Mediterranean diet, physical activity and subcutaneous advanced glycation end-products’ accumulation: a cross-sectional analysis in the ILERVAS project

Abstract

Purpose

Adherence to Mediterranean diet (MedDiet) and physical activity have been associated to lower cardiovascular risk and mortality. Our purpose was to test the modification of advanced glycation end-products (AGEs) as one of the underlying mechanisms explaining this relationship.

Methods

Cross-sectional study assessing the adherence to MedDiet (14-item Mediterranean Diet Adherence Screener) and physical activity (International Physical Activity Questionnaire short form) in 2646 middle-aged subjects without known cardiovascular disease and type 2 diabetes from the ILERVAS study. Skin autofluorescence (SAF), a non-invasive assessment of subcutaneous AGEs, was measured. Multivariable logistic regression models were done to study interactions and independent associations with a likelihood ratio test.

Results

Participants with a high adherence to MedDiet had lower SAF than those with low adherence (1.8 [IR 1.6; 2.1] vs. 2.0 [IR 1.7; 2.3] arbitrary units, p < 0.001), without differences according to categories of physical activity. There was an independent association between high adherence to MedDiet and the SAF values [OR 0.59 (0.37–0.94), p = 0.026]. When adherence to MedDiet was substituted by its individual food components, high intake of vegetables, fruits and nuts, and low intake of sugar-sweetened soft beverages were independently associated with a decreased SAF (p ≤ 0.045). No interaction between MedDiet and physical activity on SAF values was observed except for nuts consumption (p = 0.047).

Conclusions

Adherence to the MedDiet, but not physical activity, was negatively associated to SAF measurements. This association can be explained by some typical food components of the MedDiet. The present study offers a better understanding of the plausible biological conditions underlying the prevention of cardiovascular disease with MedDiet.

ClinTrials.gov identifier: NCT03228459.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. 1.

    Eckel RH, Jakicic JM, Ard JD et al (2014) 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129(25 Suppl 2):S76–99

    Article  PubMed  Google Scholar 

  2. 2.

    US Department of Health and Human Services (2008) Physical activity guidelines for americans. Washington, DC: US Department of Health and Human Services, pp 1–61. https://www.health.gov/PAGuidelines. Accessed 28 Jan 2018

  3. 3.

    Masana L, Ros E, Sudano I, Angoulvant D, Lifestyle Expert Working Group (2017) Is there a role for lifestyle changes in cardiovascular prevention? What, when and how? Atheroscler Suppl 26:2–15

    Article  PubMed  Google Scholar 

  4. 4.

    Estruch R, Ros E, Salas-Salvadó J et al (2018) Retraction and republication: primary prevention of cardiovascular disease with a Mediterranean Diet. N Engl J Med 2013 368:1279–1290 (N Engl J Med. 378: 2441–2442)

    Google Scholar 

  5. 5.

    Garcia M, Bihuniak JD, Shook J et al (2016) The effect of the traditional Mediterranean-Style Diet on metabolic risk factors: a meta-analysis. Nutrients 8:168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Salas-Salvadó J, Becerra-Tomás N, García-Gavilán JF et al (2018) Mediterranean Diet and cardiovascular disease prevention: what do we know? Prog Cardiovasc Dis 61:62–67

    Article  PubMed  Google Scholar 

  7. 7.

    Fitó M, Guxens M, Corella D et al (2007) Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med 167:1195–1203

    Article  PubMed  Google Scholar 

  8. 8.

    Mena MP, Sacanella E, Vazquez-Agell M et al (2009) Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr 89:248–256

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Fuentes F, López-Miranda J, Sánchez E et al (2001) Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men. Ann Intern Med 134:1115–1119

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Gielen S, Schuler G, Adams V (2010) Cardiovascular effects of exercise training: molecular mechanisms. Circulation 122:1221–1238

    Article  PubMed  Google Scholar 

  11. 11.

    Hambrecht R, Adams V, Erbs S et al (2003) Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 107:3152–3158

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Kuo L, Davis MJ, Chilian WM (1995) Longitudinal gradients for endothelium-dependent and-independent vascular responses in the coronary microcirculation. Circulation 92:518–525

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Laufs U, Wassmann S, Czech T et al (2005) Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis. Arterioscler Thromb Vasc Biol 25:809–814

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Willemsen S, Hartog JW, Hummel YM et al (2011) Tissue advanced glycation end products are associated with diastolic function and aerobic exercise capacity in diabetic heart failure patients. Eur J Heart Fail 13:76–82

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Kotani K, Caccavello R, Sakane N et al (2011) Influence of physical activity intervention on circulating soluble receptor for advanced glycation end products in elderly subjects. J Clin Med Res 3:252–257

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Nilsson A, Bergens O, Kadi F (2018) Physical activity alters inflammation in older adults by different intensity levels. Med Sci Sports Exerc 50:1502–1507

    Article  PubMed  Google Scholar 

  17. 17.

    Kaltsatou A, Karatzaferi C, Mitrou GI et al (2016) Intra-renal hemodynamic changes after habitual physical activity in patients with chronic kidney disease. Curr Pharm Des 22:3700–3714

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Chakravarthy U, Hayes RG, Stitt AW et al (1998) Constitutive nitric oxide synthase expression in retinal vascular endothelial cells is suppressed by high glucose and advanced glycation end products. Diabetes 47:945–952

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Barbato JE, Tzeng E (2004) Nitric oxide and arterial disease. J Vasc Surg 40:187–193

    Article  PubMed  Google Scholar 

  20. 20.

    Chaudhuri J, Bains Y, Guha S et al (2018) The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality. Cell Metab 28:337–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Hanssen NM, Wouters K, Huijberts MS et al (2014) Higher levels of advanced glycation endproducts in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype. Eur Heart J 35:1137–1146

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Couppé C, Dall CH, Svensson RB et al (2017) Skin autofluorescence is associated with arterial stiffness and insulin level in endurance runners and healthy controls—effects of aging and endurance exercise. Exp Gerontol 91:9–14

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Momma H, Niu K, Kobayashi Y et al (2011) Skin advanced glycation end product accumulation and muscle strength among adult men. Eur J Appl Physiol 111:1545–1552

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Momma H, Niu K, Kobayashi Y et al (2012) Skin advanced glycation end-product accumulation is negatively associated with calcaneal osteo-sono assessment index among non-diabetic adult Japanese men. Osteoporosis Int 23:1673–1681

    Article  CAS  Google Scholar 

  25. 25.

    Kato M, Kubo A, Sugioka Y et al (2017) Relationship between advanced glycation end-product accumulation and low skeletal muscle mass in Japanese men and women. Geriatr Gerontol Int 17:785–790

    Article  PubMed  Google Scholar 

  26. 26.

    Couppé C, Svensson RB, Grosset JF et al (2014) Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue. Age (Dordr) 36:9665

    Article  CAS  Google Scholar 

  27. 27.

    Uribarri J, Woodruff S, Goodman S et al (2010) Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc 110:911–16.e12

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Thorpe SR, Baynes JW (2003) Maillard reaction products in tissue proteins: new products and new perspectives. Amino Acids 25:275–281

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Betriu À, Farràs C, Abajo M et al (2016) Randomised intervention study to assess the prevalence of subclinical vascular disease and hidden kidney disease and its impact on morbidity and mortality: the ILERVAS project. Nefrologia 36:389–396

    Article  PubMed  Google Scholar 

  30. 30.

    Bolíbar B, Fina Avilés F, Morros R et al (2012) SIDIAP database: electronic clinical records in primary care as a source of information for epidemiologic research. Med Clin (Barc) 138:617–621

    Article  Google Scholar 

  31. 31.

    American Diabetes Association (2019) Classification and diagnosis of diabetes: standards of medical care in diabetes—2019. Diabetes Care 42:S13–S28

    Article  Google Scholar 

  32. 32.

    Schröder H, Fitó M, Estruch R et al (2011) A short screener is valid for assessing mediterranean diet adherence among older Spanish men and women. J Nutr 141:1140–1145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Estruch R, Martínez-González MA, Corella D et al (2006) Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 145:1–11

    Article  PubMed  Google Scholar 

  34. 34.

    Craig CL, Marshall AL, Sjöström M et al (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35:1381–1395

    Article  Google Scholar 

  35. 35.

    Meerwaldt R, Graaff R, Oomen PHN et al (2004) Simple non-invasive assessment of advanced glycation endproduct accumulation. Diabetologia 47:1324–1330

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Koetsier M, Lutgers HL, de Jonge C et al (2010) Reference values of skin autofluorescence. Diabetes Technol Ther 12:399–403

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Hill AB (1965) The environment and disease: association or causation? Proc R Soc Med 58:295–300

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Trichopoulou A (2004) Traditional Mediterranean diet and longevity in the elderly: a review. Public Health Nutr 7:943–947

    Article  PubMed  Google Scholar 

  39. 39.

    Lopez-Moreno J, Quintana-Navarro GM, Delgado-Lista J et al (2016) Mediterranean diet reduces serum advanced glycation end products and increases antioxidant defences in elderly adults: a randomized controlled trial. J Am Geriatr Soc 64:901–904

    Article  PubMed  Google Scholar 

  40. 40.

    Rodríguez JM, Leiva Balich L, Concha MJ et al (2015) Reduction of serum advanced glycation end-products with a low calorie Mediterranean diet. Nutr Hosp 31:2511–2517

    PubMed  Google Scholar 

  41. 41.

    Kellow NJ, Coughlan MT, Reid CM (2018) Association between habitual dietary and lifestyle behaviours and skin autofluorescence (SAF), a marker of tissue accumulation of advanced glycation endproducts (AGEs), in healthy adults. Eur J Nutr 57:2209–2216

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Chow CK, Jolly S, Rao-Melacini P et al (2010) Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation 121:750–758

    Article  PubMed  Google Scholar 

  43. 43.

    Alvarez-Alvarez I, de Rojas JP, Fernandez-Montero A et al (2018) Strong inverse associations of Mediterranean diet, physical activity and their combination with cardiovascular disease: the Seguimiento Universidad de Navarra (SUN) cohort. Eur J Prev Cardiol 25:1186–1197

    Article  PubMed  Google Scholar 

  44. 44.

    Pereira MA (2014) Sugar-sweetened and artificially-sweetened beverages in relation to obesity risk. Adv Nutr 5:797–808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Imamura F, O'Connor L, Ye Z et al (2015) Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ 351:h3576

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Narain A, Kwok CS, Mamas MA (2017) Soft drink intake and the risk of metabolic syndrome: a systematic review and meta-analysis. Int J Clin Pract. https://doi.org/10.1111/ijcp.12927

    Article  PubMed  Google Scholar 

  47. 47.

    Cheungpasitporn W, Thongprayoon C, Edmonds PJ et al (2015) Sugar and artificially sweetened soda consumption linked to hypertension: a systematic review and meta-analysis. Clin Exp Hypertens 37:587–593

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Cheungpasitporn W, Thongprayoon C, O'Corragain OA et al (2014) Associations of sugar-sweetened and artificially sweetened soda with chronic kidney disease: a systematic review and meta-analysis. Nephrology (Carlton) 19:791–797

    Article  CAS  Google Scholar 

  49. 49.

    Siqueira JM, Mill JG, Velasquez-Melendez G et al (2018) Sugar-sweetened soft drinks and fructose consumption are associated with hyperuricemia: cross-sectional analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Nutrients 10:E981

    Article  CAS  PubMed  Google Scholar 

  50. 50.

    Trichopoulou A, Martínez-González MA, Tong TY et al (2014) Definitions and potential health benefits of the Mediterranean diet: views from experts around the world. BMC Med 12:112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Trichopoulou A, Bamia C, Trichopoulous D (2009) Anatomy of health effects of Mediterranean diet Greek EPIC prospective cohort study. BMJ 338:b2337

    Article  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Hernandez-Hernandez A, Gea A, Ruiz-Canela M et al (2015) Mediterranean alcohol-drinking pattern and the incidence of cardiovascular disease and cardiovascular mortality: the SUN project. Nutrients 7:9116–9126

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Gea A, Bes-Rastrollo M, Toledo E et al (2014) Mediterranean alcohol-drinking pattern and mortality in the SUN (Seguimiento Universidad de Navarra) Project: a prospective cohort study. Br J Nutr 111:1871–1880

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Del Turco S, Basta G (2016) Can dietary polyphenols prevent the formation of toxic compounds from Maillard reaction? Curr Drug Metab 17:598–607

    Article  CAS  PubMed  Google Scholar 

  55. 55.

    Haseeb S, Alexander B, Baranchuk A (2017) Wine and cardiovascular health: a comprehensive review. Circulation 136:1434–1448

    Article  CAS  PubMed  Google Scholar 

  56. 56.

    Pavlidou E, Mantzorou M, Fasoulas A et al (2018) Wine: an aspiring agent in promoting longevity and preventing chronic diseases. Diseases 6:E73

    Article  CAS  PubMed  Google Scholar 

  57. 57.

    Snopek L, Mlcek J, Sochorova L et al (2018) Contribution of red wine consumption to human health protection. Molecules 23:E1684

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Hansen AL, Carstensen B, Helge JW et al (2013) Combined heart rate- and accelerometer-assessed physical activity energy expenditure and associations with glucose homeostasis markers in a population at high risk of developing diabetes: the ADDITION-PRO study. Diabetes Care 36:3062–3069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Taber DR, Stevens J, Murray DM et al (2009) The effect of a physical activity intervention on bias in self-reported activity. Ann Epidemiol 19:316–322

    Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Drenth H, Zuidema SU, Krijnen WP et al (2018) Advanced glycation end-products are associated with physical activity and physical functioning in the older population. J Gerontol A Biol Sci Med Sci. 73:1545–1551

    Article  CAS  PubMed  Google Scholar 

  61. 61.

    Mori H, Kuroda A, Araki M et al (2017) Advanced glycation end-products are a risk for muscle weakness in Japanese patients with type 1 diabetes. J Diabetes Investig 8:377–382

    Article  CAS  PubMed  Google Scholar 

  62. 62.

    Duda-Sobczak A, Falkowski B, Araszkiewicz A, Zozulinska-Ziolkiewicz D (2018) Association between self-reported physical activity and skin autofluorescence, a marker of tissue accumulation of advanced glycation end products in adults with type 1 diabetes: a cross-sectional study. Clin Ther 40:872–880

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by Grants from the Diputació de Lleida, Generalitat de Catalunya (2017SGR696 and SLT0021600250) and Instituto de Salud Carlos III (Action Plan II14//00008). CIBER de Diabetes y Enfermedades Metabólicas Asociadas and CIBER de Enfermedades Respiratorias are initiatives of the Instituto de Salud Carlos III. The authors would also like to thank Fundació Renal Jaume Arnó, all Nurses of the Bus of health and the Primary Care Lleida Units for recruiting subjects and their efforts in the accurate development of the ILERVAS project.

Author information

Affiliations

Authors

Consortia

Contributions

ÀB, RP, FB, FP, CF, EF, and AL designed the research; ES CL-C and CM: conducted the research; ES and JS-S analysed data; ES, ÀB and AL wrote the paper; AL had primary responsibility for final content. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Albert Lecube.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The protocol was approved by the Arnau de Vilanova University Hospital ethics committee (CEIC-1410). Additionally, the study was conducted according to the ethical guidelines of the Helsinki Declaration and Spanish legislation regarding the protection of personal information was also followed.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

The members of the ILERVAS project investigators are listed in Supplementary Material.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (TIFF 45355 kb)

Supplementary file2 (DOCX 12 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sánchez, E., Betriu, À., Salas-Salvadó, J. et al. Mediterranean diet, physical activity and subcutaneous advanced glycation end-products’ accumulation: a cross-sectional analysis in the ILERVAS project. Eur J Nutr 59, 1233–1242 (2020). https://doi.org/10.1007/s00394-019-01983-w

Download citation

Keywords

  • Advanced glycation end-products
  • Mediterranean diet
  • Physical activity
  • Questionnaire
  • Skin autofluorescence