Clinical Nutrition Research

The Korean Society of Clinical Nutrition (한국임상영양학회)
권호 표지
DOI QR코드

DOI QR Code

Interactions Between Genetic Risk Score and Healthy Plant Diet Index on Cardiometabolic Risk Factors Among Obese and Overweight Women

  • Fatemeh Gholami (Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS)) ;
  • Mahsa Samadi (Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS)) ;
  • Niloufar Rasaei (Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS)) ;
  • Mir Saeid Yekaninejad (Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences (TUMS)) ;
  • Seyed Ali Keshavarz (Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS)) ;
  • Gholamali Javdan (Food Health Research Center, Hormozgan University of Medical Sciences) ;
  • Farideh Shiraseb (Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS)) ;
  • Niki Bahrampour (Department of Nutrition, Science and Research Branch, Islamic Azad University (SRBIAU)) ;
  • Khadijeh Mirzaei (Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences (TUMS))
  • Received : 2023.05.09
  • Accepted : 2023.07.31
  • Published : 2023.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

People with higher genetic predisposition to obesity are more susceptible to cardiovascular diseases (CVDs) and healthy plant-based foods may be associated with reduced risks of obesity and other metabolic markers. We investigated whether healthy plant-foods-rich dietary patterns might have inverse associations with cardiometabolic risk factors in participants at genetically elevated risk of obesity. For this cross-sectional study, 377 obese and overweight women were chosen from health centers in Tehran, Iran. We calculated a healthy plant-based diet index (h-PDI) in which healthy plant foods received positive scores, and unhealthy plant and animal foods received reversed scores. A genetic risk score (GRS) was developed based on 3 polymorphisms. The interaction between GRS and h-PDI on cardiometabolic traits was analyzed using a generalized linear model (GLM). We found significant interactions between GRS and h-PDI on body mass index (BMI) (p = 0.02), body fat mass (p = 0.04), and waist circumference (p = 0.056). There were significant gene-diet interactions for healthful plant-derived diets and BMI-GRS on high-sensitivity C-reactive protein (p = 0.03), aspartate aminotransferase (p = 0.04), alanine transaminase (p = 0.05), insulin (p = 0.04), and plasminogen activator inhibitor 1 (p = 0.002). Adherence to h-PDI was more strongly related to decreased levels of the aforementioned markers among participants in the second or top tertile of GRS than those with low GRS. These results highlight that following a plant-based dietary pattern considering genetics appears to be a protective factor against the risks of cardiometabolic abnormalities.

Keywords

Acknowledgement

We would like to acknowledge the Tehran University of Medical Sciences, Tehran, Iran, for the fund.

References

  1. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, Ahmed M, Aksut B, Alam T, Alam K, Alla F, Alvis-Guzman N, Amrock S, Ansari H, Arnlov J, Asayesh H, Atey TM, Avila-Burgos L, Awasthi A, Banerjee A, Barac A, Barnighausen T, Barregard L, Bedi N, Belay Ketema E, Bennett D, Berhe G, Bhutta Z, Bitew S, Carapetis J, Carrero JJ, Malta DC, Castaneda-Orjuela CA, Castillo-Rivas J, Catala-Lopez F, Choi JY, Christensen H, Cirillo M, Cooper L Jr, Criqui M, Cundiff D, Damasceno A, Dandona L, Dandona R, Davletov K, Dharmaratne S, Dorairaj P, Dubey M, Ehrenkranz R, El Sayed Zaki M, Faraon EJA, Esteghamati A, Farid T, Farvid M, Feigin V, Ding EL, Fowkes G, Gebrehiwot T, Gillum R, Gold A, Gona P, Gupta R, Habtewold TD, Hafezi-Nejad N, Hailu T, Hailu GB, Hankey G, Hassen HY, Abate KH, Havmoeller R, Hay SI, Horino M, Hotez PJ, Jacobsen K, James S, Javanbakht M, Jeemon P, John D, Jonas J, Kalkonde Y, Karimkhani C, Kasaeian A, Khader Y, Khan A, Khang YH, Khera S, Khoja AT, Khubchandani J, Kim D, Kolte D, Kosen S, Krohn KJ, Kumar GA, Kwan GF, Lal DK, Larsson A, Linn S, Lopez A, Lotufo PA, El Razek HMA, Malekzadeh R, Mazidi M, Meier T, Meles KG, Mensah G, Meretoja A, Mezgebe H, Miller T, Mirrakhimov E, Mohammed S, Moran AE, Musa KI, Narula J, Neal B, Ngalesoni F, Nguyen G, Obermeyer CM, Owolabi M, Patton G, Pedro J, Qato D, Qorbani M, Rahimi K, Rai RK, Rawaf S, Ribeiro A, Safiri S, Salomon JA, Santos I, Santric Milicevic M, Sartorius B, Schutte A, Sepanlou S, Shaikh MA, Shin MJ, Shishehbor M, Shore H, Silva DAS, Sobngwi E, Stranges S, Swaminathan S, Tabares-Seisdedos R, Tadele Atnafu N, Tesfay F, Thakur JS, Thrift A, Topor-Madry R, Truelsen T, Tyrovolas S, Ukwaja KN, Uthman O, Vasankari T, Vlassov V, Vollset SE, Wakayo T, Watkins D, Weintraub R, Werdecker A, Westerman R, Wiysonge CS, Wolfe C, Workicho A, Xu G, Yano Y, Yip P, Yonemoto N, Younis M, Yu C, Vos T, Naghavi M, Murray C. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 2017;70:1-25.
  2. Mensah GA, Roth GA, Fuster V. The global burden of cardiovascular diseases and risk factors: 2020 and beyond. J Am Coll Cardiol 2019;74:2529-32.
  3. Cannon CP. Cardiovascular disease and modifiable cardiometabolic risk factors. Clin Cornerstone 2007;8:11-28.
  4. World Health Organization (WHO). Global status report on noncommunicable diseases. Geneva: WHO; 2014. 
  5. Sarrafzadegan N, Baghaei A, Sadri G, Kelishadi R, Malekafzali H, Boshtam M, Amani A, Rabie K, Moatarian A, Rezaeiashtiani A, Paradis G, O'Loughlin J. Isfahan healthy heart program: evaluation of comprehensive, community-based interventions for non-communicable disease prevention. Prev Control 2006;2:73-84. 
  6. Myers J, McAuley P, Lavie CJ, Despres JP, Arena R, Kokkinos P. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status. Prog Cardiovasc Dis 2015;57:306-14.
  7. Han TS, van Leer EM, Seidell JC, Lean ME. Waist circumference action levels in the identification of cardiovascular risk factors: prevalence study in a random sample. BMJ 1995;311:1401-5.
  8. McMillan DC, Sattar N, McArdle CS. ABC of obesity. Obesity and cancer. BMJ 2006;333:1109-11.
  9. Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R; Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009;373:1083-96.
  10. Heianza Y, Zhou T, Sun D, Hu FB, Manson JE, Qi L. Genetic susceptibility, plant-based dietary patterns, and risk of cardiovascular disease. Am J Clin Nutr 2020;112:220-8.
  11. Montagnese C, Santarpia L, Buonifacio M, Nardelli A, Caldara AR, Silvestri E, Contaldo F, Pasanisi F. European food-based dietary guidelines: a comparison and update. Nutrition 2015;31:908-15.
  12. Bolori P, Setaysh L, Rasaei N, Jarrahi F, Yekaninejad MS, Mirzaei K. Adherence to a healthy plant diet may reduce inflammatory factors in obese and overweight women-a cross-sectional study. Diabetes Metab Syndr 2019;13:2795-802.
  13. Satija A, Bhupathiraju SN, Rimm EB, Spiegelman D, Chiuve SE, Borgi L, Willett WC, Manson JE, Sun Q, Hu FB. Plant-based dietary patterns and incidence of type 2 diabetes in US men and women: results from three prospective cohort studies. PLoS Med 2016;13:e1002039.
  14. Satija A, Bhupathiraju SN, Spiegelman D, Chiuve SE, Manson JE, Willett W, Rexrode KM, Rimm EB, Hu FB. Healthful and unhealthful plant-based diets and the risk of coronary heart disease in US adults. J Am Coll Cardiol 2017;70:411-22.
  15. Shahinfar H, Amini MR, Payandeh N, Naghshi S, Sheikhhossein F, Djafarian K, Shab-Bidar S. The link between plant-based diet indices with biochemical markers of bone turn over, inflammation, and insulin in Iranian older adults. Food Sci Nutr 2021;9:3000-14.
  16. Yarizadeh H, Setayesh L, Majidi N, Rasaei N, Mehranfar S, Ebrahimi R, et al. Nutrient patterns and their relation to obesity and metabolic syndrome in Iranian overweight and obese adult women. Eat Weight Disord 2022;27:1327-37.
  17. Inouye M, Abraham G, Nelson CP, Wood AM, Sweeting MJ, Dudbridge F, Lai FY, Kaptoge S, Brozynska M, Wang T, Ye S, Webb TR, Rutter MK, Tzoulaki I, Patel RS, Loos RJF, Keavney B, Hemingway H, Thompson J, Watkins H, Deloukas P, Di Angelantonio E, Butterworth AS, Danesh J, Samani NJ; UK Biobank CardioMetabolic Consortium CHD Working Group. Genomic risk prediction of coronary artery disease in 480,000 adults: implications for primary prevention. J Am Coll Cardiol 2018;72:1883-93.
  18. Abraham G, Havulinna AS, Bhalala OG, Byars SG, De Livera AM, Yetukuri L, Tikkanen E, Perola M, Schunkert H, Sijbrands EJ, Palotie A, Samani NJ, Salomaa V, Ripatti S, Inouye M. Genomic prediction of coronary heart disease. Eur Heart J 2016;37:3267-78.
  19. Dudbridge F. Power and predictive accuracy of polygenic risk scores. PLoS Genet 2013;9:e1003348.
  20. Thorn H, Stenkula KG, Karlsson M, Ortegren U, Nystrom FH, Gustavsson J, Stralfors P. Cell surface orifices of caveolae and localization of caveolin to the necks of caveolae in adipocytes. Mol Biol Cell 2003;14:3967-76.
  21. Fernandez-Hernando C, Yu J, Davalos A, Prendergast J, Sessa WC. Endothelial-specific overexpression of caveolin-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol 2010;177:998-1003.
  22. Frank PG, Pavlides S, Cheung MW, Daumer K, Lisanti MP. Role of caveolin-1 in the regulation of lipoprotein metabolism. Am J Physiol Cell Physiol 2008;295:C242-8. 
  23. Pojoga LH, Underwood PC, Goodarzi MO, Williams JS, Adler GK, Jeunemaitre X, Hopkins PN, Raby BA, Lasky-Su J, Sun B, Cui J, Guo X, Taylor KD, Chen YD, Xiang A, Raffel LJ, Buchanan TA, Rotter JI, Williams GH. Variants of the caveolin-1 gene: a translational investigation linking insulin resistance and hypertension. J Clin Endocrinol Metab 2011;96:E1288-92.
  24. Abaj F, Koohdani F, Rafiee M, Alvandi E, Yekaninejad MS, Mirzaei K. Interactions between caveolin-1 (rs3807992) polymorphism and major dietary patterns on cardio-metabolic risk factors among obese and overweight women. BMC Endocr Disord 2021;21:138.
  25. Khatibi N, Mirzababaei A, Shiraseb F, Abaj F, Koohdani F, Mirzaei K. Interactions between caveolin 1 polymorphism and the Mediterranean and Mediterranean-DASH Intervention for Neurodegenerative Delay diet (MIND) diet on metabolic dyslipidemia in overweight and obese adult women: a cross-sectional study. BMC Res Notes 2021;14:364.
  26. Grant SF, Bradfield JP, Zhang H, Wang K, Kim CE, Annaiah K, Santa E, Glessner JT, Thomas K, Garris M, Frackelton EC, Otieno FG, Shaner JL, Smith RM, Imielinski M, Chiavacci RM, Li M, Berkowitz RI, Hakonarson H. Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry. Obesity (Silver Spring) 2009;17:1461-5.
  27. Sun Y, Sun J, Wu J, Yang M. Combined effects of FTO rs9939609 and MC4R rs17782313 on elevated nocturnal blood pressure in the Chinese Han population. Cardiovasc J S Afr 2016;27:21-4.
  28. Tschritter O, Haupt A, Preissl H, Ketterer C, Hennige AM, Sartorius T, Machicao F, Fritsche A, Haring HU. An obesity risk SNP (rs17782313) near the MC4R gene is associated with cerebrocortical insulin resistance in humans. J Obes 2011;2011:283153.
  29. Chambers JC, Elliott P, Zabaneh D, Zhang W, Li Y, Froguel P, Balding D, Scott J, Kooner JS. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet 2008;40:716-8.
  30. Xi B, Chandak GR, Shen Y, Wang Q, Zhou D. Association between common polymorphism near the MC4R gene and obesity risk: a systematic review and meta-analysis. PLoS One 2012;7:e45731.
  31. Zhang EE, Liu Y, Dentin R, Pongsawakul PY, Liu AC, Hirota T, Nusinow DA, Sun X, Landais S, Kodama Y, Brenner DA, Montminy M, Kay SA. Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med 2010;16:1152-6.
  32. Hatori M, Panda S. CRY links the circadian clock and CREB-mediated gluconeogenesis. Cell Res 2010;20:1285-8.
  33. Dashti HS, Smith CE, Lee YC, Parnell LD, Lai CQ, Arnett DK, Ordovas JM, Garaulet M. CRY1 circadian gene variant interacts with carbohydrate intake for insulin resistance in two independent populations: Mediterranean and North American. Chronobiol Int 2014;31:660-7.
  34. Yengo L, Sidorenko J, Kemper KE, Zheng Z, Wood AR, Weedon MN, Frayling TM, Hirschhorn J, Yang J, Visscher PM; GIANT Consortium. Meta-analysis of genome-wide association studies for height and body mass index in ~700000 individuals of European ancestry. Hum Mol Genet 2018;27:3641-9.
  35. Turcot V, Lu Y, Highland HM, et al. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat Genet 2018;50:26-41.
  36. Wang T, Heianza Y, Sun D, Huang T, Ma W, Rimm EB, Manson JE, Hu FB, Willett WC, Qi L. Improving adherence to healthy dietary patterns, genetic risk, and long term weight gain: gene-diet interaction analysis in two prospective cohort studies. BMJ 2018;360:j5644.
  37. Zheng Y, Li Y, Huang T, Cheng HL, Campos H, Qi L. Sugar-sweetened beverage intake, chromosome 9p21 variants, and risk of myocardial infarction in Hispanics. Am J Clin Nutr 2016;103:1179-84.
  38. Hindy G, Ericson U, Hamrefors V, Drake I, Wirfalt E, Melander O, Orho-Melander M. The chromosome 9p21 variant interacts with vegetable and wine intake to influence the risk of cardiovascular disease: a population based cohort study. BMC Med Genet 2014;15:1220.
  39. TANITA Corporation. Body composition analyzer BC-418: instruction manual. TANITA Corporation, Tokyo, Japan; 2015. 
  40. Aadahl M, Jorgensen T. Validation of a new self-report instrument for measuring physical activity. Med Sci Sports Exerc 2003;35:1196-202.
  41. Mirzaei K, Hossein-Nezhad A, Keshavarz SA, Eshaghi SM, Koohdani F, Saboor-Yaraghi AA, Hosseini S, Tootee A, Djalali M. Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study. Minerva Med 2014;105:63-78.
  42. Mirmiran P, Esfahani FH, Mehrabi Y, Hedayati M, Azizi F. Reliability and relative validity of an FFQ for nutrients in the Tehran lipid and glucose study. Public Health Nutr 2010;13:654-62.
  43. Ghaffarpour M, Houshiar-Rad A, Kianfar H. The manual for household measures, cooking yields factors and edible portion of food. Tehran Nashre Olume Keshavarzy 1999;7:42-58. 
  44. Miller SA, Dykes DD, Polesky HF; MWer S. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
  45. Myakishev MV, Khripin Y, Hu S, Hamer DH. High-throughput SNP genotyping by allele-specific PCR with universal energy-transfer-labeled primers. Genome Res 2001;11:163-9.
  46. Zlatohlavek L, Vrablik M, Motykova E, Ceska R, Vasickova L, Dlouha D, Hubacek JA. FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention. Clin Biochem 2013;46:313-6.
  47. Yarizadeh HM, Ghodoosi N, Pooyan S, Djafarian KC, Clark C, Mirzaei K. The interaction between the dietary inflammatory index and MC4R gene variants on cardiovascular risk factors. Clin Nutr 2021;40:488-95.
  48. Tangestani H, Emamat H, Yekaninejad MS, Keshavarz SA, Mirzaei K. Variants in circadian rhythm gene Cry1 interacts with healthy dietary pattern for serum leptin levels: a cross-sectional study. Clin Nutr Res 2021;10:48-58.
  49. Yu K, Li L, Zhang L, Guo L, Wang C. Association between MC4R rs17782313 genotype and obesity: a meta-analysis. Gene 2020;733:144372.
  50. Miranda AM, Steluti J, Norde MM, Fisberg RM, Marchioni DM. The association between genetic risk score and blood pressure is modified by coffee consumption: gene-diet interaction analysis in a population-based study. Clin Nutr 2019;38:1721-8.
  51. Ding M, Ellervik C, Huang T, Jensen MK, Curhan GC, Pasquale LR, Kang JH, Wiggs JL, Hunter DJ, Willett WC, Rimm EB, Kraft P, Chasman DI, Qi L, Hu FB, Qi Q. Diet quality and genetic association with body mass index: results from 3 observational studies. Am J Clin Nutr 2018;108:1291-300.
  52. Heianza Y, Zhou T, Sun D, Hu FB, Qi L. Healthful plant-based dietary patterns, genetic risk of obesity, and cardiovascular risk in the UK biobank study. Clin Nutr 2021;40:4694-701.
  53. Seral-Cortes M, Sabroso-Lasa S, De Miguel-Etayo P, Gonzalez-Gross M, Gesteiro E, Molina-Hidalgo C, De Henauw S, Erhardt E, Censi L, Manios Y, Karaglani E, Widhalm K, Kafatos A, Beghin L, Meirhaeghe A, Salazar-Tortosa D, Ruiz JR, Moreno LA, Esteban LM, Labayen I. Interaction effect of the Mediterranean diet and an obesity genetic risk score on adiposity and metabolic syndrome in adolescents: the HELENA study. Nutrients 2020;12:3841.
  54. Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, Qi L. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med 2012;367:1387-96.
  55. Tyrrell J, Wood AR, Ames RM, Yaghootkar H, Beaumont RN, Jones SE, Tuke MA, Ruth KS, Freathy RM, Davey Smith G, Joost S, Guessous I, Murray A, Strachan DP, Kutalik Z, Weedon MN, Frayling TM. Gene-obesogenic environment interactions in the UK Biobank study. Int J Epidemiol 2017;46:559-75.
  56. Olsen NJ, Angquist L, Larsen SC, Linneberg A, Skaaby T, Husemoen LL, Toft U, Tjonneland A, Halkjaer J, Hansen T, Pedersen O, Overvad K, Ahluwalia TS, Sorensen TI, Heitmann BL. Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference. Am J Clin Nutr 2016;104:816-26.
  57. Wang T, Huang T, Kang JH, Zheng Y, Jensen MK, Wiggs JL, Pasquale LR, Fuchs CS, Campos H, Rimm EB, Willett WC, Hu FB, Qi L. Habitual coffee consumption and genetic predisposition to obesity: gene-diet interaction analyses in three US prospective studies. BMC Med 2017;15:97.
  58. Casas-Agustench P, Arnett DK, Smith CE, Lai CQ, Parnell LD, Borecki IB, Frazier-Wood AC, Allison M, Chen YD, Taylor KD, Rich SS, Rotter JI, Lee YC, Ordovas JM. Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two US populations. J Acad Nutr Diet 2014;114:1954-66.
  59. Celis-Morales CA, Lyall DM, Gray SR, Steell L, Anderson J, Iliodromiti S, Welsh P, Guo Y, Petermann F, Mackay DF, Bailey MES, Pell JP, Gill JMR, Sattar N. Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants. Int J Obes 2017;41:1761-8.
  60. Calpe-Berdiel L, Escola-Gil JC, Blanco-Vaca F. New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis 2009;203:18-31.
  61. Park S, Yang HJ, Kim MJ, Hur HJ, Kim SH, Kim MS. Interactions between polygenic risk scores, dietary pattern, and menarche age with the obesity risk in a large hospital-based cohort. Nutrients 2021;13:3772.
  62. Kang HW, Lee SG, Otieno D, Ha K. Flavonoids, potential bioactive compounds, and non-shivering thermogenesis. Nutrients 2018;10:1168.
  63. Mele L, Bidault G, Mena P, Crozier A, Brighenti F, Vidal-Puig A, Del Rio D. Dietary (poly)phenols, brown adipose tissue activation, and energy expenditure: a narrative review. Adv Nutr 2017;8:694-704.
  64. Wang F, Zheng J, Yang B, Jiang J, Fu Y, Li D. Effects of vegetarian diets on blood lipids: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc 2015;4:e002408.
  65. Schwingshackl L, Hoffmann G, Iqbal K, Schwedhelm C, Boeing H. Food groups and intermediate disease markers: a systematic review and network meta-analysis of randomized trials. Am J Clin Nutr 2018;108:576-86.
  66. Haddad D, Al Madhoun A, Nizam R, Al-Mulla F. Role of caveolin-1 in diabetes and its complications. Oxid Med Cell Longev 2020;2020:9761539.
  67. Eichelmann F, Schwingshackl L, Fedirko V, Aleksandrova K. Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials. Obes Rev 2016;17:1067-79.
  68. Qi L, Hu FB. Dietary glycemic load, whole grains, and systemic inflammation in diabetes: the epidemiological evidence. Curr Opin Lipidol 2007;18:3-8.
  69. Schwingshackl L, Hoffmann G. Long-term effects of low glycemic index/load vs. high glycemic index/load diets on parameters of obesity and obesity-associated risks: a systematic review and meta-analysis. Nutr Metab Cardiovasc Dis 2013;23:699-706.
  70. Luscher TF. Ageing, inflammation, and oxidative stress: final common pathways of cardiovascular disease. Eur Heart J 2015;36:3381-3.
  71. Nassar AL, Marot LP, Ovidio PP, Castro GS, Jordao AA Jr. Oxidative stress and fatty acid profile in Wistar rats subjected to acute food restriction and refeeding with high-fat diets. Acta Cir Bras 2014;29:178-85.
  72. Galarregui C, Zulet MA, Cantero I, Marin-Alejandre BA, Monreal JI, Elorz M, Benito-Boillos A, Herrero JI, Tur JA, Abete I, Martinez JA. Interplay of glycemic index, glycemic load, and dietary antioxidant capacity with insulin resistance in subjects with a cardiometabolic risk profile. Int J Mol Sci 2018;19:3662.
  73. Kahleova H, Tura A, Hill M, Holubkov R, Barnard ND. A plant-based dietary intervention improves beta-cell function and insulin resistance in overweight adults: a 16-week randomized clinical trial. Nutrients 2018;10:189.
  74. McEwen BJ. The influence of diet and nutrients on platelet function. Semin Thromb Hemost 2014;40:214-26.
  75. Lyall DM, Celis-Morales C, Ward J, Iliodromiti S, Anderson JJ, Gill JMR, Smith DJ, Ntuk UE, Mackay DF, Holmes MV, Sattar N, Pell JP. Association of body mass index with cardiometabolic disease in the UK biobank: a mendelian randomization study. JAMA Cardiol 2017;2:882-9.
  76. Martinez-Gonzalez MA, Sanchez-Tainta A, Corella D, Salas-Salvado J, Ros E, Aros F, Gomez-Gracia E, Fiol M, Lamuela-Raventos RM, Schroder H, Lapetra J, Serra-Majem L, Pinto X, Ruiz-Gutierrez V, Estruch R; PREDIMED Group. A provegetarian food pattern and reduction in total mortality in the Prevencion con Dieta Mediterranea (PREDIMED) study. Am J Clin Nutr 2014;100 Suppl 1:320S-328S.
  77. Orlich MJ, Singh PN, Sabate J, Jaceldo-Siegl K, Fan J, Knutsen S, Beeson WL, Fraser GE. Vegetarian dietary patterns and mortality in Adventist Health Study 2. JAMA Intern Med 2013;173:1230-8.