Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Reproducibility and dietary correlates of plasma polyphenols in the JPHC-NEXT Protocol Area study



In recent years, an increasing number of epidemiological studies have suggested a role of polyphenols in the prevention of chronic diseases. Prospective cohort studies have typically measured polyphenol concentrations in a single blood sample and the reproducibility of plasma polyphenol measurements is largely unknown.


We evaluated the reproducibility of 35 plasma polyphenols collected at an interval of 1-year. We also examined correlations of these polyphenols with food group intakes calculated from weighed food records (WFR) and food frequency questionnaire (FFQ).


The study included 227 middle-aged participants from the JPHC-NEXT Protocol Area in Japan. We measured 35 polyphenols in plasma collected at two points 1-year apart. Food group intakes were calculated from 12-day WFR and FFQ. For the reproducibility analysis, the intraclass correlation coefficient (ICC) of 35 polyphenol concentrations were examined between the two points. Pearson’s partial correlations was used to assess the correlation between polyphenols and food groups.


Moderate- to high ICCs were observed for tea-originated polyphenols such as gallic acid, quercetin, epigallocatechin, and kaempferol - and coffee-derived polyphenols, such as caffeic acid, and ferulic acid. For the dietary analyses, moderate correlations were observed for non-alcoholic beverages intake and epigallocatechin, epicatechin, catechin, and gallic acid. For green tea, higher correlations were observed with these polyphenols.


Plasma concentrations of tea and coffee-related polyphenols, except for catechin, had good reproducibility over a 1-year period. The correlations between intake of non-alcoholic beverages, particularly green tea, and tea polyphenols, indicated moderate- to high correlations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Study design of the JPHC-NEXT Protocol Area.
Fig. 2: Pearson correlation heatmap between polyphenols (N = 221).

Similar content being viewed by others

Data availability

For information on how to submit an application to gain access to Japan Public Health Center-based data/or biospecimens, please follow the instructions at


  1. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79:727–47.

    Article  CAS  Google Scholar 

  2. Gardeazabal I, Romanos-Nanclares A, Martinez-Gonzalez MA, Sanchez-Bayona R, Vitelli-Storelli F, Gaforio JJ, et al. Total polyphenol intake and breast cancer risk in the SUN cohort. Br J Nutr. 2019;122:542–51.

    Article  CAS  PubMed  Google Scholar 

  3. Wang ZJ, Ohnaka K, Morita M, Toyomura K, Kono S, Ueki T, et al. Dietary polyphenols and colorectal cancer risk: the Fukuoka colorectal cancer study. World J Gastroenterol. 2013;19:2683–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Adriouch S, Lampure A, Nechba A, Baudry J, Assmann K, Kesse-Guyot E, et al. Prospective association between total and specific dietary polyphenol intakes and cardiovascular disease risk in the Nutrinet-Sante French Cohort. Nutrients. 2018;10:1587.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tresserra-Rimbau A, Rimm EB, Medina-Remon A, Martinez-Gonzalez MA, de la Torre R, Corella D, et al. Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study. Nutr Metab Cardiovasc Dis. 2014;24:639–47.

    Article  CAS  PubMed  Google Scholar 

  6. Lefevre-Arbogast S, Gaudout D, Bensalem J, Letenneur L, Dartigues JF, Hejblum BP, et al. Pattern of polyphenol intake and the long-term risk of dementia in older persons. Neurology. 2018;90:e1979–e88.

    Article  CAS  Google Scholar 

  7. Barnes S. Soy isoflavones–phytoestrogens and what else? J Nutr. 2004;134:1225s–8s.

    Article  PubMed  Google Scholar 

  8. Ozdal T, Sela DA, Xiao J, Boyacioglu D, Chen F, Capanoglu E. The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients. 2016;8:78.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Williamson G, Clifford MN. Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr. 2010;104:S48–66.

    Article  CAS  PubMed  Google Scholar 

  10. Zamora-Ros R, Rabassa M, Cherubini A, Urpi-Sarda M, Llorach R, Bandinelli S, et al. Comparison of 24-h volume and creatinine-corrected total urinary polyphenol as a biomarker of total dietary polyphenols in the Invecchiare InCHIANTI study. Anal Chim Acta. 2011;704:110–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xu Y, Le Sayec M, Roberts C, Hein S, Rodriguez-Mateos A, Gibson R. Dietary assessment methods to estimate (Poly)phenol intake in epidemiological studies: a systematic review. Adv Nutr. 2021;12:1781–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bhakta D, dos Santos Silva I, Higgins C, Sevak L, Kassam-Khamis T, Mangtani P, et al. A semiquantitative food frequency questionnaire is a valid indicator of the usual intake of phytoestrogens by South Asian women in the UK relative to multiple 24-h dietary recalls and multiple plasma samples. J Nutr. 2005;135:116–23.

    Article  CAS  PubMed  Google Scholar 

  13. Verkasalo PK, Appleby PN, Allen NE, Davey G, Adlercreutz H, Key TJ. Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European Prospective Investigation into Cancer and Nutrition). Br J Nutr. 2001;86:415–21.

    Article  CAS  PubMed  Google Scholar 

  14. Cao J, Zhang Y, Chen W, Zhao X. The relationship between fasting plasma concentrations of selected flavonoids and their ordinary dietary intake. Br J Nutr. 2010;103:249–55.

    Article  CAS  PubMed  Google Scholar 

  15. Radtke J, Linseisen J, Wolfram G. Fasting plasma concentrations of selected flavonoids as markers of their ordinary dietary intake. Eur J Nutr. 2002;41:203–9.

    Article  CAS  PubMed  Google Scholar 

  16. Ruidavets J, Teissedre P, Ferrieres J, Carando S, Bougard G, Cabanis J. Catechin in the Mediterranean diet: vegetable, fruit or wine? Atherosclerosis. 2000;153:107–17.

    Article  CAS  PubMed  Google Scholar 

  17. Arai Y, Uehara M, Sato Y, Kimira M, Eboshida A, Adlercreutz H, et al. Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. J Epidemiol. 2000;10:127–35.

    Article  CAS  PubMed  Google Scholar 

  18. Frankenfeld CL, Patterson RE, Horner NK, Neuhouser ML, Skor HE, Kalhorn TF, et al. Validation of a soy food-frequency questionnaire and evaluation of correlates of plasma isoflavone concentrations in postmenopausal women. Am J Clin Nutr. 2003;77:674–80.

    Article  CAS  PubMed  Google Scholar 

  19. Wu AH, Yu MC, Tseng CC, Twaddle NC, Doerge DR. Plasma isoflavone levels versus self-reported soy isoflavone levels in Asian-American women in Los Angeles County. Carcinogenesis. 2004;25:77–81.

    Article  PubMed  Google Scholar 

  20. Frankenfeld CL, Patterson RE, Kalhorn TF, Skor HE, Howald WN, Lampe JW. Validation of a soy food frequency questionnaire with plasma concentrations of isoflavones in US adults. J Am Diet Assoc. 2002;102:1407–13.

    Article  PubMed  Google Scholar 

  21. Yokoyama Y, Takachi R, Ishihara J, Ishii Y, Sasazuki S, Sawada N, et al. Validity of short and long self-administered food frequency questionnaires in ranking dietary intake in middle-aged and elderly Japanese in the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) protocol area. J Epidemiol. 2016;26:420–32.

    Article  PubMed  Google Scholar 

  22. Achaintre D, Gicquiau A, Li L, Rinaldi S, Scalbert A. Quantification of 38 dietary polyphenols in plasma by differential isotope labelling and liquid chromatography electrospray ionization tandem mass spectrometry. J Chromatogr A. 2018;1558:50–8.

    Article  CAS  PubMed  Google Scholar 

  23. Mori N, Murphy N, Sawada N, Achaintre D, Yamaji T, Scalbert A, et al. Prediagnostic plasma polyphenol concentrations and colon cancer risk: the JPHC nested case-control study. Clin Nutr. 2022;41:1950–60.

    Article  CAS  Google Scholar 

  24. Maruyama K, Ikeda A, Ishihara J, Takachi R, Sawada N, Shimazu T, et al. Food frequency questionnaire reproducibility for middle-aged and elderly Japanese. Asia Pac J Clin Nutr. 2019;28:362–70.

    PubMed  Google Scholar 

  25. Dempster AP. Maximum Likelihood from Incomplete Data via the EM Algorithm on JSTOR. 1977;39:–38.

  26. Willett W, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol. 1986;124:17–27.

    Article  CAS  Google Scholar 

  27. Olthof MR, Hollman PC, Buijsman MN, van Amelsvoort JM, Katan MB. Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr. 2003;133:1806–14.

    Article  CAS  Google Scholar 

  28. Taguchi C, Kishimoto Y, Takeuchi I, Tanaka M, Iwashima T, Fukushima Y, et al. Estimated dietary polyphenol intake and its seasonal variations among Japanese university students. J Nutr Sci Vitaminol. 2019;65:192–5.

    Article  CAS  PubMed  Google Scholar 

  29. Zamora-Ros R, Lujan-Barroso L, Achaintre D, Franceschi S, Kyrø C, Overvad K, et al. Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Am J Clin Nutr. 2020;113:162–71.

    Article  PubMed Central  Google Scholar 

  30. Phenol-Explorer: Database on Polyphenol content in foods [Internet]. INRA, AFSSA, University of Alberta, the University of Barcelona, IARC and In Siliflo. 2015. Available from:

  31. Watanabe T, Yamamoto A, Nagai S, Terabe S. Simultaneous analysis of tyrosol, tryptophol and ferulic acid in commercial sake samples by micellar electrokinetic chromatography. J Chromatogr A. 1998;825:102–6.

    Article  CAS  Google Scholar 

  32. Iwasaki M, Inoue M, Otani T, Sasazuki S, Kurahashi N, Miura T, et al. Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group. J Clin Oncol. 2008;26:1677–83.

    Article  CAS  PubMed  Google Scholar 

  33. Sasazuki S, Inoue M, Miura T, Iwasaki M, Tsugane S. Plasma tea polyphenols and gastric cancer risk: a case-control study nested in a large population-based prospective study in Japan. Cancer Epidemiol Biomark Prev. 2008;17:343–51.

    Article  CAS  Google Scholar 

Download references


JPHC members (as of November 2021) are listed at the following site: The study was supported by World Cancer Research Fund (WCRF) International Regular Grant Programme 2017/18 (grant number: IIG_2018_1698), National Cancer Research and Development Fund [23-A-31 (Toku) and 26-A-2] (since 2010), and Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (from 1989 to 2010).

Author information

Authors and Affiliations



NMurphy, NS, AS, MJG, and ST designed the study. NMori performed the analyses, prepared the tables and drafted the paper. DA, and AS analyzed the samples. NMurphy, NS, DA, and AS supported analyses, discussions and finalizing of the paper. All authors contributed to the interpretation of the results and have read and approved the final manuscript.

Corresponding author

Correspondence to Nagisa Mori.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Disclaimer Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mori, N., Murphy, N., Sawada, N. et al. Reproducibility and dietary correlates of plasma polyphenols in the JPHC-NEXT Protocol Area study. Eur J Clin Nutr 78, 34–42 (2024).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links