Skip to main content

Thank you for visiting nature.com. 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:

Food and health

Intake of isoflavones reduces the risk of all-cause mortality in middle-aged Japanese

European Journal of Clinical Nutrition volume 75, pages 1781–1791 (2021)Cite this article

Subjects

Abstract

Background/Objectives

To clarify the effects of intake of legumes and isoflavones on all-cause mortality in middle-aged and older Japanese.

Subject/Methods

The subjects were 2136 randomly chosen community-dwelling Japanese men and women aged 40–79 years who participated in a first-wave survey (1997–2000; baseline). The subjects were followed from baseline to December 31, 2017 (mean period of 16.6 ± 4.2 years). Intake of legumes, soybeans, and isoflavones at baseline was assessed using a 3-day dietary record with photographs. The relationships of intake amounts of legumes and isoflavones to mortality were assessed using Cox proportional hazards regression controlling for age, sex, education, employment, body mass index, smoking habits, medical histories, drinking, and energy intake.

Results

There were 491 deaths during the follow-up period. We found inverse associations of the intake of total soy products and intake of each of the isoflavones with all-cause mortality (p for trend < 0.05) in subjects aged < 60 years: the multivariate-adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the highest intake group (third tertile) of total soy products and total isoflavones were 0.32 (0.13–0.78) and 0.35 (0.17–0.73), respectively, compared with the reference group (first tertile). In contrast, there were no significant associations of intake amounts of legumes, soybeans, and isoflavones with all-cause mortality in subjects aged 60 years or older.

Conclusions

The findings suggest that a higher intake of isoflavones might decrease the risk of all-cause mortality, especially in middle-aged Japanese.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Flowchart of subject selection.

Similar content being viewed by others

References

  1. Christensen K, Delhomme G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet. 2009;374:1196–208.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Nagy CL, Bernard MA, Hodes RJ. National Institute on Aging at middle age-its past, present, and future. J Am Geriatr Soc. 2012;60:1165–9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cabinet Office, Government of Japan. White paper on aged society. Cabinet Office, Government of Japan; 2017. https://www8.cao.go.jp/kourei/whitepaper/w-2018/html/zenbun/s1_1_1.html. Accessed 2 Mar 2019.

  4. Willett WC. Diet and health: what should we eat? Science. 1994;264:532–7.

    Article  CAS  PubMed  Google Scholar 

  5. Magee PJ, Rowland IR. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr. 2004;91:513–31.

    Article  CAS  PubMed  Google Scholar 

  6. Ren MQ, Kuhn G, Wegner J, Chen J. Isoflavones, substances with multi-biological and clinical properties. Eur J Nutr. 2001;40:135–46.

    Article  CAS  PubMed  Google Scholar 

  7. Miksicek RJ. Estrogenic flavonoids: structural requirements for biological activity. Proc Soc Exp Biol Med. 1995;208:44–50.

    Article  CAS  PubMed  Google Scholar 

  8. Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, et al. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology. 1998;139:4252–63.

    Article  CAS  PubMed  Google Scholar 

  9. Uifălean A, Schneider S, Ionescu C, Lalk M, Iuga CA. Soy isoflavones and breast cancer cell lines: molecular mechanisms and future perspectives. Molecules. 2015;21:E13.

    Article  PubMed  Google Scholar 

  10. He S, Simpson BK, Sun H, Ngadi MO, Ma Y, Huang T. Phaseolus vulgaris lectins: a systematic review of characteristics and health implications. Crit Rev Food Sci Nutr. 2018;58:70–83.

    Article  CAS  PubMed  Google Scholar 

  11. Shi J, Arunasalam K, Yeung D, Kakuda Y, Mittal G, Jiang Y. Saponins from edible legumes: chemistry, processing, and health benefits. J Med Food. 2004;7:67–78.

    Article  CAS  PubMed  Google Scholar 

  12. Grosso G, Micek A, Godos J, Pajak A, Sciacca S, Galvano F, et al. Dietary flavonoid and lignan intake and mortality in prospective cohort studies: systematic review and dose-response meta-analysis. Am J Epidemiol. 2017;185:1304–16.

    Article  PubMed  Google Scholar 

  13. Nachvak SM, Moradi S, Anjom-Shoae J, Rahmani J, Nasiri M, Maleki V, et al. Soy, soy isoflavones, and protein intake in relation to mortality from all causes, cancers, and cardiovascular diseases: a systematic review and dose-response meta-analysis of prospective cohort studies. J Acad Nutr Diet. 2019;119:1483–1500.e17.

    Article  PubMed  Google Scholar 

  14. Nagata C, Takatsuka N, Shimizu H. Soy and fish oil intake and mortality in a Japanese community. Am J Epidemiol. 2002;156:824–31.

    Article  PubMed  Google Scholar 

  15. Leo QJ, Ollberding NJ, Wilkens LR, Kolonel LN, Henderson BE, Le Marchand L, et al. Nutritional factors and non-Hodgkin lymphoma survival in an ethnically diverse population: the Multiethnic Cohort. Eur J Clin Nutr. 2016;70:41–46.

    Article  CAS  PubMed  Google Scholar 

  16. Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, et al. Dietary isoflavone intake and all-cause mortality in breast cancer survivors: the Breast Cancer Family Registry. Cancer. 2017;123:2070–9.

    Article  CAS  PubMed  Google Scholar 

  17. Ponzo V, Goitre I, Fadda M, Gambino R, De Francesco A, Soldati L, et al. Dietary flavonoid intake and cardiovascular risk: a population-based cohort study. J Transl Med. 2015;13:218.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yamasaki K, Kayaba K, Ishikawa S. Soy and soy products intake, all-cause mortality, and cause-specific mortality in japan: the Jichi Medical School Cohort Study. Asia Pac J Public Health. 2015;27:531–41.

    Article  PubMed  Google Scholar 

  19. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007;85:895–909.

    Article  CAS  PubMed  Google Scholar 

  20. Nechuta SJ, Caan BJ, Chen WY, Lu W, Chen Z, Kwan ML, et al. Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women. Am J Clin Nutr. 2012;96:123–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Conroy SM, Maskarinec G, Park SY, Wilkens LR, Henderson BE, Kolonel LN. The effects of soy consumption before diagnosis on breast cancer survival: the multiethnic cohort study. Nutr Cancer. 2013;65:527–37.

    Article  CAS  PubMed  Google Scholar 

  22. Shimokata H, Ando F, Niino N. A new comprehensive study on aging-the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA). J Epidemiol. 2000;10:S1–9.

    Article  CAS  PubMed  Google Scholar 

  23. Imai T, Sakai S, Mori K, Ando F, Niino N, Shimokata H. Nutritional assessments of 3-day dietary records in National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). J Epidemiol. 2000;10:S70–6.

    Article  CAS  PubMed  Google Scholar 

  24. Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese intake of flavonoids and isoflavonoids from foods. J Epidemiol. 1998;8:168–75.

    Article  CAS  PubMed  Google Scholar 

  25. 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 

  26. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr. 2000;130:2243–50.

    Article  CAS  PubMed  Google Scholar 

  27. Lleras-Muney A. The relationship between education and adult mortality in the United States. Rev Econ Stud. 2005;72:189–221.

    Article  Google Scholar 

  28. Vathesatogkit P, Batty GD, Woodward M. Socioeconomic disadvantage and disease-specific mortality in Asia: systematic review with meta-analysis of population-based cohort studies. J Epidemiol Community Health. 2014;68:375–83.

    Article  PubMed  Google Scholar 

  29. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309:71–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet. 2003;362:847–52.

    Article  PubMed  Google Scholar 

  31. Sica DA. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Curr Hypertens Rep. 2002;4:321–3.

    Article  PubMed  Google Scholar 

  32. Tenkanen L, Mänttäri M, Kovanen PT, Virkkunen H, Manninen V. Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch Intern Med. 2006;166:743–8.

    Article  CAS  PubMed  Google Scholar 

  33. Di Castelnuovo A, Costanzo S, Bagnardi V, Donati MB, Iacoviello L, de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies. Arch Intern Med. 2006;166:2437–45.

    Article  PubMed  Google Scholar 

  34. Lee SA, Wen W, Xiang YB, Barnes S, Liu D, Cai Q, et al. Assessment of dietary isoflavone intake among middle-aged Chinese men. J Nutr. 2007;137:1011–6.

    Article  PubMed  Google Scholar 

  35. Zamora-Ros R, Knaze V, Luján-Barroso L, Kuhnle GG, Mulligan AA, Touillaud M, et al. Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort. Eur J Clin Nutr. 2012;66:932–41.

    Article  CAS  PubMed  Google Scholar 

  36. Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2011;125:315–23.

    Article  CAS  PubMed  Google Scholar 

  37. Tomar RS, Shiao R. Early life and adult exposure to isoflavones and breast cancer risk. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2008;26:113–73.

    Article  CAS  PubMed  Google Scholar 

  38. Korde LA, Wu AH, Fears T, Nomura AM, West DW, Kolonel LN, et al. Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomark Prev. 2009;18:1050–9.

    Article  CAS  Google Scholar 

  39. Tamakoshi A, Kawado M, Ozasa K, Tamakoshi K, Lin Y, Yagyu K, et al. Impact of smoking and other lifestyle factors on life expectancy among japanese: findings from the Japan Collaborative Cohort (JACC) Study. J Epidemiol. 2010;20:370–6.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Li Y, Pan A, Wang DD, Liu X, Dhana K, Franco OH, et al. Impact of healthy lifestyle factors on life expectancies in the US population. Circulation. 2018;138:345–55.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ribeiro AI, Krainski ET, Carvalho MS, De Fátima de Pina M. The influence of socioeconomic deprivation, access to healthcare and physical environment on old-age survival in Portugal. Geospat Health. 2017;12:581.

    PubMed  Google Scholar 

  42. Ribeiro AI, Krainski ET, Autran R, Teixeira H, Carvalho MS, de Pina MF. The influence of socioeconomic, biogeophysical and built environment on old-age survival in a Southern European city. Health Place. 2016;41:100–9.

    Article  PubMed  Google Scholar 

  43. Wegman DH, McGee JP, editors. Health and safety needs of older workers. USA: National Academies Press; 2004.

  44. Umeno A, Horie M, Murotomi K, Nakajima Y, Yoshida Y. Antioxidative and antidiabetic effects of natural polyphenols and isoflavones. Molecules. 2016;21:E708.

    Article  PubMed  Google Scholar 

  45. Vita JA. Polyphenols and cardiovascular disease: effects on endothelial and platelet function. Am J Clin Nutr. 2005;81:292S–297S.

    Article  CAS  PubMed  Google Scholar 

  46. Osmancik P, Louckova A. Biomarkers of apoptosis, inflammation, and cardiac extracellular matrix remodelling in the prognosis of heart failure. Kardiol Pol. 2017;75:295–305.

    Article  PubMed  Google Scholar 

  47. Sun WW, Hu JA, Niu WQ, Gao BL, Xu ZH. Significance of NLDA, the commixed index of inflammation, immune responses, hemostasis, and nutrition, for predicting metastatic non-small cell lung cancer prognosis and metastases. Oncotarget. 2017;8:81978–93.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Touillaud M, Gelot A, Mesrine S, Bennetau-Pelissero C, Clavel-Chapelon F, Arveux P, et al. Use of dietary supplements containing soy isoflavones and breast cancer risk among women aged >50 y: a prospective study. Am J Clin Nutr. 2019;109:597–605.

    Article  PubMed  Google Scholar 

  49. Qin LQ, Xu JY, Wang PY, Hoshi K. Soyfood intake in the prevention of breast cancer risk in women: a meta-analysis of observational epidemiological studies. J Nutr Sci Vitaminol. 2006;52:428–36.

    Article  CAS  PubMed  Google Scholar 

  50. Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med. 2006;354:270–82.

    Article  CAS  PubMed  Google Scholar 

  51. Wakimoto P, Block G. Dietary intake, dietary patterns, and changes with age: an epidemiological perspective. J Gerontol A Biol Sci Med Sci. 2001;56:65–80.

    Article  PubMed  Google Scholar 

  52. Zhu K, Devine A, Suleska A, Tan CY, Toh CZ, Kerr D, et al. Adequacy and change in nutrient and food intakes with aging in a seven-year cohort study in elderly women. J Nutr Health Aging. 2010;14:723–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the study participants and their colleagues at NILS-LSA for their assistance with the survey in this study.

Funding

This work was supported in part by a grant from the Research Funding for Longevity Sciences of the National Center for Geriatrics and Gerontology, Japan (No. 19–10), and by grants from JSPS KAKENHI: JP15K16228 and JP20K05925. The funders/sponsors had no role in the design, conduct, or reporting of the study or in the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Public Health and Applied Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Mariko Nakamoto & Tohru Sakai

  2. Section of NILS-LSA, National Center for Geriatrics and Gerontology, Aichi, Japan

    Mariko Nakamoto, Rei Otsuka, Chikako Tange, Makiko Tomida, Tomoko Imai, Fujiko Ando & Hiroshi Shimokata

  3. Department of Epidemiology of Aging, National Center for Geriatrics and Gerontology, Aichi, Japan

    Yukiko Nishita

  4. Faculty of Human Life and Science, Doshisha Women’s College of Liberal Arts, Kyoto, Japan

    Tomoko Imai

  5. Faculty of Health and Medical Sciences, Aichi Shukutoku University, Aichi, Japan

    Fujiko Ando

  6. Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Aichi, Japan

    Hiroshi Shimokata

Authors
  1. Mariko Nakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rei Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chikako Tange
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yukiko Nishita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Makiko Tomida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoko Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tohru Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fujiko Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hiroshi Shimokata
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors developed the idea for this study and approved the final version of the manuscript. RO, FA, and HS collected the data. RO, YN, and CT obtained the measurements and performed data analysis. FA and HS provided medical advice regarding interpretation of the data. MN drafted the manuscript with help of RO, FA, and HS.

Corresponding author

Correspondence to Mariko Nakamoto.

Ethics declarations

Conflict of interest

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.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakamoto, M., Otsuka, R., Tange, C. et al. Intake of isoflavones reduces the risk of all-cause mortality in middle-aged Japanese. Eur J Clin Nutr 75, 1781–1791 (2021). https://doi.org/10.1038/s41430-021-00890-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-021-00890-w

This article is cited by

Search

Advanced search

Quick links