The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials

Abstract

Purpose

Some but not all randomized controlled trials (RCTs) of soy isoflavones showed their beneficial effect on arterial stiffness, a predictor of cardiovascular events, dementia, and all-cause mortality, independent of traditional risk factors. To test the hypothesis that supplementation of soy isoflavones reduces arterial stiffness, we performed a systematic review and meta-analysis of RCTs of soy isoflavones on arterial stiffness.

Methods

The protocol of this systematic review was registered with PROSPERO (CRD42019126128) and written in accordance with PRISMA. The PubMed, Embase, and clinicaltrials.gov databases were searched using the following criteria: human subjects, soy isoflavones as intervention, and arterial stiffness as primary outcome. A random-effects meta-analysis was used to pool estimates across studies. Standardized mean difference (SMD) was used to synthesize quantitative results.

Results

Among 998 articles retrieved, 8 articles met our criteria. Duration of intervention was relatively short (maximum of 12 weeks). Outcome measurements extracted were pulse wave velocity (PWV), systemic arterial compliance (SAC), augmentation index (AI), and cardio-ankle vascular index (CAVI). Soy isoflavones reduced arterial stiffness compared to placebo (standardized mean difference − 0.33, 95% confidence interval − 0.47, − 0.19). Subgroup analyses showed no difference between treatment effects for intervention duration (< 6 weeks vs. ≥ 6 weeks) or gender (women only vs. men only vs. combined). Sensitivity analysis showed no difference in the effect of soy isoflavones between PWV, CAVI, SAC, and AI.

Conclusion

Supplementation of soy isoflavones reduced arterial stiffness. Longer duration trials with larger number of participants are warranted.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. 1.

    Townsend RR, Wilkinson IB, Schiffrin EL, Avolio AP, Chirinos JA, Cockcroft JR et al (2015) Recommendations for improving and standardizing vascular research on arterial stiffness: a scientific statement from the american heart association. Hypertension (Dallas, Tex:1979) 66(3):698–722

    CAS  Google Scholar 

  2. 2.

    Cui C, Sekikawa A, Kuller LH, Lopez OL, Newman AB, Kuipers AL et al (2018) Aortic stiffness is associated with increased risk of incident dementia in older adults. J Alzheimer's Dis 66(1):297–306

    CAS  Google Scholar 

  3. 3.

    Vlachopoulos C, Aznaouridis K, Stefanadis C (2010) Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 55(13):1318–1327

    PubMed  Google Scholar 

  4. 4.

    Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA et al (2006) Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation 113(5):657–663

    Google Scholar 

  5. 5.

    Messina M (2016) Soy and health update: evaluation of the clinical and epidemiologic literature. Nutrients 8:12

    Google Scholar 

  6. 6.

    Wang Q, Ge X, Tian X, Zhang Y, Zhang J, Zhang P (2013) Soy isoflavone: the multipurpose phytochemical (review). Biomed Rep 1(5):697–701

    CAS  PubMed  Google Scholar 

  7. 7.

    Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, Watanabe S (2007) Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 85(4):1148–1156

    CAS  PubMed  Google Scholar 

  8. 8.

    Liu XX, Li SH, Chen JZ, Sun K, Wang XJ, Wang XG et al (2012) Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials. Nutr Metabol Cardiovasc Dis 22(6):463–470

    CAS  Google Scholar 

  9. 9.

    Zhuo XG, Melby MK, Watanabe S (2004) Soy isoflavone intake lowers serum LDL cholesterol: a meta-analysis of 8 randomized controlled trials in humans. J Nutr 134(9):2395–2400

    CAS  PubMed  Google Scholar 

  10. 10.

    Uemura H, Katsuura-Kamano S, Nakamoto M, Yamaguchi M, Fujioka M, Iwasaki Y et al (2018) Inverse association between soy food consumption, especially fermented soy products intake and soy isoflavone, and arterial stiffness in Japanese men. Sci Rep 8(1):9667

    PubMed  Google Scholar 

  11. 11.

    Ohkuma T, Ninomiya T, Tomiyama H, Kario K, Hoshide S, Kita Y et al (2017) Brachial-ankle pulse wave velocity and the risk prediction of cardiovascular disease: an individual participant data meta-analysis. Hypertension (Dallas, Tex: 1979) 69(6):1045–1052

    CAS  Google Scholar 

  12. 12.

    Vlachopoulos C, Aznaouridis K, Terentes-Printzios D, Ioakeimidis N, Stefanadis C (2012) Prediction of cardiovascular events and all-cause mortality with brachial-ankle elasticity index: a systematic review and meta-analysis. Hypertension (Dallas, Tex: 1979) 60(2):556–562

    CAS  Google Scholar 

  13. 13.

    Hazim S, Curtis PJ, Schär MY, Ostertag LM, Kay CD, Minihane AM et al (2016) Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. Am J Clin Nutr 103(3):694–702

    CAS  PubMed  Google Scholar 

  14. 14.

    Nestel PJ, Yamashita T, Sasahara T, Pomeroy S, Dart A, Komesaroff P et al (1997) Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol 17(12):3392–3398

    CAS  PubMed  Google Scholar 

  15. 15.

    Reverri EJ, LaSalle CD, Franke AA, Steinberg FM (2015) Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol Nutr Food Res 59(2):323–333

    CAS  PubMed  Google Scholar 

  16. 16.

    Richter CK, Skulas-Ray AC, Fleming JA, Link CJ, Mukherjea R, Krul ES et al (2017) Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial. Br J Nutr 117(10):1403–1413

    CAS  PubMed  Google Scholar 

  17. 17.

    Teede HJ, Dalais FS, Kotsopoulos D, Liang YL, Davis S, McGrath BP (2001) Dietary soy has both beneficial and potentially adverse cardiovascular effects: a placebo-controlled study in men and postmenopausal women. J Clin Endocrinol Metab 86(7):3053–3060

    CAS  PubMed  Google Scholar 

  18. 18.

    Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ (2003) Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol 23(6):1066–1071

    CAS  PubMed  Google Scholar 

  19. 19.

    Tormala R, Appt S, Clarkson TB, Groop PH, Ronnback M, Ylikorkala O et al (2008) Equol production capability is associated with favorable vascular function in postmenopausal women using tibolone; no effect with soy supplementation. Atherosclerosis 198(1):174–178

    PubMed  Google Scholar 

  20. 20.

    Usui T, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A et al (2013) Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol 78(3):365–372

    CAS  Google Scholar 

  21. 21.

    Pase MP, Grima NA, Sarris J (2011) The effects of dietary and nutrient interventions on arterial stiffness: a systematic review. Am J Clin Nutr 93(2):446–454

    CAS  PubMed  Google Scholar 

  22. 22.

    PRISMA (2015) Preferred reporting items for systematic reviews and meta-analyses (PRISMA). https://www.prisma-statement.org/ Accessed 10 June 2020

  23. 23.

    Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (2019). Cochrane handbook for systematic reviews of interventions version 6.0 (updated July 2019). https://www.training.cochrane.org/handbook. Accessed 10 June 2020

  24. 24.

    Pereira T, Correia C, Cardoso J (2015) Novel methods for pulse wave velocity measurement. J Med Biol Eng 35(5):555–565

    PubMed  Google Scholar 

  25. 25.

    Matsushita K, Ding N, Kim ED, Budoff M, Chirinos JA, Fernhall B et al (2019) Cardio-ankle vascular index and cardiovascular disease: systematic review and meta-analysis of prospective and cross-sectional studies. J Clin Hypertens (Greenwich, Conn) 21(1):16–24

    CAS  Google Scholar 

  26. 26.

    Laskey WK, Parker HG, Ferrari VA, Kussmaul WG, Noordergraaf A (1990) Estimation of total systemic arterial compliance in humans. J Appl Physiol (Bethesda, Md: 1985) 69(1):112–119

    CAS  Google Scholar 

  27. 27.

    Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ (2000) The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol 525(Pt 1):263–270

    CAS  PubMed  Google Scholar 

  28. 28.

    Lilamand M, Kelaiditi E, Guyonnet S, Antonelli Incalzi R, Raynaud-Simon A, Vellas B et al (2014) Flavonoids and arterial stiffness: promising perspectives. Nutr Metabol Cardiovasc Dis 24(7):698–704

    CAS  Google Scholar 

  29. 29.

    Morito K, Aomori T, Hirose T, Kinjo J, Hasegawa J, Ogawa S et al (2002) Interaction of phytoestrogens with estrogen receptors alpha and beta (II). Biol Pharmaceut Bull 25(1):48–52

    CAS  Google Scholar 

  30. 30.

    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 Pharmaceut Bull 24(4):351–356

    CAS  Google Scholar 

  31. 31.

    Goszcz K, Duthie GG, Stewart D, Leslie SJ, Megson IL (2017) Bioactive polyphenols and cardiovascular disease: chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response? Br J Pharmacol 174(11):1209–1225

    CAS  PubMed  Google Scholar 

  32. 32.

    Zhang H, Tsao R (2016) Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr Opin Food Sci 8:33–42

    Google Scholar 

  33. 33.

    Taku K, Lin N, Cai D, Hu J, Zhao X, Zhang Y et al (2010) Effects of soy isoflavone extract supplements on blood pressure in adult humans: systematic review and meta-analysis of randomized placebo-controlled trials. J Hypertens 28(10):1971–1982

    CAS  PubMed  Google Scholar 

  34. 34.

    Wiseman H, O'Reilly JD, Adlercreutz H, Mallet AI, Bowey EA, Rowland IR et al (2000) Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 72(2):395–400

    CAS  PubMed  Google Scholar 

  35. 35.

    Li Y, Zhang H (2017) Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2-mediated antioxidant responses. Food Funct 8(8):2935–2944

    CAS  PubMed  Google Scholar 

  36. 36.

    Charles C, Yuskavage J, Carlson O, John M, Tagalicud AS, Maggio M et al (2009) Effects of high-dose isoflavones on metabolic and inflammatory markers in healthy postmenopausal women. Menopause (NY) 16(2):395–400

    Google Scholar 

  37. 37.

    Ferguson JF, Ryan MF, Gibney ER, Brennan L, Roche HM, Reilly MP (2014) Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers. Nutr Metabol Cardiovasc Dis 24(9):996–1003

    CAS  Google Scholar 

  38. 38.

    Jenkins DJ, Kendall CW, Connelly PW, Jackson CJ, Parker T, Faulkner D et al (2002) Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism Clin Exper 51(7):919–924

    CAS  Google Scholar 

  39. 39.

    Ryan-Borchers TA, Park JS, Chew BP, McGuire MK, Fournier LR, Beerman KA (2006) Soy isoflavones modulate immune function in healthy postmenopausal women. Am J Clin Nutr 83(5):1118–1125

    CAS  PubMed  Google Scholar 

  40. 40.

    Hughes TM, Kuller LH, Barinas-Mitchell EJ, Mackey RH, McDade EM, Klunk WE et al (2013) Pulse wave velocity is associated with beta-amyloid deposition in the brains of very elderly adults. Neurology 81(19):1711–1718

    CAS  PubMed  Google Scholar 

  41. 41.

    Hughes TM, Kuller LH, Barinas-Mitchell EJ, McDade EM, Klunk WE, Cohen AD et al (2014) Arterial stiffness and beta-amyloid progression in nondemented elderly adults. JAMA Neurol 71(5):562–568

    PubMed  Google Scholar 

  42. 42.

    Cui C, Birru RL, Snitza BE, Ihara M, Kakuta C et al (2020) Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 78:134–144

    PubMed  Google Scholar 

Download references

Acknowledgements

The present systematic review and meta-analysis is funded in part by the National Institutes of Health (NIH) grants (NIEHS) R21 ES029734 and (NIA) RF1 AG051615.

Author information

Affiliations

Authors

Contributions

CC, BM, AS, and XZ were essential to the entire research process including formulating the research question, designing and carrying out the study, and providing revisions at every stage. EB-M and DS provided crucial insight into the analysis of data and revision of intellectual content including careful examination of the article along with corresponding tables/figures. BM drafted the article and ran statistical analysis under the counsel of the other authors.

Corresponding author

Correspondence to Akira Sekikawa.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest in relation to this research.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Man, B., Cui, C., Zhang, X. et al. The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr (2020). https://doi.org/10.1007/s00394-020-02300-6

Download citation

Keywords

  • Soy isoflavones
  • Arterial stiffness
  • Meta-analysis
  • Randomized controlled trials