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. 2019 Sep;119(9):1483-1500.e17. doi: 10.1016/j.jand.2019.04.011. Epub 2019 Jul 2.


Objective: We conducted a systematic review and dose-response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases.

Methods: Online databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose-response associations. Between-study heterogeneity was assessed by I2 value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test.

Results: In total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I2=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I2=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality.

Conclusions: Soy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.

Keywords: Cancer; Isoflavones; Meta-analysis; Mortality; Soy foods.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Breast Neoplasms / mortality
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Cohort Studies
  • Diet / mortality*
  • Female
  • Glycine max* / chemistry
  • Humans
  • Isoflavones / administration & dosage*
  • Male
  • Neoplasms / mortality*
  • Prospective Studies
  • Risk Factors
  • Soybean Proteins / administration & dosage*


  • Isoflavones
  • Soybean Proteins