Urinary phytoestrogens and cancer, cardiovascular, and all-cause mortality in the continuous National Health and Nutrition Examination Survey
Experimental studies suggest that phytoestrogen intake alters cancer and cardiovascular risk. This study investigated the associations of urinary phytoestrogens with total cancer (n = 79), cardiovascular (n = 108), and all-cause (n = 290) mortality among 5179 participants in the continuous National Health and Nutrition Examination Survey (1999–2004).
Urinary phytoestrogens were measured using high-performance liquid chromatography with tandem mass spectrometric detection. Survival analysis was performed to evaluate hazard ratios (HRs) and 95 % confidence intervals (CIs) for each of the three outcomes in relation to urinary phytoestrogens.
After adjustment for confounders, higher urinary concentrations of total enterolignans were associated with a reduced risk of death from cardiovascular disease (HR for tertile 3 vs. tertile 1 0.48; 95 % CI 0.24, 0.97), whereas higher urinary concentrations of total isoflavones (HR for tertile 3 vs. tertile 1 2.14; 95 % CI 1.03, 4.47) and daidzein (HR for tertile 3 vs. tertile 1 2.05; 95 % CI 1.02, 4.11) were associated with an increased risk. A reduction in all-cause mortality was observed for elevated urinary concentrations of total enterolignans (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.43, 0.96) and enterolactone (HR for tertile 3 vs. tertile 1 0.65; 95 % CI 0.44, 0.97).
Some urinary phytoestrogens were associated with cardiovascular and all-cause mortality in a representative sample of the US population. This is one of the first studies that used urinary phytoestrogens as biomarkers of their dietary intake to evaluate the effect of these bioactive compounds on the risk of death from cancer and cardiovascular disease.
KeywordsCancer Cardiovascular disease Cohort study Mortality Urinary phytoestrogens
There was no specific funding for reported research.
Conflict of interest
The authors declare that they have no conflict of interest.
The de-identified data analyzed in the present study are freely available in public domains, and the approval for such data analysis by the Institutional Review Board of Indiana University was sought but determined not to be applicable.
- 1.Murphy SL, Xu J, Kochanek KD (2013) Deaths: final data for 2010. Centers for Disease Control and Prevention, AtlantaGoogle Scholar
- 2.World Health Organization (2013) The top 10 causes of death: Fact Sheet Number 310Google Scholar
- 3.Latest world cancer statistics—Press release number 223 (2013) World Health Organization, Lyon Google Scholar
- 7.Thomas BF, Zeisel SH, Busby MG, Hill JM, Mitchell RA, Scheffler NM, Brown SS, Bloeden LT, Dix KJ, Jeffcoat AR (2001) Quantitative analysis of the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversed-phase high-performance liquid chromatography with ultraviolet detection. J Chromatogr B Biomed Sci Appl 760(2):191–205CrossRefGoogle Scholar
- 11.Lampe JW (2003) Isoflavonoid and lignan phytoestrogens as dietary biomarkers. J Nutr 133(Suppl):956S–964SGoogle Scholar
- 16.Branham WA, Dial SL, Moland CL, Hass BS, Blair RM, Fang H, Shi L, Tong W, Perkins RG, Sheehan DM (2002) Phytoestrogens and mycoestrogens bind to the rat uterine estrogen receptor. J Nutr 132(4):658–664Google Scholar
- 19.Kuipper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139(10):4252–4263Google Scholar
- 22.Weber KS, Setchell KD, Stocco DM, Lephart ED (2001) Dietary soy-phytoestrogens decrease testosterone levels and prostate weight without altering LH, prostate 5-alpha-reductase or testicular steroidogenic acute regulatory peptide levels in adult male Sprague-Dawley rats. J Endocrinol 170(3):591–599CrossRefGoogle Scholar
- 25.Ziegler RG (2004) Phytoestrogens and breast cancer. Am J Clin Nutr 79(2):183–184Google Scholar
- 32.Seow A, Shi CY, Franke AA, Hankin JH, Lee HP, Yu MC (1998) Isoflavonoid levels in spot urine are associated with frequency of dietary soy intake in a population-based sample of middle aged and older Chinese in Singapore. Cancer Epidemiol Biomarkers Prev 7:135–140Google Scholar
- 34.Maskarinec G, Singh S, Meng L, Franke AA (1998) Dietary soy intake and urinary isoflavone excretion among women from a multiethnic population. Cancer Epidemiol Biomarkers Prev 7(7):613–619Google Scholar
- 35.Jaceldo-Siegl K, Fraser GE, Chan J, Franke A, Sabate J (2008) Validation of soy protein estimates from a food-frequency questionnaire with repeated 24-h recalls and isoflavonoid excretion in overnight urine in a western population with a wide range of soy intakes. Am J Clin Nutr 87(5):1422–1427Google Scholar
- 36.Lampe JW, Gustafson DR, Hutchins AM, Martini MC, Li S, Wahala K, Grandits GA, Potter JD, Slavin JL (1999) Urinary isoflavonoid and lignan excretion on a western diet: relation to soy, vegetable, and fruit intake. Cancer Epidemiol Biomarkers Prev 8:699–707Google Scholar
- 37.NHANES (1999–2004) Public-use Linked Mortality Files (2006) (2013) National Health and Nutrition Examination SurveyGoogle Scholar
- 38.NHANES 1999–2000 Public Data Release File Documentation (2000). US Department of Health and Human Services, Centers for Disease Control and Prevention, HyattsvilleGoogle Scholar
- 39.Analytic and Reporting Guidelines: The National Health and Nutrition Examination Survey (NHANES) (2006) Centers for Disease Control and Prevention, HyattsvilleGoogle Scholar
- 41.Parker DL (2004) Division of laboratory sciences laboratory protocol: phytoestrogens. National Center for Health Statistics, HyatsvilleGoogle Scholar
- 42.National Health and Nutrition Examination Survey (1999-2004) Linked Mortality Files (2009) Office of Analysis and Epidemiology, HyatsvilleGoogle Scholar
- 50.Rao CV, Wang C-X, Simi B, Lubet R, Kelloff G, Steele V, Reddy BS (1997) Enhancement of experimental colon cancer by genistein. Cancer Res 57:3717–3722Google Scholar
- 62.Carmeliet P, Ng YS, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I, Ehler E, Kakkar VV, Stalmans I, Mattot V, Perriard JC, Dewerchin M, Flameng W, Nagy A, Lupu F, Moons L, Collen D, D’Amore PA, Shima DT (1999) Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF 164 and VEGF188. Nat Med 5(5):495–502CrossRefGoogle Scholar
- 63.Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, Petitti D, Whitfield-Maxwell L, Yan M, Franke AA, Selzer RH (2011) Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial. Stroke 42:3168–3175CrossRefGoogle Scholar
- 65.van der Schouw YT, Sampson L, Willett WC, Rimm EB (2005) The usual intake of lignans but not that of isoflavones may be related to cardiovascular risk factors in U.S. men. J Nutr 135(2):260–266Google Scholar
- 68.Liggins J, Bluck LJ, Runswick S, Atkinson C, Coward WA, Bingham SA (2000) Daidzein and genistein contents of vegetables. Br J Nutr 84:717–725Google Scholar
- 70.Rowland I, Faughnan M, Hoey L, Wahala K, Williamson G, Cassidy A (2003) Bioavailability of phyto-oestrogens. Br J Nutr 89:S45–S58Google Scholar
- 71.Bhaqwat S, Haytowitz DB, Holden JM (2008) USDA Database for the Isoflavone Content of Selected Foods, vol 2. Nutrient Data Laboratory, BeltsvilleGoogle Scholar
- 73.Atkinson C, Skor HE, Fitzgibbons ED, Scholes D, Chen C, Wahala K, Schwartz SM, Lampe JW (2002) Overnight urinary isoflavone excretion in a population of women living in the United States, and its relationship to isoflavone intake. Cancer Epidemiol Biomarkers Prev 11:253–260Google Scholar
- 75.Grace PB, Taylor JI, Low Y-L, Luben RN, Mulligan AA, Botting NP, Dowsett M, Welch AA, Khaw K-T, Wareham NJ, Day NE, Bingham SA (2004) Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European Prospective Investigation of Cancer and Nutrition-Norfolk. Cancer Epidemiol Biomarkers Prev 13(5):698–708Google Scholar