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.

  • Original Article
  • Published:

Vitamins and plant ingredients

Effect of whole soy and purified daidzein on ambulatory blood pressure and endothelial function—a 6-month double-blind, randomized controlled trial among Chinese postmenopausal women with prehypertension

European Journal of Clinical Nutrition volume 69, pages 1161–1168 (2015)Cite this article

Subjects

Abstract

Background/Objectives:

Although observational studies suggest that soy foods or isoflavones are cardio-protective, clinical trials on whole soy or isoflavone daidzein (one major isoflavone and the precursor of equol) on blood pressure (BP) and endothelial function (EF) are few and have not been specifically conducted among equol producers, a population most likely to benefit from soy treatment.

Subjects/Methods:

We performed a 6-month double-blind, randomized, placebo-controlled trial to examine the effect of whole soy (soy flour) or purified daidzein on BP and EF in prehypertensive or untreated hypertensive postmenopausal women verified to be equol producers. A total of 270 eligible women were recruited and randomized to either one of the three treatment groups, 40 g soy flour (whole soy group), 40 g low-fat milk powder+63 mg daidzein (daidzein group) or 40 g low-fat milk powder (active control group) daily, each given as a solid beverage powder for 6 months. The primary outcome measures were 24 h ambulatory BP (ABP) and EF assessed by flow-mediated dilation using brachial artery ultrasound.

Results:

A total of 253 subjects completed the study according to protocol. Urinary isoflavones indicated good compliance with the interventions. Intention to treat and per-protocol analysis indicated that there was no significant difference in the 6-month changes or % changes in parameters of ABP and brachial flow-mediated dilation among the three treatment groups. A further subgroup analysis among hypertensive women (n=138) did not alter the conclusions.

Conclusions:

Whole soy and purified daidzein had no significant effect on BP and vascular function among equol-producing postmenopausal women with prehypertension or untreated hypertension.

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

Similar content being viewed by others

References

  1. Chobanian A, Bakris G, Black H, Cushman W, Green L, Izzo J et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.

    Article  CAS  Google Scholar 

  2. Mosca L, Appel LJ, Benjamin EJ, Berra K, Chandra-Strobos N, Fabunmi RP et al. Evidence-based guidelines for cardiovascular disease prevention in women. Circulation 2004; 109: 672–693.

    Article  Google Scholar 

  3. He J, Klag M, Wu Z, Whelton P . Stroke in the People's Republic of China. II. Meta-analysis of hypertension and risk of stroke. Stroke 1995; 26: 2228–2232.

    Article  CAS  Google Scholar 

  4. August P . Initial treatment of hypertension. N Engl J Med 2003; 348: 610–617.

    Article  Google Scholar 

  5. Yang G, Shu XO, Jin F, Zhang X, Li HL, Li Q et al. Longitudinal study of soy food intake and blood pressure among middle-aged and elderly Chinese women. Am J Clin Nutr 2005; 81: 1012–1017.

    Article  CAS  Google Scholar 

  6. 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: 2553–2562.

    Article  CAS  Google Scholar 

  7. Sharma S, Singh M, Sharma P . Ameliorative effect of daidzein: a caveolin-1 inhibitor in vascular endothelium dysfunction induced by ovariectomy. Indian J Exp Biol 2012; 50: 28–34.

    CAS  PubMed  Google Scholar 

  8. Nevala R, Vaskonen T, Vehniainen J, Korpela R, Vapaatalo H . Soy based diet attenuates the development of hypertension when compared to casein based diet in spontaneously hypertensive rat. Life Sci 2000; 66: 115–124.

    Article  CAS  Google Scholar 

  9. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995; 26: 1235–1241.

    Article  CAS  Google Scholar 

  10. Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M et al. Soy protein, isoflavones, and cardiovascular health. Circulation 2006; 113: 1034–1044.

    Article  CAS  Google Scholar 

  11. Beavers D, Beavers K, Miller M, Stamey J, Messina M . Exposure to isoflavone-containing soy products and endothelial function: a Bayesian meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 2012; 22: 182–191.

    Article  CAS  Google Scholar 

  12. Roghani M, Vaez Mahdavi MR, Jalali-Nadoushan MR, Baluchnejadmojarad T, Naderi G, Roghani-Dehkordi F et al. Chronic administration of daidzein, a soybean isoflavone, improves endothelial dysfunction and attenuates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 2012; 27: 112–117.

    Article  Google Scholar 

  13. Setchell KD, 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: 3577–3584.

    Article  CAS  Google Scholar 

  14. Reinwald S, Akabas SR, Weaver CM . Whole versus the piecemeal approach to evaluating soy. J Nutr 2010; 140: 2335S–2343SS.

    Article  CAS  Google Scholar 

  15. Weaver C, Cheong J . Soy isoflavones and bone health: the relationship is still unclear. J Nutr 2005; 135: 1243–1247.

    Article  CAS  Google Scholar 

  16. Setchell K, Cole SJ . Method of defining equol-producer status and its frequency among vegetarians. J Nutr 2006; 136: 2188–2193.

    Article  CAS  Google Scholar 

  17. Liu Z, Ho S, Chen Y, Woo J . Effect of soy protein and isoflavones on blood pressure and endothelial cytokines: a 6-month randomized controlled trial among postmenopausal women. J Hypertens 2012; 29: 29.

    Google Scholar 

  18. Song T, Barua K, Buseman G, Murphy P . Soy isoflavone analysis: quality control and a new internal standard. Am J Clin Nutr 1998; 68: 1474S–1479SS.

    Article  CAS  Google Scholar 

  19. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the subcommittee of professional and public education of the american heart association council on high blood pressure research. Hypertension 2005 p 697–716.

  20. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Rand WM, Udelson JE et al. Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. J Am Coll Cardiol 2001; 38: 1843–1849.

    Article  CAS  Google Scholar 

  21. Duncan AM, Merz-Demlow BE, Xu X, Phipps WR, Kurzer MS . Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2000; 9: 581–586.

    CAS  PubMed  Google Scholar 

  22. Wu J, Oka J, Ezaki J, Ohtomo T, Ueno T, Uchiyama S et al. Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women: a double-blind, randomized, controlled trial. Menopause 2007; 14: 866–874.

    Article  Google Scholar 

  23. Liu XX, Li SH, Chen JZ, Sun K, Wang XJ, Wang XG et al. Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 2012; 22: 463–470.

    Article  CAS  Google Scholar 

  24. Meyer BJ, Larkin TA, Owen AJ, Astheimer LB, Tapsell LC, Howe PR . Limited lipid-lowering effects of regular consumption of whole soybean foods. Ann Nutr Metab 2004; 48: 67–78.

    Article  CAS  Google Scholar 

  25. Kurowska EM, Jordan J, Spence JD, Wetmore S, Piche LA, Radzikowski M et al. Effects of substituting dietary soybean protein and oil for milk protein and fat in subjects with hypercholesterolemia. Clin Invest Med 1997; 20: 162–170.

    CAS  PubMed  Google Scholar 

  26. Azadbakht L, Nurbakhsh S . Effect of soy drink replacement in a weight reducing diet on anthropometric values and blood pressure among overweight and obese female youths. Asia Pac J Clin Nutr 2011; 20: 383–389.

    CAS  PubMed  Google Scholar 

  27. Rivas M, Garay RP, Escanero JF, Cia P Jr, Cia P, Alda JO . Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. J Nutr 2002; 132: 1900–1902.

    Article  CAS  Google Scholar 

  28. Li Y, Wang J, Gao P, Guo H, Nawrot T, Wang G et al. Are published characteristics of the ambulatory blood pressure generalizable to rural Chinese? The JingNing population study. Blood Press Monit 2005; 10: 125–134.

    Article  Google Scholar 

  29. Zhao ZY, Wang YQ, Yan ZH, Cui J, Li YY . Quantitative study of circadian variations of ambulatory blood pressure in Chinese healthy, hypertensive, and diabetes subjects. Clin Exp Hypertens 2005; 27: 187–194.

    Article  Google Scholar 

  30. He J, Wofford MR, Reynolds K, Chen J, Chen CS, Myers L et al. Effect of dietary protein supplementation on blood pressure: a randomized, controlled trial. Circulation 2011; 124: 589–595.

    Article  CAS  Google Scholar 

  31. Sathyapalan T, Manuchehri AM, Thatcher NJ, Rigby AS, Chapman T, Kilpatrick ES et al. The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab 2011; 96: 1442–1449.

    Article  CAS  Google Scholar 

  32. Welty FK, Lee KS, Lew NS, Zhou JR . Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arc Intern Med 2007; 167: 1060–1067.

    Article  CAS  Google Scholar 

  33. Nestel P, Fujii A, Zhang L . An isoflavone metabolite reduces arterial stiffness and blood pressure in overweight men and postmenopausal women. Atherosclerosis 2007; 192: 184–189.

    Article  CAS  Google Scholar 

  34. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr. et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206–1252.

    Article  CAS  Google Scholar 

  35. Stamler J, Stamler R, Neaton J . Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153: 598–615.

    Article  CAS  Google Scholar 

  36. Li S, Liu X, Bai Y, Wang X, Sun K, Chen J et al. Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am J Clin Nutr 2010; 91: 480–486.

    Article  CAS  Google Scholar 

  37. Rivas M, Garay RP, Escanero JF, Cia P Jr, Cia P, Alda JO . Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. J Nutr 2002; 132: 1900–1902.

    Article  CAS  Google Scholar 

  38. Teede HJ, Dalais FS, Kotsopoulos D, Liang Y-L, Davis S, McGrath BP . Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal w omen. J Clin Endocrinol Metab 2001; 86: 3053–3060.

    CAS  PubMed  Google Scholar 

  39. Society CN Dietary Guidelines For Chinese Residents 2007. 2007; Available from: http://www.cnsoc.org/.

  40. Zhang X, Shu XO, Gao YT, Yang G, Li Q, Li H et al. Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 2003; 133: 2874–2878.

    Article  CAS  Google Scholar 

  41. 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 

  42. Kris-Etherton P, Grieger J, Hilpert K, West S . Milk products, dietary patterns and blood pressure management. J Am Coll Nutr 2009; 28: 103S–119SS.

    Article  CAS  Google Scholar 

  43. Weiss G, Skurnick J, Goldsmith L, Santoro N, Park S . Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA 2004; 292: 2991–2996.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Professor Suzanne C Ho, Dr Liu zhao-min, Prof Chen Yu-ming and Prof Jean Woo conceptualized and designed the trial and obtained the grant. Dr Liu zhao-min conducted data collection, analyzed the data and drafted the manuscript. Professor Tomlinson provided assistance in the primary outcome measures of 24 ABP. Professor Yu-ming Chen helped in urinary analysis of isoflavones and in dietary assessment. Professor Kenneth conducted the randomization and supplement labeling. Dr Stella Ho helped in training and consultation in ultrasound measurement of brachial EF of FMD.

Trial registration. The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737)

Author information

Authors and Affiliations

  1. Division of Geriatrics, Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong,, China

    Z-M Liu, B Tomlinson & J Woo

  2. Division of Epidemiology, The Jockey Club of School of Public Health and Primary Care, the Chinese University of Hong Kong, Hong Kong,, China

    S C Ho

  3. Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China

    Y-M Chen

  4. Department of Imaging and Interventional Radiology, the Chinese University of Hong Kong, Hong Kong,, China

    S Ho

  5. School of Pharmacy, the Chinese University of Hong Kong, Hong Kong,, China

    K To

Authors
  1. Z-M Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S C Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y-M Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K To
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Z-M Liu, S C Ho or J Woo.

Ethics declarations

Competing interests

The authors declare no conflict of interest. Neither the RGC-GRF nor the soy and dairy company had any role in the design and conduct of the study, the collection, analysis and interpretation of the data, or in the preparation, review or approval of the manuscript.

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

Liu, ZM., Ho, S., Chen, YM. et al. Effect of whole soy and purified daidzein on ambulatory blood pressure and endothelial function—a 6-month double-blind, randomized controlled trial among Chinese postmenopausal women with prehypertension. Eur J Clin Nutr 69, 1161–1168 (2015). https://doi.org/10.1038/ejcn.2015.24

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2015.24

This article is cited by

Search

Advanced search

Quick links