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.

  • Original Article
  • Published:


Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts



Evidence regarding the consumption of soy foods and isoflavones in relation to risk of type 2 diabetes (T2D) is scarce. Our study was to evaluate the association between soy food and isoflavone consumption and risk of T2D in US men and women.


We followed 63 115 women in the Nurses’ Health Study (1998–2012), 79 061 women in the Nurses’ Health Study II (1999–2013) and 21 281 men in the Health Professionals Follow-Up Study (2002–2010). Diet was assessed by a validated food-frequency questionnaire and was updated every 4 years. Self-reports of incident T2D were confirmed by a validated supplementary questionnaire.


During 1 966 321 person-years of follow-up, 9185 incident T2D cases were documented. After multivariate adjustment for covariates, consumption of soy foods (tofu and soy milk) was not associated with a lower T2D risk. Compared with non-consumers of soy foods, the hazard ratio (HR) was 1.00 (95% confidence interval (CI): 0.93, 1.07) for <1 serving/week and 0.93 (95% CI: 0.83, 1.03) for 1 serving/week of soy foods (P for trend=0.14). In contrast, intake of total isoflavones was inversely associated with T2D risk. Comparing extreme quintiles of isoflavones, the HR was 0.89 (95% CI: 0.83, 0.96; P for trend=0.009). Inverse associations were also found for consumption of major individual isoflavones, including daidzein and genistein, with risk of T2D.


Intake of isoflavones was associated with a modestly lower T2D risk in US men and women who typically consumed low-to-moderate amounts of soy foods. These findings warrant replications in other populations with similar soy intake levels.

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

Similar content being viewed by others


  1. International Diabetes Federation IDF Diabetes Atlas, 6th edn. International Diabetes Federation: Brussels, Belgium, 2013.

  2. Hu FB . Do functional foods have a role in the prevention of cardiovascular disease? Circulation 2011; 124: 538–540.

    Article  Google Scholar 

  3. Muraki I, Imamura F, Manson JE, Hu FB, Willett WC, van Dam RM et al. Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies. BMJ 2013; 347: f5001.

    Article  Google Scholar 

  4. van Dam RM, Hu FB . Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005; 294: 97–104.

    Article  CAS  Google Scholar 

  5. Ding M, Bhupathiraju SN, Chen M, van Dam RM, Hu FB . Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis. Diabetes Care 2014; 37: 569–586.

    Article  Google Scholar 

  6. Bhagwat S, Haytowitz DB, Holden JM. USDA Database for the Isoflavone Content of Selected Foods, Release 2.0 U.S. Department of Agriculture: Beltsville, MD, USA, 2008.

  7. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L . Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004; 79: 727–747.

    Article  CAS  Google Scholar 

  8. Muthyala RS, Ju YH, Sheng S, Williams LD, Doerge DR, Katzenellenbogen BS et al. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem 2004; 12: 1559–1567.

    Article  CAS  Google Scholar 

  9. Kostelac D, Rechkemmer G, Briviba K . Phytoestrogens modulate binding response of estrogen receptors alpha and beta to the estrogen response element. J Agric Food Chem 2003; 51: 7632–7635.

    Article  CAS  Google Scholar 

  10. Ricci E, Cipriani S, Chiaffarino F, Malvezzi M, Parazzini F . Effects of soy isoflavones and genistein on glucose metabolism in perimenopausal and postmenopausal non-Asian women: a meta-analysis of randomized controlled trials. Menopause 2010; 17: 1080–1086.

    Article  Google Scholar 

  11. Liu ZM, Chen YM, Ho SC . Effects of soy intake on glycemic control: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2011; 93: 1092–1101.

    Article  CAS  Google Scholar 

  12. Yang B, Chen Y, Xu T, Yu Y, Huang T, Hu X et al. Systematic review and meta-analysis of soy products consumption in patients with type 2 diabetes mellitus. Asia Pac J Clin Nutr 2011; 20: 593–602.

    CAS  PubMed  Google Scholar 

  13. Sievenpiper JL, Kendall CW, Esfahani A, Wong JM, Carleton AJ, Jiang HY et al. Effect of non-oil-seed pulses on glycaemic control: a systematic review and meta-analysis of randomised controlled experimental trials in people with and without diabetes. Diabetologia 2009; 52: 1479–1495.

    Article  CAS  Google Scholar 

  14. Zamora-Ros R, Forouhi NG, Sharp SJ, González CA, Buijsse B, Guevara M et al. The association between dietary flavonoid and lignan intakes and incident type 2 diabetes in European populations: the EPIC-InterAct study. Diabetes Care 2013; 36: 3961–3970.

    Article  CAS  Google Scholar 

  15. Feskanich D, Rimm EB, Giovannucci EL, Colditz GA, Stampfer MJ, Litin LB et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc 1993; 93: 790–796.

    Article  CAS  Google Scholar 

  16. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB, Willett WC et al. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol 1992; 135: 1114–1126 (discussion 1127–1136).

    Article  CAS  Google Scholar 

  17. Salvini S, Hunter DJ, Sampson L, Stampfer MJ, Colditz GA, Rosner B et al. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol 1989; 18: 858–867.

    Article  CAS  Google Scholar 

  18. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi J et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol 1985; 122: 51–65.

    Article  CAS  Google Scholar 

  19. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–1197.

  20. Manson JE, Rimm EB, Stampfer MJ, Colditz GA, Willett WC, Krolewski AS et al. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet 1991; 338: 774–778.

    Article  CAS  Google Scholar 

  21. Hu FB, Leitzmann MF, Stampfer MJ, Colditz GA, Willett WC, Rimm EB . Physical activity and television watching in relation to risk for type 2 diabetes mellitus in men. Arch Intern Med 2001; 161: 1542–1548.

    Article  CAS  Google Scholar 

  22. Villegas R, Gao YT, Yang G, Li HL, Elasy TA, Zheng W et al. Legume and soy food intake and the incidence of type 2 diabetes in the Shanghai Women's Health Study. Am J Clin Nutr 2008; 87: 162–167.

    Article  CAS  Google Scholar 

  23. Mueller NT, Odegaard AO, Gross MD, Koh WP, Yu MC, Yuan JM et al. Soy intake and risk of type 2 diabetes in Chinese Singaporeans [corrected]. Eur J Nutr 2012; 51: 1033–1040.

    Article  CAS  Google Scholar 

  24. 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: 580–586.

    Article  CAS  Google Scholar 

  25. Morimoto Y, Steinbrecher A, Kolonel LN, Maskarinec G . Soy consumption is not protective against diabetes in Hawaii: the Multiethnic Cohort. Eur J Clin Nutr 2011; 65: 279–282.

    Article  CAS  Google Scholar 

  26. Messina MJ, Wood CE . Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutr J 2008; 7: 17.

    Article  Google Scholar 

  27. Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N et al. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr 2003; 133: 1238–1243.

    Article  CAS  Google Scholar 

  28. Kim S, Sohn I, Ahn JI, Lee KH, Lee YS, Lee YS . Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model. Gene 2004; 340: 99–109.

    Article  CAS  Google Scholar 

  29. Mezei O, Li Y, Mullen E, Ross-Viola JS, Shay NF . Dietary isoflavone supplementation modulates lipid metabolism via PPARalpha-dependent and -independent mechanisms. Physiol Genomics 2006; 26: 8–14.

    Article  CAS  Google Scholar 

  30. Babu PV, Liu D, Gilbert ER . Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 2013; 24: 1777–1789.

    Article  CAS  Google Scholar 

  31. Cederroth CR, Vinciguerra M, Gjinovci A, Kühne F, Klein M, Cederroth M et al. Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism. Diabetes 2008; 57: 1176–1185.

    Article  CAS  Google Scholar 

  32. Barros RP, Gustafsson JA . Estrogen receptors and the metabolic network. Cell Metab 2011; 14: 289–299.

    Article  CAS  Google Scholar 

  33. Misso ML, Murata Y, Boon WC, Jones ME, Britt KL, Simpson ER . Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse. Endocrinology 2003; 144: 1474–1480.

    Article  CAS  Google Scholar 

Download references


This study was funded by research grants CA186107, CA176726, CA167552, DK58845, DK58785 and DK082486 from the National Institutes of Health. Dr Sun was supported by a career development award R00HL098459 from the National Heart, Lung and Blood Institute. The funding sources had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors are not affiliated with the funding institutions.

Author contributions

QS and FBH obtained funding from the National Institutes of Health. MD, analyzed the data and wrote the first draft of the manuscript. AP, JAEM, WCW, VM, BR and EG contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. QS is the guarantor of this investigation.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Q Sun.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, M., Pan, A., Manson, J. et al. Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts. Eur J Clin Nutr 70, 1381–1387 (2016).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links