The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption
Open accessAbstract
Some epidemiologic studies reported an association between a low ratio of urinary 2-hydroxyestrogens (2-hydroxyestradiol + 2-hydroxyestrone) to 16alpha-hydroxyestrone (2:16OHE(1)) and increased breast cancer risk. Some studies show that soy consumption increases this ratio, and it is suggested that this effect may reduce breast cancer risk. We hypothesized that consumption of probiotic bacteria would alter fecal bacteria and enzymes involved in soy isoflavone metabolism, thereby increasing isoflavone bioavailability and enhancing the beneficial effects of soy on estrogen metabolism. Breast cancer survivors (n = 20) and controls (n = 20) were given 4 treatments for 6 wk each, separated by 2-wk washout periods, in a randomized, crossover design: soy protein (26.6 +/- 4.5 g protein/d containing 44.4 +/- 7.5 mg isoflavones/d); soy protein + probiotics (10(9) colony-forming units Lactobacillus acidophilus DDS(R)+1 & Bifidobacterium longum, 15-30 mg fructooligosaccharide/d); milk protein (26.6 +/- 4.5 g protein/d); and milk protein + probiotics. Survivors tended to have a lower baseline urine 2:16OHE(1) ratio than controls (P = 0.10). In the group as a whole, soy consumption tended to increase urinary 2-hydroxyestrogens (P = 0.07) and 16alpha-hydroxyestrone (P = 0.11) but had no effect on the urinary 2:16OHE(1) ratio. When subjects were divided into groups by plasma concentrations and urinary levels of the daidzein metabolite equol, soy increased urinary 2-hydroxyestrogens (P = 0.01) and the 2:16OHE(1) ratio (P = 0.04) only in subjects with high plasma equol concentrations. None of these results were influenced by probiotic consumption. These results are consistent with studies that found lower urine 2:16OHE(1) ratios in women with breast cancer and suggest that soy consumption increases this ratio only in women who are equol producers.
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The remaining three RCTs found significant increases in 2-hydroxyestrone or 2:16α hydroxyestrone ratio.
“The remaining three studies found significant increases in 2-hydroxyestrone or 2:16α hydroxyestrone ratio [141,152,154], which has been thought to represent an anticancer shift in estrogen metabolism.”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [141]
The Results (page not provided) report that soy significantly increased urinary 2-hydroxyestrogens and the 2:16α-hydroxyestrone ratio in equol producers. The citing sentence omits that qualification: neither increase was significant in nonproducers, and the ratio did not increase in the group as a whole. (LLM, conf=0.88)
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- Swaneck, G. E. & Fishman, J. (1988) Covalent binding of the endog- enous estrogen 16 alpha-hydroxyestrone to estradiol receptor in human breast cancer cells: characterization and intranuclear localization. Proc. Natl. Acad. Sci.
- Bradlow, H. L., Hershcopf, R. J., Martucci, C. P. & Fishman, J. (1985) Estradiol 16 alpha-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans. Proc. Natl. Acad. Sci. U.S.A. 82: 6295-6299.
- Schneider, J., Kinne, D., Fracchia, A., Pierce, V., Anderson, K. E., Brad- low, H. L. & Fishman, J. (1982) Abnormal oxidative metabolism of estradiol in women with breast cancer. Proc. Natl. Acad. Sci. U.S.A. 79: 3047-3051.
- Lampe, J. W., Karr, S. C., Hutchins, A. M. & Slavin, J. L. (1998) Urinary equol excretion with a soy challenge: influence of habitual diet. Proc. Soc. Exp. Biol. Med. 217: 335-339.
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Mayo, B., Vázquez, L., & Flórez, A. B. (2019) · Nutrients · doi:10.3390/nu11092231 · Cited by 416 · see citing works
Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review
Fritz, H., Seely, D., Flower, G., Skidmore, B., Fernandes, R., Vadeboncoeur, S., Kennedy, D., Cooley, K., Wong, R., Sagar, S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081968 · Cited by 188 · see citing works
Wu, W. H., Lu, S. C., Wang, T. F., Jou, H. J., & Wang, T. A. (2006) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602328 · Cited by 70 · see citing works
- Authors
- Nettleton, J. A., Greany, K. A., Thomas, W., Wangen, K. E., Adlercreutz, H., & Kurzer, M. S.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Kurzer, Mindy S.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 135
- Issue
- 3
- Pages
- 603-608
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W1906526942
- Cited by
- 62
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 6 · 2012: 7
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- University of Minnesota (MO1-RR00400)
- Johnson and Johnson
- U.S. Army
- National Center for Research Resources (M01RR000400, RR00-400, MO 1 RR00400)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- soy consumption, equol, soy isoflavones, estrogen metabolism, breast cancer risk, postmenopausal women, probiotics, Lactobacillus acidophilus, Bifidobacterium longum, fructooligosaccharides
- MeSH terms
- Bifidobacterium, Breast Neoplasms, Estrogens, Feeding Behavior, Female, Humans, Hydroxyestrones, Isoflavones, Lactobacillus acidophilus, Middle Aged, Reference Values, Glycine max, Postmenopause, Probiotics, Equol
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