworkopen.2024.21976","article-title":"Mediterranean Diet and Cardiometabolic Biomarkers in Children and Adolescents: A Systematic Review and Meta-Analysis","volume":"7","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ajcnut.2023.04.013","article-title":"Higher Intake of Dietary Flavonols, Specifically Dietary Quercetin, Is Associated with Lower Odds of Frailty Onset over 12 Years of Follow-up among Adults in the Framingham Heart Study","volume":"118","author":"Oei","year":"2023","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/ana.23594","article-title":"Dietary Intakes of Berries and Flavonoids in Relation to Cognitive Decline","volume":"72","author":"Devore","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.clnesp.2017.03.004","article-title":"Flavonoid Intake and Mortality from Cardiovascular Disease and All Causes: A Meta-Analysis of Prospective Cohort Studies","volume":"20","author":"Kim","year":"2017","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"889","DOI":"10.3945\/an.116.012138","article-title":"Mediterranean Diet, Cognitive Function, and Dementia: A Systematic Review of the Evidence","volume":"7","author":"Petersson","year":"2016","journal-title":"Adv. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Whyte, A.R., Cheng, N., Fromentin, E., and Williams, C.M. (2018). A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlueTM) in Maintenance of Episodic and Working Memory in Older Adults. Nutrients, 10.","DOI":"10.3390\/nu10060660"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ahles, S., Joris, P.J., and Plat, J. (2021). Effects of Berry Anthocyanins on Cognitive Performance, Vascular Function and Cardiometabolic Risk Markers: A Systematic Review of Randomized Placebo-Controlled Intervention Studies in Humans. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126482"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Gantenbein, K.V., and Kanaka-Gantenbein, C. (2021). Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing. Nutrients, 13.","DOI":"10.3390\/nu13061951"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e14390","DOI":"10.1002\/alz.14390","article-title":"Association between Dietary Inflammatory Index Score and Incident Dementia","volume":"21","author":"Mesa","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/S0271-5317(02)00430-X","article-title":"Effect of Low Dose Lycopene Intake on Lycopene Bioavailability and Oxidative Stress","volume":"22","author":"Rao","year":"2002","journal-title":"Nutr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1447-0756.2006.00410.x","article-title":"LycoRed as an Alternative to Hormone Replacement Therapy in Lowering Serum Lipids and Oxidative Stress Markers: A Randomized Controlled Clinical Trial","volume":"32","author":"Misra","year":"2006","journal-title":"J. Obs. Gynaecol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/oby.24036","article-title":"Altered Proteome Profiles Related to Visceral Adiposity May Mediate the Favorable Effect of Green Mediterranean Diet: The DIRECT-PLUS Trial","volume":"32","author":"Zelicha","year":"2024","journal-title":"Obesity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1291\/hypres.28.711","article-title":"Antihypertensive Effect of Green Coffee Bean Extract on Mildly Hypertensive Subjects","volume":"28","author":"Kozuma","year":"2005","journal-title":"Hypertens. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1111\/j.1582-4934.2009.00897.x","article-title":"Chemical and Molecular Mechanisms of Antioxidants: Experimental Approaches and Model Systems","volume":"14","author":"Lin","year":"2010","journal-title":"J. Cell Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bruna-Mejias, A., San Martin, J., Arciniegas-Diaz, D., Meneses-Caroca, T., Salamanca-Cerda, A., Beas-Gambi, A., Paola-Loaiza-Giraldo, J., Ortiz-Ahumada, C., Nova-Baeza, P., and Oyanedel-Amaro, G. (2025). Comparison of the Mediterranean Diet and Other Therapeutic Strategies in Metabolic Syndrome: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125887"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.2174\/1389557511313080002","article-title":"The Effect of Polyphenol Consumption on Blood Pressure","volume":"13","author":"Estruch","year":"2013","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_59","first-page":"1299","article-title":"Olive Oil Polyphenols Decrease Blood Pressure and Improve Endothelial Function in Young Women with Mild Hypertension","volume":"25","author":"Miranda","year":"2012","journal-title":"Am. J. Hypertens."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1016\/j.clnu.2021.01.030","article-title":"Mediterranean Diet and Blood Pressure Reduction in Adults with and without Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"40","author":"Filippou","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_61","first-page":"379","article-title":"Metabolic Syndrome under Fire: Weighing in on the Truth","volume":"22","author":"Cheng","year":"2006","journal-title":"Can. J. Cardiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1177\/2042018810374290","article-title":"The Metabolic Syndrome: What\u2019s in a Name?","volume":"1","author":"Matfin","year":"2010","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/advances\/nmz065","article-title":"Recent Research on the Health Benefits of Blueberries and Their Anthocyanins","volume":"11","author":"Kalt","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8461","DOI":"10.1002\/alz.14277","article-title":"Association of MIND Diet with Cognitive Decline among Black and White Older Adults","volume":"20","author":"Agarwal","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1021\/jf053033c","article-title":"Effect of a Tomato-Based Drink on Markers of Inflammation, Immunomodulation, and Oxidative Stress","volume":"54","author":"Riso","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"216","DOI":"10.2174\/1570159X17666191021111809","article-title":"Pharmacologic Overview of Chlorogenic Acid and Its Metabolites in Chronic Pain and Inflammation","volume":"18","author":"Bagdas","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"101349","DOI":"10.1016\/j.ctcp.2021.101349","article-title":"Effect of Green Coffee Bean Extract Supplementation on Liver Function and Inflammatory Biomarkers: A Meta-Analysis of Randomized Clinical Trials","volume":"43","author":"Asbaghi","year":"2021","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mustafa, I., and Chin, N.L. (2023). Antioxidant Properties of Dried Ginger (Zingiber officinale Roscoe) Var. Bentong. Foods, 12.","DOI":"10.3390\/foods12010178"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1080\/14786419.2016.1236097","article-title":"The Effect and Safety of Highly Standardized Ginger (Zingiber officinale) and Echinacea (Echinacea angustifolia) Extract Supplementation on Inflammation and Chronic Pain in NSAIDs Poor Responders. A Pilot Study in Subjects with Knee Arthrosis","volume":"31","author":"Rondanelli","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e13612","DOI":"10.1111\/jfbc.13612","article-title":"Effect of Ginger (Zingiber officinale) Supplementation on Oxidative Stress Parameters: A Systematic Review and Meta-Analysis","volume":"45","author":"Morvaridzadeh","year":"2021","journal-title":"J. Food Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1111\/j.1526-4637.2011.01261.x","article-title":"The Use of Ginger (Zingiber officinale) for the Treatment of Pain: A Systematic Review of Clinical Trials","volume":"12","author":"Terry","year":"2011","journal-title":"Pain. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"155224","DOI":"10.1016\/j.cyto.2020.155224","article-title":"Effect of Ginger (Zingiber officinale) on Inflammatory Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"135","author":"Morvaridzadeh","year":"2020","journal-title":"Cytokine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.jff.2014.12.018","article-title":"Oxygen Radical Absorbance Capacity (ORAC): New Horizons in Relating Dietary Antioxidants\/Bioactives and Health Benefits","volume":"18","author":"Prior","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0921-8734(92)90030-S","article-title":"Free Radical Theory of Aging","volume":"275","author":"Harman","year":"1992","journal-title":"Mutat. Res.\/DNAging"},{"key":"ref_75","unstructured":"McBride, J. (2025, October 30). High-ORAC Foods May Slow Aging: USDA ARS, Available online: https:\/\/www.ars.usda.gov\/news-events\/news\/research-news\/1999\/high-orac-foods-may-slow-aging\/."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"118","DOI":"10.4103\/0973-7847.70902","article-title":"Free Radicals, Antioxidants and Functional Foods: Impact on Human Health","volume":"4","author":"Lobo","year":"2010","journal-title":"Pharmacogn. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.mam.2004.02.005","article-title":"Mitochondrial Free Radical Production and Cell Signaling","volume":"25","author":"Cadenas","year":"2004","journal-title":"Mol. Asp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"22028","DOI":"10.1016\/S0021-9258(18)54740-2","article-title":"Detection of Catalase in Rat Heart Mitochondria","volume":"266","author":"Radi","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/15216540051080912","article-title":"Mitochondrial Production of Hydrogen Peroxide Regulation by Nitric Oxide and the Role of Ubisemiquinone","volume":"50","author":"Boveris","year":"2000","journal-title":"IUBMB Life"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0891-5849(00)00301-4","article-title":"Reactions of Peroxynitrite in the Mitochondrial Matrix","volume":"29","author":"Valdez","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_81","first-page":"15","article-title":"Can Foods Forestall Aging? Some with High Antioxidant Activity Appear to Aid Memory","volume":"47","author":"Weller","year":"1999","journal-title":"USDA ARS Online Mag."},{"key":"ref_82","unstructured":"(2025, December 01). ORAC Values: Antioxidant Values of Foods & Beverages 2026. Available online: https:\/\/superfoodly.com\/orac-values\/."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1080\/10408398.2018.1427044","article-title":"The Effects of Ginger Intake on Weight Loss and Metabolic Profiles among Overweight and Obese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"59","author":"Maharlouei","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_84","first-page":"153018","article-title":"Effects of Green Coffee Bean Extract on Weight Loss: An Updated Meta-Analysis of Randomized Clinical Trials","volume":"6","author":"Hausenblas","year":"2014","journal-title":"Nat. Med. J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1177\/0003319714568792","article-title":"Effect of a Natural Supplement Containing Curcuma Longa, Guggul, and Chlorogenic Acid in Patients With Metabolic Syndrome","volume":"66","author":"Patti","year":"2015","journal-title":"Angiology"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Castellino, G., Nikolic, D., Mag\u00e1n-Fern\u00e1ndez, A., Malfa, G.A., Chianetta, R., Patti, A.M., Amato, A., Montalto, G., Toth, P.P., and Banach, M. (2019). Altilix\u00ae 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, 11.","DOI":"10.3390\/nu11112580"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.nut.2014.11.008","article-title":"Tomato Juice Supplementation in Young Women Reduces Inflammatory Adipokine Levels Independently of Body Fat Reduction","volume":"31","author":"Li","year":"2015","journal-title":"Nutrition"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1002\/ptr.6481","article-title":"The Effect of Green Coffee Extract Supplementation on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"33","author":"Han","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/ajcn\/80.4.1012","article-title":"Olive Oil, the Mediterranean Diet, and Arterial Blood Pressure: The Greek European Prospective Investigation into Cancer and Nutrition (EPIC) Study","volume":"80","author":"Psaltopoulou","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-Pel\u00e1ez, S., Fito, M., and Castaner, O. (2020). Mediterranean Diet Effects on Type 2 Diabetes Prevention, Disease Progression, and Related Mechanisms. A Review. Nutrients, 12.","DOI":"10.3390\/nu12082236"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.3945\/ajcn.117.161968","article-title":"Pomegranate Juice, but Not an Extract, Confers a Lower Glycemic Response on a High-Glycemic Index Food: Randomized, Crossover, Controlled Trials in Healthy Subjects","volume":"106","author":"Kerimi","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.nut.2014.11.020","article-title":"Effects of Ginger on Serum Glucose, Advanced Glycation End Products, and Inflammation in Peritoneal Dialysis Patients","volume":"31","author":"Imani","year":"2015","journal-title":"Nutrition"},{"key":"ref_93","first-page":"625","article-title":"Investigating the Nutraceutical Potential of Apple Peel Extract Supplementation for Regulating the Glucose Metabolism in Hyperlipidemic Female Human Subjects","volume":"36","author":"Iftikhar","year":"2023","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Sleiman, D., Al-Badri, M.R., and Azar, S.T. (2015). Effect of Mediterranean Diet in Diabetes Control and Cardiovascular Risk Modification: A Systematic Review. Front. Public. Health, 3.","DOI":"10.3389\/fpubh.2015.00069"},{"key":"ref_95","unstructured":"WHO (2025, November 10). Cardiovascular Diseases (CVDs). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ctim.2017.10.014","article-title":"Efficacy and Safety of a Combination of Red Yeast Rice and Olive Extract in Hypercholesterolemic Patients with and without Statin-Associated Myalgia","volume":"35","author":"Ahn","year":"2017","journal-title":"Complement. Ther. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.numecd.2019.10.002","article-title":"The Effects of Green Coffee Bean Extract Supplementation on Lipid Profile in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"30","author":"Ding","year":"2020","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1002\/fsn3.2309","article-title":"Effect of Onion on Blood Lipid Profile: A Meta-Analysis of Randomized Controlled Trials","volume":"9","author":"Huang","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/fft2.81","article-title":"Phytochemicals: Do They Belong on Our Plate for Sustaining Healthspan?","volume":"2","author":"Fahey","year":"2021","journal-title":"Food Front."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ammar, A., Trabelsi, K., Boukhris, O., Bouaziz, B., M\u00fcller, P., M Glenn, J., Bott, N.T., M\u00fcller, N., Chtourou, H., and Driss, T. (2020). Effects of Polyphenol-Rich Interventions on Cognition and Brain Health in Healthy Young and Middle-Aged Adults: Systematic Review and Meta-Analysis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051598"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3233\/NHA-240006","article-title":"Effect of Polyphenols on Inflammation Related to Cognitive Function: A Systematic Review and Meta-Analysis of Human Randomized Controlled Trials","volume":"9","author":"Mekhora","year":"2024","journal-title":"Nutr. Healthy Aging"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Ruiz-Iglesias, P., Gorgori-Gonz\u00e1lez, A., Massot-Cladera, M., Castell, M., and P\u00e9rez-Cano, F.J. (2021). Does Flavonoid Consumption Improve Exercise Performance? Is It Related to Changes in the Immune System and Inflammatory Biomarkers? A Systematic Review of Clinical Studies since 2005. Nutrients, 13.","DOI":"10.3390\/nu13041132"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1007\/s40279-017-0675-5","article-title":"Polyphenols and Performance: A Systematic Review and Meta-Analysis","volume":"47","author":"Somerville","year":"2017","journal-title":"Sports Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/obr.12409","article-title":"Effects of Dietary Polyphenols on Metabolic Syndrome Features in Humans: A Systematic Review","volume":"17","author":"Amiot","year":"2016","journal-title":"Obes. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Del Bo\u2019, C., Bernardi, S., Marino, M., Porrini, M., Tucci, M., Guglielmetti, S., Cherubini, A., Carrieri, B., Kirkup, B., and Kroon, P. (2019). Systematic Review on Polyphenol Intake and Health Outcomes: Is There Sufficient Evidence to Define a Health-Promoting Polyphenol-Rich Dietary Pattern?. Nutrients, 11.","DOI":"10.3390\/nu11061355"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e00031-18","DOI":"10.1128\/mSystems.00031-18","article-title":"American Gut: An Open Platform for Citizen Science Microbiome Research","volume":"3","author":"McDonald","year":"2018","journal-title":"mSystems"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1016\/j.cell.2023.08.003","article-title":"Biomarkers of Aging for the Identification and Evaluation of Longevity Interventions","volume":"186","author":"Moqri","year":"2023","journal-title":"Cell"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"21658","DOI":"10.1038\/s41598-023-49064-7","article-title":"Longitudinal Changes and Variation in Human DNA Methylation Analysed with the Illumina MethylationEPIC BeadChip Assay and Their Implications on Forensic Age Prediction","volume":"13","author":"Refn","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"102115","DOI":"10.1016\/j.legalmed.2022.102115","article-title":"Epigenome-Wide Screening of CpG Markers to Develop a Multiplex Methylation SNaPshot Assay for Age Prediction","volume":"59","author":"Ye","year":"2022","journal-title":"Leg. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6156","DOI":"10.2174\/1381612811319340010","article-title":"Epigenetic and Disease Targets by Polyphenols","volume":"19","author":"Pan","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Yaskolka Meir, A., Keller, M., Hoffmann, A., Rinott, E., Tsaban, G., Kaplan, A., Zelicha, H., Hagemann, T., Ceglarek, U., and Isermann, B. (2023). The Effect of Polyphenols on DNA Methylation-Assessed Biological Age Attenuation: The DIRECT PLUS Randomized Controlled Trial. BMC Med., 21.","DOI":"10.1186\/s12916-023-03067-3"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Collins, C., Brown, J., and Berkley, N. (2024). MuhdoAge: A Novel Saliva Based Epigenetic Clock That Has a Strong Association with Ageing in a Healthy, Disease-Free Cohort. Preprints, 2024040985.","DOI":"10.20944\/preprints202404.0985.v2"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:34:34Z","timestamp":1776674074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,19]]},"references-count":112,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083634"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083634","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,19]]}}}