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Benefits of Soybean in the Era of Precision Medicine: A Review of Clinical Evidence

  • Jung Hyun Kang (Department of Food and Nutrition, Gyeongsang National University) ;
  • Zigang Dong (Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University) ;
  • Seung Ho Shin (Department of Food and Nutrition, Gyeongsang National University)
  • 투고 : 2023.08.11
  • 심사 : 2023.08.21
  • 발행 : 2023.12.28

초록

Soybean (Glycine max) is an important ingredient of cuisines worldwide. While there is a wealth of evidence that soybean could be a good source of macronutrients and phytochemicals with healthpromoting effects, concerns regarding adverse effects have been raised. In this work, we reviewed the current clinical evidence focusing on the benefits and risks of soybean ingredients. In breast, prostate, colorectal, ovarian, and lung cancer, epidemiological studies showed an inverse association between soybean food intake and cancer risks. Soybean intake was inversely correlated with risks of type 2 diabetes mellitus (T2DM), and soy isoflavones ameliorated osteoporosis and hot flashes. Notably, soybean was one of the dietary protein sources that may reduce the risk of breast cancer and T2DM. However, soybean had adverse effects on certain types of drug treatment and caused allergies. In sum, this work provides useful considerations for planning clinical soybean research and selecting dietary protein sources for human health.

키워드

과제정보

This work was supported by the National Natural Science Foundation of China (No. 82002620, No. 81972839, NO. 8207112153, Z.D.), the Science and Technology Project of Henan Province (No. 212102310698, NO. 222102310102, Z.D.) and the National Research Foundation of Korea grant funded by the Korean government (MSIP) (NRF-2021R1C1C1013592).

참고문헌

  1. Khojely DM, Ibrahim SE, Sapey E, Han T. 2018. History, current status, and prospects of soybean production and research in sub-Saharan Africa. Crop. J. 6: 226-235.
  2. Shin D, Jeong D. 2015. Korean traditional fermented soybean products: Jang. J. Ethnic Foods 2: 2-7.
  3. Ibrahim SA. 2020. Microbiology and technology of fermented foods. J. Dairy Res. 87: 138-139.
  4. Zhang P, Zhang P, Wu J, Tao D, Wu R. 2019. Effects of Leuconostoc mesenteroides on physicochemical and microbial succession characterization of soybean paste, Da-jiang. LWT 115: 108028.
  5. Tamang JP, Anupma A, Nakibapher Jones Shangpliang H. 2022. Ethno-microbiology of Tempe, an Indonesian fungal-fermented soybean food and Koji, a Japanese fungal starter culture. Curr. Opin. Food Sci. 48: 100912.
  6. Kharnaior P, Tamang JP. 2021. Bacterial and fungal communities and their predictive functional profiles in kinema, a naturally fermented soybean food of India, Nepal and Bhutan. Food Res. Int. 140: 110055.
  7. Yang H, Yang L, Zhang J, Li H, Tu Z, Wang X. 2019. Exploring functional core bacteria in fermentation of a traditional Chinese food, Aspergillus-type douchi. PLoS One 14: e0226965.
  8. Han DM, Chun BH, Feng T, Kim HM, Jeon CO. 2020. Dynamics of microbial communities and metabolites in ganjang, a traditional Korean fermented soy sauce, during fermentation. Food Microbiol. 92: 103591.
  9. Ghosh K, Kang HS, Hyun WB, Kim KP. 2018. High prevalence of Bacillus subtilis-infecting bacteriophages in soybean-based fermented foods and its detrimental effects on the process and quality of Cheonggukjang. Food Microbiol. 76: 196-203.
  10. Kusumoto KI, Yamagata Y, Tazawa R, Kitagawa M, Kato T, Isobe K, et al. 2021. Japanese traditional Miso and Koji making. J. Fungi (Basel) 7: 579.
  11. Wang F, Meng J, Sun L, Weng Z, Fang Y, Tang X, et al. 2020. Study on the tofu quality evaluation method and the establishment of a model for suitable soybean varieties for Chinese traditional tofu processing. LWT 117: 108441.
  12. Ding J, Wen J, Wang J, Tian R, Yu L, Jiang L, et al. 2020. The physicochemical properties and gastrointestinal fate of oleosomes from non-heated and heated soymilk. Food Hydrocoll. 100: 105418.
  13. Messina M, Rogero MM, Fisberg M, Waitzberg D. 2017. Health impact of childhood and adolescent soy consumption. Nutr. Rev. 75: 500-515.
  14. Mortensen A, Kulling SE, Schwartz H, Rowland I, Ruefer CE, Rimbach G, et al. 2009. Analytical and compositional aspects of isoflavones in food and their biological effects. Mol. Nutr. Food Res. 53: S266-S309.
  15. Springmann M, Godfray HC, Rayner M, Scarborough P. 2016. Analysis and valuation of the health and climate change cobenefits of dietary change. Proc. Natl. Acad. Sci. USA 113: 4146-4151.
  16. McClements DJ, Grossmann L. 2021. A brief review of the science behind the design of healthy and sustainable plant-based foods. NPJ Sci. Food 5: 17.
  17. Messina M, Sievenpiper JL, Williamson P, Kiel J, Erdman Jr JW. 2022. Perspective: soy-based meat and dairy alternatives, despite classification as ultra-processed foods, deliver high-quality nutrition on par with unprocessed or minimally processed animalbased counterparts. Adv. Nutr. 13: 726-738.
  18. Blanco Mejia S, Messina M, Li SS, Viguiliouk E, Chiavaroli L, Khan TA, et al. 2019. A Meta-analysis of 46 studies identified by the FDA demonstrates that soy protein decreases circulating LDL and total cholesterol concentrations in adults. J. Nutr. 149: 968-981.
  19. Food and Drug Administration. 2017. Food Labeling: Health Claims; Soy Protein and Coronary Heart Disease. Fed. Regist. 82: 50324-50346.
  20. Gu L, House SE, Prior RL, Fang N, Ronis MJ, Clarkson TB, et al. 2006. Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys, and women. J. Nutr. 136: 1215-1221.
  21. Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. 2018. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392: 1736-1788.
  22. Siegel RL, Miller KD, Wagle NS, Jemal A. 2023. Cancer statistics, 2023. CA Cancer J. Clin. 73: 17-48.
  23. Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. 2020. Epidemiology of type 2 diabetes-global burden of disease and forecasted trends. J. Epidemiol. Glob. Health 10: 107.
  24. Zimmet P, Alberti KG, Magliano DJ, Bennett PH. 2016. Diabetes mellitus statistics on prevalence and mortality: facts and fallacies. Nat. Rev. Endocrinol. 12: 616-622.
  25. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, et al. 1999. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 100: 1134-1146.
  26. Ji M-X, Yu Q. 2015. Primary osteoporosis in postmenopausal women. Chronic Dis. Transl. Med. 1: 9-13.
  27. Tang S, Du Y, Oh C, No J. 2020. Effects of soy foods in postmenopausal women: a focus on osteosarcopenia and obesity. J. Obes. Metab. Syndr. 29: 180.
  28. Chatterjee C, Gleddie S, Xiao CW. 2018. Soybean bioactive peptides and their functional properties. Nutrients 10: 1211.
  29. Mourtzinis S, Gaspar AP, Naeve SL, Conley SP. 2017. Planting date, maturity, and temperature effects on soybean seed yield and composition. Agron. J. 109: 2040-2049.
  30. Vasconcellos F, Woiciechowski A, Soccol V, Mantovani D, Soccol C. 2014. Antimicrobial and antioxidant properties of-conglycinin and glycinin from soy protein isolate. Int. J. Curr. Microbiol. Appl. Sci. 3: 144-157.
  31. Wang Y, Wang Z, Handa CL, Xu J. 2017. Effects of ultrasound pre-treatment on the structure of β-conglycinin and glycinin and the antioxidant activity of their hydrolysates. Food Chem. 218: 165-172.
  32. Sitohy MZ, Mahgoub SA, Osman AO. 2012. In vitro and in situ antimicrobial action and mechanism of glycinin and its basic subunit. Int. J. Food Microbiol. 154: 19-29.
  33. Xu J, Zhou A, Wang Z, Ai D. 2010. Effects of glycinin and β-conglycinin on integrity and immune responses of mouse intestinal epithelial cells. J. Anim. Plant Sci. 20: 170-174.
  34. Rebollo-Hernanz M, Bringe NA, Gonzalez de Mejia E. 2022. Selected soybean varieties regulate hepatic LDL-cholesterol homeostasis depending on their glycinin: β-conglycinin ratio. Antioxidants 12: 20.
  35. Wang W, Bringe NA, Berhow MA, Gonzalez de Mejia E. 2008. β-Conglycinins among sources of bioactives in hydrolysates of different soybean varieties that inhibit leukemia cells in vitro. J. Agric. Food Chem. 56: 4012-4020.
  36. Lammi C, Zanoni C, Arnoldi A. 2015. Three peptides from soy glycinin modulate glucose metabolism in human hepatic HepG2 cells. Int. J. Mol. Sci. 16: 27362-27370.
  37. Ravindranath MH, Muthugounder S, Presser N, Viswanathan S. 2004. Anticancer therapeutic potential of soy isoflavone, genistein. Adv. Exp. Med. Biol. 546: 121-165.
  38. Lee CH, Yang L, Xu JZ, Yeung SYV, Huang Y, Chen Z-Y. 2005. Relative antioxidant activity of soybean isoflavones and their glycosides. Food Chem. 90: 735-741.
  39. Hsiao Y-H, Ho C-T, Pan M-H. 2020. Bioavailability and health benefits of major isoflavone aglycones and their metabolites. J. Funct. Foods 74: 104164.
  40. Rizzo G, Baroni L. 2018. Soy, soy foods and their role in vegetarian diets. Nutrients 10: 43.
  41. Sui X, Zhang T, Jiang L. 2021. Soy protein: molecular structure revisited and recent advances in processing technologies. Ann. Rev. Food Sci. Technol. 12: 119-147.
  42. Zhang T, Dou W, Zhang X, Zhao Y, Zhang Y, Jiang L, et al. 2021. The development history and recent updates on soy protein-based meat alternatives. Trends Food Sci. Technol. 109: 702-710.
  43. Rader AFB, Weinmuller M, Reichart F, Schumacher-Klinger A, Merzbach S, Gilon C, et al. 2018. Orally active peptides: is there a magic bullet? Angew. Chem. Int. Ed. Engl. 57: 14414-14438.
  44. Cruz-Casas DE, Aguilar CN, Ascacio-Valdes JA, Rodriguez-Herrera R, Chavez-Gonzalez ML, Flores-Gallegos AC. 2021. Enzymatic hydrolysis and microbial fermentation: the most favorable biotechnological methods for the release of bioactive peptides. Food Chem. 3: 100047.
  45. Jayachandran M, Xu B. 2019. An insight into the health benefits of fermented soy products. Food Chem. 271: 362-371.
  46. Liu L, Chen X, Hao L, Zhang G, Jin Z, Li C, et al. 2022. Traditional fermented soybean products: processing, flavor formation, nutritional and biological activities. Crit. Rev. Food Sci. Nutr. 62: 1971-1989.
  47. Messina M, Nagata C, Wu AH. 2006. Estimated Asian adult soy protein and isoflavone intakes. Nutr. Cancer 55: 1-12.
  48. Dai Q, Shu XO, Jin F, Potter JD, Kushi LH, Teas J, et al. 2001. Population-based case-control study of soyfood intake and breast cancer risk in Shanghai. Br. J. Cancer 85: 372-378.
  49. Kim MK, Kim JH, Nam SJ, Ryu S, Kong G. 2008. Dietary intake of soy protein and tofu in association with breast cancer risk based on a case-control study. Nutr. Cancer 60: 568-576.
  50. Woo HW, Kim MK, Lee YH, Shin DH, Shin MH, Choi BY. 2018. Habitual consumption of soy protein and isoflavones and risk of metabolic syndrome in adults ≥ 40 years old: a prospective analysis of the Korean Multi-Rural Communities Cohort Study (MRCohort). Eur. J. Nutr. 58: 2835-2850.
  51. Ho SC, Woo JL, Leung SS, Sham AL, Lam TH, Janus ED. 2000. Intake of soy products is associated with better plasma lipid profiles in the Hong Kong Chinese population. J. Nutr. 130: 2590-2593.
  52. Nagata C. 2000. Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan. Int. J. Epidemiol. 29: 832-836.
  53. Xiao CW. 2008. Health effects of soy protein and isoflavones in humans. J. Nutr. 138: 1244S-1249S.
  54. Wang H-j, Murphy PA. 1994. Isoflavone content in commercial soybean foods. J. Agric. Food Chem. 42: 1666-1673.
  55. Ceccarelli I, Bioletti L, Peparini S, Solomita E, Ricci C, Casini I, et al. 2022. Estrogens and phytoestrogens in body functions. Neurosci.Biobehav. Rev. 132: 648-663.
  56. Kostelac D, Rechkemmer G, Briviba K. 2003. Phytoestrogens modulate binding response of estrogen receptors alpha and beta to the estrogen response element. J. Agric. Food Chem. 51: 7632-7635.
  57. Morito K, Hirose T, Kinjo J, Hirakawa T, Okawa M, Nohara T, et al. 2001. Interaction of phytoestrogens with estrogen receptors alpha and beta. Biol. Pharm. Bull. 24: 351-356.
  58. Munro IC, Harwood M, Hlywka JJ, Stephen AM, Doull J, Flamm WG, et al. 2003. Soy isoflavones: a safety review. Nutr. Rev. 61: 1-33.
  59. Zaheer K, Humayoun Akhtar M. 2017. An updated review of dietary isoflavones: nutrition, processing, bioavailability and impacts on human health. Crit. Rev. Food Sci Nutr. 57: 1280-1293.
  60. Ganesan K, Xu B. 2017. A Critical review on polyphenols and health benefits of black soybeans. Nutrients 9: 455.
  61. Joannou GE, Kelly GE, Reeder AY, Waring M, Nelson C. 1995. A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J. Steroid Biochem. Mol. Biol. 54: 167-184.
  62. Matthies A, Loh G, Blaut M, Braune A. 2012. Daidzein and genistein are converted to equol and 5-hydroxy-equol by human intestinal Slackia isoflavoniconvertens in gnotobiotic rats. J. Nutr. 142: 40-46.
  63. Bhathena SJ, Velasquez MT. 2002. Beneficial role of dietary phytoestrogens in obesity and diabetes. Am. J. Clin. Nutr. 76: 1191-1201.
  64. Pabich M, Materska M. 2019. Biological effect of soy isoflavones in the prevention of civilization diseases. Nutrients 11: 1660.
  65. Ishihara J, Sobue T, Yamamoto S, Sasaki S, Tsugane S, Group JS. 2003. Demographics, lifestyles, health characteristics, and dietary intake among dietary supplement users in Japan. Int. J. Epidemiol. 32: 546-553.
  66. Somekawa Y, Chiguchi M, Ishibashi T, Aso T. 2001. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet. Gynecol. 97: 109-115.
  67. Nagata C, Takatsuka N, Kawakami N, Shimizu H. 2001. Soy product intake and premenopausal hysterectomy in a follow-up study of Japanese women. Eur. J. Clin. Nutr. 55: 773-777.
  68. Yamamoto S, Sobue T, Sasaki S, Kobayashi M, Arai Y, Uehara M, et al. 2001. Validity and reproducibility of a self-administered foodfrequency questionnaire to assess isoflavone intake in a japanese population in comparison with dietary records and blood and urine isoflavones. J. Nutr. 131: 2741-2747.
  69. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N. 2000. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J. Nutr. 130:2243-2250.
  70. Frankenfeld CL, Lampe JW, Shannon J, Gao DL, Ray RM, Prunty J, et al. 2004. Frequency of soy food consumption and serum isoflavone concentrations among Chinese women in Shanghai. Public Health Nutr. 7: 765-772.
  71. Liu Z, Li W, Sun J, Liu C, Zeng Q, Huang J, et al. 2004. Intake of soy foods and soy isoflavones by rural adult women in China. Asia Pac. J. Clin. Nutr. 13: 204-209.
  72. Chen Z, Zheng W, Custer LJ, Dai Q, Shu XO, Jin F, et al. 1999. Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai. Nutr. Cancer 33: 82-87.
  73. Yang G, Shu XO, Jin F, Zhang X, Li HL, Li Q, et al. 2005. Longitudinal study of soy food intake and blood pressure among middleaged and elderly Chinese women. Am. J. Clin. Nutr. 81: 1012-1017.
  74. Kim J, Kwon C. 2001. Estimated dietary isoflavone intake of Korean population based on National Nutrition Survey. Nutr. Res. 21: 947-953.
  75. Lee MJ, Kim JH. 2007. Estimated dietary isoflavone intake among Korean adults. Nutr. Res. Pract. 1: 206-211.
  76. Jakes RW, Duffy SW, Ng FC, Gao F, Ng EH, Seow A, et al. 2002. Mammographic parenchymal patterns and self-reported soy intake in Singapore Chinese women. Cancer Epidemiol. Biomarkers Prev. 11: 608-613.
  77. de Kleijn MJ, van der Schouw YT, Wilson PW, Adlercreutz H, Mazur W, Grobbee DE, et al. 2001. Intake of dietary phytoestrogens is low in postmenopausal women in the United States: the Framingham study(1-4). J. Nutr. 131: 1826-1832.
  78. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, et al. 2001. Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am. J. Epidemiol. 154: 434-441.
  79. Messina M. 2016. Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients 8: 754.
  80. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. 2011. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am. J. Clin. Nutr. 93: 950-962.
  81. Nachvak SM, Moradi S, Anjom-Shoae J, Rahmani J, Nasiri M, Maleki V, et al. 2019. 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 119: 1483-1500.e.17.
  82. Baena Ruiz R, Salinas Hernandez P. 2016. Cancer chemoprevention by dietary phytochemicals: epidemiological evidence. Maturitas 94: 13-19.
  83. Rosen PP, Menendez-Botet CJ, Nisselbaum JS, Urban JA, Mike V, Fracchia A, et al. 1975. Pathological review of breast lesions analyzed for estrogen receptor protein. Cancer Res. 35: 3187-3194.
  84. Dong JY, Qin LQ. 2011. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res. Treat. 125: 315-323.
  85. Chen M, Rao Y, Zheng Y, Wei S, Li Y, Guo T, et al. 2014. Association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women: a meta-analysis of epidemiological studies. PLoS One 9: e89288.
  86. Wu YC, Zheng D, Sun JJ, Zou ZK, Ma ZL. 2015. Meta-analysis of studies on breast cancer risk and diet in Chinese women. Int. J. Clin. Exp. Med. 8: 73-85.
  87. Woo HD, Park S, Oh K, Kim HJ, Shin HR, Moon HK, et al. 2014. Diet and cancer risk in the Korean population: a meta- analysis. Asian Pac. J. Cancer Prev. 15: 8509-8519.
  88. Wei Y, Lv J, Guo Y, Bian Z, Gao M, Du H, et al. 2020. Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose-response meta-analysis. Eur. J. Epidemiol. 35: 567-578.
  89. Yang J, Shen H, Mi M, Qin Y. 2023. Isoflavone consumption and risk of breast cancer: an updated systematic review with metaanalysis of observational studies. Nutrients 15: 2402.
  90. Ioannis Boutas, Adamantia Kontogeorgi, Constantine Dimitrakakis, Sophia N Kalantaridou. 2022. Soy isoflavones and breast cancer risk: a meta-analysis. In Vivo 36: 556-562.
  91. Tan MM, Ho WK, Yoon SY, Mariapun S, Hasan SN, Lee DS, et al. 2018. A case-control study of breast cancer risk factors in 7,663 women in Malaysia. PLoS One 13: e0203469.
  92. Qiu S, Jiang C. 2018. Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and metaanalysis. Eur. J. Nutr. 58: 3079-3090.
  93. Kang X, Zhang Q, Wang S, Huang X, Jin S. 2010. Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy. CMAJ 182: 1857-1862.
  94. Woo HD, Park KS, Ro J, Kim J. 2012. Differential influence of dietary soy intake on the risk of breast cancer recurrence related to HER2 status. Nutr. Cancer 64: 198-205.
  95. Chi F, Wu R, Zeng YC, Xing R, Liu Y, Xu ZG. 2013. Post-diagnosis soy food intake and breast cancer survival: a meta-analysis of cohort studies. Asian Pac. J. Cancer Prev. 14: 2407-2412.
  96. Baglia ML, Zheng W, Li H, Yang G, Gao J, Gao YT, et al. 2016. The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status. Int. J. Cancer 139: 742-748.
  97. Wu J, Zeng R, Huang J, Li X, Zhang J, Ho JC, et al. 2016. Dietary protein sources and incidence of breast cancer: a dose-response meta-analysis of prospective studies. Nutrients 8: 730.
  98. Zhao TT, Jin F, Li JG, Xu YY, Dong HT, Liu Q, et al. 2019. Dietary isoflavones or isoflavone-rich food intake and breast cancer risk: a meta-analysis of prospective cohort studies. Clin. Nutr. 38: 136-145.
  99. Wu AH, Yu MC, Tseng CC, Pike MC. 2008. Epidemiology of soy exposures and breast cancer risk. Br. J. Cancer 98: 9-14.
  100. Haas GP, Delongchamps N, Brawley OW, Wang CY, de la Roza G. 2008. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. Can. J. Urol. 15: 3866-3871.
  101. Applegate CC, Rowles JL, Ranard KM, Jeon S, Erdman JW. 2018. Soy consumption and the risk of prostate cancer: an updated systematic review and meta-analysis. Nutrients 10: 40.
  102. Dalais FS, Meliala A, Wattanapenpaiboon N, Frydenberg M, Suter DA, Thomson WK, et al. 2004. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urology 64: 510-515.
  103. Pendleton JM, Tan WW, Anai S, Chang M, Hou W, Shiverick KT, et al. 2008. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy. BMC Cancer 8: 132.
  104. Fleshner NE, Kapusta L, Donnelly B, Tanguay S, Chin J, Hersey K, et al. 2011. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J. Clin. Oncol. 29: 2386-2390.
  105. Bosland MC, Kato I, Zeleniuch-Jacquotte A, Schmoll J, Enk Rueter E, Melamed J, et al. 2013. Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial. JAMA 310: 170-178.
  106. Ko KP, Yeo Y, Yoon JH, Kim CS, Tokudome S, Ngoan LT, et al. 2018. Plasma phytoestrogens concentration and risk of colorectal cancer in two different Asian populations. Clin. Nutr. 37: 1675-1682.
  107. Tse G, Eslick GD. 2016. Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis. Eur. J. Nutr. 55: 63-73.
  108. Yan L, Spitznagel EL, Bosland MC. 2010. Soy consumption and colorectal cancer risk in humans: a meta-analysis. Cancer Epidemiol. Biomarkers Prev. 19: 148-158.
  109. Hua X, Yu L, You R, Yang Y, Liao J, Chen D, et al. 2016. Association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk: a meta-analysis. PLoS One 11: e0151134.
  110. Qu XL, Fang Y, Zhang M, Zhang YZ. 2014. Phytoestrogen intake and risk of ovarian cancer: a meta- analysis of 10 observational studies. Asian Pac. J. Cancer Prev. 15: 9085-9091.
  111. Yang WS, Va P, Wong MY, Zhang HL, Xiang YB. 2011. Soy intake is associated with lower lung cancer risk: results from a metaanalysis of epidemiologic studies. Am. J. Clin. Nutr. 94: 1575-1583.
  112. Wu SH, Liu Z. 2013. Soy food consumption and lung cancer risk: a meta-analysis using a common measure across studies. Nutr. Cancer 65: 625-632.
  113. American Diabetes A. 2021. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2021. Diabetes Care 44: S15-S33.
  114. Li W, Ruan W, Peng Y, Wang D. 2018. Soy and the risk of type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies. Diabetes Res. Clin. Pract. 137: 190-199.
  115. Pearce M, Fanidi A, Bishop TRP, Sharp SJ, Imamura F, Dietrich S, et al. 2021. Associations of total legume, pulse, and soy consumption with incident type 2 diabetes: federated meta-analysis of 27 studies from diverse world regions. J. Nutr. 151: 1231-1240.
  116. Tian S, Xu Q, Jiang R, Han T, Sun C, Na L. 2017. Dietary protein consumption and the risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies. Nutrients 9: 982.
  117. Liu ZM, Chen YM, Ho SC. 2011. Effects of soy intake on glycemic control: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 93: 1092-1101.
  118. Yang B, Chen Y, Xu T, Yu Y, Huang T, Hu X, et al. 2011. Systematic review and meta-analysis of soy products consumption in patients with type 2 diabetes mellitus. Asia Pac. J. Clin. Nutr. 20: 593-602.
  119. Kanis JA, Melton LJ, 3rd, Christiansen C, Johnston CC, Khaltaev N. 1994. The diagnosis of osteoporosis. J. Bone Miner. Res. 9: 1137-1141.
  120. Lorentzon M, Cummings SR. 2015. Osteoporosis: the evolution of a diagnosis. J. Intern. Med. 277: 650-661.
  121. Eastell R, Szulc P. 2017. Use of bone turnover markers in postmenopausal osteoporosis. Lancet Diabetes Endocrinol. 5: 908-923.
  122. Nielsen TF, Ravn P, Bagger YZ, Warming L, Christiansen C. 2004. Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study. Osteoporos Int. 15: 168-174.
  123. Pouilles JM, Tremollieres F, Ribot C. 1995. Effect of menopause on femoral and vertebral bone loss. J. Bone Miner. Res. 10: 1531-1536.
  124. Akhlaghi M, Ghasemi Nasab M, Riasatian M, Sadeghi F. 2019. Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials. Crit. Rev. Food Sci. Nutr. 60: 2327-2341.
  125. Kanadys W, Baranska A, Blaszczuk A, Polz-Dacewicz M, Drop B, Malm M, et al. 2021. Effects of soy isoflavones on biochemical markers of bone metabolism in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Int. J. Environ. Res. Public Health 18: 5346.
  126. Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, et al. 2015. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern. Med. 175: 531-539.
  127. Adlercreutz H, Hamalainen E, Gorbach S, Goldin B. 1992. Dietary phyto-oestrogens and the menopause in Japan. Lancet 339: 1233.
  128. Taku K, Melby MK, Kronenberg F, Kurzer MS, Messina M. 2012. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. Menopause 19: 776-790.
  129. James W Daily, Byoung-Seob Ko, Jina Ryuk, Meiling Liu, Weijun Zhang, Sunmin Park. 2019. Equol decreases hot flashes in postmenopausal women: a systematic review and meta-analysis of randomized clinical trials. J. Med. Food 22: 127-139.
  130. Bode AM, Dong Z. 2015. Toxic phytochemicals and their potential risks for human cancer. Cancer Prev. Res. 8: 1-8.
  131. Demers LM. 1994. Effects of Fadrozole (CGS 16949A) and Letrozole (CGS 20267) on the inhibition of aromatase activity in breast cancer patients. Breast Cancer Res. Treat. 30: 95-102.
  132. van Duursen MB, Nijmeijer SM, de Morree ES, de Jong PC, van den Berg M. 2011. Genistein induces breast cancer-associated aromatase and stimulates estrogen-dependent tumor cell growth in in vitro breast cancer model. Toxicology 289: 67-73.
  133. Ju YH, Doerge DR, Woodling KA, Hartman JA, Kwak J, Helferich WG. 2008. Dietary genistein negates the inhibitory effect of letrozole on the growth of aromatase-expressing estrogen-dependent human breast cancer cells (MCF-7Ca) in vivo. Carcinogenesis 29: 2162-2168.
  134. Florsheim EB, Sullivan ZA, Khoury-Hanold W, Medzhitov R. 2021. Food allergy as a biological food quality control system. Cell 184: 1440-1454.
  135. Kay AB. 2000. Overview of 'allergy and allergic diseases: with a view to the future'. Br. Med. Bull. 56: 843-864.
  136. Aalberse RC, Akkerdaas J, van Ree R. 2001. Cross-reactivity of IgE antibodies to allergens. Allergy 56: 478-490.
  137. Cabanillas B, Jappe U, Novak N. 2018. Allergy to peanut, soybean, and other legumes: recent advances in allergen characterization, stability to processing and IgE cross-reactivity. Mol. Nutr. Food Res. 62. doi: 10.1002/mnfr.201700446. Epub 2017 Nov 3.
  138. Cox AL, Eigenmann PA, Sicherer SH. 2021. Clinical relevance of cross-reactivity in food allergy. J. Allergy Clin. Immunol. Pract. 9: 82-99.
  139. Sicherer SH, Sampson HA. 2006. 9. Food allergy. J. Allergy Clin. Immunol. 117: S470-475.
  140. Savage JH, Kaeding AJ, Matsui EC, Wood RA. 2010. The natural history of soy allergy. J. Allergy Clin. Immunol. 125: 683-686.
  141. Komata T, Soderstrom L, Borres MP, Tachimoto H, Ebisawa M. 2009. Usefulness of wheat and soybean specific IgE antibody titers for the diagnosis of food allergy. Allergol. Int. 58: 599-603.
  142. Cordle CT. 2004. Soy protein allergy: incidence and relative severity. J. Nutr. 134: 1213S-1219S.
  143. Wilson S, Blaschek K, de Mejia E. 2005. Allergenic proteins in soybean: processing and reduction of P34 allergenicity. Nutr. Rev. 63: 47-58.
  144. Magishi N, Yuikawa N, Kobayashi M, Taniuchi S. 2017. Degradation and removal of soybean allergen in Japanese soy sauce. Mol. Med. Rep. 16: 2264-2268.
  145. Quaas AM, Kono N, Mack WJ, Hodis HN, Felix JC, Paulson RJ, et al. 2013. Effect of isoflavone soy protein supplementation on endometrial thickness, hyperplasia, and endometrial cancer risk in postmenopausal women: a randomized controlled trial. Menopause 20: 840-844.
  146. Hamilton-Reeves JM, Banerjee S, Banerjee SK, Holzbeierlein JM, Thrasher JB, Kambhampati S, et al. 2013. Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial. PLoS One 8: e68331.
  147. Shike M, Doane AS, Russo L, Cabal R, Reis-Filho JS, Gerald W, et al. 2014. The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study. J. Natl. Cancer Inst. 106: dju189.