, Volume 2, Issue 4, pp 235–241 | Cite as

Metabolic profiling in validation of plasma biomarkers for green tea polyphenols

  • Haitao Luo
  • Stephen B. Cox
  • Weimin Gao
  • Jiahua Yu
  • Lili Tang
  • Jia-Sheng WangEmail author

Green tea polyphenols (GTP) effectively protect against chronic diseases in various animal models but human studies have been inconclusive. GTP components and metabolites in body fluids have been suggested as potential biomarkers, but validation of these biomarkers has rarely been done in human populations. A randomized, double-blinded, and placebo-controlled phase IIa chemoprevention study with GTP was conducted in 120 human subjects for 3 months. To validate GTP biomarker profiles, plasma samples were collected at baseline, 1-month, and 3-month and were analyzed by HPLC-Coularray electrochemical detection (ECD) for specific GTP components as well as for non-targeted metabolites. The levels of 2 GTP components, epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), were homogenous at baseline (p > 0.45) but were significantly elevated (p < 0.01) by GTP treatment. Metabolic profiling identified 106 metabolites, and 56 of them were chosen to construct discriminant functions (DFs) based on the data at 3 months. The DFs clearly separated the placebo, 500 mg GTP, and 1000 mg GTP groups with an accuracy rate of 97.3%. When the DFs were applied to the combined baseline and 1-month data, the accuracy rate was 62.9% in classifying subjects into the 3 intervention groups. DFs derived from 1-month data showed similar results. Overall, this study validated plasma EGCG and ECG as reliable biomarkers for GTP consumption, and found metabolic profiles effective in discriminating different GTP dosages.


green tea polyphenols plasma biomarker metabolic profiling human study 



This study was supported by research grants NIEHS ES11442 and NCI CA90997.


  1. Ahmad N., Mukhtar H. (1999) Green tea polyphenols and cancer: biologic mechanisms and practical implications. Nutr. Rev. 57:78–83PubMedCrossRefGoogle Scholar
  2. Balentine D.A., Wiseman S.A., Bouwens L.C. (1997) The chemistry of tea flavonoids. Crit. Rev. Food Sci. Nutr. 37:693–704PubMedCrossRefGoogle Scholar
  3. Chan D.K., Woo J., Ho S.C., et al. (1998) Genetic and environmental risk factors for Parkinson’s disease in a Chinese population. J. Neurol. Neurosurg. Psychiatry 65:781–784PubMedGoogle Scholar
  4. Duran A.L., Yang J., Wang L., Sumner L.W. (2003) Metabolomics spectral formatting, alignment and conversion tools (MSFACTs). Bioinformatics 19:2283–2293PubMedCrossRefGoogle Scholar
  5. Goodacre R., Vaidyanathan S., Dunn W.B., Harrigan G.G., Kell D.B. (2004) Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol. 22:245–252PubMedCrossRefGoogle Scholar
  6. Gordon G.J., Jensen R.V., Hsiao L.L., et al. (2002) Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma. Cancer Res. 62:4963–4967 (MS Excel Macro for heat map available from: Scholar
  7. Graham H.N. (1992) Green tea composition, consumption, and polyphenol chemistry. Prev. Med. 21:334–350PubMedCrossRefGoogle Scholar
  8. Hand D.J. (1981) Discrimination and Classification John Wiley & Sons, New YorkGoogle Scholar
  9. Higdon J.V., Frei B. (2003) Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit. Rev. Food Sci. Nutr. 43:89–143PubMedCrossRefGoogle Scholar
  10. Hollman P.C., Feskens E.J., Katan M.B. (1999) Tea flavonols in cardiovascular disease and cancer epidemiology. Proc. Soc. Exp. Biol. Med. 220:198–202PubMedCrossRefGoogle Scholar
  11. Huang T., Yu J., Tang L., et al. (2004) Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver Cancer: I. Design, clinical outcomes, and baseline biomarker data. Int. J. Cancer Prev. 1:269–280Google Scholar
  12. Lambert, J.D. and Yang, C.S. (2003). Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Mutat. Res. 523524, 201–208Google Scholar
  13. Lee M.J., Wang Z.Y., Li H., et al. (1995) Analysis of plasma and urinary tea polyphenols in human subjects. Cancer Epidemiol. Biomarkers Prev. 4:393–399PubMedGoogle Scholar
  14. Lee M.J., Maliakal P., Chen L., et al. (2002) Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol. Biomarkers Prev. 11:1025–1032PubMedGoogle Scholar
  15. Lin J.K. (2002) Cancer chemoprevention by tea polyphenols through modulating signal transduction pathways. Arch. Pharm. Res. 25:561–571PubMedCrossRefGoogle Scholar
  16. Lu H., Meng X., Li C., et al. (2003) Glucuronides of tea catechins: enzymology of biosynthesis and biological activities. Drug Metab. Dispos. 31:452–461PubMedCrossRefGoogle Scholar
  17. Luo H., Tang L., Tang M., et al. (2006) Phase IIa chemoprevention trial of green tea polyphenols in high-risk individuals of liver cancer: modulation of urinary excretion of green tea polyphenols and 8-hydroxydeoxyguanosine. Carcinogenesis 27:262–268PubMedCrossRefGoogle Scholar
  18. Meng X., Lee M.J., Li C., et al. (2001) Formation and identification of 4′-O-methyl-(−)-epigallocatechin in humans. Drug Metab. Dispos. 29:789–793PubMedGoogle Scholar
  19. Park O.J., Surh Y.J. (2004) Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies. Toxicol. Lett. 150:43–56PubMedCrossRefGoogle Scholar
  20. Steuer R., Kurths J., Fiehn O., Weckwerth W. (2003) Observing and interpreting correlations in metabolomic networks. Bioinformatics 19:1019–1026PubMedCrossRefGoogle Scholar
  21. Sun C.L., Yuan J.M., Koh W.P., Yu M.C. (2006a) Green tea, black tea and colorectal cancer risk: a meta-analysis of epidemiologic studies. Carcinogenesis 27:1301–1309CrossRefGoogle Scholar
  22. Sun C.L., Yuan J.M., Koh W.P., Yu M.C. (2006b) Green tea, black tea and breast cancer risk: a meta-analysis of epidemiologic studies. Carcinogenesis 27:1310–1315CrossRefGoogle Scholar
  23. Unno T., Tamemoto K., Yayabe F., Kakuda T. (2003) Urinary excretion of 5-(3′,4′-dihydroxyphenyl)-gamma-valerolactone, a ring-fission metabolite of (−)-epicatechin, in rats and its in vitro antioxidant activity. J. Agric. Food Chem. 51:6893–6898PubMedCrossRefGoogle Scholar
  24. USNIH. (2000) Guideline of Chemoprevention Trials. Bethesda, MD: National Institute of HealthGoogle Scholar
  25. Weckwerth W. (2003) Metabolomics in systems biology. Annu. Rev. Plant Biol. 54:669–689PubMedCrossRefGoogle Scholar
  26. Wickens T.D. (1995) The Geometry of Multivariate Statistics Lawrence Erlbaum Associates. New JerseyGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Haitao Luo
    • 1
  • Stephen B. Cox
    • 1
  • Weimin Gao
    • 1
  • Jiahua Yu
    • 1
    • 2
  • Lili Tang
    • 1
  • Jia-Sheng Wang
    • 1
    Email author
  1. 1.The Institute of Environmental and Human Health & Department of Environmental ToxicologyTexas Tech UniversityLubbockUSA
  2. 2.Guangxi Cancer InstituteNanning, GuangxiP.R. China

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