Keywords
Mediterranean diet
Metabolic syndrome
Effect mechanisms
Metabolic syndrome
Effect mechanisms
Abstract
Metabolic syndrome, also as known as Syndrome X or Insulin Resistance Syndrome, is a complex health problem featuring visceral obesity (the main diagnostic criterion), insulin resistance, dyslipidemia and high blood pressure. Currently, this health condition has gained a momentum globally while raising concerns among health-related communities. The World Health Organization, American Heart Association and International Diabetes Federation have formulated diagnostic criteria for metabolic syndrome. Diet and nutrition can influence this syndrome: for example, the Western diet is associated with increased risk of metabolic syndrome, whereas the Nordic and Mediterranean diets and the Dietary Approach to Stop Hypertension are potentially beneficial. The Mediterranean diet can affect the components of metabolic syndrome due to its high dietary fiber, omega 3 and 9 fatty acids, complex carbohydrates, antioxidants, minerals, vitamins and bioactive substances, such as polyphenols. These nutrients and bioactive substances can combat obesity, dyslipidemia, hypertension and diabetes mellitus. The mechanisms by which they do so are generally related to oxidative stress, inflammation (the most common risk factors for metabolic syndrome) and gastrointestinal function. The literature also shows examples of positive effects of the Mediterranean diet on the metabolic syndrome. In this review of the literature, we shed light on the effects, mechanisms and dynamic relationship between the Mediterranean diet and metabolic syndrome.
References
[1] Belete R, Ataro Z, Abdu A, Sheleme M. Global prevalence of metabolic syndrome among patients with type I diabetes mellitus: A systematic review and meta-analysis. Diabetol Metab Syndr 2021;13:1-13. https://doi.org/10.1186/s13098-021-00641-8
[2] Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: Pathophysiology, management and modulation by natural compounds. Ther Adv in Cardiovasc Dis 2017;11:21525. https://doi.org/10.1177/1753944717711379
[3] Collins KH, Herzog W, MacDonald GZ, Reimer RA, Rios JL, Smith IC, Zernicke RF, Hart DA. Obesity, metabolic syndrome and musculoskeletal disease: Common inflammatory pathways suggest a central role for loss of muscle integrity. Front Physiol 2018;9:1-25. https://doi.org/10.3389/fphys.2018.00112
[4] McCracken E, Monaghan M, Sreenivasan S, Edin FRCP. Pathophysiology of the metabolic syndrome. Clin Dermatol 2018;36:14-20. https://doi.org/10.1016/j.clindermatol.2017.09.004
[5] Lee SH, Tao S, Kim HS. The prevalence of metabolic syndrome and its related risk complications among Koreans. Nutrients 2019;11:1-9. https://doi.org/10.3390/nu11081755
[6] Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA 2015;313:1973-4. https://doi.org/10.1001/jama.2015.4260
[7] Liang XP, Or CY, Tsoi MF, Cheung CL, Cheung BMY. Prevalence of metabolic syndrome in the United States National Health and Nutrition Examination Survey (NHANES) 2011-2018. Eur Heart J 2021;42:1-24. https://doi.org/10.1093/eurheartj/ehab724.2420
[8] Syed MA, Al Nuaimi AS, Zainel AJAL, A/Qotba HA. Prevalence of metabolic syndrome in primary health settings in Qatar: A cross sectional study. BMC Public Health 2020;20:1-7. https://doi.org/10.1186/s12889-020-08609-5
[9] Naghipour M, Joukar F, Nikbakht HA, Hassanipour S,Asgharnezhad M, Arab-Zozani M, Mansour-Ghanaei F. High prevalence of metabolic syndrome and its related demographic factors in North of Iran: Results from the PERSIAN Guilan Cohort Study. Int J Endocrinol 2021:1-9. https://doi.org/10.1155/2021/8862456
[10] Grosso G, Mistretta A, Marventano S, Purrello A, Vitaglione P, Calabrese G, Drago F, Galvano F. Beneficial effects of the Mediterranean diet on metabolic syndrome. Curr Pharm Des 2014;20:5039-44. https://doi.org/10.2174/1381612819666131 206112144
[11] Papadaki A, Nolen-Doerr E, Mantzoros CS. The effect of the Mediterranean diet on metabolic health: A systematic review and meta-analysis of controlled trials in adults. Nutrients 2020;12:1-21. https://doi.org/10.3390/nu12113342
[12] Bakaloudi DR, Chrysoula L, Kotzakioulafi E, Theodoridis X, Chourdakis M. 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 2021;13:1-25. https://doi.org/10.3390/nu13051514
[13] Müller MJ, Geisler C. Defining obesity as a disease. Eur J Clin Nutr 2017;71:1256-8. https://doi.org/10.1038/ejcn.2017.155
[14] Eberechukwu LE, Eyam ES, Nsan E. Types of obesity and its effect on blood pressure of secondary school students in rural and urban areas of Cross River State, Nigeria. IOSR J Pharm 2013;3:60-6. https://doi.org/10.9790/3013-0343060-66
[15] Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: An update. Gac Méd Méx 2017;153:197-209.
[16] Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífkovά R, Dorminiczak AF, Grassi G, Jordan J, Poulter NR, Rodgers A, Whelton PK. Hypertension. Nat Rev Dis Primers 2019;4:1-48. https://doi.org/10.1038/nrdp.2018.14
[17] Yuan Y, Chen W, Luo L, Xu C. Dyslipidemia: Causes, symptoms and treatment. IJTSRD 2021;5:1013-6. Available at: www.ijtsrd.com. (Accessed on: January 01 2022).
[18] World Health Organization-WHO (1999). Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1: Diagnosis and classification of diabetes mellitus. World Health Organization: Geneva, Switzerland; 1999. Available at: http://www.whqlibdoc. who.int/hq/1999/WHO_NCD_NCS_99.2.pdf. (Accessed on: January 01 2022).
[19] International Diabetes Federation-IDF (2006). The IDF consensus worldwide definition of the Metabolic Syndrome. Part: Worldwide definition for use in clinical practice. International Diabetes Federation: Brussels, Belgium; 2006. Available at: https://www.idf.org/component/attachments/attachments. html?id=705&task=download (Accessed on: January 01 2022).
[20] Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Jr Smith SC, Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome: An American Heart Association/ National Heart, Lung and Blood Institute Scientific Statement. Circulation 2005;112:2735-52. https://doi.org/10.1161/ CIRCULATIONAHA.105.169404
[21] Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WPT, Loria CM, Smith SC. 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;120:16405. https://doi.org/10.1161/CIRCULATIONAHA.109.192644
[22] American Heart Association-AHA (2016). Symptoms and Diagnosis of Metabolic Syndrome. How Is Metabolic Syndrome Diagnosed? American Heart Association: Dallas, Texas; 2016. Available at: https://www.heart.org/en/health-topics/metabolic-syndrome/symptoms-and-diagnosis-of-metabolic-syndrome. (Accessed on: January 01 2022)
[23] Al-Qawasmeh RH, Tayyem RF. Dietary and lifestyle risk factors and metabolic syndrome: Literature review. Curr Res Nutr Food Sci 2018;6:594-608. https://doi.org/10.12944/CRNFSJ.6.3.03
[24] Drake I, Sonestedt E, Eriscon U, Wallström P, Orho-Melander M. A Western dietary pattern is prospectively associated with cardio-metabolic traits and incidence of the metabolic syndrome. Br J Nutr 2018;119:1168-76. https://doi.org/10.1017/S000711451800079X
[25] Strate LL, Keeley BR, Cao Y, Wu K, Giovannucci EL, Chan AT. Western dietary pattern increases and prudent dietary pattern decreases, risk of incident diverticulitis in a prospective cohort study. Gastroenterology 2017;152:1023-30. https://doi.org/10.1053/j.gastro.2016.12.038
[26] Statovci D, Aguilera M, MacSharry J, Melgar S. The impact of Western diet and nutrients on the microbiota and immune response at mucosal interfaces. Front Immunol 2017;8:1-21. https://doi.org/10.3389/fimmu.2017.00838
[27] Kopp W. How Western diet and lifestyle drive the pandemic of obesity and civilization diseases. Diabetes Metab Syndr Obes 2019;12:2221-36. https://doi.org/10.2147/DMSO.S216791
[28] Gallard-Alfaro L, Bibiloni MM, Mascaró CM, Montemayor S, Ruiz-Canela M, Salas-Salvadó J, Corella D, Fito M, Romaguera D, Vioque J, Alonso-Gomez AM, Warnberg J, Martinez JA, Serra-Majem L, Estruch R, Fernandez-Garcia JC, Lapetra J, Pinto X, Rios AG, Bueno-Cavanillas A, Gaforio JJ, MatiaMartin P, Daimiel L, Mico-Perez RM, Vidal J, Vazquez C, Ros E, Fernandez-Lazaro CI, Becerra-Tomas N, Gimenez-Alba IM, Zomeno MD, Konieczna J, Compan-Gabucio L, Tojal-Sierra L, Perez-Lopez J, Zulet MA, Casanas-Quintana T, Castro-Barquero S, Gomez-Perez AM, Santos-Lozano JM, Galera A, BasterraGortari FJ, Basora J, Saiz C, Perez-Vega KA, Galmes-Panades AM, Tercero-Macia C, Sorto-Sanchez C, Sayon-Orea C, GarciaGavilan J, Munoz-Martinez J, Tur JA. Leisure-time physical activity, sedentary behavior and diet quality are associated with metabolic syndrome severity: The PREDIMED-Plus study. Nutrients 2020;12:1-20. https://doi.org/10.3390/nu12041013
[29] Myers J, Kokkinos P, Nyelin E. Physical activity, cardiorespiratory fitness and the metabolic syndrome. Nutrients 2019;11:1-18. https://doi.org/10.3390/nu11071652
[30] Hwang GY, Cho YJ, Chung RH, Kim SH. The relationship between smoking level and metabolic syndrome in male health check-up examinees over 40 years of age. Korean J Fam Med 2014;35:219-26. https://doi.org/10.4082/kjfm.2014.35.5.219
[31] Vieira IMM, Santos BLP, Ruzene DS, Brάnyık T, Teixeira JA, E Silva JBDA, Silva DP. Alcohol and health: Standards of consumption, benefits and harm – A review. Czech J Food Sci 2018;36:427-40. https://doi.org/10.17221/117/2018-CJFS
[32] Grosso G, Fresάn U, Bes-Rastrollo M, Marventano S, Galvano F. Environmental impact of dietary choices: Role of the Mediterranean and other dietary patterns in an Italian cohort. Int J Environ Res Public Health 2020;17:1-13. https://doi.org/10.3390/ijerph17051468
[33] Wickman BE, Enkhmaa B, Ridberg R, Romero E, Cadeiras M, Meyers F, Steinberg F. Dietary management of heart failure: DASH diet and precision nutrition perspectives. Nutrients 2021;13:1-24. https://doi.org/10.3390/nu13124424
[34] Adamsson V, Reumark A, Cederholm T, Vessby B, Risérus U, Johansson G. What is a healthy Nordic diet? Foods and nutrients in the NORDIET study. Food Nutr Res 2012;56:1-8. https://doi.org/10.3402/fnr.v56i0.18189
[35] Ventriglio A, Sancassiani F, Contu MP, Latorre M, Di Slavatore M, Fornaro M, Bhugra D. Mediterranean diet and its benefits on health and mental health: A literature review. Clin Pract Epidemiol Ment Health 2020;16:156-64. https://doi.org/10.2174/1745017902016010156
[36] Carrera-Bastos P, Fontes-Villalba M, O’Keefe JH, Lindeberg S, Cordain L. The Western diet and lifestyle and diseases of civilization. Res Rep Clin Cardiol 2011;2:15-35. https://doi.org/10.2147/RRCC.S16919
[37] United Nations Educational, Scientific and Cultural Organization-UNESCO (2013). Culture, Intangible Heritage, Mediterranean Diet. United Nations Educational, Scientific and Cultural Organization: United Nations; 2013. Available at: https://ich.unesco.org/en/RL/mediterranean-diet-00884. (Accessed on: January 01 2022)
[38] Trichopoulou A, Martínez-Gonzάlez MA, Tong TY, Forouhi NG, Khandelwal S, Prabhakaran D, Mozaffarian D, de Lorgeril M. Definitions and potential health benefits of the Mediterranean diet: views from experts around the world. BMC Medicine 2014;12:1-16. https://doi.org/10.1186/1741-7015-12-112
[39] D’Innocenzo S, Biagi C, Lanari M. Obesity and the Mediterranean diet: A review of evidence of the role and sustainability of the Mediterranean diet. Nutrients 2019;11:125. https://doi.org/10.3390/nu11061306
[40] Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A, Dernini S, Medina FX, Battino M, Belahsen R, Miranda G, Serra-Majem L. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr 2011;14:2274-84. https://doi.org/10.1017/S1368980011002515
[41] Serra-Majem L, Tomaino L, Dernini S, Berry EM, Lairon D, de la Cruz JN, Bach-Faig A, Donini LM, Medina FX, Belahsen R, Piscopo S, Capone R, Aranceta-Bartrina J, Vecchia CL, Trichopoulou A. Updating the Mediterranean diet pyramid towards sustainability: Focus on environmental concerns. Int J Environ Res Public Health 2020;17:1-20. https://doi.org/10.3390/ijerph17238758
[42] Cyprus Modification of the Mediterranean Diet Pyramid: Adherence to the Mediterranean Diet and Consumption Frequencies of the Traditional Foods of Adults in the Island of Cyprus, Taygun Dayi, Near East University, 2021.
[43] Santos-Buelgo C, Gonzάlez-Manzano S, Gonzάlez-Paramάs AM. Wine, polyphenols and Mediterranean diets. What else is there to say? Molecules 2021;26:1-21. https://doi.org/10.3390/ molecules26185537
[44] [44] Cannataro R, Fazio A, Torre CL, Caroleo MC, Cione E. Polyphenols in the Mediterranean diet: From dietary sources to microRNA modulation. Antioxidants 2021;10:1-24. https://doi.org/10.3390/antiox10020328
[45] Giroli MG, Werba JP, Risé P, Porro B, Sala A, Amato M, Tremoli E, Bonomi A, Veglia F. Effects of Mediterranean diet or low-fat diet on blood fatty acids in patients with coronary heart disease. A randomized intervention study. Nutrients 2021;13:1-11. https://doi.org/10.3390/nu13072389
[46] Schwingshackl L, Morze J, Hoffmann G. Mediterranean diet and health status: Active ingredients and pharmacological mechanisms. Br J Pharmacol 2020;177:1241-57. https://doi.org/10.1111/bph.14778
[47] Saibandith B, Spencer JPE, Rowland IR, Commane DM. Olive polyphenols and the metabolic syndrome. Molecules 2017;22:115. https://doi.org/10.3390/molecules22071082
[48] [48] de Souza PAL, Marcadenti A, Portal VL. Effects of olive oil phenolic compounds on inflammation in the prevention and treatment of coronary artery disease. Nutrients 2017;9:1-22. https://doi.org/10.3390/nu9101087
[49] Hou CY, Tain YL, Yu HR, Huang LT. The effects of resveratrol in the treatment of metabolic syndrome. Int J Mol Sci 2019;20:1-15. https://doi.org/10.3390/ijms20030535
[50] Chaplin A, Carpéné C, Mercader J. Resveratrol, metabolic syndrome and gut microbiota. Nutrients 2018;10:1-29. https://doi.org/10.3390/nu10111651
[51] Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin on metabolic syndrome and their mechanisms of action. Adv Nutr 2014;5:404-17. https://doi.org/10.3945/an.113.005603
[52] Liu K, Luo M, Wei S. The bioprotective effects of polyphenols on metabolic syndrome against oxidative stress: Evidences and perspectives. Oxid Med Cell Longev 2019;2019:1-16. https://doi.org/10.1155/2019/6713194
[53] Kasprzak-Drozd K, Oniszczuk T, Stasiak M, Oniszczuk A. Beneficial effects of phenolic compounds on gut microbiota and metabolic syndrome. Int J Mol Sci 2021;22:1-24. https://doi.org/10.3390/ijms22073715
[54] Finicelli M, Squillaro T, Cristo FD, Salle AD, Melone MAB, Galderisi U, Peluso G. Metabolic syndrome, Mediterranean diet, and polyphenols: Evidence and perspectives. J Cell Physiol 2019;234:5807-26. https://doi.org/10.1002/jcp.27506
[55] Rehman K, Haider K, Jabeen K, Akash MSH. Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes. Rev Endocr Metab Disord 2020;21:63143. https://doi.org/10.1007/s11154-020-09549-6
[56] Karacor K, Cam M. Effects of oleic acid. MSD 2015;2:125-32. https://doi.org/10.17546/msd.25609
[57] Massaro M, Scoditti E, Carluccio MA, Calabriso N, Santarpino G, Verri T, De Caterina R. Effects of olive oil on blood pressure: Epidemiological, clinical and mechanistic evidence. Nutrients 2020;12:1-22. https://doi.org/10.3390/nu12061548
[58] Poudyal H, Panchal SK, Diwan V, Brown L. Omega-3 fatty acids and metabolic syndrome: Effects and emerging mechanisms of action. Prog Lipid Res 2011;50:372-87. https://doi.org/10.1016/j.plipres.2011.06.003
[59] Khalili L, Valdes-Ramos R, Harbige LS. Effect of n-3 (Omega-3) polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers and body weight in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of RCTs. Metabolites 2021;11:1-22. https://doi.org/10.3390/ metabo11110742
[60] Nevara GA, Muhammad SKS, Zawawi N, Mustapha NA, Karim R. Dietary fiber: Fractionation, characterization and potential sources from defatted oilseeds. Foods 2021;10:1-19. https://doi.org/10.3390/foods10040754
[61] Chen JP, Chen GC, Wang XP, Qin L, Bai Y. Dietary fiber and metabolic syndrome: A meta-analysis and review of related mechanisms. Nutrients 2018;10:1-17. https://doi.org/10.3390/ nu10010024
[62] Slavin JL. Dietary fiber and body weight. Nutrition 2005;21:4118. https://doi.org/10.1016/j.nut.2004.08.018
[63] Pezzali JG, Shoveller AK, Ellis J. Examining the effects of diet composition, soluble fiber and species on total fecal excretion of bile acids: A meta-analysis. Front Vet Sci 2021;8:1-14. https://doi.org/10.3389/fvets.2021.748803
[64] Khan Khattak MMA. Physiological effects of dietary complex carbohydrates and its metabolites role in certain disease. Pak J Nutr 2002;4:161-8. https://doi.org/10.3923/pjn.2002.161.168
[65] Higgins MR, Izadi A, Kaviani M. Antioxidants and exercise performance: With a focus on vitamin E and C supplementation. Int J Environ Res Public Health 2020;17:1-26. https://doi.org/10.3390/ijerph17228452
[66] Tomoeda M, Kubo C, Yoshizawa H, Yuki M, Kitamura M, Nagata S, Murakami M, Nishizawa Y, Tomita Y. Role of antioxidant vitamins administration on the oxidative stress. Cent Eur J Med 2013;8:509-16. https://doi.org/10.2478/s11536-013-0173-6
[67] Said E, Mousa S, Fawzi M, Sabry NA, Farid S. Combined effect of high-dose vitamin A, vitamin E supplementation and zinc on adult patients with diabetes: A randomized trial. J Adv Res 2021;28:27-33. https://doi.org/10.1016/j.jare.2020.06.013
[68] Pellegrino D. Antioxidants and cardiovascular risk factors. Diseases 2016;4:1-9. https://doi.org/10.3390/diseases4010011
[69] Chiu HF, Venkatakrishnan K, Golovinskaia O, Wang CK. Impact of micronutrients on hypertension: Evidence from clinical trials with a special focus on meta-analysis. Nutrients 2021;13:1-19. https://doi.org/10.3390/nu13020588
[70] Houston MC, Harper KJ. Potassium, magnesium and calcium: Their role in both the cause and treatment of hypertension. J Clin Hypertens 2008;10:3-11. https://doi.org/10.1111/j.17517176.2008.08575.x
[71] Villa-Etchegoyen C, Lombarte M, Matamoros N, Belizάn JM, Cormick G. Mechanisms involved in the relationship between low calcium intake and high blood pressure. Nutrients 2019;11:1-16. https://doi.org/10.3390/nu11051112
[72] Onor ICO, Hill LM, Famodimu MM, Coleman MR, Huynh CH, Beyl RA, Payne CJ, Johnston EK, Okogbaa JI, Gillard CJ, Sarpong DF, Borghol A, Okpechi SC, Norbert I, Sanne SE, Guillory SG. Association of serum magnesium with blood pressure in patients with hypertensive crises: A retrospective cross-sectional study. Nutrients 2021;13:1-14. https://doi.org/10.3390/nu13124213
[73] Iqbal S, Klammer N, Ekmekcioglu C. The effect of electrolytes on blood pressure: A brief summary of meta-analyses. Nutrients 2019;11:1-18. https://doi.org/10.3390/nu11061362
[74] Davis C, Bryan J, Hodgson J, Murphy K. Definition of the Mediterranean diet: A literature review. Nutrients 2015;7:913953. https://doi.org/10.3390/nu7115459
[75] Lakka TA, Laaksonen DE. Physical activity in prevention and treatment of the metabolic syndrome. Appl Physiol Nutr Metab 2007;32:76-88. https://doi.org/10.1139/H06-113
[76] Moradi Y, Albatineh AN, Mahmoodi H, Gheshlagh RG. The relationship between depression and risk of metabolic syndrome: A meta‐analysis of observational studies. Clin Diabetes Endocrinol 2021;7:1-12. https://doi.org/10.1186/ s40842-021-00117-8
[77] Mansur RB, Brietzke E, Mclntyre RS. Is there a “metabolicmood syndrome”? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev 2015;52:89-104. https://doi.org/10.1016/j.neubiorev.2014.12.017
[78] Kastorini CM, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, Panagiotakos DB. The effect of Mediterranean diet on metabolic syndrome and its components. J Am Coll Cardiol 2011;57:1299-1313. https://doi.org/10.1016/j. jacc.2010.09.073
[79] Huo R, Du T, XuY, Xu W, Chen X, Sun K,Yu X. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2diabetes individuals: a meta-analysis. Eur J Clin Nutr 2015;69:1200-8. https://doi.org/10.1038/ejcn.2014.243
[80] Richard C, Couture P, Desroches S, Lamarche B. Effect of the Mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome. Obesity 2013;21:51-7. https://doi.org/10.1038/oby.2012.148
[81] Moosavian SP, Arab A, Paknahad Z. The effect of a Mediterranean diet on metabolic parameters in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Clin Nutr ESPEN 2020;35:40-6. https://doi.org/10.1016/j.clnesp.2019.10.008
[82] Mayneris-Perxachs J, Sala-Vila A, Chisaguano M, Castellote AI, Estruch R, Covas MI, Fito M, Salas-Salvado J, MartinezGonzalez MA, Lamuela-Raventos R, Ros E, Lopez-Sabater MC. Effects of 1-year intervention with a Mediterranean diet on plasma fatty acid composition and metabolic syndrome in a population at high cardiovascular risk. PLoS One 2014;9:1-11. https://doi.org/10.1371/journal.pone.0085202
[83] Pavić E, Hadžiabdić MO, Mucalo I, Martinis I, Romić Z, Božikov V, Rahelić D. Effect of the Mediterranean diet in combination with exercise on metabolic syndrome parameters: 1-year randomized controlled trial. Int J Vitam Nutr Res 2019;89:132-43. https://doi.org/10.1024/0300-9831/a000462
[84] Meslier V, Laiola M, Roager HM, De Flippis F, Roume H, Quinquis B, Giacco R, Mennella I, Ferracane R, Pons N, Pasolli E, Rivellese A, Dragsted LO, Vitaglione P, Ehrlich SD, Ercolini D. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut 2020;69:1258-68. https://doi.org/10.1136/ gutjnl-2019-320438
[2] Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: Pathophysiology, management and modulation by natural compounds. Ther Adv in Cardiovasc Dis 2017;11:21525. https://doi.org/10.1177/1753944717711379
[3] Collins KH, Herzog W, MacDonald GZ, Reimer RA, Rios JL, Smith IC, Zernicke RF, Hart DA. Obesity, metabolic syndrome and musculoskeletal disease: Common inflammatory pathways suggest a central role for loss of muscle integrity. Front Physiol 2018;9:1-25. https://doi.org/10.3389/fphys.2018.00112
[4] McCracken E, Monaghan M, Sreenivasan S, Edin FRCP. Pathophysiology of the metabolic syndrome. Clin Dermatol 2018;36:14-20. https://doi.org/10.1016/j.clindermatol.2017.09.004
[5] Lee SH, Tao S, Kim HS. The prevalence of metabolic syndrome and its related risk complications among Koreans. Nutrients 2019;11:1-9. https://doi.org/10.3390/nu11081755
[6] Aguilar M, Bhuket T, Torres S, Liu B, Wong RJ. Prevalence of the metabolic syndrome in the United States, 2003-2012. JAMA 2015;313:1973-4. https://doi.org/10.1001/jama.2015.4260
[7] Liang XP, Or CY, Tsoi MF, Cheung CL, Cheung BMY. Prevalence of metabolic syndrome in the United States National Health and Nutrition Examination Survey (NHANES) 2011-2018. Eur Heart J 2021;42:1-24. https://doi.org/10.1093/eurheartj/ehab724.2420
[8] Syed MA, Al Nuaimi AS, Zainel AJAL, A/Qotba HA. Prevalence of metabolic syndrome in primary health settings in Qatar: A cross sectional study. BMC Public Health 2020;20:1-7. https://doi.org/10.1186/s12889-020-08609-5
[9] Naghipour M, Joukar F, Nikbakht HA, Hassanipour S,Asgharnezhad M, Arab-Zozani M, Mansour-Ghanaei F. High prevalence of metabolic syndrome and its related demographic factors in North of Iran: Results from the PERSIAN Guilan Cohort Study. Int J Endocrinol 2021:1-9. https://doi.org/10.1155/2021/8862456
[10] Grosso G, Mistretta A, Marventano S, Purrello A, Vitaglione P, Calabrese G, Drago F, Galvano F. Beneficial effects of the Mediterranean diet on metabolic syndrome. Curr Pharm Des 2014;20:5039-44. https://doi.org/10.2174/1381612819666131 206112144
[11] Papadaki A, Nolen-Doerr E, Mantzoros CS. The effect of the Mediterranean diet on metabolic health: A systematic review and meta-analysis of controlled trials in adults. Nutrients 2020;12:1-21. https://doi.org/10.3390/nu12113342
[12] Bakaloudi DR, Chrysoula L, Kotzakioulafi E, Theodoridis X, Chourdakis M. 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 2021;13:1-25. https://doi.org/10.3390/nu13051514
[13] Müller MJ, Geisler C. Defining obesity as a disease. Eur J Clin Nutr 2017;71:1256-8. https://doi.org/10.1038/ejcn.2017.155
[14] Eberechukwu LE, Eyam ES, Nsan E. Types of obesity and its effect on blood pressure of secondary school students in rural and urban areas of Cross River State, Nigeria. IOSR J Pharm 2013;3:60-6. https://doi.org/10.9790/3013-0343060-66
[15] Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: An update. Gac Méd Méx 2017;153:197-209.
[16] Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífkovά R, Dorminiczak AF, Grassi G, Jordan J, Poulter NR, Rodgers A, Whelton PK. Hypertension. Nat Rev Dis Primers 2019;4:1-48. https://doi.org/10.1038/nrdp.2018.14
[17] Yuan Y, Chen W, Luo L, Xu C. Dyslipidemia: Causes, symptoms and treatment. IJTSRD 2021;5:1013-6. Available at: www.ijtsrd.com. (Accessed on: January 01 2022).
[18] World Health Organization-WHO (1999). Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1: Diagnosis and classification of diabetes mellitus. World Health Organization: Geneva, Switzerland; 1999. Available at: http://www.whqlibdoc. who.int/hq/1999/WHO_NCD_NCS_99.2.pdf. (Accessed on: January 01 2022).
[19] International Diabetes Federation-IDF (2006). The IDF consensus worldwide definition of the Metabolic Syndrome. Part: Worldwide definition for use in clinical practice. International Diabetes Federation: Brussels, Belgium; 2006. Available at: https://www.idf.org/component/attachments/attachments. html?id=705&task=download (Accessed on: January 01 2022).
[20] Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Jr Smith SC, Spertus JA, Costa F. Diagnosis and management of the metabolic syndrome: An American Heart Association/ National Heart, Lung and Blood Institute Scientific Statement. Circulation 2005;112:2735-52. https://doi.org/10.1161/ CIRCULATIONAHA.105.169404
[21] Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WPT, Loria CM, Smith SC. 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;120:16405. https://doi.org/10.1161/CIRCULATIONAHA.109.192644
[22] American Heart Association-AHA (2016). Symptoms and Diagnosis of Metabolic Syndrome. How Is Metabolic Syndrome Diagnosed? American Heart Association: Dallas, Texas; 2016. Available at: https://www.heart.org/en/health-topics/metabolic-syndrome/symptoms-and-diagnosis-of-metabolic-syndrome. (Accessed on: January 01 2022)
[23] Al-Qawasmeh RH, Tayyem RF. Dietary and lifestyle risk factors and metabolic syndrome: Literature review. Curr Res Nutr Food Sci 2018;6:594-608. https://doi.org/10.12944/CRNFSJ.6.3.03
[24] Drake I, Sonestedt E, Eriscon U, Wallström P, Orho-Melander M. A Western dietary pattern is prospectively associated with cardio-metabolic traits and incidence of the metabolic syndrome. Br J Nutr 2018;119:1168-76. https://doi.org/10.1017/S000711451800079X
[25] Strate LL, Keeley BR, Cao Y, Wu K, Giovannucci EL, Chan AT. Western dietary pattern increases and prudent dietary pattern decreases, risk of incident diverticulitis in a prospective cohort study. Gastroenterology 2017;152:1023-30. https://doi.org/10.1053/j.gastro.2016.12.038
[26] Statovci D, Aguilera M, MacSharry J, Melgar S. The impact of Western diet and nutrients on the microbiota and immune response at mucosal interfaces. Front Immunol 2017;8:1-21. https://doi.org/10.3389/fimmu.2017.00838
[27] Kopp W. How Western diet and lifestyle drive the pandemic of obesity and civilization diseases. Diabetes Metab Syndr Obes 2019;12:2221-36. https://doi.org/10.2147/DMSO.S216791
[28] Gallard-Alfaro L, Bibiloni MM, Mascaró CM, Montemayor S, Ruiz-Canela M, Salas-Salvadó J, Corella D, Fito M, Romaguera D, Vioque J, Alonso-Gomez AM, Warnberg J, Martinez JA, Serra-Majem L, Estruch R, Fernandez-Garcia JC, Lapetra J, Pinto X, Rios AG, Bueno-Cavanillas A, Gaforio JJ, MatiaMartin P, Daimiel L, Mico-Perez RM, Vidal J, Vazquez C, Ros E, Fernandez-Lazaro CI, Becerra-Tomas N, Gimenez-Alba IM, Zomeno MD, Konieczna J, Compan-Gabucio L, Tojal-Sierra L, Perez-Lopez J, Zulet MA, Casanas-Quintana T, Castro-Barquero S, Gomez-Perez AM, Santos-Lozano JM, Galera A, BasterraGortari FJ, Basora J, Saiz C, Perez-Vega KA, Galmes-Panades AM, Tercero-Macia C, Sorto-Sanchez C, Sayon-Orea C, GarciaGavilan J, Munoz-Martinez J, Tur JA. Leisure-time physical activity, sedentary behavior and diet quality are associated with metabolic syndrome severity: The PREDIMED-Plus study. Nutrients 2020;12:1-20. https://doi.org/10.3390/nu12041013
[29] Myers J, Kokkinos P, Nyelin E. Physical activity, cardiorespiratory fitness and the metabolic syndrome. Nutrients 2019;11:1-18. https://doi.org/10.3390/nu11071652
[30] Hwang GY, Cho YJ, Chung RH, Kim SH. The relationship between smoking level and metabolic syndrome in male health check-up examinees over 40 years of age. Korean J Fam Med 2014;35:219-26. https://doi.org/10.4082/kjfm.2014.35.5.219
[31] Vieira IMM, Santos BLP, Ruzene DS, Brάnyık T, Teixeira JA, E Silva JBDA, Silva DP. Alcohol and health: Standards of consumption, benefits and harm – A review. Czech J Food Sci 2018;36:427-40. https://doi.org/10.17221/117/2018-CJFS
[32] Grosso G, Fresάn U, Bes-Rastrollo M, Marventano S, Galvano F. Environmental impact of dietary choices: Role of the Mediterranean and other dietary patterns in an Italian cohort. Int J Environ Res Public Health 2020;17:1-13. https://doi.org/10.3390/ijerph17051468
[33] Wickman BE, Enkhmaa B, Ridberg R, Romero E, Cadeiras M, Meyers F, Steinberg F. Dietary management of heart failure: DASH diet and precision nutrition perspectives. Nutrients 2021;13:1-24. https://doi.org/10.3390/nu13124424
[34] Adamsson V, Reumark A, Cederholm T, Vessby B, Risérus U, Johansson G. What is a healthy Nordic diet? Foods and nutrients in the NORDIET study. Food Nutr Res 2012;56:1-8. https://doi.org/10.3402/fnr.v56i0.18189
[35] Ventriglio A, Sancassiani F, Contu MP, Latorre M, Di Slavatore M, Fornaro M, Bhugra D. Mediterranean diet and its benefits on health and mental health: A literature review. Clin Pract Epidemiol Ment Health 2020;16:156-64. https://doi.org/10.2174/1745017902016010156
[36] Carrera-Bastos P, Fontes-Villalba M, O’Keefe JH, Lindeberg S, Cordain L. The Western diet and lifestyle and diseases of civilization. Res Rep Clin Cardiol 2011;2:15-35. https://doi.org/10.2147/RRCC.S16919
[37] United Nations Educational, Scientific and Cultural Organization-UNESCO (2013). Culture, Intangible Heritage, Mediterranean Diet. United Nations Educational, Scientific and Cultural Organization: United Nations; 2013. Available at: https://ich.unesco.org/en/RL/mediterranean-diet-00884. (Accessed on: January 01 2022)
[38] Trichopoulou A, Martínez-Gonzάlez MA, Tong TY, Forouhi NG, Khandelwal S, Prabhakaran D, Mozaffarian D, de Lorgeril M. Definitions and potential health benefits of the Mediterranean diet: views from experts around the world. BMC Medicine 2014;12:1-16. https://doi.org/10.1186/1741-7015-12-112
[39] D’Innocenzo S, Biagi C, Lanari M. Obesity and the Mediterranean diet: A review of evidence of the role and sustainability of the Mediterranean diet. Nutrients 2019;11:125. https://doi.org/10.3390/nu11061306
[40] Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A, Dernini S, Medina FX, Battino M, Belahsen R, Miranda G, Serra-Majem L. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr 2011;14:2274-84. https://doi.org/10.1017/S1368980011002515
[41] Serra-Majem L, Tomaino L, Dernini S, Berry EM, Lairon D, de la Cruz JN, Bach-Faig A, Donini LM, Medina FX, Belahsen R, Piscopo S, Capone R, Aranceta-Bartrina J, Vecchia CL, Trichopoulou A. Updating the Mediterranean diet pyramid towards sustainability: Focus on environmental concerns. Int J Environ Res Public Health 2020;17:1-20. https://doi.org/10.3390/ijerph17238758
[42] Cyprus Modification of the Mediterranean Diet Pyramid: Adherence to the Mediterranean Diet and Consumption Frequencies of the Traditional Foods of Adults in the Island of Cyprus, Taygun Dayi, Near East University, 2021.
[43] Santos-Buelgo C, Gonzάlez-Manzano S, Gonzάlez-Paramάs AM. Wine, polyphenols and Mediterranean diets. What else is there to say? Molecules 2021;26:1-21. https://doi.org/10.3390/ molecules26185537
[44] [44] Cannataro R, Fazio A, Torre CL, Caroleo MC, Cione E. Polyphenols in the Mediterranean diet: From dietary sources to microRNA modulation. Antioxidants 2021;10:1-24. https://doi.org/10.3390/antiox10020328
[45] Giroli MG, Werba JP, Risé P, Porro B, Sala A, Amato M, Tremoli E, Bonomi A, Veglia F. Effects of Mediterranean diet or low-fat diet on blood fatty acids in patients with coronary heart disease. A randomized intervention study. Nutrients 2021;13:1-11. https://doi.org/10.3390/nu13072389
[46] Schwingshackl L, Morze J, Hoffmann G. Mediterranean diet and health status: Active ingredients and pharmacological mechanisms. Br J Pharmacol 2020;177:1241-57. https://doi.org/10.1111/bph.14778
[47] Saibandith B, Spencer JPE, Rowland IR, Commane DM. Olive polyphenols and the metabolic syndrome. Molecules 2017;22:115. https://doi.org/10.3390/molecules22071082
[48] [48] de Souza PAL, Marcadenti A, Portal VL. Effects of olive oil phenolic compounds on inflammation in the prevention and treatment of coronary artery disease. Nutrients 2017;9:1-22. https://doi.org/10.3390/nu9101087
[49] Hou CY, Tain YL, Yu HR, Huang LT. The effects of resveratrol in the treatment of metabolic syndrome. Int J Mol Sci 2019;20:1-15. https://doi.org/10.3390/ijms20030535
[50] Chaplin A, Carpéné C, Mercader J. Resveratrol, metabolic syndrome and gut microbiota. Nutrients 2018;10:1-29. https://doi.org/10.3390/nu10111651
[51] Alam MA, Subhan N, Rahman MM, Uddin SJ, Reza HM, Sarker SD. Effect of citrus flavonoids, naringin and naringenin on metabolic syndrome and their mechanisms of action. Adv Nutr 2014;5:404-17. https://doi.org/10.3945/an.113.005603
[52] Liu K, Luo M, Wei S. The bioprotective effects of polyphenols on metabolic syndrome against oxidative stress: Evidences and perspectives. Oxid Med Cell Longev 2019;2019:1-16. https://doi.org/10.1155/2019/6713194
[53] Kasprzak-Drozd K, Oniszczuk T, Stasiak M, Oniszczuk A. Beneficial effects of phenolic compounds on gut microbiota and metabolic syndrome. Int J Mol Sci 2021;22:1-24. https://doi.org/10.3390/ijms22073715
[54] Finicelli M, Squillaro T, Cristo FD, Salle AD, Melone MAB, Galderisi U, Peluso G. Metabolic syndrome, Mediterranean diet, and polyphenols: Evidence and perspectives. J Cell Physiol 2019;234:5807-26. https://doi.org/10.1002/jcp.27506
[55] Rehman K, Haider K, Jabeen K, Akash MSH. Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes. Rev Endocr Metab Disord 2020;21:63143. https://doi.org/10.1007/s11154-020-09549-6
[56] Karacor K, Cam M. Effects of oleic acid. MSD 2015;2:125-32. https://doi.org/10.17546/msd.25609
[57] Massaro M, Scoditti E, Carluccio MA, Calabriso N, Santarpino G, Verri T, De Caterina R. Effects of olive oil on blood pressure: Epidemiological, clinical and mechanistic evidence. Nutrients 2020;12:1-22. https://doi.org/10.3390/nu12061548
[58] Poudyal H, Panchal SK, Diwan V, Brown L. Omega-3 fatty acids and metabolic syndrome: Effects and emerging mechanisms of action. Prog Lipid Res 2011;50:372-87. https://doi.org/10.1016/j.plipres.2011.06.003
[59] Khalili L, Valdes-Ramos R, Harbige LS. Effect of n-3 (Omega-3) polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers and body weight in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of RCTs. Metabolites 2021;11:1-22. https://doi.org/10.3390/ metabo11110742
[60] Nevara GA, Muhammad SKS, Zawawi N, Mustapha NA, Karim R. Dietary fiber: Fractionation, characterization and potential sources from defatted oilseeds. Foods 2021;10:1-19. https://doi.org/10.3390/foods10040754
[61] Chen JP, Chen GC, Wang XP, Qin L, Bai Y. Dietary fiber and metabolic syndrome: A meta-analysis and review of related mechanisms. Nutrients 2018;10:1-17. https://doi.org/10.3390/ nu10010024
[62] Slavin JL. Dietary fiber and body weight. Nutrition 2005;21:4118. https://doi.org/10.1016/j.nut.2004.08.018
[63] Pezzali JG, Shoveller AK, Ellis J. Examining the effects of diet composition, soluble fiber and species on total fecal excretion of bile acids: A meta-analysis. Front Vet Sci 2021;8:1-14. https://doi.org/10.3389/fvets.2021.748803
[64] Khan Khattak MMA. Physiological effects of dietary complex carbohydrates and its metabolites role in certain disease. Pak J Nutr 2002;4:161-8. https://doi.org/10.3923/pjn.2002.161.168
[65] Higgins MR, Izadi A, Kaviani M. Antioxidants and exercise performance: With a focus on vitamin E and C supplementation. Int J Environ Res Public Health 2020;17:1-26. https://doi.org/10.3390/ijerph17228452
[66] Tomoeda M, Kubo C, Yoshizawa H, Yuki M, Kitamura M, Nagata S, Murakami M, Nishizawa Y, Tomita Y. Role of antioxidant vitamins administration on the oxidative stress. Cent Eur J Med 2013;8:509-16. https://doi.org/10.2478/s11536-013-0173-6
[67] Said E, Mousa S, Fawzi M, Sabry NA, Farid S. Combined effect of high-dose vitamin A, vitamin E supplementation and zinc on adult patients with diabetes: A randomized trial. J Adv Res 2021;28:27-33. https://doi.org/10.1016/j.jare.2020.06.013
[68] Pellegrino D. Antioxidants and cardiovascular risk factors. Diseases 2016;4:1-9. https://doi.org/10.3390/diseases4010011
[69] Chiu HF, Venkatakrishnan K, Golovinskaia O, Wang CK. Impact of micronutrients on hypertension: Evidence from clinical trials with a special focus on meta-analysis. Nutrients 2021;13:1-19. https://doi.org/10.3390/nu13020588
[70] Houston MC, Harper KJ. Potassium, magnesium and calcium: Their role in both the cause and treatment of hypertension. J Clin Hypertens 2008;10:3-11. https://doi.org/10.1111/j.17517176.2008.08575.x
[71] Villa-Etchegoyen C, Lombarte M, Matamoros N, Belizάn JM, Cormick G. Mechanisms involved in the relationship between low calcium intake and high blood pressure. Nutrients 2019;11:1-16. https://doi.org/10.3390/nu11051112
[72] Onor ICO, Hill LM, Famodimu MM, Coleman MR, Huynh CH, Beyl RA, Payne CJ, Johnston EK, Okogbaa JI, Gillard CJ, Sarpong DF, Borghol A, Okpechi SC, Norbert I, Sanne SE, Guillory SG. Association of serum magnesium with blood pressure in patients with hypertensive crises: A retrospective cross-sectional study. Nutrients 2021;13:1-14. https://doi.org/10.3390/nu13124213
[73] Iqbal S, Klammer N, Ekmekcioglu C. The effect of electrolytes on blood pressure: A brief summary of meta-analyses. Nutrients 2019;11:1-18. https://doi.org/10.3390/nu11061362
[74] Davis C, Bryan J, Hodgson J, Murphy K. Definition of the Mediterranean diet: A literature review. Nutrients 2015;7:913953. https://doi.org/10.3390/nu7115459
[75] Lakka TA, Laaksonen DE. Physical activity in prevention and treatment of the metabolic syndrome. Appl Physiol Nutr Metab 2007;32:76-88. https://doi.org/10.1139/H06-113
[76] Moradi Y, Albatineh AN, Mahmoodi H, Gheshlagh RG. The relationship between depression and risk of metabolic syndrome: A meta‐analysis of observational studies. Clin Diabetes Endocrinol 2021;7:1-12. https://doi.org/10.1186/ s40842-021-00117-8
[77] Mansur RB, Brietzke E, Mclntyre RS. Is there a “metabolicmood syndrome”? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev 2015;52:89-104. https://doi.org/10.1016/j.neubiorev.2014.12.017
[78] Kastorini CM, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, Panagiotakos DB. The effect of Mediterranean diet on metabolic syndrome and its components. J Am Coll Cardiol 2011;57:1299-1313. https://doi.org/10.1016/j. jacc.2010.09.073
[79] Huo R, Du T, XuY, Xu W, Chen X, Sun K,Yu X. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2diabetes individuals: a meta-analysis. Eur J Clin Nutr 2015;69:1200-8. https://doi.org/10.1038/ejcn.2014.243
[80] Richard C, Couture P, Desroches S, Lamarche B. Effect of the Mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome. Obesity 2013;21:51-7. https://doi.org/10.1038/oby.2012.148
[81] Moosavian SP, Arab A, Paknahad Z. The effect of a Mediterranean diet on metabolic parameters in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Clin Nutr ESPEN 2020;35:40-6. https://doi.org/10.1016/j.clnesp.2019.10.008
[82] Mayneris-Perxachs J, Sala-Vila A, Chisaguano M, Castellote AI, Estruch R, Covas MI, Fito M, Salas-Salvado J, MartinezGonzalez MA, Lamuela-Raventos R, Ros E, Lopez-Sabater MC. Effects of 1-year intervention with a Mediterranean diet on plasma fatty acid composition and metabolic syndrome in a population at high cardiovascular risk. PLoS One 2014;9:1-11. https://doi.org/10.1371/journal.pone.0085202
[83] Pavić E, Hadžiabdić MO, Mucalo I, Martinis I, Romić Z, Božikov V, Rahelić D. Effect of the Mediterranean diet in combination with exercise on metabolic syndrome parameters: 1-year randomized controlled trial. Int J Vitam Nutr Res 2019;89:132-43. https://doi.org/10.1024/0300-9831/a000462
[84] Meslier V, Laiola M, Roager HM, De Flippis F, Roume H, Quinquis B, Giacco R, Mennella I, Ferracane R, Pons N, Pasolli E, Rivellese A, Dragsted LO, Vitaglione P, Ehrlich SD, Ercolini D. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut 2020;69:1258-68. https://doi.org/10.1136/ gutjnl-2019-320438