Skip to main content

Effects of Mediterranean Diet on the Metabolome

  • Chapter
  • First Online:
Mediterranean Diet

Abstract

The metabolome has been defined as the sum of all low molecular weight metabolites or chemicals present in a cell, organ, tissue, biological fluid, or organism. Metabolic profiling (metabolomics/metabonomics) experiments are typically conducted using nuclear magnetic resonance (NMR) or mass spectrometry (MS) coupled to either liquid chromatography (LC) or gas chromatography (GC).

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lindon JC, Holmes E, Nicholson JK. Metabonomics in pharmaceutical R&D. FEBS J. 2007;274(5):1140–51.

    Article  PubMed  CAS  Google Scholar 

  2. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Azia F, Dong E, et al. HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res. 2013;41(Database issue):D801–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB. Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 2004;22(5):245–52.

    Article  PubMed  CAS  Google Scholar 

  4. Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29(11):1181–9.

    Article  PubMed  CAS  Google Scholar 

  5. Fiehn O. Metabolomics—the link between genotypes and phenotypes. Plant Mol Biol. 2002;48(1-2):155–71.

    Article  PubMed  CAS  Google Scholar 

  6. Nicholson JK, Lindon JC. Systems biology: metabonomics. Nature. 2008;455(7216):1054–6.

    Article  PubMed  CAS  Google Scholar 

  7. Holmes E, Wilson ID, Nicholson JK. Metabolic phenotyping in health and disease. Cell. 2008;134(5):714–7.

    Article  PubMed  CAS  Google Scholar 

  8. Cloarec O, Dumas ME, Tryg J, Craig A, Barton RH, Lindon JC, Nicholson JK, Holmes E. Evaluation of the orthogonal projection on latent structure model limitations caused by chemical shift variability and improved visualization of biomarker changes in 1H NMR spectroscopic metabonomic studies. Anal Chem. 2005;77(2):517–26.

    Article  PubMed  CAS  Google Scholar 

  9. Cloarec O, Dumas ME, Craig A, Barton RH, Trygg J, Hudson J, Blancher C, Gauguier D, Lindon JC, Holmes E, et al. Statistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets. Anal Chem. 2005;77(5):1282–9.

    Article  PubMed  CAS  Google Scholar 

  10. Astarita G, Langridge J. An emerging role for metabolomics in nutrition science. J Nutrigenet Nutrigenomics. 2013;6(4):179–98.

    Google Scholar 

  11. Fave G, Beckmann ME, Draper JH, Mathers JC. Measurement of dietary exposure: a challenging problem which may be overcome thanks to metabolomics? Genes Nutr. 2009;4(2):135–41.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Scalbert A, Brennan L, Fiehn O, Hankemeier T, Kristal BS, van Ommen B, Pujos-Guillot E, Verheij E, Wishart D, Wopereis S. Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research. Metabolomics. 2009;5(4):435–58.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  13. Wild CP, Scalbert A, Herceg Z. Measuring the exposome: a powerful basis for evaluating environmental exposures and cancer risk. Environ Mol Mutagen. 2013;54(7):480–99.

    Article  PubMed  CAS  Google Scholar 

  14. Martin FP, Montoli I, Kochhar S, Rezzi S. Chemometric strategy for modeling metabolic biological space along the gastrointestinal tract and assessing microbial influences. Anal Chem. 2010;82(23):9803–11.

    Article  PubMed  CAS  Google Scholar 

  15. Llorach R, Garcia-Aloy M, Tulipani S, Vazquez-Fresn R, Andres-Lacueva C. Nutrimetabolomic strategies to develop new biomarkers of intake and health effects. J Agric Food Chem. 2012;60(36):8797–808.

    Article  PubMed  CAS  Google Scholar 

  16. Santosh C, Brennan D, McCabe C, Macrae IM, Holmes WM, Graham DI, Gallaghe L, Condon B, Hadley DM, Muir KW, et al. Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra. J Cereb Blood Flow Metab. 2008;28(10):1742–53.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Yap IK, Brown IJ, Chan Q, Wijeyesekera A, Garcia-Perez I, Bictash M, Loo RL, Chadeau-Hyam M, Ebbels T, De Iorio M, et al. Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study. J Proteome Res. 2010;9(12):6647–54.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Stamler J, Brown IJ, Yap IK, Chan Q, Wijeyesekera A, Garcia-Perez I, Chadeau-Hyam M, Ebbels TM, De Iorio M, Posma J, et al. Dietary and urinary metabonomic factors possibly accounting for higher blood pressure of black compared with white Americans: results of International Collaborative Study on macro-/micronutrients and blood pressure. Hypertension. 2013;62(6):1074–80.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Riboli E, Kaaks R. The EPIC Project: rationale and study design. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol. 1997;26 Suppl 1:S6–14.

    Article  PubMed  Google Scholar 

  20. Chadeau-Hyam M, Athersuch TJ, Keun HC, De Iorio M, Ebbels TM, Jenab M, Sacerdote C, Bruce SJ, Holmes E, Vineis P. Meeting-in-the-middle using metabolic profiling—a strategy for the identification of intermediate biomarkers in cohort studies. Biomarkers. 2011;16(1):83–8.

    Article  PubMed  CAS  Google Scholar 

  21. Murphy N, Norat T, Ferrari P, Jenab M, Bueno-de-Mesquita B, Skeie G, Dahm CC, Overvad K, Olsen A, Tjonneland A, et al. Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC). PLoS One. 2012;7(6), e39361.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Saadatian-Elahi M, Slimani N, Chajes V, Jenab M, Goudable J, Biessy C, Ferrari P, Byrnes G, Autier P, Peeters PH, et al. Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr. 2009;89(1):331–46.

    Article  PubMed  CAS  Google Scholar 

  23. Altmaier E, Kastenmuller G, Romisch-Margl W, Thorand B, Weinberger KM, Illig T, Adamski J, Doring A, Suhre K. Questionnaire-based self-reported nutrition habits associate with serum metabolism as revealed by quantitative targeted metabolomics. Eur J Epidemiol. 2011;26(2):145–56.

    Article  PubMed  Google Scholar 

  24. Santoro A, Pini E, Scurti M, Palmas G, Berendsen A, Brzozowska A, Pietruszka B, Szczecinska A, Cano N, Meunier N, et al. Combating inflammaging through a Mediterranean whole diet approach: The NU-AGE project’s conceptual framework and design. Mech Ageing Dev. 2014;136–137:3–13.

    Article  PubMed  Google Scholar 

  25. Dais P, Hatzakis E. Quality assessment and authentication of virgin olive oil by NMR spectroscopy: a critical review. Anal Chim Acta. 2013;765:1–27.

    Article  PubMed  CAS  Google Scholar 

  26. D’Imperio M, Mannina L, Capitani D, Bidet O, Enrico R, Bucarelli FM, Quaglia GB, Annalaura S. NMR and statistical study of olive oils from Lazio: A geographical, ecological and agronomic characterization. Food Chem. 2007;105:1256–67.

    Article  CAS  Google Scholar 

  27. Martin-Pelaez S, Covas MI, Fito M, Kusar A, Pravst I. Health effects of olive oil polyphenols: recent advances and possibilities for the use of health claims. Mol Nutr Food Res. 2013;57(5):760–71.

    Article  PubMed  CAS  Google Scholar 

  28. Razquin C, Martinez JA, Martinez-Gonzalez MA, Fernandez-Crehuet J, Santos JM, Marti A. A Mediterranean diet rich in virgin olive oil may reverse the effects of the -174G/C IL6 gene variant on 3-year body weight change. Mol Nutr Food Res. 2010;54 Suppl 1:S75–82.

    Article  PubMed  CAS  Google Scholar 

  29. Razquin C, Martinez JA, Martinez-Gonzalez MA, Bes-Rastrollo M, Fernandez-Crehuet J, Marti A. A 3-year intervention with a Mediterranean diet modified the association between the rs9939609 gene variant in FTO and body weight changes. Int J Obes. 2010;34(2):266–72.

    Article  CAS  Google Scholar 

  30. Razquin C, Martine JA, Martinez-Gonzalez MA, Salas-Salvado J, Estruch R, Marti A. A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change. Eur J Nutr. 2010;49(5):311–9.

    Article  PubMed  CAS  Google Scholar 

  31. Waterman E, Lockwood B. Active components and clinical applications of olive oil. Altern Med Rev. 2007;12(4):331–42.

    PubMed  Google Scholar 

  32. Garcia-Villalba R, Carrasco-Pancorbo A, Nevedomskaya E, Mayboroda OA, Deelder AM, Segura-Carretero A, Fernandez-Gutierrez A. Exploratory analysis of human urine by LC-ESI-TOF MS after high intake of olive oil: understanding the metabolism of polyphenols. Anal Bioanal Chem. 2010;398(1):463–75.

    Article  PubMed  CAS  Google Scholar 

  33. Lemonakis N, Gikas E, Halabalaki M, Skaltsounis AL. Development and validation of a combined methodology for assessing the total quality control of herbal medicinal products—application to oleuropein preparations. PLoS One. 2013;8(10), e78277.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  34. Fernandez-Arroyo S, Gomez-Martinez A, Rocamora-Reverte L, Quirantes-Pine R, Segura-Carretero A, Fernandez-Gutierrez A, Ferragut JA. Application of nanoLC-ESI-TOF-MS for the metabolomic analysis of phenolic compounds from extra-virgin olive oil in treated colon-cancer cells. J Pharm Biomed Anal. 2012;63:128–34.

    Article  PubMed  CAS  Google Scholar 

  35. Corona G, Tzounis X, Assunta Dessi M, Deiana M, Debnam ES, Visioli F, Spencer JP. The fate of olive oil polyphenols in the gastrointestinal tract: implications of gastric and colonic microflora-dependent biotransformation. Free Radic Res. 2006;40(6):647–58.

    Article  PubMed  CAS  Google Scholar 

  36. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009;106(10):3698–703.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Stradling C, Hamid M, Fisher K, Taheri S, Thomas GN. A review of dietary influences on cardiovascular health: part 1: the role of dietary nutrients. Cardiovasc Hematol Disord Drug Targets. 2013;13(3):208–30.

    Article  PubMed  CAS  Google Scholar 

  38. Arnold C, Konkel A, Fischer R, Schunck WH. Cytochrome P450-dependent metabolism of omega-6 and omega-3 long-chain polyunsaturated fatty acids. Pharmacol Rep. 2010;62(3):536–47.

    Article  PubMed  CAS  Google Scholar 

  39. Chapkin RS, Seo J, McMurray DN, Lupton JR. Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine. Chem Phys Lipids. 2008;153(1):14–23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Mannina L, Sobolev AP, Capitani D. Applications of NMR metabolomics to the study of foodstuffs: truffle, kiwifruit, lettuce, and sea bass. Electrophoresis. 2012;33(15):2290–313.

    Article  PubMed  CAS  Google Scholar 

  41. Mannina L, Sobolev AP, Capitani D, Iaffaldano N, Rosato MP, Ragni P, Reale A, Sorrentino E, D’Amico I, Coppola R. NMR metabolic profiling of organic and aqueous sea bass extracts: implications in the discrimination of wild and cultured sea bass. Talanta. 2008;77(1):433–44.

    Article  PubMed  CAS  Google Scholar 

  42. Lloyd AJ, Fave G, Beckmann M, Lin W, Tailliart K, Xie L, Mathers JC, Draper J. Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods. Am J Clin Nutr. 2011;94(4):981–91.

    Article  PubMed  CAS  Google Scholar 

  43. al-Waiz M, Mikov M, Mitchell SC, Smith RL. The exogenous origin of trimethylamine in the mouse. Metab Clin Exp. 1992;41(2):135–6.

    Article  PubMed  CAS  Google Scholar 

  44. Nakanishi M, Rosenberg DW. Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol. 2013;35(2):123–37.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Zhao Y, Agarwal VR, Mendelson CR, Simpson ER. Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology. 1996;137(12):5739–42.

    PubMed  CAS  Google Scholar 

  46. Brudvik KW, Tasken K. Modulation of T cell immune functions by the prostaglandin E(2)—cAMP pathway in chronic inflammatory states. Br J Pharmacol. 2012;166(2):411–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Kawabata A. Prostaglandin E2 and pain—an update. Biol Pharm Bull. 2011;34(8):1170–3.

    Article  PubMed  CAS  Google Scholar 

  48. Ding XZ, Hennig R, Adrian TE. Lipoxygenase and cyclooxygenase metabolism: new insights in treatment and chemoprevention of pancreatic cancer. Mol Cancer. 2003;2:10.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Matsuyama M, Yoshimura R. The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer. Biologics. 2008;2(4):725–32.

    PubMed Central  PubMed  CAS  Google Scholar 

  50. Yang J, Schmelzer K, Georgi K, Hammock BD. Quantitative profiling method for oxylipin metabolome by liquid chromatography electrospray ionization tandem mass spectrometry. Anal Chem. 2009;81(19):8085–93.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  51. Schuchardt JP, Schmidt S, Kressel G, Willenberg I, Hammock BD, Hahn A, Schebb NH. Modulation of blood oxylipin levels by long-chain omega-3 fatty acid supplementation in hyper- and normolipidemic men. Prostaglandins Leukot Essent Fat Acids. 2014;90(2–3):27–37.

    Article  CAS  Google Scholar 

  52. West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut. 2010;59(7):918–25.

    Article  PubMed  CAS  Google Scholar 

  53. Hull MA, Sandell AC, Montgomery AA, Logan RF, Clifford GM, Rees CJ, Loadman PM, Whitham D. A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial. Trials. 2013;14(1):237.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  54. Dragsted LO. Biomarkers of meat intake and the application of nutrigenomics. Meat Sci. 2010;84(2):301–7.

    Article  PubMed  CAS  Google Scholar 

  55. Stella C, Beckwith-Hall B, Cloarec O, Holmes E, Lindon JC, Powell J, van der Ouderaa F, Bingham S, Cross AJ, Nicholson JK. Susceptibility of human metabolic phenotypes to dietary modulation. J Proteome Res. 2006;5(10):2780–8.

    Article  PubMed  CAS  Google Scholar 

  56. Xu J, Yang S, Cai S, Dong J, Li X, Chen Z. Identification of biochemical changes in lactovegetarian urine using 1H NMR spectroscopy and pattern recognition. Anal Bioanal Chem. 2010;396(4):1451–63.

    Article  PubMed  CAS  Google Scholar 

  57. O’Sullivan A, Gibney MJ, Brennan L. Dietary intake patterns are reflected in metabolomic profiles: potential role in dietary assessment studies. Am J Clin Nutr. 2011;93(2):314–21.

    Article  PubMed  CAS  Google Scholar 

  58. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Heinzmann SS, Merrifield CA, Rezzi S, Kochhar S, Lindon JC, Holmes E, Nicholson JK. Stability and robustness of human metabolic phenotypes in response to sequential food challenges. J Proteome Res. 2012;11(2):643–55.

    Article  PubMed  CAS  Google Scholar 

  60. Grosso G, Buscemi S, Galvano F, Mistretta A, Marventano S, Vela V, Drago F, Gangi S, Basile F, Biondi A. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC Surg. 2013;13 Suppl 2:S14.

    Article  PubMed Central  PubMed  Google Scholar 

  61. Cho SS, Qi L, Fahey Jr GC, Klurfeld DM. Consumption of cereal fiber, mixtures of whole grains and bran, and whole grains and risk reduction in type 2 diabetes, obesity, and cardiovascular disease. Am J Clin Nutr. 2013;98(2):594–619.

    Article  PubMed  CAS  Google Scholar 

  62. Martinez-Gonzalez MA, Fernandez-Jarne E, Martinez-Losa E, Prado-Santamaria M, Brugarolas-Brufau C, Serrano-Martinez M. Role of fibre and fruit in the Mediterranean diet to protect against myocardial infarction: a case-control study in Spain. Eur J Clin Nutr. 2002;56(8):715–22.

    Article  PubMed  CAS  Google Scholar 

  63. Bertram HC, Bach Knudsen KE, Serena A, Malmendal A, Nielsen NC, Frette XC, Andersen HJ. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high-fibre rye bread. Br J Nutr. 2006;95(5):955–62.

    Article  PubMed  CAS  Google Scholar 

  64. Rasmussen LG, Winning H, Savorani F, Ritz C, Engelsen SB, Astrup A, Larsen TM, Dragsted LO. Assessment of dietary exposure related to dietary GI and fibre intake in a nutritional metabolomic study of human urine. Genes Nutr. 2012;7(2):281–93.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  65. Boeing H, Bechthold A, Bub A, Ellinger S, Haller D, Kroke A, Leschik-Bonnet E, Muller MJ, Oberritter H, Schulze M, et al. Critical review: vegetables and fruit in the prevention of chronic diseases. Eur J Nutr. 2012;51(6):637–63.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Manach C, Hubert J, Llorach R, Scalbert A. The complex links between dietary phytochemicals and human health deciphered by metabolomics. Mol Nutr Food Res. 2009;53(10):1303–15.

    Article  PubMed  CAS  Google Scholar 

  67. van Duynhoven J, Vaughan EE, Jacobs DM, Kemperman RA, van Velzen EJ, Gross G, Roger LC, Possemiers S, Smilde AK, Dore J, et al. Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci U S A. 2011;108 Suppl 1:4531–8.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Grun CH, van Dorsten FA, Jacobs DM, Le Belleguic M, van Velzen EJ, Bingham MO, Janssen HG, van Duynhoven JP. GC-MS methods for metabolic profiling of microbial fermentation products of dietary polyphenols in human and in vitro intervention studies. J Chromatogr B Anal Technol Biomed Life Sci. 2008;871(2):212–9.

    Article  CAS  Google Scholar 

  69. Walsh MC, Brennan L, Pujos-Guillot E, Sebedio JL, Scalbert A, Fagan A, Higgins DG, Gibney MJ. Influence of acute phytochemical intake on human urinary metabolomic profiles. Am J Clin Nutr. 2007;86(6):1687–93.

    PubMed  CAS  Google Scholar 

  70. Nile SH, Park SW. Edible berries: bioactive components and their effect on human health. Nutrition. 2014;30(2):134–44.

    Article  PubMed  CAS  Google Scholar 

  71. Sun J, Xiao Z, Lin LZ, Lester GE, Wang Q, Harnly JM, Chen P. Profiling polyphenols in five Brassica species microgreens by UHPLC-PDA-ESI/HRMS(n.). J Agric Food Chem. 2013;61(46):10960–70.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  72. Heinzmann SS, Brown IJ, Chan Q, Bictash M, Dumas ME, Kochhar S, Stamler J, Holmes E, Elliott P, Nicholson JK. Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. Am J Clin Nutr. 2010;92(2):436–43.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  73. Lloyd AJ, Beckmann M, Fave G, Mathers JC, Draper J. Proline betaine and its biotransformation products in fasting urine samples are potential biomarkers of habitual citrus fruit consumption. Br J Nutr. 2011;106(6):812–24.

    Article  PubMed  CAS  Google Scholar 

  74. Atkinson W, Downer P, Lever M, Chambers ST, George PM. Effects of orange juice and proline betaine on glycine betaine and homocysteine in healthy male subjects. Eur J Nutr. 2007;46(8):446–52.

    Article  PubMed  CAS  Google Scholar 

  75. Miller JA, Thompson PA, Hakim IA, Chow H-HS, Thomson CA. D-limonene: a bioactive food component in the Mediterranean diet and evidence for a potential role in breast cancer prevention. Oncol Rev. 2011;5:31–42.

    Article  Google Scholar 

  76. Miller JA, Lang JE, Ley M, Nagle R, Hsu CH, Thompson PA, Cordova C, Waer A, Chow HH. Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer. Cancer Prev Res. 2013;6(6):577–84.

    Article  CAS  Google Scholar 

  77. Miller JA, Pappan K, Wulff J, Want EJ, Siskos AP, Keun HC, Hu C, Thompson PA, Lang JE, Chow HHS. Analysis of changes in the plasma metabolomic profiles of breast cancer patients after short-term limonene intervention. Cancer Prev Res. 2015;8(1):86–93.

    Google Scholar 

  78. Bouchenak M, Lamri-Senhadji M. Nutritional quality of legumes, and their role in cardiometabolic risk prevention: a review. J Med Food. 2013;16(3):185–98.

    Article  PubMed  CAS  Google Scholar 

  79. Nagaraju GP, Zafar SF, El-Rayes BF. Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases. Nutr Rev. 2013;71(8):562–72.

    Article  PubMed  Google Scholar 

  80. Cassidy A. Potential risks and benefits of phytoestrogen-rich diets. Int J Vitam Nutr Res. 2003;73(2):120–6.

    Article  PubMed  Google Scholar 

  81. Solanky KS, Bailey NJ, Beckwith-Hall BM, Davis A, Bingham S, Holmes E, Nicholson JK, Cassidy A. Application of biofluid 1H nuclear magnetic resonance-based metabonomic techniques for the analysis of the biochemical effects of dietary isoflavones on human plasma profile. Anal Biochem. 2003;323(2):197–204.

    Article  PubMed  CAS  Google Scholar 

  82. Solanky KS, Bailey NJ, Beckwith-Hall BM, Bingham S, Davis A, Holmes E, Nicholson JK, Cassidy A. Biofluid 1H NMR-based metabonomic techniques in nutrition research—metabolic effects of dietary isoflavones in humans. J Nutr Biochem. 2005;16(4):236–44.

    Article  PubMed  CAS  Google Scholar 

  83. Goodman MT, Shvetsov YB, Wilkens LR, Franke AA, Le Marchand L, Kakazu KK, Nomura AM, Henderson BE, Kolonel LN. Urinary phytoestrogen excretion and postmenopausal breast cancer risk: the multiethnic cohort study. Cancer Prev Res (Phila). 2009;2(10):887–94.

    Article  Google Scholar 

  84. Chiva-Blanch G, Arranz S, Lamuela-Raventos RM, Estruch R. Effects of wine, alcohol and polyphenols on cardiovascular disease risk factors: evidences from human studies. Alcohol Alcohol. 2013;48(3):270–7.

    Article  PubMed  CAS  Google Scholar 

  85. van Dorsten FA, Grun CH, van Velzen EJ, Jacobs DM, Draijer R, van Duynhoven JP. The metabolic fate of red wine and grape juice polyphenols in humans assessed by metabolomics. Mol Nutr Food Res. 2010;54(7):897–908.

    Article  PubMed  CAS  Google Scholar 

  86. Jacobs DM, Deltimple N, van Velzen E, van Dorsten FA, Bingham M, Vaughan EE, van Duynhoven J. (1)H NMR metabolite profiling of feces as a tool to assess the impact of nutrition on the human microbiome. NMR Biomed. 2008;21(6):615–26.

    Article  PubMed  CAS  Google Scholar 

  87. Vazquez-Fresno R, Llorach R, Alcaro F, Rodriguez MA, Vinaixa M, Chiva-Blanch G, Estruch R, Correig X, Andres-Lacueva C. (1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors. Electrophoresis. 2012;33(15):2345–54.

    Article  PubMed  CAS  Google Scholar 

  88. Boto-Ordonez M, Urpi-Sarda M, Queipo-Ortuno MI, Corella D, Tinahones FJ, Estruch R, Andres-Lacueva C. Microbial metabolomic fingerprinting in urine after regular dealcoholized red wine consumption in humans. J Agric Food Chem. 2013;61(38):9166–75.

    Article  PubMed  CAS  Google Scholar 

  89. Brown L, Kroon PA, Das DK, Das S, Tosaki A, Chan V, Singer MV, Feick P. The biological responses to resveratrol and other polyphenols from alcoholic beverages. Alcohol Clin Exp Res. 2009;33(9):1513–23.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: a molecule whose time has come? And gone? Clin Biochem. 1997;30(2):91–113.

    Article  PubMed  CAS  Google Scholar 

  91. Kopp P. Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the ‘French paradox’? Eur J Endocrinol. 1998;138(6):619–20.

    Article  PubMed  CAS  Google Scholar 

  92. Catalgol B, Batirel S, Taga Y, Ozer NK. Resveratrol: French paradox revisited. Front Pharmacol. 2012;3:141.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Szekeres T, Fritzer-Szekeres M, Saiko P, Jager W. Resveratrol and resveratrol analogues—structure-activity relationship. Pharm Res. 2010;27(6):1042–8.

    Article  PubMed  CAS  Google Scholar 

  94. Kroon PA, Iyer A, Chunduri P, Chan V, Brown L. The cardiovascular nutrapharmacology of resveratrol: pharmacokinetics, molecular mechanisms and therapeutic potential. Curr Med Chem. 2010;17(23):2442–55.

    Article  PubMed  CAS  Google Scholar 

  95. Zamora-Ros R, Urpi-Sarda M, Lamuela-Raventos RM, Estruch R, Martinez-Gonzalez MA, Bullo M, Aros F, Cherubini A, Andres-Lacueva C. Resveratrol metabolites in urine as a biomarker of wine intake in free-living subjects: The PREDIMED Study. Free Radic Biol Med. 2009;46(12):1562–6.

    Article  PubMed  CAS  Google Scholar 

  96. Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res. 2001;61(20):7456–63.

    PubMed  CAS  Google Scholar 

  97. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275(5297):218–20.

    Article  PubMed  CAS  Google Scholar 

  98. Jang M, Pezzuto JM. Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin. Cancer Lett. 1998;134(1):81–9.

    Article  PubMed  CAS  Google Scholar 

  99. Li ZG, Hong T, Shimada Y, Komoto I, Kawabe A, Ding Y, Kaganoi J, Hashimoto Y, Imamura M. Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol. Carcinogenesis. 2002;23(9):1531–6.

    Article  PubMed  CAS  Google Scholar 

  100. Schneider Y, Duranton B, Gosse F, Schleiffer R, Seiler N, Raul F. Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis. Nutr Cancer. 2001;39(1):102–7.

    Article  PubMed  CAS  Google Scholar 

  101. Provinciali M, Re F, Donnini A, Orlando F, Bartozzi B, Di Stasio G, Smorlesi A. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int J Cancer. 2005;115(1):36–45.

    Article  PubMed  CAS  Google Scholar 

  102. Carbo N, Costelli P, Baccino FM, Lopez-Soriano FJ, Argiles JM. Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model. Biochem Biophys Res Commun. 1999;254(3):739–43.

    Article  PubMed  CAS  Google Scholar 

  103. Delmas D, Lancon A, Colin D, Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Curr Drug Targets. 2006;7(4):423–42.

    Article  PubMed  CAS  Google Scholar 

  104. Signorelli P, Ghidoni R. Resveratrol as an anticancer nutrient: molecular basis, open questions and promises. J Nutr Biochem. 2005;16(8):449–66.

    Article  PubMed  CAS  Google Scholar 

  105. Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res. 2004;24(5A):2783–840.

    PubMed  CAS  Google Scholar 

  106. Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol. 2007;224(3):274–83.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  107. Jager W, Gruber A, Giessrigl B, Krupitza G, Szekeres T, Sonntag D. Metabolomic analysis of resveratrol-induced effects in the human breast cancer cell lines MCF-7 and MDA-MB-231. OMICS. 2011;15(1-2):9–14.

    Article  PubMed  CAS  Google Scholar 

  108. Massimi M, Tomassini A, Sciubba F, Sobolev AP, Devirgiliis LC, Miccheli A. Effects of resveratrol on HepG2 cells as revealed by (1)H-NMR based metabolic profiling. Biochim Biophys Acta. 2012;1820(1):1–8.

    Article  PubMed  CAS  Google Scholar 

  109. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6):493–506.

    Article  PubMed  CAS  Google Scholar 

  110. Rivera L, Moron R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol. 2009;77(6):1053–63.

    Article  PubMed  CAS  Google Scholar 

  111. Zhou M, Wang S, Zhao A, Wang K, Fan Z, Yang H, Liao W, Bao S, Zhao L, Zhang Y, et al. Transcriptomic and metabonomic profiling reveal synergistic effects of quercetin and resveratrol supplementation in high fat diet fed mice. J Proteome Res. 2012;11(10):4961–71.

    Article  PubMed  CAS  Google Scholar 

  112. Valls-Pedret C, Lamuela-Raventos RM, Medina-Remon A, Quintana M, Corella D, Pinto X, Martinez-Gonzalez MA, Estruch R, Ros E. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis. 2012;29(4):773–82.

    PubMed  CAS  Google Scholar 

  113. Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. 2011;51(4):363–73.

    Article  PubMed  CAS  Google Scholar 

  114. Crozier A, Jaganath IB, Clifford MN. Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep. 2009;26(8):1001–43.

    Article  PubMed  CAS  Google Scholar 

  115. Spiller MA. Caffeine. Boca Raton: CRC Press; 1998.

    Google Scholar 

  116. Ito H, Gonthier MP, Manach C, Morand C, Mennen L, Remesy C, Scalbert A. Polyphenol levels in human urine after intake of six different polyphenol-rich beverages. Br J Nutr. 2005;94(4):500–9.

    Article  PubMed  CAS  Google Scholar 

  117. Allard E, Backstrom D, Danielsson R, Sjoberg PJ, Bergquist J. Comparing capillary electrophoresis-mass spectrometry fingerprints of urine samples obtained after intake of coffee, tea, or water. Anal Chem. 2008;80(23):8946–55.

    Article  PubMed  CAS  Google Scholar 

  118. Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Cavin C, Steiling H, Williamson G, Crozier A. Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: identification of biomarkers of coffee consumption. Drug Metab Dispos. 2009;37(8):1749–58.

    Article  PubMed  CAS  Google Scholar 

  119. Nagy K, Redeuil K, Williamson G, Rezzi S, Dionisi F, Longet K, Destaillats F, Renouf M. First identification of dimethoxycinnamic acids in human plasma after coffee intake by liquid chromatography-mass spectrometry. J Chromatogr A. 2011;1218(3):491–7.

    Article  PubMed  CAS  Google Scholar 

  120. Redeuil K, Smarrito-Menozzi C, Guy P, Rezzi S, Dionisi F, Williamson G, Nagy K, Renouf M. Identification of novel circulating coffee metabolites in human plasma by liquid chromatography-mass spectrometry. J Chromatogr A. 2011;1218(29):4678–88.

    Article  PubMed  CAS  Google Scholar 

  121. Altmaier E, Kastenmuller G, Romisch-Margl W, Thorand B, Weinberger KM, Adamski J, Illig T, Doring A, Suhre K. Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics. Mol Nutr Food Res. 2009;53(11):1357–65.

    Article  PubMed  CAS  Google Scholar 

  122. Mendez MA, Popkin BM, Jakszyn P, Berenguer A, Tormo MJ, Sanchez MJ, Quiros JR, Pera G, Navarro C, Martinez C, et al. Adherence to a Mediterranean diet is associated with reduced 3-year incidence of obesity. J Nutr. 2006;136(11):2934–8.

    PubMed  CAS  Google Scholar 

  123. Kochhar S, Jacobs DM, Ramadan Z, Berruex F, Fuerholz A, Fay LB. Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics. Anal Biochem. 2006;352(2):274–81.

    Article  PubMed  CAS  Google Scholar 

  124. Morris C, O’Grada C, Ryan M, Roche HM, Gibney MJ, Gibney ER, Brennan L. The relationship between BMI and metabolomic profiles: a focus on amino acids. Proc Nutr Soc. 2012;71(4):634–8.

    Article  PubMed  CAS  Google Scholar 

  125. Shanahan F. Microbes and metabolic health. Gut. 2012;61(12):1655–6.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jessica A. Martinez Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Martinez, J.A., Keun, H.C., Siskos, A.P. (2016). Effects of Mediterranean Diet on the Metabolome. In: Romagnolo, D., Selmin, O. (eds) Mediterranean Diet. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-27969-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-27969-5_10

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-27967-1

  • Online ISBN: 978-3-319-27969-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics