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Soy intake and chronic disease risk: findings from prospective cohort studies in Japan


There has been much interest in the potential role of soy in reducing the risk of chronic diseases. Soy foods are uniquely rich in isoflavones, a fact that has triggered much research including intervention studies. However, there have been few long-term prospective observational studies that include disease itself as an outcome. High intake of soy foods is intrinsic to the Japanese diet, which can be advantageous for conducting such studies in Japan. The present report reviews the findings from Japanese prospective cohort studies on soy intake and the risk of cardiovascular diseases, cancer, type 2 diabetes, osteoporosis, menopausal symptoms, and dementia. The results suggest a beneficial role of soy in several chronic diseases, but they are not without controversy. Discrepancies have been observed in the findings of studies of Japanese or other Asians as compared to those of non Asians. This review discusses the issues to be explored in future studies.

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  1. 1.

    Murphy PA, Barua K, Hauck CC. Solvent extraction selection in the determination of isoflavones in soy foods. J Chromatogr B Anal Technol Biomed Life Sci. 2002;777:129–38.

    CAS  Google Scholar 

  2. 2.

    Pabich M, Materska M. Biological effect of soy isoflavones in the prevention of civilization diseases. Nutrients. 2019;11.

  3. 3.

    Miyazaki K. Novel approach for evaluation of estrogenic and anti-estrogenic activities of genistein and daidzain using B16 melanoma cells and dendricity assay. Pigment Cell Res. 2004;17:407–12.

    CAS  PubMed  Google Scholar 

  4. 4.

    Zhu Y, Yao Y, Shi Z, Everaert N, Ren G. Synergic effect of bioactive anticarcinogens from soybean on anti-proliferative activity in MDA-MB-231 and MCF-7 human breast cancer cells in vitro. Nutrients. 2018;23:1557.

    Google Scholar 

  5. 5.

    Kojima K, Asai K, Kubo H, Sugitani A, Kyomoto Y, Okamoto A, et al. Isoflavone aglycones attenuate cigarette smoke-induced emphysema via suppression of neurotrophilic inflammation in a COPD murine model. Nutrients. 2019;11:2023.

    CAS  PubMed Central  Google Scholar 

  6. 6.

    Rabiau N, Kossai M, Braud M, Chalabi N, Satih S, Bignon YJ, et al. Genistein and daidzein act on a panel of genes implicated in cell cycle and angiogenesis by polymerase chain reaction arrays in human prostate cancer cell lines. Cancer Epidemiol. 2010;34:200–6.

    CAS  PubMed  Google Scholar 

  7. 7.

    Choi MS, Lee MK, Jung UJ, Kim HJ, Do GM, Park YB, et al. Metabolic response of soy pinitol on lipid-lowering, antioxidant and hepatoprotective action in hamsters fed-high fat and high cholesterol diet. Mol Nutr Food Res. 2009;53:751–9.

    CAS  PubMed  Google Scholar 

  8. 8.

    Lu Y, An Y, Lv C, Ma W, Xi Y, Xiao R. Dietary soy bean isoflavones in Alzheimer’s disease prevention. Asia Pac J Clin Nutr. 2018;27:946–54.

    CAS  PubMed  Google Scholar 

  9. 9.

    Matori H, Umar S, Nadadur RD, Sharma S, Partow-Navid R, et al. Genistein, a soy phytoestrogen, revers pulmonary hypertention and prevents right heart failure in rats. Hypertension. 2012;60:425–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Clarkson TB, Anthony MS, Morgan TM. Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens. J Clin Endocrinol Metab. 2001;86:41–7.

    CAS  PubMed  Google Scholar 

  11. 11.

    Ascencio C, Torres N, Isoard-Acosta F, Gomez-Perez FJ, Hernandez-Pando R, Tovar AR. Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liver in rats. J Nutr. 2004;134:522–9.

    CAS  PubMed  Google Scholar 

  12. 12.

    Kingsley K, Truong K, Low E, Hill CK, Chokshi SB, Phipps D, et al. Soy protein extract (spe) exhibits differential in vitro cell proliferation effects in oral cancer and normal cell lines. J Diet. 2011;8 Suppl:169–88.

    CAS  Google Scholar 

  13. 13.

    Kobayashi H. Prevention of cancer and inflammation by soybean inhibitors. Front Biosci. 2013;E5:966–73.

    CAS  Google Scholar 

  14. 14.

    The National Health and Nutrition Survey in Japan, 2017. Ministry of Health, Labour, and Welfare, Japan, 2018.

  15. 15.

    Bai W, Wang C, Ren C. Intakes of total and individual flavonoids by US adults. Int J Food Sci Nutr. 2014;65:9–20.

    CAS  PubMed  Google Scholar 

  16. 16.

    Mulligan AA, Kuhnle GGC, Lentjes MAH, van Scheltinga V, Powell NA, McTaggart A, et al. Intakes and sources of isoflavones, lignans, enterolignans, coumestrol and soya-containing foods in the Norfolk arm of the European prospective Investigation into Cancer and Nutrition (EPIC-Norfolk), from 7 d food diaries, using a newly updated database. Public Health Nutr. 2012;16:1454–62.

    PubMed  Google Scholar 

  17. 17.

    Wakai K, Egami I, Kato K, Kawamura T, Tamakoshi A, Lin Y, et al. Dietary intake and sources of isoflavones among Japanese. Nutr Cancer. 1999;33:139–45.

    CAS  PubMed  Google Scholar 

  18. 18.

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

    CAS  PubMed  Google Scholar 

  19. 19.

    Kim K, Vance TM, Chun OK. Estimated intake and major food soutces of flavonoids among US adults; changes between 1999-2002 and 2007-2010 in NHANES. Eur J Nutr. 2016;55:833–43.

    CAS  PubMed  Google Scholar 

  20. 20.

    Hirayama T. Life-style and mortality: a large-scale census-based cohort study in Japan. Basel, Switzerland: Karger; 1990.

    Google Scholar 

  21. 21.

    Ozasa K, Grant EJ, Kodama K. Japanese legacy cohorts: the Life Span Study atomic survivor cohort and survivors’ offspring. J Epidemiol. 2018;28:162–9.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Sauvaget C, Lagarde F, Nagano J, Soda M, Koyama K, Kodama K. Lifestyle factors, radiation and gastric cancer in atomic-bomb survivors (Japan). Cancer Causes Control. 2005;16:773–80.

    PubMed  Google Scholar 

  23. 23.

    Nippon data 80 Research Group. Impact of elevated blood pressure on mortality from all causes, cardiovascular diseases, heart disease and stroke among Japanese: 14 year follow-up of randomly selected population from Japanese. J Hum Hypertens. 2003;17:851–7.

    Google Scholar 

  24. 24.

    Khan MMH, Goto R, Kobayashi K, Suzumura S, Nagata Y, Sonoda T, et al. Dietary habits and cancer mortality among middle aged and older Japanese living in Hokkaido, Japan by cancer site and sex. Asian Pac J Cancer Prev. 2004;5:58–65.

    CAS  PubMed  Google Scholar 

  25. 25.

    Mizoue T, Tokui N, Nishisaka K, Nishisaka S, Ogimoto I, Ikeda M, et al. Prospective study on the relation of cigarette smoking with cancer of the liver and stomach in an endemic region. Int J Epidemiol. 2000;29:232–7.

    CAS  PubMed  Google Scholar 

  26. 26.

    Sekita A, Ninomiya T, Tanizaki Y, Doi Y, Hata J, Yonemoto K, et al. Trends in prevalence of Alzheimer’s disease and vascular dementia in a Japanese community: the Hisayama Study. Acta Psychiatr Scand. 2010;122:319–23.

    CAS  PubMed  Google Scholar 

  27. 27.

    Tamakoshi A, Yoshimura T, Inaba Y, Ito Y, Watanabe Y, Fukuda K, et al. Profile of the JACC study. J Epidemiol. 2005;15 Suppl 1:S4–8.

    PubMed  Google Scholar 

  28. 28.

    Tsugane S, Sawada N. The JPHC study design and some findings on the typical Japanese diet. Jpn J Clin Oncol. 2014;44:777–82.

    PubMed  Google Scholar 

  29. 29.

    Shimizu H. The basic report on Takayama Study. Gifu, Japan: Department of Public Health, Gifu University School of Medicine; 1996.

    Google Scholar 

  30. 30.

    Ishikawa S, Gotoh T, Nago N, Kayaba K. The Jichi Medical School (JMS) cohort study: design, baseline data and standardized mortality ratios. J Epidemiol. 2002;12:408–17.

    PubMed  Google Scholar 

  31. 31.

    Iki M, Tamaki J, Sato Y, Morita A, Ikeda Y, Kajita E, et al. Cohort profile: the Japanese population-based Osteoporosis (JPOS) Cohort Study. Int J Epidemiol. 2015;44:405–14.

    PubMed  Google Scholar 

  32. 32.

    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 1 Suppl:S70–6.

    PubMed  Google Scholar 

  33. 33.

    Kuriyama S, Nakaya N, Ohmori-Matuda K, Shimazu T, Kikuchi N, Kakizaki M, et al. The Ohsaki cohort 2006 study: design of study and profile of participants at baseline. J Epidemiol. 2010;20:253–8.

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Tatsumi Y, Morimoto A, Deura K, Mizuno S, Ohno Y, Watanabe S. Effects of soybean product intake on fasting and postload hyperglycemia and type 2 diabetes in Japanese men with high body mass index: the Saku study. J Diabetes Investig. 2013.

  35. 35.

    Yamamoto S, Sobue T, Sasaki S, Kobayashi M, Arai Y, Uehara M, et al. Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a Japanese population in comparison with dietary records and blood and urine Isoflavones. J Nutr. 2001;131:2741–7.

    CAS  PubMed  Google Scholar 

  36. 36.

    Nagata C, Takatsuka N, Kawakami N, Shimizu H. A prospective cohort study of soy product intake and stomach cancer death. Br J Cancer. 2002;87:31–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Kokubo Y, Iso H, Ishihara J, Okada K, Inoue M, Tsugane S. Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations. The Japan Public Health Center-based (JPHC) study cohort I. Circulation. 2007;116:2553–62.

    CAS  PubMed  Google Scholar 

  38. 38.

    Yamazaki 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.

    Google Scholar 

  39. 39.

    Nguyen HN, Miyagawa N, Miura K, Okuda N, Yoshita K, Arai Y, et al. Dietary tofu intake and long-term risk of death from stroke in a general population. Clin Nutr. 2018;37:182–8.

    PubMed  Google Scholar 

  40. 40.

    Nagata C, Wada K, Tmura T, Konoshi K, Goto Y, koda S, et al. Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study. Am J Clin Nutr. 2017;105:426–31.

    CAS  PubMed  Google Scholar 

  41. 41.

    Katagiri R, Sawada N, Goto A, Yamaji T, Iwasaki M, Noda M, et al. Association of soy and fermented soy product intake with total and cause specific mortality: prospective cohort study. BMJ. 2020;368:m34.

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro S. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull. 1995;18:1387–91.

    CAS  PubMed  Google Scholar 

  43. 43.

    Namazi N, saneei P, Larijani B, Esmaillzadeh A. Soy product consumption and the risk of all-cause, cardiovascular and cancer mortality: a systematic review and meta-analysis of cohort studies. Food Funct. 2018;9:2576.

    CAS  PubMed  Google Scholar 

  44. 44.

    Yan Z, Zhang X, Li C, Jiao S, Dong W. Association between consumption of soy and risk of cardiovascular disease: a meta-analysis of observational studies. Eur J Prev Cardiol. 2017;24:735–47.

    PubMed  Google Scholar 

  45. 45.

    Nanri A, Mizoue T, Takahashi Y, Kirii K, Inoue M, Noda M, et al. Soy product and isoflavone intakes are associated with a lower risk of type 2 diabetes in overweight Japanese women. J Nutr. 2010;140:580–6.

    CAS  PubMed  Google Scholar 

  46. 46.

    Konishi K, Wada K, Yamakawa M, Goto Y, Mizuta F, Koda S, et al. Dietary soy intake is inversely associated with risk of type 2 diabetes in Japanese women but not in men. J Nutr. 2019;149:1208–14.

    PubMed  Google Scholar 

  47. 47.

    Tang J, wan Y, Zhao M, Zhong H, Zheng JS, Feng F. Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies. Am J Clin Nutr. 2020;00:1–12.

    Google Scholar 

  48. 48.

    Key TJ, Sharp GB, Appleby PN, Beral V, Goodman MT, Soda M, et al. Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan. Br J Cancer. 1999;81:1248–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Nisho K, Niwa Y, Toyoshima H. Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study. Cancer Cause Control. 2007;18:801–8.

    Google Scholar 

  50. 50.

    Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst. 2003;95:906–13.

    CAS  PubMed  Google Scholar 

  51. 51.

    Wada K, Nakamura K, Tamai Y, Tsuji M, Kawachi T, Hori A, et al. Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study. Int J Cancer. 2013;133:952–60.

    CAS  PubMed  Google Scholar 

  52. 52.

    Nagata C, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, et al. Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2014;44:282–5.

    PubMed  Google Scholar 

  53. 53.

    Sasazuki S, Inoue M, Shimazu T, Wakai K, Naito M, Nagata C, et al. Evidence-based cancer prevention recommendations for Japanese. Jpn J Clin Oncol. 2018;48:576–86.

    CAS  PubMed  Google Scholar 

  54. 54.

    Zhao TT, Jin F, Li JG, Xu YY, Dong HT, Liu Q, et al. Dietary isoflavones or isoflavone-rich food intakeand breast cancer risk: a meta-analysis of prospective cohort studies. Clin Nutr. 2019;38:136–45.

    CAS  PubMed  Google Scholar 

  55. 55.

    Allen NE, Sauvaget C, Roddam AW, Appleby P, Nagano J, Suzuki G, et al. A prospective study of diet and prostate cancer in Japanese men. Cancer Causes Control. 2004;15:911–20.

    PubMed  Google Scholar 

  56. 56.

    Ozasa K, Nakao M, Watanabe Y, Hayashi K, Miki T, Mikami K, et al. Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men. Cancer Sci. 2004;95:65–71.

    CAS  PubMed  Google Scholar 

  57. 57.

    Kurahashi N, Iwasaki M, Sasazuki S, Otani T, Inoue M, Tsugane S. Soy product and isoflavone consumption in relation to prostate cancer in Japanese men. Cancer Epidemiol Biomark Prev. 2007;16:538–45.

    CAS  Google Scholar 

  58. 58.

    Kurahashi N, Iwasaki M, Inoue M, Sasazuki S, Tsugane S. Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center. J Clin Oncol. 2008;26:5923–9.

    PubMed  Google Scholar 

  59. 59.

    Applegate CC, Rowles III, JJ, Ranard KM, Joen S, Erdman Jr JW. Soy consumption and the risk of prostate cancer: an updated systematic review and meta-analysis. Nutrients. 2018;40.

  60. 60.

    Ngoan LT, Mizoue T, Fujino Y, Tokui N, Yoshimura T. Dietary factors and stomach cancer mortality. Br J Cancer. 2002;87:37–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Tokui N, Yoshimura T, Fujino Y, Mizoue T, Hoshiyama Y, Yatsuya H, et al. Dietary habits and stomach cancer risk in the JACC study. J Epidemiol. 2005;15Suppl 2:S96–108.

    Google Scholar 

  62. 62.

    Hara A, Sasazuki S, Inoue M, Iwasaki M, Shimazu T, Sawada N, et al. Isoflavone intake and risk of gastric cancer: a population-based prospective cohort study in Japan. Am J Clin Nutr. 2012;95:147–54.

    CAS  PubMed  Google Scholar 

  63. 63.

    Wada K, Tsuji M, Tamura T, Konishi K, Kawachi T, Hori A, et al. Soy isoflavone intake and stomach cancer risk in Japan: from the takayama study. Int J Cancer. 2015;137:885–92.

    CAS  PubMed  Google Scholar 

  64. 64.

    Oba S, Nagata C, Shimizu N, Shimizu H, Kametani M, Takeyama N, et al. Soy product consumption and the risk of colon cancer: a prospective study in Takayama. Jpn Nutr Cance r. 2007;57:151–7.

    CAS  Google Scholar 

  65. 65.

    Akhter M, Inoue M, Kurahashi N, Iwasaki M, Sasazuki S, Tsugane S. Dietary soy and isoflavone intake and risk of colorectal cancer in the Japan Public Health Center-based prospective study. Cancer Epidemiol Biomark Prev. 2008;17:2128–35.

    CAS  Google Scholar 

  66. 66.

    Kurozawa Y, Ogimoto I, Shibata A, Nose T, Yoshimura T, Suzuki H, et al. Dietary habits and risk of death due to hepatocellular carcinoma in a large scale cohort study in Japan. Univariate analysis of JACC study data. Kurum Med J. 2004;51:141–9.

    Google Scholar 

  67. 67.

    Sharp GB, Lagarde F, Mizuno T, Sauvaget C, Fukuhara T, Allen N, et al. Relationship of hepatocellular carcinoma to soya food consumption: a cohort-based, case-control study in Japan. Int J Cancer. 2005;115:290–5.

    CAS  PubMed  Google Scholar 

  68. 68.

    Kurahashi N, Inoue M, Iwasaki M, Tanaka Y, Mizukami M, Tsugane S. Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a population-based prospective cohort of Japanese men and women. Int J Cancer. 2009;124:1644–9.

    CAS  PubMed  Google Scholar 

  69. 69.

    Ozasa K, Watanabe Y, Ito Y, Suzuki K, Tamakoshi A, Seki N, et al. Dietary habits and risk of lung cancer death in a large-scale cohort study (JACC study) in Japan by sex and smoking habit. Jpn J Cancer Res. 2001;92:1259–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Shimazu T, Inoue M, sasazuki S, Iwasaki M, Sawada N, Yamaji T, et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr. 2010;91:722–8.

    CAS  PubMed  Google Scholar 

  71. 71.

    Wada K, Tsuji M, Tamura T, Konishi K, Goto Y, Mizuta F, et al. Soy isoflavone intake and bladder cancer risk in Japan: from the Takayama study. Cancer Epidemiol Biomark Prev. 2018;27:1371–5.

    CAS  Google Scholar 

  72. 72.

    Sakauchi F, Khan MMH, Mori M, Kubo T, Fujino Y, Suzuki S, et al. Dietary habits and risk of ovarian cancer death in a large-scale cohort study (JACC study) in Japan. Nutr Cancer. 2007;57:138–45.

    PubMed  Google Scholar 

  73. 73.

    Budhathoki S, Iwasaki M, Sawada N, Yamaji T, Shimazu S, Sasazuki S, et al. Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study. BJOG 2015;122:304–11.

    CAS  PubMed  Google Scholar 

  74. 74.

    Akhlaghi M, Ghasemi NM, Riasatian M, Sadeghi F. Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2019.

  75. 75.

    Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, et al. Natto intake is inversely associated with osteoporotic fracture risk in postmenopausal Japanese women. J Nutr. 2019;150:599–605.

    Google Scholar 

  76. 76.

    Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT, et al. prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med. 2005;165:1890–5.

    PubMed  Google Scholar 

  77. 77.

    Koh WP, Wu AH, Wang R, Ang LW, Heng D, Yuan JM, et al. Gender-specific association between soy and risk of hip fracture in the Singapore Chinese Health Study. Am J Epidemiol. 2009;170:901–9.

    PubMed  PubMed Central  Google Scholar 

  78. 78.

    Cauley JA, Chalhoub D, Kassem AM, Fuleihan Gel H. Geographic and ethnic disparities in osteoporotic fractures. Nat Rev Endocrinol. 2014;10:338–51.

    PubMed  Google Scholar 

  79. 79.

    Franco OH, Chowdhury R, Troup J, Voortman T, Kunutsoy S, Kavousi M, et al. Use of plant-based therapies and menopausal symptoms. A systematic review and meta-analysis. JAMA. 2016;315:2554–63.

    CAS  PubMed  Google Scholar 

  80. 80.

    Nagata C, Takatsuka N, Kawakami N, Shimizu H. Soy product intake and hot flashes in Japanese women: results from a community-based prospective study. Am J Epidemiol. 2001;153:790–3.

    CAS  PubMed  Google Scholar 

  81. 81.

    Dunneram Y, Chung HF, Cade JE, Greenwood DC, Dobson AJ, Mitchell ES, et al. Soy intake and vasomotor menopausal symptoms among midlife women: a pooled analysis of five studies from InterLACE consortium. Eur J Clin Nutr. 2019;73:1501–11.

    CAS  PubMed  Google Scholar 

  82. 82.

    Cui C, Birru RL, Snitz B, Ihara M, Higashiyama A, Kakuta C, et al. Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2020;78:134–44.

    PubMed  Google Scholar 

  83. 83.

    Ozawa M, Ninomiya T, Ohara T, Doi Y, Uchida K, Shirota T, et al. Dietary patterns and risk of dementia in an elderly Japanese population: the Hisayama Study. Am J Clin Nutr. 2013;97:1076–82.

    CAS  PubMed  Google Scholar 

  84. 84.

    Tomata Y, Sugiyama K, Kaiho Y, Honkura K, Watanabe T, Zhang S, et al. Dietary patterns and incident dementia in elderly Japanese: the Ohsaki cohort 2006 study. J Gerontol A Biol Sci Med Sci. 2016;71:1322–8.

    PubMed  Google Scholar 

  85. 85.

    Nakamoto M, Otsuka R, Nishita Y, Tange C, Tomida M, Kato Y, et al. Soy food and isoflavone intake reduces the risk of cognitive impairment in elderly Japanese women. Eur J Clin Nutr. 2018;72:1458–62.

    CAS  PubMed  Google Scholar 

  86. 86.

    Talael M, Feng L, Yuan JM, Pan A, Koh WP. Dairy, soy, and calcium consumption and risk of cognotove impairment: the Singapore Chinese Health study. Eur J Nutr. 2020;59:1541–52.

    Google Scholar 

  87. 87.

    Nagata C. Factors to consider in the association between soy isoflavone intake and breast cancer risk. J Epidemiol. 2010;20:83–9.

    PubMed  PubMed Central  Google Scholar 

  88. 88.

    Visentin S, Grumolato F, Nardelli GB, Di Camillo B, Grisan E, Cosmi E. Early origins of adult disease: low birth weight and vascular remodeling. Atherosclerosis 2014;237:391–9.

    CAS  PubMed  Google Scholar 

  89. 89.

    Trichopoulos D. Hypothesis: does breast cancer originate in utero. Lancet 1990;335:939–40.

    CAS  PubMed  Google Scholar 

  90. 90.

    Lobaccaro JA, Trousson A. Environmental estrogen exposure during fetal life: a time bomb for prostate cancer. Endocrinology. 2014;155:656–8.

    PubMed  Google Scholar 

  91. 91.

    Messina M, Rogero MM, Fisberg, Waitzberg D. Health impact of childhood and adolescent soy consumption. Nutr Rev. 2017;75:500–1.

    PubMed  Google Scholar 

  92. 92.

    Setchell KDR, Brown NM, Lydeking-Olsen E. the clinical importance of the metabolite equol—a clue to the effectiveness of soy and its isoflavones. J Nutr. 2002;132:3577–84.

    CAS  PubMed  Google Scholar 

  93. 93.

    Sekikawa A, Ihara M, Lopez O, Kakuta C, Lopresti B, Higashiyama A, et al. Effect of S-equol and soy isoflavones on heart and brain. Curr Cardiol Rev. 2019;15:114–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Zhang X, Gao YT, Yang G, Li H, Cai Q, Xiang YB, et al. Urinary isoflavonoids and risk of coronary heart disease. Int J Epidemiol. 2012;41:1367–75.

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Perez-Comago A, Appleby PN, Boeing H, Gil L, Kyrø C, Recceri F, et al. Circulating isoflavone and lignin concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls. Int J Cancer. 2018;143:2677–86.

    Google Scholar 

  96. 96.

    Ashton EL, Dalais FS, Ball MJ. Effect of meat replacement by tofu on risk factors including copper induced LDL oxidation. J Am Coll Nutr. 2000;19:761–7.

    CAS  PubMed  Google Scholar 

  97. 97.

    Azadbakht L, Kimiaga M, Mehrabi Y, Esmailzadeh A, Hu FB, Willett WC. Dietary soya intake alters plasma antioxidant status and lipid peroxidation in postmenopausal women with the metabolic syndrome. Br J Nutr. 2007;98:807–13.

    CAS  PubMed  Google Scholar 

  98. 98.

    Ruscica M, Pavenello C, Gandini S, Gomaraschi M, Vitali C, Macchi C, et al. Effect of soy on metabolic syndrome and cardiovascular risk factors: a randomized controlled trial. Eur J Nutr. 2018;57:499–51.

    CAS  PubMed  Google Scholar 

  99. 99.

    Sacks FM, Lichtenstein A, van Horn L, Harris W, Kris-Etherton P, Winston M. Soy protein, isoflavons, and cardiovascular health. An American Heart Association Science Advisory for professionals from the nutrition committee. Circulation. 2006;113:1034–44.

    CAS  PubMed  Google Scholar 

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This work is supported by the National Cancer Center Research and Development Funds (30-A-15), Japan.

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Correspondence to Chisato Nagata.

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Nagata, C. Soy intake and chronic disease risk: findings from prospective cohort studies in Japan. Eur J Clin Nutr 75, 890–901 (2021).

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