Metabolomic Approaches in Vitamin E Research

  • John K. LodgeEmail author
Part of the Nutrition and Health book series (NH)


Metabolomics aims to characterise changes to the complement of metabolites in a biological sample (metabolome), and this technology is gaining interest in nutrition research as it can define perturbations to metabolism induced by dietary factors. There have been a number of metabolomic studies in human and animal models based around vitamin E supplementation or deficiency that have highlighted potential areas in metabolism that vitamin E may play a role. In humans, vitamin E supplementation has been shown to influence phospholipid metabolism and amino acid metabolism, and discriminatory metabolites have included several vitamin E metabolites. Proteomic studies looking at associations with vitamin E concentrations have demonstrated consistent relationships with several apoproteins. Metabolomic studies in animal models include studies on zebrafish foetal development that showed changes to antioxidant status and lipid peroxidation with vitamin E deficiency and rodent models of vitamin E deficiency that showed influences on central metabolism. Metabolomics has proven to be a useful research tool to identify novel functions of vitamin E.


Metabolomics Proteomics Vitamin E Metabolites Human Animal 


  1. 1.
    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.PubMedGoogle Scholar
  2. 2.
    Kell DB. Metabolomics and systems biology: making sense of the soup. Curr Opin Microbiol. 2004;7(3):296–307.PubMedGoogle Scholar
  3. 3.
    Whitfield PD, German AJ, Noble PJ. Metabolomics: an emerging post-genomic tool for nutrition. Br J Nutr. 2004;92(4):549–55.PubMedGoogle Scholar
  4. 4.
    Rezzi S, Ramadan Z, Martin FP, Fay LB, Bladeren PV, Lindon JC, et al. Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals. J Proteome Res. 2007;6(11):4469–77.PubMedGoogle Scholar
  5. 5.
    Zeisel SH, Freake HC, Bauman DE, Bier DM, Burrin DG, German JB, et al. The nutritional phenotype in the age of metabolomics. J Nutr. 2005;135(7):1613–6.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Valianpour F, Selhorst JJ, van Lint LE, van Gennip AH, Wanders RJ, Kemp S. Analysis of very long-chain fatty acids using electrospray ionization mass spectrometry. Mol Genet Metab. 2003;79(3):189–96.PubMedGoogle Scholar
  7. 7.
    Fu H, Xu L, Lv Q, Wang JZ, Xiao HZ, Zhao YF. Electrospray ionization mass spectra of amino acid phosphoramidates of adenosine. Rapid Commun Mass Spectrom. 2000;14(19):1813–22.PubMedGoogle Scholar
  8. 8.
    Ohdoi C, Nyhan WL, Kuhara T. Chemical diagnosis of Lesch-Nyhan syndrome using gas chromatography-mass spectrometry detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;792(1):123–30.PubMedGoogle Scholar
  9. 9.
    Pelander A, Ojanpera I, Laks S, Rasanen I, Vuori E. Toxicological screening with formula-based metabolite identification by liquid chromatography/time-of-flight mass spectrometry. Anal Chem. 2003;75(21):5710–8.PubMedGoogle Scholar
  10. 10.
    Beckonert O, Monnerjahn J, Bonk U, Leibfritz D. Visualizing metabolic changes in breast-cancer tissue using 1H-NMR spectroscopy and self-organizing maps. NMR Biomed. 2003;16(1):1–11.PubMedGoogle Scholar
  11. 11.
    Beckmann M, Enot DP, Overy DP, Draper J. Representation, comparison, and interpretation of metabolome fingerprint data for total composition analysis and quality trait investigation in potato cultivars. J Agric Food Chem. 2007;55(9):3444–51.PubMedGoogle Scholar
  12. 12.
    Catchpole GS, Beckmann M, Enot DP, Mondhe M, Zywicki B, Taylor J, et al. Hierarchical metabolomics demonstrates substantial compositional similarity between genetically modified and conventional potato crops. Proc Natl Acad Sci U S A. 2005;102(40):14458–62.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Shaham O, Wei R, Wang TJ, Ricciardi C, Lewis GD, Vasan RS, et al. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity. Mol Syst Biol. 2008;4:214.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhao X, Peter A, Fritsche J, Elcnerova M, Fritsche A, Haring HU, et al. Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at? Am J Physiol Endocrinol Metab. 2009;296(2):E384–93.PubMedGoogle Scholar
  15. 15.
    Fave G, Beckmann M, Lloyd AJ, Zhou S, Harold G, Lin W, et al. Development and validation of a standardized protocol to monitor human dietary exposure by metabolite fingerprinting of urine samples. Metabolomics. 2011;7(4):469–84.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Lloyd AJ, Fave G, Beckmann M, Lin W, Tailliart K, Xie L, et al. Use of mass spectrometry fingerprinting to identify urinary metabolites after consumption of specific foods. Am J Clin Nutr. 2011;94(4):981–91.PubMedGoogle Scholar
  17. 17.
    Primrose S, Draper J, Elsom R, Kirkpatrick V, Mathers JC, Seal C, et al. Metabolomics and human nutrition. Br J Nutr. 2011;105(8):1277–83.PubMedGoogle Scholar
  18. 18.
    Beckmann M, Joosen AM, Clarke MM, Mugridge O, Frost G, Engel B, et al. Changes in the human plasma and urinary metabolome associated with acute dietary exposure to sucrose and the identification of potential biomarkers of sucrose intake. Mol Nutr Food Res. 2016;60(2):444–57.PubMedGoogle Scholar
  19. 19.
    Lodge JK. Symposium 2: modern approaches to nutritional research challenges: targeted and non-targeted approaches for metabolite profiling in nutritional research. Proc Nutr Soc. 2010;69(1):95–102.PubMedGoogle Scholar
  20. 20.
    Drake SK, Bowen RA, Remaley AT, Hortin GL. Potential interferences from blood collection tubes in mass spectrometric analyses of serum polypeptides. Clin Chem. 2004;50(12):2398–401.PubMedGoogle Scholar
  21. 21.
    Teahan O, Gamble S, Holmes E, Waxman J, Nicholson JK, Bevan C, et al. Impact of analytical bias in metabonomic studies of human blood serum and plasma. Anal Chem. 2006;78(13):4307–18.PubMedGoogle Scholar
  22. 22.
    Maher AD, Zirah SF, Holmes E, Nicholson JK. Experimental and analytical variation in human urine in 1H NMR spectroscopy-based metabolic phenotyping studies. Anal Chem. 2007;79(14):5204–11.PubMedGoogle Scholar
  23. 23.
    Walsh MC, Brennan L, Malthouse JP, Roche HM, Gibney MJ. Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans. Am J Clin Nutr. 2006;84(3):531–9.PubMedGoogle Scholar
  24. 24.
    Beckmann M, Lloyd AJ, Haldar S, Fave G, Seal CJ, Brandt K, et al. Dietary exposure biomarker-lead discovery based on metabolomics analysis of urine samples. Proc Nutr Soc. 2013;72(3):352–61.PubMedGoogle Scholar
  25. 25.
    Dunn WB, Broadhurst D, Ellis DI, Brown M, Halsall A, O’Hagan S, et al. A GC-TOF-MS study of the stability of serum and urine metabolomes during the UK Biobank sample collection and preparation protocols. Int J Epidemiol. 2008;37(Suppl 1):i23–30.PubMedGoogle Scholar
  26. 26.
    Gika HG, Theodoridis GA, Wingate JE, Wilson ID. Within-day reproducibility of an HPLC-MS-based method for metabonomic analysis: application to human urine. J Proteome Res. 2007;6(8):3291–303.PubMedGoogle Scholar
  27. 27.
    Want EJ, O’Maille G, Smith CA, Brandon TR, Uritboonthai W, Qin C, et al. Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry. Anal Chem. 2006;78(3):743–52.PubMedGoogle Scholar
  28. 28.
    Bruce SJ, Jonsson P, Antti H, Cloarec O, Trygg J, Marklund SL, et al. Evaluation of a protocol for metabolic profiling studies on human blood plasma by combined ultra-performance liquid chromatography/mass spectrometry: from extraction to data analysis. Anal Biochem. 2008;372(2):237–49.PubMedGoogle Scholar
  29. 29.
    Wong MC, Lee WT, Wong JS, Frost G, Lodge J. An approach towards method development for untargeted urinary metabolite profiling in metabonomic research using UPLC/QToF MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871(2):341–8.PubMedGoogle Scholar
  30. 30.
    Guy PA, Tavazzi I, Bruce SJ, Ramadan Z, Kochhar S. Global metabolic profiling analysis on human urine by UPLC-TOFMS: issues and method validation in nutritional metabolomics. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;871(2):253–60.PubMedGoogle Scholar
  31. 31.
    Sangster TP, Wingate JE, Burton L, Teichert F, Wilson ID. Investigation of analytical variation in metabonomic analysis using liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2007;21(18):2965–70.PubMedGoogle Scholar
  32. 32.
    Torquato P, Ripa O, Giusepponi D, Galarini R, Bartolini D, Wallert M, et al. Analytical strategies to assess the functional metabolome of vitamin E. J Pharm Biomed Anal. 2016;124:399–412.PubMedGoogle Scholar
  33. 33.
    Westerhuis JA, Hoefsloot HCJ, Smit S, Vis DJ, Smilde AK, Velzen EJJ, et al. Assessment of PLSDA cross validation. Metabolomics. 2008;4(1):81–9.Google Scholar
  34. 34.
    Wishart DS, Tzur D, Knox C, Eisner R, Guo AC, Young N, et al. HMDB: the human metabolome database. Nucleic Acids Res. 2007;35(Database issue):D521–6.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, et al. METLIN: a metabolite mass spectral database. Ther Drug Monit. 2005;27(6):747–51.PubMedGoogle Scholar
  36. 36.
    Go VL, Nguyen CT, Harris DM, Lee WN. Nutrient-gene interaction: metabolic genotype-phenotype relationship. J Nutr. 2005;135(12 Suppl):3016S–20S.PubMedGoogle Scholar
  37. 37.
    Wong M, Lodge JK. A metabolomic investigation of the effects of vitamin E supplementation in humans. Nutr Metab. 2012;9(1):110.Google Scholar
  38. 38.
    Johnson CH, Slanar O, Krausz KW, Kang DW, Patterson AD, Kim JH, et al. Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry-based metabolomics. Am J Clin Nutr. 2012;96(4):818–30.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Mondul AM, Moore SC, Weinstein SJ, Evans AM, Karoly ED, Mannisto S, et al. Serum metabolomic response to long-term supplementation with all-rac-α-tocopheryl acetate in a randomized controlled trial. J Nutr Metab. 2016;2016:6158436.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Bruno RS, Traber MG. Cigarette smoke alters human vitamin E requirements. J Nutr. 2005;135(4):671–4.PubMedGoogle Scholar
  41. 41.
    Jeanes YM, Hall WL, Proteggente AR, Lodge JK. Cigarette smokers have decreased lymphocyte and platelet α-tocopherol levels and increased excretion of the γ-tocopherol metabolite γ-carboxyethyl-hydroxychroman (γ-CEHC). Free Radic Res. 2004;38(8):861–8.PubMedGoogle Scholar
  42. 42.
    Cheng J, Joyce A, Yates K, Aouizerat B, Sanyal AJ. Metabolomic profiling to identify predictors of response to vitamin E for non-alcoholic steatohepatitis (NASH). PLoS One. 2012;7(9):e44106.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Da Costa LA, Garcia-Bailo B, Borchers CH, Badawi A, El-Sohemy A. Association between the plasma proteome and plasma α-tocopherol concentrations in humans. J Nutr Biochem. 2013;24(1):396–400.PubMedGoogle Scholar
  44. 44.
    West KP Jr, Cole RN, Shrestha S, Schulze KJ, Lee SE, Betz J, et al. A plasma α-tocopherome can be identified from proteins associated with vitamin E status in school-aged children of Nepal. J Nutr. 2015;145(12):2646–56.PubMedGoogle Scholar
  45. 45.
    Cole RN, Ruczinski I, Schulze K, Christian P, Herbrich S, Wu L, et al. The plasma proteome identifies expected and novel proteins correlated with micronutrient status in undernourished Nepalese children. J Nutr. 2013;143(10):1540–8.PubMedGoogle Scholar
  46. 46.
    Moazzami AA, Andersson R, Kamal-Eldin A. Changes in the metabolic profile of rat liver after α-tocopherol deficiency as revealed by metabolomics analysis. NMR Biomed. 2011;24(5):499–505.PubMedGoogle Scholar
  47. 47.
    Adachi K, Izumi M, Mitsuma T. Effect of vitamin E deficiency on rat brain monoamine metabolism. Neurochem Res. 1999;24(10):1307–11.PubMedGoogle Scholar
  48. 48.
    Moazzami AA, Frank S, Gombert A, Sus N, Bayram B, Rimbach G, et al. Non-targeted 1H-NMR-metabolomics suggest the induction of master regulators of energy metabolism in the liver of vitamin E-deficient rats. Food Funct. 2015;6(4):1090–7.PubMedGoogle Scholar
  49. 49.
    Starnes JW, Parry TL, O’Neal SK, Bain JR, Muehlbauer MJ, Honcoop A, et al. Exercise-induced alterations in skeletal muscle, heart, liver, and serum metabolome identified by non-targeted metabolomics analysis. Meta. 2017;7(3):40.Google Scholar
  50. 50.
    McDougall M, Choi J, Truong L, Tanguay R, Traber MG. Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets. Free Radic Biol Med. 2017;110:250–60.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Choi J, Leonard SW, Kasper K, McDougall M, Stevens JF, Tanguay RL, et al. Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. J Lipid Res. 2015;56(6):1182–90.PubMedPubMedCentralGoogle Scholar
  52. 52.
    McDougall MQ, Choi J, Stevens JF, Truong L, Tanguay RL, Traber MG. Lipidomics and H2(18)O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos. Redox Biol. 2016;8:165–74.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Cho JY, Kang DW, Ma X, Ahn SH, Krausz KW, Luecke H, et al. Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation. J Lipid Res. 2009;50(5):924–37.PubMedPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Applied Sciences, Faculty of Health and Life SciencesNorthumbria UniversityNewcastle upon TyneUK

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