Epidemiologic studies highlight soy’s potential associations with prevention of cancer, CVD, and diabetes

Epidemiologic studies are not designed to establish cause and effect relationships because it is not possible to control for all potentially confounding variables. Additionally, it is difficult to accurately assess dietary intake. Nevertheless, epidemiologic studies have played an important role in informing dietary guidelines. Although intervention studies carry the most weight within the scientific community, their expense and complexity limit their utility. For example, due to the necessary size and duration, a clinical study evaluating the effect of diet on the prevention of cardiovascular events in a healthy population is not feasible. In contrast, this type of endpoint is routinely examined in observational studies.

Prospective studies, as opposed to cross-sectional and case-control studies, are the most credible type of epidemiologic study. For this reason, a recently published scoping review of meta-analyses of prospective studies that examined the impact of soy consumption on a range of chronic diseases is especially notable. Yip et al.1 identified 28 meta-analyses published between 2000 and 2021 that analyzed associations between soy intake and cardiovascular disease, cancer, and type II diabetes. Six of these meta-analyses were judged to be of high quality, 10 as moderate quality and 12 low quality. Estimates from 11 reports were identified as the best-identified meta-analysis estimate for total soy intakes.

As shown in Table 1, of the 27 values reported, all show relative risks below 1.0 except for 1 outcome (gastric cancer and fermented soy intake) and of the 26 relative risks below 1.0, all were significant except 1 (total soy intake and cancer mortality). In other words, a very consistent pattern emerges which is that soy and isoflavone intake is associated with protection against several cancers, CVD, and diabetes. The positive association between fermented soy intake and gastric cancer is not a new observation. More than 20 years ago, this relationship was identified in a meta-analysis by Wu et al.2  A number of explanations for this association have been proposed including the salt content of and nitroso compounds in fermented soy and a possible loss of antioxidants with fermentation.3

In addition to the publication by Yip et al.,1 in a large recently published cross-sectional study involving nearly 30,000 Chinese adults, soy intake was associated with higher handgrip strength.4 Handgrip strength is increasingly viewed as an indication of overall frailty. Bohannon5 recently concluded that the use of grip strength can be recommended as a stand-alone measurement or as a component of a small battery of measurements for identifying older adults at risk of poor health status. Handgrip strength is inversely related to mortality.6,7

In this Chinese study by Wu et al.,4 after adjustments, handgrip strength increased in a stepwise fashion according to soy intake. More specifically, handgrip strength (kg) was 35.5, 36.1, 36.3, and 36.6 among men and women who consumed soy less than once per week, once per week, 2-3 times per week and at least 4 times per week, respectively. The odds ratios of having low handgrip strength (<28 kg, men; <18 kg, women) was inversely related to soy intake. Both findings were statistically significant.

When considering the research by Yip et al.,1 and Wu et al.,4 soy intake is associated with higher handgrip strength, an overall measure of frailty, and with protection against several chronic diseases. Is it biologically plausible that soy could exert such benefits? Certainly, the effect on handgrip strength could be related to the protein content of soyfoods, a possibility discussed by Wu et al.4 And the isoflavones in soy have pleiotropic effects that could result in their reducing risk of different types of cancers.8  It could also be that the lifestyles of consumers of soyfoods are different from those of non-consumers, and the overall lifestyle, not soy per se, accounts for these beneficial associations. Findings are typically adjusted for a considerable number of potentially confounding variables but as noted at the onset, it is not possible to control for all such variables.

On the other hand, the differences between soy-consumers and non-soy-consumers in Asia, where these studies were conducted, is likely to be a lot less than the differences among these groups in non-Asian countries. In any event, these recent epidemiologic findings certainly suggest that at the very least, soyfood consumption is compatible with better overall health.

Table 1.  Relative risks when comparing high vs low intake

References

1. Yip CSC, Yip YC, and Chan W. The associations of soya intakes with non-communicable diseases: a scoping review of meta-analyses. Br J Nutr 2023;129(135-146).

2. Wu AH, Yang D, and Pike MC. A meta-analysis of soyfoods and risk of stomach cancer: the problem of potential confounders. Cancer Epidemiol Biomarkers Prev 2000;9(10):1051-8.

3. Kim J, Kang M, Lee JS, Inoue M, Sasazuki S, and Tsugane S. Fermented and non-fermented soy food consumption and gastric cancer in Japanese and Korean populations: a meta-analysis of observational studies. Cancer Sci 2011;102(1):231-44.

4. Wu H, Quan J, Wang X, Gu Y, Zhang S, Meng G, Zhang Q, Liu L, Wang X, Sun S, et al. Soy Food Consumption Is Inversely Associated with Handgrip Strength: Results from the TCLSIH Cohort Study. Nutrients 2023;15(2):

5. Bohannon RW. Grip strength: An indispensable biomarker for older adults. Clin Interv Aging 2019;14(1681-1691).

6. Lopez-Bueno R, Andersen LL, Calatayud J, Casana J, Grabovac I, Oberndorfer M, and Del Pozo Cruz B. Associations of handgrip strength with all-cause and cancer mortality in older adults: a prospective cohort study in 28 countries. Age Ageing 2022;51(5):

7. Kim J. Handgrip strength to predict the risk of all-cause and premature mortality in Korean adults: A 10-year cohort study. Int J Environ Res Public Health 2022;19(39).

8. Bernatoniene J, Kazlauskaite JA, and Kopustinskiene DM. Pleiotropic Effects of Isoflavones in Inflammation and Chronic Degenerative Diseases. Int J Mol Sci 2021;22(11):

9. Nachvak SM, Moradi S, Anjom-Shoae J, Rahmani J, Nasiri M, Maleki V, and Sadeghi O. 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;119(9):1483-1500 e17.

10. Yan Z, Zhang X, Li C, Jiao S, and Dong W. Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies. Eur J Prev Cardiol 2017;24(7):735-747.

11. Li W, Ruan W, Peng Y, and Wang D. Soy and the risk of type 2 diabetes mellitus: A systematic review and meta-analysis of observational studies. Diabetes Res Clin Pract 2018;137(190-199).

12. Yang WS, Va P, Wong MY, Zhang HL, and Xiang YB. Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies. Am J Clin Nutr 2011;94(6):1575-83.

13. Tse G and Eslick GD. Soy and isoflavone consumption and risk of gastrointestinal cancer: a systematic review and meta-analysis. Eur J Nutr 2016;55(1):63-73.

14. Lu D, Pan C, and Ye C. Meta-analysis of soy consumption and gastrointestinal cancer risk. Sci Rep 2017;7(4048).

15. Yu Y, Jing X, Li H, Zhao X, and Wang D. Soy isoflavone consumption and colorectal cancer risk: a systematic review and meta-analysis. Sci Rep 2016;6(25939).

16. Myung SK, Ju W, Choi HJ, and Kim SC. Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis. BJOG 2009;116(13):1697-705.

17. Zhang GQ, Chen JL, Liu Q, Zhang Y, Zeng H, and Zhao Y. Soy intake is associated with lower endometrial cancer risk: A systematic review and meta-analysis of observational studies. Medicine (Baltimore) 2015;94(50):e2281.

18. Zhong X and Zhang C. Soy food intake and breast cancer risk: a meta-analysis, Sun. J Hygiene Res 2012;41(670–676).

19. Yan L and Spitznagel EL. Soy consumption and prostate cancer risk in men: a revisit of a meta-analysis. Am J Clin Nutr 2009;89(4):1155-63.

20. Applegate CC, Rowles JL, Ranard KM, Jeon S, and Erdman JW. Soy consumption and the risk of prostate cancer: An updated systematic review and meta-analysis. Nutrients 2018;10(1):

21. Namazi N, Saneei P, Larijani B, and Esmaillzadeh A. Soy product consumption and the risk of all-cause, cardiovascular and cancer mortality: a systematic review and meta-analysis of cohort studies. Food Funct 2018;9(5):2576-2588.

22. Wei Y, Lv J, Guo Y, Bian Z, Gao M, Du H, Yang L, Chen Y, Zhang X, Wang T, et al. Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose-response meta-analysis. Eur J Epidemiol 2020;35(6):567-578.

 This blog is sponsored by SNI Global and U.S. Soy.