Cardiometabolic risk and gut microbial phytoestrogen metabolite phenotypes

Molecular Nutrition and Food Research

Volumn 61, Issue 1, 2017, Pages

  Frankenfeld, Cara L ^a  

^a GEORGE MASON UNIVERSITY   (United States)

Author keywords

Cardiometabolic; Enterolignans; Equol; Microbiome; O desmethylangolensin

Indexed keywords

ISOFLAVONE DERIVATIVE; PHYTOESTROGEN;

CARDIOVASCULAR DISEASES; HUMAN; INTESTINE FLORA; METABOLISM; MICROBIOLOGY; PHYSIOLOGY; RISK FACTOR;

CARDIOVASCULAR DISEASES; GASTROINTESTINAL MICROBIOME; HUMANS; ISOFLAVONES; PHYTOESTROGENS; RISK FACTORS;

EID: 85007566482     PISSN: 16134125     EISSN: 16134133     Source Type: Journal    
DOI: 10.1002/mnfr.201500900     Document Type: Review

References (128)

1. Centers for Disease Control and Prevention (CDC), (2015). Heart Disease Facts. http://www.cdc.gov/heartdisease/facts.htm (Accessed: September 2015).
2. World Health Organization (WHO) (2016). Cardiovascular diseases (CVDs) Fact sheet N317. http://www.who.int/mediacentre/factsheets/fs317/en/ (Accessed: August 2016).
3. Institute for Health Metrics and Evaluation (2015). Global Burden of Disease Compare ∣ Viz Hub. http://vizhub.healthdata.org/gbd-compare/arrow (Accessed: September 2015)
4. Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K. et al., Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation 2015, 131, e29–e322.
5. Ripatti, S., Tikkanen, E., Orho-Melander, M., Havulinna, A. S. et al., A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet 2010, 376, 1393–1400.
6. Leiter, L. A., Fitchett, D. H., Gilbert, R. E., Gupta, M. et al., Cardiometabolic risk in Canada: a detailed analysis and position paper by the cardiometabolic risk working group. Can. J. Cardiol. 2011, 27, e1–e33.
7. Global Burden of Metabolic Risk Factors for Chronic Disease Prevention, Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment. Lancet Diabetes Endocrinol. 2014, 2, 634–647.
8. Gurka, M. J., Lilly, C. L., Oliver, M. N., DeBoer, M. D., An examination of sex and racial/ethnic differences in the metabolic syndrome among adults: a confirmatory factor analysis and a resulting continuous severity score. Metabolism 2014, 63, 218–225.
9. Tang, W. H., Hazen, S. L., The contributory role of gut microbiota in cardiovascular disease. J. Clin. Invest. 2014, 124, 4204–4211.
10. Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., Knight, R., Diversity, stability and resilience of the human gut microbiota. Nature 2012, 489, 220–230.
11. Turnbaugh, P. J., Quince, C., Faith, J. J., McHardy, A. C. et al., Organismal, genetic, and transcriptional variation in the deeply sequenced gut microbiomes of identical twins. Proc. Natl. Acad. Sci. USA 2010, 107, 7503–7508.
12. Candela, M., Maccaferri, S., Turroni, S., Carnevali, P. et al., Functional intestinal microbiome, new frontiers in prebiotic design. Int. J. Food Microbiol. 2010, 140, 93–101.
13. Gloux, K., Berteau, O., El Oumami, H., Beguet, F. et al., Microbes and Health Sackler Colloquium: a metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome. Proc. Natl. Acad. Sci. USA 2011, 108 Suppl 1, 4539–4546.
14. Tasse, L., Bercovici, J., Pizzut-Serin, S., Robe, P. et al., Functional metagenomics to mine the human gut microbiome for dietary fiber catabolic enzymes. Genome Res. 2010, 20, 1605–1612.
15. Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L. et al., A core gut microbiome in obese and lean twins. Nature 2009, 457, 480–484.
16. Vaishampayan, P. A., Kuehl, J. V., Froula, J. L., Morgan, J. L. et al., Comparative metagenomics and population dynamics of the gut microbiota in mother and infant. Genome Biol. Evol. 2010, 2, 53–66.
17. Dutton, R. J., Turnbaugh, P. J., Taking a metagenomic view of human nutrition. Curr. Opin. Clin. Nutr. Metab. Care 2012, 15, 448–454.
18. Lampe, J. W., Navarro, S. L., Hullar, M. A., Shojaie, A., Inter-individual differences in response to dietary intervention: integrating omics platforms towards personalised dietary recommendations. Proc. Nutr. Soc. 2013, 72, 207–218.
19. Xie, G., Li, X., Li, H., Jia, W., Toward personalized nutrition: comprehensive phytoprofiling and metabotyping. J. Proteome Res. 2013, 12, 1547–1559.
20. Cassidy, A., Potential risks and benefits of phytoestrogen-rich diets. Int. J. Vitam. Nutr. Res. 2003, 73, 120–126.
21. Bingham, S. A., Atkinson, C., Liggins, J., Bluck, L. et al., Phyto-oestrogens: where are we now? Br. J. Nutr. 1998, 79, 393–406.
22. Sirotkin, A. V., Harrath, A. H., Phytoestrogens and their effects. Eur J Pharmacol 2014, 741, 230–236.
23. Mense, S. M., Hei, T. K., Ganju, R. K., Bhat, H. K., Phytoestrogens and breast cancer prevention: possible mechanisms of action. Environ. Health. Perspect. 2008, 116, 426–433.
24. Turner, J. V., Agatonovic-Kustrin, S., Glass, B. D., Molecular aspects of phytoestrogen selective binding at estrogen receptors. J. Pharm. Sci. 2007, 96, 1879–1885.
25. Landete, J. M., Arques, J., Medina, M., Gaya, P. et al., Bioactivation of phytoestrogens: intestinal bacteria and health. Crit. Rev. Food Sci. Nutr. 2016, 56, 1826–1843.
26. Nakamura, Y., Tsuji, S., Tonogai, Y., Determination of the levels of isoflavonoids in soybeans and soy-derived foods and estimation of isoflavonoids in the Japanese daily intake. J. AOAC Int. 2000, 83, 635–650.
27. Cao, H., Chen, X., Jassbi, A. R., Xiao, J., Microbial biotransformation of bioactive flavonoids. Biotechnol. Adv. 2015, 33, 214–223.
28. Kano, M., Takayanagi, T., Harada, K., Sawada, S., Ishikawa, F., Bioavailability of isoflavones after ingestion of soy beverages in healthy adults. J. Nutr. 2006, 136, 2291–2296.
29. Kim, M., Lee, J., Han, J., Deglycosylation of isoflavone C-glycosides by newly isolated human intestinal bacteria. J. Sci. Food Agric. 2015, 95, 1925–1931.
30. Rowland, I., Faughnan, M., Hoey, L., Wahala, K. et al., Bioavailability of phyto-oestrogens. Br. J. Nutr. 2003, 89(1), S45–S58.
31. Chan, S. G., Ho, S. C., Kreiger, N., Darlington, G. et al., Dietary sources and determinants of soy isoflavone intake among midlife Chinese Women in Hong Kong. J. Nutr. 2007, 137, 2451–2455.
32. Messina, M., Nagata, C., Wu, A. H., Estimated Asian adult soy protein and isoflavone intakes. Nutr. Cancer 2006, 55, 1–12.
33. Chun, O. K., Chung, S. J., Song, W. O., Urinary isoflavones and their metabolites validate the dietary isoflavone intakes in US adults. J. Am. Diet. Assoc. 2009, 109, 245–254.
34. Frankenfeld, C. L., Patterson, R. E., Kalhorn, T. F., Skor, H. E. et al., Validation of a soy food frequency questionnaire with plasma concentrations of isoflavones in US adults. J. Am. Diet. Assoc. 2002, 102, 1407–1413.
35. Maskarinec, G., Singh, S., Meng, L., Franke, A. A., Dietary soy intake and urinary isoflavone excretion among women from a multiethnic population. Cancer Epidemiol. Biomarkers Prev. 1998, 7, 613–619.
36. Boker, L. K., Van der Schouw, Y. T., De Kleijn, M. J., Jacques, P. F. et al., Intake of dietary phytoestrogens by Dutch women. J. Nutr. 2002, 132, 1319–1328.
37. Cotterchio, M., Boucher, B. A., Kreiger, N., Mills, C. A. et al., Dietary phytoestrogen intake–lignans and isoflavones–and breast cancer risk (Canada). Cancer Causes Control 2008, 19, 259–272.
38. Ward, H. A., Kuhnle, G. G., Mulligan, A. A., Lentjes, M. A. et al., Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database. Am. J. Clin. Nutr. 2010, 91, 440–448.
39. Horn-Ross, P. L., Barnes, S., Lee, M., Coward, L. et al., Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control 2000, 11, 289–298.
40. Heinonen, S., Wähälä, K., Adlercreutz, H., Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6'-OH-O-dma, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. Anal. Biochem. 1999, 274, 211–219.
41. Frankenfeld, C. L., Atkinson, C., Wahala, K., Lampe, J. W., Obesity prevalence in relation to gut microbial environments capable of producing equol or O-desmethylangolensin from the isoflavone daidzein. Eur. J. Clin. Nutr. 2014, 68, 526–530.
42. Roncaglia, L., Amaretti, A., Raimondi, S., Leonardi, A. et al., Role of bifidobacteria in the activation of the lignan secoisolariciresinol diglucoside. Appl. Microbiol. Biotechnol. 2011, 92, 159–168.
43. Jin, J. S., Hattori, M., Human intestinal bacterium, strain END-2 is responsible for demethylation as well as lactonization during plant lignan metabolism. Biol. Pharm. Bull. 2010, 33, 1443–1447.
44. Xie, L. H., Akao, T., Hamasaki, K., Deyama, T. et al., Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol. Chem. Pharm. Bull. 2003, 51, 508–515.
45. Clavel, T., Henderson, G., Engst, W., Dore, J., Blaut, M., Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside. FEMS Microbiol. Ecol. 2006, 55, 471–478.
46. Rafii, F., The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites 2015, 5, 56–73.
47. Frankenfeld, C. L., O-Desmethylangolensin: the importance of equol's lesser known cousin to health human. Adv. Nutr. 2011, 2, 317–324.
48. Atkinson, C., Frankenfeld, C. L., Lampe, J. W., Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp. Biol. Med. (Maywood) 2005, 230, 155–170.
49. Franke, A. A., Lai, J. F., Halm, B. M., Pagano, I. et al., Equol production changes over time in postmenopausal women. J. Nutr. Biochem. 2012, 23, 573–579.
50. Franke, A. A., Lai, J. F., Pagano, I., Morimoto, Y. et al., Equol production changes over time in pre-menopausal women. Br. J. Nutr. 2012, 107, 1201–1206.
51. Schoefer, L., Mohan, R., Braune, A., Birringer, M. et al., Anaerobic C-ring cleavage of genistein and daidzein by Eubacterium ramulus. FEMS Microbiol. Lett. 2002, 208, 197–202.
52. Hur, H. G., Beger, R. D., Heinze, T. M., Lay Jr., J. O. et al., Isolation of an anaerobic intestinal bacterium capable of cleaving the C-ring of the isoflavonoid daidzein. Arch. Microbiol. 2002, 178, 8–12.
53. Di Cagno, R., Mazzacane, F., Rizzello, C. G., Vincentini, O. et al., Synthesis of isoflavone aglycones and equol in soy milks fermented by food-related lactic acid bacteria and their effect on human intestinal Caco-2 cells. J. Agric. Food Chem. 2010, 58, 10338–10346.
54. Jin, J. S., Nishihata, T., Kakiuchi, N., Hattori, M., Biotransformation of C-glucosylisoflavone puerarin to estrogenic (3S)-equol in co-culture of two human intestinal bacteria. Biol. Pharm. Bull. 2008, 31, 1621–1625.
55. Frankenfeld, C. L., Lampe, J. W., Shannon, J., Gao, D. L. et al., Frequency of soy food consumption and serum isoflavone concentrations among Chinese women in Shanghai. Public Health Nutr. 2004, 7, 765–772.
56. Yamasaki, K., Kayaba, K., Ishikawa, S., Soy and soy products intake, all-cause mortality, and cause-specific mortality in Japan: The Jichi Medical School Cohort Study. Asia Pac. J. Public Health 2015, 27, 531–541.
57. Nishio, K., Niwa, Y., Toyoshima, H., Tamakoshi, K. et al., Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study. Cancer Causes Control 2007, 18, 801–808.
58. Oba, S., Nagata, C., Shimizu, N., Shimizu, H. et al., Soy product consumption and the risk of colon cancer: a prospective study in Takayama, Japan. Nutr. Cancer 2007, 57, 151–157.
59. Liu, Z., Li, W., Sun, J., Liu, C. et al., Intake of soy foods and soy isoflavones by rural adult women in China. Asia Pac. J. Clin. Nutr. 2004, 13, 204–209.
60. Lee, M. M., Gomez, S. L., Chang, J. S., Wey, M. et al., Soy and isoflavone consumption in relation to prostate cancer risk in China. Cancer Epidemiol. Biomarkers Prev. 2003, 12, 665–668.
61. Frankenfeld, C. L., Dairy consumption is a significant correlate of urinary equol concentration in a representative sample of US adults. Am. J. Clin. Nutr. 2011, 93, 1109–1116.
62. Adlercreutz, H., Fotsis, T., Lampe, J., Wahala, K. et al., Quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography-mass spectrometry. Scand. J. Clin. Lab. Invest. Suppl. 1993, 215, 5–18.
63. Morton, M., Arisaka, O., Miyake, A., Evans, B., Analysis of phyto-oestrogens by gas chromatography-mass spectrometry. Environ. Toxicol. Pharmacol. 1999, 7, 221–225.
64. Adlercreutz, H., Fotsis, T., Bannwart, C., Wähälä, K. et al., Isotope dilution gas chromatographic-mass spectrometric method for the determination of lignans and isoflavonoids in human urine, including identification of genistein. Clin. Chim. Acta 1991, 199, 263–278.
65. Adlercreutz, H., Fotsis, T., Bannwart, C., Wähälä, K. et al., Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets. J. Steroid Biochem. 1986, 25, 791–797.
66. Frankenfeld, C. L., Atkinson, C., Thomas, W. K., Goode, E. L. et al., Familial correlations, segregation analysis, and nongenetic correlates of soy isoflavone-metabolizing phenotypes. Exp. Biol. Med. (Maywood) 2004, 229, 902–913.
67. Acharjee, S., Zhou, J. R., Elajami, T. K., Welty, F. K., Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status. Metabolism 2015, 64, 236–243.
68. Greany, K. A., Nettleton, J. A., Wangen, K. E., Thomas, W. et al., Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women. Eur. J. Clin. Nutr. 2008, 62, 1419–1425.
69. Hall, W. L., Vafeiadou, K., Hallund, J., Bugel, S. et al., Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production. Am. J. Clin. Nutr. 2005, 82, 1260–1268, quiz 1365–1266.
70. Mangano, K. M., Hutchins-Wiese, H. L., Kenny, A. M., Walsh, S. J. et al., Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial. Nutr. Res. (New York, N.Y.) 2013, 33, 1026–1033.
71. Cai, Y., Guo, K., Chen, C., Wang, P. et al., Soya isoflavone consumption in relation to carotid intima-media thickness in Chinese equol excretors aged 40-65 years. Br. J. Nutr. 2012, 108, 1698–1704.
72. Clerici, C., Setchell, K. D., Battezzati, P. M., Pirro, M. et al., Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J. Nutr. 2007, 137, 2270–2278.
73. Guo, K., Zhang, B., Chen, C., Uchiyama, S. et al., Daidzein-metabolising phenotypes in relation to serum lipids and uric acid in adults in Guangzhou, China. Br. J. Nutr. 2010, 104, 118–124.
74. Liu, Z. M., Ho, S. C., Chen, Y. M., Liu, J. et al., Cardiovascular risks in relation to daidzein metabolizing phenotypes among Chinese postmenopausal women. PLoS One 2014, 9, e87861.
75. Reverri, E. J., LaSalle, C. D., Franke, A. A., Steinberg, F. M., Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol. Nutr. Food Res. 2015, 59, 323–333.
76. Thorp, A. A., Howe, P. R., Mori, T. A., Coates, A. M. et al., Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers. Am. J. Clin. Nutr. 2008, 88, 298–304.
77. Qin, Y., Shu, F., Zeng, Y., Meng, X. et al., Daidzein supplementation decreases serum triglyceride and uric acid concentrations in hypercholesterolemic adults with the effect on triglycerides being greater in those with the GA compared with the GG genotype of ESR-beta RsaI. J. Nutr. 2014, 144, 49–54.
78. Newton, K. M., Reed, S. D., Uchiyama, S., Qu, C. et al., A cross-sectional study of equol producer status and self-reported vasomotor symptoms. Menopause 2015, 22, 489–495.
79. Hong, K. W., Ko, K. P., Ahn, Y., Kim, C. S. et al., Epidemiological profiles between equol producers and nonproducers: a genomewide association study of the equol-producing phenotype. Genes Nutr. 2012, 7, 567–574.
80. Atkinson, C., Newton, K. M., Bowles, E. J., Yong, M. et al., Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States. Am. J. Clin. Nutr. 2008, 87, 679–687.
81. Frankenfeld, C. L., Atkinson, C., Thomas, W. K., Goode, E. L. et al., Familial correlations, segregation analysis, and nongenetic correlates of soy isoflavone-metabolizing phenotypes. Exp. Biol. Med. (Maywood) 2004, 229, 902–913.
82. Frankenfeld, C. L., McTiernan, A., Tworoger, S. S., Atkinson, C. et al., Serum steroid hormones, sex hormone-binding globulin concentrations, and urinary hydroxylated estrogen metabolites in post-menopausal women in relation to daidzein-metabolizing phenotypes. J. Steroid Biochem. Mol. Biol. 2004, 88, 399–408.
83. Song, K. B., Atkinson, C., Frankenfeld, C. L., Jokela, T. et al., Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls. J. Nutr. 2006, 136, 1347–1351.
84. Virk-Baker, M. K., Barnes, S., Krontiras, H., Nagy, T. R., S-(-)equol producing status not associated with breast cancer risk among low isoflavone-consuming US postmenopausal women undergoing a physician-recommended breast biopsy. Nutr. Res. (New York, N.Y.) 2014, 34, 116–125.
85. Setchell, K. D., Brown, N. M., Summer, S., King, E. C. et al., Dietary factors influence production of the soy isoflavone metabolite s-(-)equol in healthy adults. J. Nutr. 2013, 143, 1950–1958.
86. Frankenfeld, C. L., Atkinson, C., Thomas, W. K., Gonzalez, A. et al., High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart. Br. J. Nutr. 2005, 94, 873–876.
87. Usui, T., Tochiya, M., Sasaki, Y., Muranaka, K. et al., Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin. Endocrinol. 2013, 78, 365–372.
88. Hazim, S., Curtis, P. J., Schar, M. Y., Ostertag, L. M. et al., 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. 2016, 103, 694–702.
89. Centers for Disease Control and Prevention, National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey, http://www.cdc.gov/nchs/nhanes/index.htm (Accessed: September 2015).
90. Jeng, H. A., Kantaria, K., Beydoun, H. A., Urinary phytoestrogens in relation to metabolic disturbances among children and adolescents. J. Environ Sci Health B 2015, 50, 121–127.
91. Shi, L., Ryan, H. H., Jones, E., Simas, T. A. et al., Urinary isoflavone concentrations are inversely associated with cardiometabolic risk markers in pregnant U.S. women. J. Nutr. 2014, 144, 344–351.
92. Xu, C., Liu, Q., Zhang, Q., Gu, A. et al., Urinary enterolactone is associated with obesity and metabolic alteration in men in the US National Health and Nutrition Examination Survey 2001-10. Br. J. Nutr. 2015, 113, 683–690.
93. Cavallini, D. C., Manzoni, M. S., Bedani, R., Roselino, M. N. et al., Probiotic soy product supplemented with isoflavones improves the lipid profile of moderately hypercholesterolemic men: a randomized controlled trial. Nutrients 2016, 8, 52.
94. Wong, J. M., Kendall, C. W., Marchie, A., Liu, Z. et al., Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods. Am. J. Clin. Nutr. 2012, 95, 564–571.
95. Hall, W. L., Vafeiadou, K., Hallund, J., Bugel, S. et al., Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production. Am. J. Clin. Nutr. 2006, 83, 592–600.
96. Liu, J., Sun, L. L., He, L. P., Ling, W. H. et al., Soy food consumption, cardiometabolic alterations and carotid intima-media thickness in Chinese adults. Nutr. Metab. Cardiovasc. Dis. 2014, 24, 1097–1104.
97. Curtis, P. J., Potter, J., Kroon, P. A., Wilson, P. et al., Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial. Am. J. Clin. Nutr. 2013, 97, 936–942.
98. Bourque, S. L., Davidge, S. T., Adams, M. A., The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives. Am J Physiol. Regul. Integr. Comp. Physiol. 2011, 300, R1288–R1295.
99. Peterson, J., Dwyer, J., Adlercreutz, H., Scalbert, A. et al., Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr. Rev. 2010, 68, 571–603.
100. Smeds, A. I., Eklund, P. C., Willfor, S. M., Content, composition, and stereochemical characterisation of lignans in berries and seeds. Food Chem. 2012, 134, 1991–1998.
101. Smeds, A. I., Eklund, P. C., Sjoholm, R. E., Willfor, S. M. et al., Quantification of a broad spectrum of lignans in cereals, oilseeds, and nuts. J. Agric. Food Chem. 2007, 55, 1337–1346.
102. Milder, I. E., Arts, I. C., van de Putte, B., Venema, D. P. et al., Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. Br. J. Nutr. 2005, 93, 393–402.
103. Neveu, V. J. P.-J., Vos, F., Crespy, V. et al., 2010. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database, doi: 10.1093/database/bap024.
104. Zamora-Ros, R., Agudo, A., Lujan-Barroso, L., Romieu, I. et al., Dietary flavonoid and lignan intake and gastric adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Am. J. Clin. Nutr. 2012, 96, 1398–1408.
105. Clavel, T., Borrmann, D., Braune, A., Dore, J., Blaut, M., Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 2006, 12, 140–147.
106. Clavel, T., Henderson, G., Alpert, C. A., Philippe, C. et al., Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl. Environ. Microbiol. 2005, 71, 6077–6085.
107. Valentin-Blasini, L., Sadowski, M. A., Walden, D., Caltabiano, L. et al., Urinary phytoestrogen concentrations in the U.S. population (1999-2000). J. Expo. Anal. Environ. Epidemiol. 2005, 15, 509–523.
108. Kuijsten, A., Arts, I. C., van'tVeer, P., Hollman, P. C., The relative bioavailability of enterolignans in humans is enhanced by milling and crushing of flaxseed. J. Nutr. 2005, 135, 2812–2816.
109. Lampe, J. W., Martini, M. C., Kurzer, M. S., Adlercreutz, H. et al., Urinary lignan and isoflavonoid excretion in premenopausal women consuming flaxseed powder. Am. J. Clin. Nutr. 1994, 60, 122–128.
110. Lampe, J. W., Atkinson, C., Hullar, M. A., Assessing exposure to lignans and their metabolites in humans. J. AOAC Int. 2006, 89, 1174–1181.
111. Hullar, M. A., Lancaster, S. M., Li, F., Tseng, E. et al., Enterolignan-producing phenotypes are associated with increased gut microbial diversity and altered composition in premenopausal women in the United States. Cancer Epidemiol. Biomarkers Prev. 2015, 24, 546–554.
112. Cornish, S. M., Chilibeck, P. D., Paus-Jennsen, L., Biem, H. J. et al., A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults. Appl. Physiol. Nutr. Metab. 2009, 34, 89–98.
113. Pan, A., Sun, J., Chen, Y., Ye, X. et al., Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial. PLoS One 2007, 2, e1148.
114. Pan, A., Yu, D., Demark-Wahnefried, W., Franco, O. H. et al., Meta-analysis of the effects of flaxseed interventions on blood lipids. Am. J. Clin. Nutr. 2009, 90, 288–297.
115. Wu, J. H., Hodgson, J. M., Puddey, I. B., Belski, R. et al., Sesame supplementation does not improve cardiovascular disease risk markers in overweight men and women. Nutr. Metab. Cardiovasc. Dis. 2009, 19, 774–780.
116. Zhang, W., Wang, X., Liu, Y., Tian, H. et al., Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects. Br. J. Nutr. 2008, 99, 1301–1309.
117. Hallund, J., Tetens, I., Bugel, S., Tholstrup, T. et al., The effect of a lignan complex isolated from flaxseed on inflammation markers in healthy postmenopausal women. Nutr. Metab. Cardiovasc. Dis. 2008, 18, 497–502.
118. Pan, A., Demark-Wahnefried, W., Ye, X., Yu, Z. et al., Effects of a flaxseed-derived lignan supplement on C-reactive protein, IL-6 and retinol-binding protein 4 in type 2 diabetic patients. Br. J. Nutr. 2009, 101, 1145–1149.
119. Frankenfeld, C. L., Relationship of obesity and high urinary enterolignan concentrations in 6806 children and adults: analysis of National Health and Nutrition Examination Survey data. Eur. J. Clin. Nutr. 2013, 67, 887–889.
120. Frankenfeld, C. L., Cardiometabolic risk factors are associated with high urinary enterolactone concentration, independent of urinary enterodiol concentration and dietary fiber intake in adults. J. Nutr. 2014, 144, 1445–1453.
121. Xu, C., Liu, Q., Zhang, Q., Jiang, Z. Y. et al., Urinary enterolactone associated with liver enzyme levels in US adults: National Health and Nutrition Examination Survey (NHANES). Br. J. Nutr. 2015, 114, 91–97.
122. Struja, T., Richard, A., Linseisen, J., Eichholzer, M. et al., The association between urinary phytoestrogen excretion and components of the metabolic syndrome in NHANES. Eur. J. Nutr. 2013, 53, 1371–1381.
123. Penalvo, J. L., Lopez-Romero, P., Urinary enterolignan concentrations are positively associated with serum HDL cholesterol and negatively associated with serum triglycerides in U.S. adults. J. Nutr. 2012, 142, 751–756.
124. Sun, Q., Wedick, N. M., Pan, A., Townsend, M. K. et al., Gut microbiota metabolites of dietary lignans and risk of type 2 diabetes: a prospective investigation in two cohorts of U.S. women. Diabetes Care 2014, 37, 1287–1295.
125. Hu, Y., Song, Y., Franke, A. A., Hu, F. B. et al., A prospective investigation of the association between urinary excretion of dietary lignan metabolites and weight change in US women. Am. J. Epidemiol. 2015, 182, 503–511.
126. Boto-Ordonez, M., Urpi-Sarda, M., Queipo-Ortuno, M. I., Corella, D. et al., Microbial metabolomic fingerprinting in urine after regular dealcoholized red wine consumption in humans. J. Agric. Food Chem. 2013, 61, 9166–9175.
127. Urpi-Sarda, M., Monagas, M., Khan, N., Lamuela-Raventos, R. M. et al., Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Anal. Bioanal. Chem. 2009, 394, 1545–1556.
128. Possemiers, S., Bolca, S., Eeckhaut, E., Depypere, H. et al., Metabolism of isoflavones, lignans and prenylflavonoids by intestinal bacteria: producer phenotyping and relation with intestinal community. FEMS Microbiol. Ecol. 2007, 61, 372–383.