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Fan L, Fike LT, Munro H, Yu D, Si H, Shrubsole MJ, Dai Q. Dietary polyphenols and risk of breast cancer in a predominantly low-income population: a prospective analysis in the Southern Community Cohort Study (SCCS). Am J Clin Nutr 2025:S0002-9165(25)00145-5. [PMID: 40127717 DOI: 10.1016/j.ajcnut.2025.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 03/14/2025] [Accepted: 03/19/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Few studies have examined the associations of specific dietary polyphenols with breast cancer (BC) risks or among non-Hispanic Black (NHB) female individuals in the United States. OBJECTIVES We aim to evaluate the associations between total and subclasses of polyphenol intake and BC risk, stratified by body mass index (BMI), estrogen receptor (ER)/progesterone receptor (PR) status, menopausal status, and racial and ethnic subgroups. METHODS The study included 42,260 female participants from the Southern Community Cohort Study, a large prospective cohort of predominantly low-income NHB Americans. The dietary polyphenol components were assessed using a validated culturally sensitive 89-item food frequency questionnaire designed specifically for nutrient intakes in the South. Cox proportional hazards model was used to assess the associations after adjustment for confounders including sociodemographic and lifestyle factors. RESULTS Intakes of total polyphenols were higher in non-Hispanic white (1122 ± 727 mg/d) than in NHB female individuals (535±349 mg/d). Intakes of total polyphenol, particularly phenolic acids, were associated with reduced risk of BC incidence among female individuals with the ER+ and PR+ BC type comparing the highest to the lowest quintile [hazard ratio (HR) 0.69; 95% confidence interval (CI): 0.51, 0.94; P-trend = 0.003; HR 0.70; 95% CI: 0.53, 0.95; P-trend = 0.005, respectively]. Phenolic acid was inversely related to BC among postmenopausal female individuals (HR 0.76; 95% CI: 0.59, 0.97; P-trend = 0.02) and female individuals with a BMI ≥ 25 kg/m2 (HR 0.77; 95% CI: 0.60, 0.98; P-trend = 0.01) comparing the highest to the lowest quintile. Intakes of tyrosols were associated with increased risk of BC among NHB female individuals (HR 1.34; 95% CI: 1.03, 1.73; P-trend = 0.01) and female individuals with a BMI ≥ 25 kg/m2 (HR 1.31; 95% CI: 1.04, 1.65; P-trend = 0.004). CONCLUSIONS In this predominantly low-income United States population, intakes of total polyphenol and phenolic acids were associated with reduced risk of BC among those with ER+ and PR+ BC type, postmenopausal, and female individuals with overweight/obesity.
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Affiliation(s)
- Lei Fan
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Landon T Fike
- Department of Radiology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Heather Munro
- Department of Medicine, Division of Epidemiology, International Epidemiology Field Station, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Danxia Yu
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Hongwei Si
- Department of Food and Animal Sciences, Tennessee State University, Nashville, TN, United States
| | - Martha J Shrubsole
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States; Department of Medicine, Division of Epidemiology, International Epidemiology Field Station, Vanderbilt University Medical Center, Nashville, TN, United States.
| | - Qi Dai
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, United States.
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Kang JH, Dong Z, Shin SH. Benefits of Soybean in the Era of Precision Medicine: A Review of Clinical Evidence. J Microbiol Biotechnol 2023; 33:1552-1562. [PMID: 37674385 PMCID: PMC10774093 DOI: 10.4014/jmb.2308.08016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 08/16/2023] [Accepted: 08/21/2023] [Indexed: 09/08/2023]
Abstract
Soybean (Glycine max) is an important ingredient of cuisines worldwide. While there is a wealth of evidence that soybean could be a good source of macronutrients and phytochemicals with health-promoting effects, concerns regarding adverse effects have been raised. In this work, we reviewed the current clinical evidence focusing on the benefits and risks of soybean ingredients. In breast, prostate, colorectal, ovarian, and lung cancer, epidemiological studies showed an inverse association between soybean food intake and cancer risks. Soybean intake was inversely correlated with risks of type 2 diabetes mellitus (T2DM), and soy isoflavones ameliorated osteoporosis and hot flashes. Notably, soybean was one of the dietary protein sources that may reduce the risk of breast cancer and T2DM. However, soybean had adverse effects on certain types of drug treatment and caused allergies. In sum, this work provides useful considerations for planning clinical soybean research and selecting dietary protein sources for human health.
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Affiliation(s)
- Jung Hyun Kang
- Department of Food and Nutrition, Gyeongsang National University, Jinju 52828, Republic of Korea
| | - Zigang Dong
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, P.R. China
- China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou 450008, Henan, P.R. China
| | - Seung Ho Shin
- Department of Food and Nutrition, Gyeongsang National University, Jinju 52828, Republic of Korea
- Department of Bio & Medical Bigdata (BK4 Program), Gyeongsang National University, Jinju 52828, Republic of Korea
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Abstract
OBJECTIVE Postmenopausal vasomotor symptoms disrupt quality of life. This study tested the effects of a dietary intervention on vasomotor symptoms and menopause-related quality of life. METHODS Postmenopausal women (n = 84) reporting at least two moderate-to-severe hot flashes daily were randomly assigned, in two successive cohorts, to an intervention including a low-fat, vegan diet and cooked soybeans (½ cup [86 g] daily) or to a control group making no dietary changes. During a 12-week period, a mobile application was used to record hot flashes (frequency and severity), and vasomotor, psychosocial, physical, and sexual symptoms were assessed with the Menopause-Specific Quality of Life questionnaire. Between-group differences were assessed for continuous ( t tests) and binary ( χ2 /McNemar tests) outcomes. In a study subsample, urinary equol was measured after the consumption of ½ cup (86 g) of cooked whole soybeans twice daily for 3 days. RESULTS In the intervention group, moderate-to-severe hot flashes decreased by 88% ( P < 0.001) compared with 34% for the control group ( P < 0.001; between-group P < 0.001). At 12 weeks, 50% of completers in the intervention group reported no moderate-to-severe hot flashes at all. Among controls, there was no change in this variable from baseline ( χ2 test, P < 0.001). Neither seasonality nor equol production status was associated with the degree of improvement. The intervention group reported greater reductions in the Menopause-Specific Quality of Life questionnaire vasomotor ( P = 0.004), physical ( P = 0.01), and sexual ( P = 0.03) domains. CONCLUSIONS A dietary intervention consisting of a plant-based diet, minimizing oils, and daily soybeans significantly reduced the frequency and severity of postmenopausal hot flashes and associated symptoms.
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Ohishi T, Miyoshi N, Mori M, Sagara M, Yamori Y. Health Effects of Soy Isoflavones and Green Tea Catechins on Cancer and Cardiovascular Diseases Based on Urinary Biomarker Levels. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27248899. [PMID: 36558031 PMCID: PMC9781513 DOI: 10.3390/molecules27248899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Revised: 12/07/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022]
Abstract
Plant polyphenols have various health effects. Genistein, which is abundant in soybeans, and epigallocatechin-3-gallate, which is abundant in green tea, are major flavonoids, a subclass group of polyphenols. Several epidemiological studies have shown that these flavonoids have beneficial effects against cancer and cardiovascular diseases. However, other studies did not show such effects. Several confounding factors, including recall bias, are related to these inconsistent findings, and the determination of metabolites in the urine may be useful in reducing the number of confounding factors. Equipment, which can be used by research participants to collect samples from a portion of voided urine within 24 h without the help of medical workers, has been developed for epidemiological investigations. Previous studies, in which flavonoid metabolites in these urine samples were measured, revealed that soy intake was correlated with a reduced risk of certain types of cancer and cardiovascular diseases worldwide. Although soybeans and green tea consumption may have protective effects against cancer and cardiovascular diseases, further clinical studies that consider different confounding factors are required to provide evidence for the actual impact of dietary flavonoids on human diseases, including cancer and cardiovascular diseases. One possible mechanism involved is discussed in relation to the downregulation of reactive oxygen species and the upregulation of 5'-adenosine monophosphate-activated protein kinase elicited by these flavonoids.
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Affiliation(s)
- Tomokazu Ohishi
- Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka 410-0301, Japan
- Laboratory of Oncology, Institute of Microbial Chemistry (BIKAKEN), Microbial Chemistry Research Foundation, Tokyo 141-0021, Japan
- Correspondence: (T.O.); (Y.Y.)
| | - Noriyuki Miyoshi
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
| | - Mari Mori
- Department of Health Management, School of Health Studies, Tokai University, Kanagawa 259-1292, Japan
- NPO World Health Frontier Institute, Nishinomiya 663-8143, Japan
- Institute for World Health Development, Mukogawa Women’s University, Nishinomiya 663-8143, Japan
| | - Miki Sagara
- Institute for World Health Development, Mukogawa Women’s University, Nishinomiya 663-8143, Japan
- Disease Model Cooperative Research Association, Kyoto 606-0805, Japan
| | - Yukio Yamori
- Institute for World Health Development, Mukogawa Women’s University, Nishinomiya 663-8143, Japan
- Correspondence: (T.O.); (Y.Y.)
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Zhou R, Cui DJ, Zhao Q, Liu KK, Zhao WB, Liu Q, Ma RN, Jiao Z, Dong L, Shan CX. Effective control of microbial spoilage in soybeans by water-soluble ZnO nanoparticles. Food Chem 2022; 388:132994. [PMID: 35460964 DOI: 10.1016/j.foodchem.2022.132994] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 04/01/2022] [Accepted: 04/13/2022] [Indexed: 11/17/2022]
Abstract
The microbial spoilage of soybeans during soaking process severely deteriorates the quality of soybean products and threatens human health. Herein, water-soluble aminated zinc oxide nanoparticles (ZnO NPs) were developed to effectively control the microbial spoilage in soybeans during soaking. ZnO NPs achieved significant inactivation of three dominant spoilage bacteria (bacillus cereus, bacillus megaterium and enterococcus faecium) isolated from the deteriorated soybeans, which could adhere to the bacterial surface and damage the cell wall/membrane, but also generate large amounts of reactive oxygen species (ROS). Compared to two commercial ZnO, water-soluble ZnO exhibited superior antibacterial properties due to producing more ROS and bacteria-adhered ability. After ZnO NPs treatment, the content of the residual Zn (51.1 mg/kg) in soybeans was the safety standards of Zn element in soybeans products for human). Therefore, the water-soluble ZnO NPs showed great potentials as efficient and safe antimicrobial agents for soybeans preservation during soaking process.
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Affiliation(s)
- Rui Zhou
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Dong-Jie Cui
- Henan Key Laboratory of Ion-Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Qi Zhao
- Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
| | - Kai-Kai Liu
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Wen-Bo Zhao
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Qian Liu
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Ruo-Nan Ma
- Henan Key Laboratory of Ion-Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou 450052, People's Republic of China.
| | - Zhen Jiao
- Henan Key Laboratory of Ion-Beam Bioengineering, School of Agricultural Sciences, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Lin Dong
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, People's Republic of China
| | - Chong-Xin Shan
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, People's Republic of China.
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Langa S, Landete JM. Strategies to achieve significant physiological concentrations of bioactive phytoestrogens in plasma. Crit Rev Food Sci Nutr 2021; 63:2203-2215. [PMID: 34470513 DOI: 10.1080/10408398.2021.1971946] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The benefits to health attributed to the intake of phytoestrogens (PEs) have been demonstrated in previous studies with significant physiological concentrations of bioactive PEs, such as genistein, equol, enterolignans and urolithins in plasma. However, the achievement of high bioactive PE levels in plasma is restricted to a select population group, mainly due to the low intake of plant PEs and/or the absence, or inhibition, of the microbiota capable of producing these bioactive forms. In this study, the intake of plant PEs, the concentration of bioactive PEs in plasma, the ability of the intestinal microbiota to produce bioactive PEs, as well as the different mechanisms used by GRAS bacteria to increase the level of bioactive PEs were evaluated concluding that the use of GRAS bacteria bioactive PE producers and the development of fermented foods enriched in bioactive PEs in addition to a high intake of plant PEs and taking care of the intestinal microbiota, are some of the different strategies to achieve significant physiological concentrations of bioactive PEs in the intestine and, subsequently, in plasma and targets organs which are essential to improve menopausal symptoms or reduce the risk of some pathologies such as breast and colon cancer, or cardiovascular disease.
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Affiliation(s)
- Susana Langa
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
| | - José M Landete
- Departamento de Tecnología de Alimentos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
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Barnard ND, Kahleova H, Holtz DN, del Aguila F, Neola M, Crosby LM, Holubkov R. The Women's Study for the Alleviation of Vasomotor Symptoms (WAVS): a randomized, controlled trial of a plant-based diet and whole soybeans for postmenopausal women. Menopause 2021; 28:1150-1156. [PMID: 34260478 PMCID: PMC8462449 DOI: 10.1097/gme.0000000000001812] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/08/2021] [Accepted: 04/08/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This study aimed to assess the effects of the combination of a low-fat plant-based diet and soybeans on the frequency and severity of menopausal hot flashes. METHODS Postmenopausal women (n = 38) reporting two or more hot flashes/day were randomly assigned to a low-fat, vegan diet, including ½ cup (86 g) of cooked soybeans daily, or to no diet changes for 12 weeks. Frequency and severity of hot flashes were recorded using a mobile application, and vasomotor, psychosocial, physical, and sexual symptoms were assessed using the Menopause-Specific Quality of Life Questionnaire. Significance was assessed using t-tests (continuous outcomes) and chi-squared/McNemar tests (binary outcomes). RESULTS Total hot flashes decreased 79% in the intervention group (P < 0.001) and 49% in the control group (P = 0.002; between-group P = 0.01). Moderate-to-severe hot flashes decreased 84% in the intervention group (P < 0.001) and 42% in the control group P = 0.009; between-group P = 0.01). From 0 to 12 weeks, 59% (10/17) of intervention-group participants reported becoming free of moderate and severe hot flashes (P = 0.002). There was no change in this variable in the control group (between-group P < 0.001). The Menopause-Specific Quality of Life Questionnaire revealed significantly greater reductions in the intervention group in vasomotor (P < 0.0001), psychosocial (P = 0.04), physical (P < 0.002), and sexual (P = 0.01) domains. CONCLUSIONS The combination of a low-fat, vegan diet and whole soybeans was associated with reduced frequency and severity of hot flashes and improved quality of life in vasomotor, psychosocial, physical, and sexual domains in postmenopausal women. During the 12-week study period, the majority of intervention-group participants became free of moderate-to-severe hot flashes.
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Affiliation(s)
- Neal D. Barnard
- Physicians Committee for Responsible Medicine, Washington, DC
- Adjunct Faculty, George Washington University School of Medicine, Washington, DC
| | - Hana Kahleova
- Physicians Committee for Responsible Medicine, Washington, DC
| | | | | | - Maggie Neola
- Physicians Committee for Responsible Medicine, Washington, DC
| | - Lelia M. Crosby
- Physicians Committee for Responsible Medicine, Washington, DC
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The Potential Effects of Phytoestrogens: The Role in Neuroprotection. Molecules 2021; 26:molecules26102954. [PMID: 34065647 PMCID: PMC8156305 DOI: 10.3390/molecules26102954] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 12/20/2022] Open
Abstract
Phytoestrogens are naturally occurring non-steroidal phenolic plant compounds. Their structure is similar to 17-β-estradiol, the main female sex hormone. This review offers a concise summary of the current literature on several potential health benefits of phytoestrogens, mainly their neuroprotective effect. Phytoestrogens lower the risk of menopausal symptoms and osteoporosis, as well as cardiovascular disease. They also reduce the risk of brain disease. The effects of phytoestrogens and their derivatives on cancer are mainly due to the inhibition of estrogen synthesis and metabolism, leading to antiangiogenic, antimetastatic, and epigenetic effects. The brain controls the secretion of estrogen (hypothalamus-pituitary-gonads axis). However, it has not been unequivocally established whether estrogen therapy has a neuroprotective effect on brain function. The neuroprotective effects of phytoestrogens seem to be related to both their antioxidant properties and interaction with the estrogen receptor. The possible effects of phytoestrogens on the thyroid cause some concern; nevertheless, generally, no serious side effects have been reported, and these compounds can be recommended as health-promoting food components or supplements.
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9
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Chen Y, Li T, Ji H, Wang X, Sun X, Miao M, Wang Y, Wu Q, Liang H, Yuan W. Associations of maternal soy product consumption and urinary isoflavone concentrations with neonatal anthropometry: A prospective cohort study. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 274:115752. [PMID: 33190984 DOI: 10.1016/j.envpol.2020.115752] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 09/10/2020] [Accepted: 09/28/2020] [Indexed: 06/11/2023]
Abstract
Isoflavones (ISOs) are naturally occurring endocrine-disrupting compounds. Few human studies have evaluated the effects of ISO exposure on neonatal anthropometry. This study aimed to examine the associations of maternal soy product consumption and urinary ISO concentrations, including genistein, daidzein, glycitein, and equol, with neonatal anthropometry, based on a Chinese cohort study. In Shanghai-Minhang Birth Cohort Study, pregnant women at 12-16 weeks of gestation were recruited, and they completed a structured questionnaire to assess soy product consumption during pregnancy. They also provided a single spot urine sample for the ISO assay. Neonatal anthropometric indices (birth weight; arm, waist, and head circumference; and triceps, back, and abdominal skinfold thickness) were measured at birth. Multivariable linear regression analysis was performed among the 1188 mother-infant pairs to examine the associations between maternal soy product consumption and neonatal anthropometry. The same statistical model was applied to examine the associations between maternal ISO exposure and neonatal anthropometry among 480 mother-infant pairs. Neonate girls born to mothers who "sometimes" and "frequent" consumed soy products had 169.1 g (95% confidence interval [CI], -68.9-407.1) and 256.5 g (95% CI, 17.1-495.8) higher birth weight, respectively, than those born to mothers who "never" consumed soy products during pregnancy. We observed consistent associations between higher maternal urine ISO concentrations and increased anthropometric indices (birth weight, arm and waist circumference, and triceps and abdominal skinfold thickness) in neonate girls, while no association was observed among boys. The findings suggested that maternal dietary ISO intake during pregnancy is associated with fetal development in a sex-specific pattern. In addition, follow-up studies are required to evaluate whether the observed changes in anthropometric indices at birth are associated with health conditions later in life.
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Affiliation(s)
- Yao Chen
- NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, China
| | - Tao Li
- Affiliated Hospital of Shanghai Institute of Planned Parenthood Research, China
| | - Honglei Ji
- NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, China
| | - Xin Wang
- Affiliated Hospital of Shanghai Institute of Planned Parenthood Research, China
| | - Xiaowei Sun
- NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, China
| | - Maohua Miao
- NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, China
| | - Yan Wang
- School of Pharmacy, Shanghai Jiaotong University, China
| | - Qian Wu
- Shanghai Center for Bioinformation Technology & Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai Industrial Technology Institute, China
| | - Hong Liang
- NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, China.
| | - Wei Yuan
- NHC Key Lab. of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, China
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Kumar NB, Pow-Sang J, Spiess P, Dickinson S, Schell MJ. A phase II randomized clinical trial using aglycone isoflavones to treat patients with localized prostate cancer in the pre-surgical period prior to radical prostatectomy. Oncotarget 2020; 11:1218-1234. [PMID: 32292572 PMCID: PMC7147089 DOI: 10.18632/oncotarget.27529] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 03/03/2020] [Indexed: 01/11/2023] Open
Abstract
Prostate cancer (PCa) is the most common cancer in American men. Additionally, African American Men (AAM) are 60% more likely to be diagnosed with PCa and 2.4 times more likely to die from this disease compared to Caucasian men (CM). To date, there are few strategies effective for chemoprevention for men with localized PCa. There is thus a need to continue to evaluate agents and strategies for chemoprevention of prostate cancer. Epidemiological, laboratory and early phase clinical trials have shown that the isoflavones modulates several biomarkers implicated in prostate carcinogenesis. The goal of this phase II randomized clinical trial was to explore the comparative effectiveness and safety of 40 mgs of aglycone isoflavones in AAM and CM with localized PCa in the pre-surgical period prior to radical prostatectomy. Thirty six participants (25 CM, 6AAM) were randomized to the isoflavone arm and 34 (25 CM, 7AAM) to the placebo arm, with 62 completing the intervention. Results indicated that isoflavones at a dose of 20 mgs BID for 3-6 weeks was well tolerated but did not reduce tissue markers of proliferation. A significant reduction in serum PSA was observed with isoflavone supplementation in CM compared to the placebo arm, but not observed in AAM. We observed no changes in serum steroid hormones with isoflavone supplementation. In AAM, a reduction in serum IGF-1 concentrations and IGF1: IGFBP-3 ratios were observed with isoflavone supplementation. Well-powered studies for longer duration of intervention may inform future trials with isoflavones, for chemoprevention of PCa.
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Affiliation(s)
- Nagi B Kumar
- Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA
| | - Julio Pow-Sang
- Department of Urology, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA
| | - Philippe Spiess
- Department of Urology, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA
| | - Shohreh Dickinson
- Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA
| | - Michael J Schell
- Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL, USA
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Qi W, Wang Y, Yao J, Sun H, Duan X, Song G, Pang S, Wang C, Li A. Genistein inhibits AOM/DSS-induced colon cancer by regulating lipid droplet accumulation and the SIRT1/FOXO3a pathway in high-fat diet-fed female mice. FOOD AGR IMMUNOL 2019. [DOI: 10.1080/09540105.2019.1684452] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Affiliation(s)
- Wentao Qi
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
| | - Yong Wang
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
| | - Jinli Yao
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
- College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, People’s Republic of China
| | - Hui Sun
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
| | - Xiaoliang Duan
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
| | - Ge Song
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
| | - Shaojie Pang
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
| | - Chunling Wang
- College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, People’s Republic of China
| | - Aike Li
- Academy of National Food and Strategic Reserves Administration, Beijing, People’s Republic of China
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Sri Harsha PSC, Wahab RA, Garcia-Aloy M, Madrid-Gambin F, Estruel-Amades S, Watzl B, Andrés-Lacueva C, Brennan L. Biomarkers of legume intake in human intervention and observational studies: a systematic review. GENES AND NUTRITION 2018; 13:25. [PMID: 30214640 PMCID: PMC6131749 DOI: 10.1186/s12263-018-0614-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 08/14/2018] [Indexed: 11/10/2022]
Abstract
There is a growing interest in assessing dietary intake more accurately across different population groups, and biomarkers have emerged as a complementary tool to replace traditional dietary assessment methods. The purpose of this study was to conduct a systematic review of the literature available and evaluate the applicability and validity of biomarkers of legume intake reported across various observational and intervention studies. A systematic search in PubMed, Scopus, and ISI Web of Knowledge identified 44 studies which met the inclusion criteria for the review. Results from observational studies focused on soy or soy-based foods and demonstrated positive correlations between soy intake and urinary, plasma or serum isoflavonoid levels in different population groups. Similarly, intervention studies demonstrated increased genistein and daidzein levels in urine and plasma following soy intake. Both genistein and daidzein exhibited dose-response relationships. Other isoflavonoid levels such as O-desmethylangolensin (O-DMA) and equol were also reported to increase following soy consumption. Using a developed scoring system, genistein and daidzein can be considered as promising candidate markers for soy consumption. Furthermore, genistein and daidzein also served as good estimates of soy intake as evidenced from long-term exposure studies marking their status as validated biomarkers. On the contrary, only few studies indicated proposed biomarkers for pulses intake, with pipecolic acid and S-methylcysteine reported as markers reflecting dry bean consumption, unsaturated aliphatic, hydroxyl-dicarboxylic acid related to green beans intake and trigonelline reported as marker of peas consumption. However, data regarding criteria such as specificity, dose-response and time-response relationship, reliability, and feasibility to evaluate the validity of these markers is lacking. In conclusion, despite many studies suggesting proposed biomarkers for soy, there is a lack of information on markers of other different subtypes of legumes. Further discovery and validation studies are needed in order to identify reliable biomarkers of legume intake.
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Affiliation(s)
- Pedapati S C Sri Harsha
- 1UCD School of Agriculture and Food Science, UCD Institute of Food and Health, UCD, Belfield, Dublin 4, Ireland
| | - Roshaida Abdul Wahab
- 1UCD School of Agriculture and Food Science, UCD Institute of Food and Health, UCD, Belfield, Dublin 4, Ireland
| | - Mar Garcia-Aloy
- 2Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.,3CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Barcelona, Spain
| | - Francisco Madrid-Gambin
- 2Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.,3CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Barcelona, Spain
| | - Sheila Estruel-Amades
- 2Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
| | - Bernhard Watzl
- 4Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany
| | - Cristina Andrés-Lacueva
- 2Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, XaRTA, INSA, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.,3CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Barcelona, Spain
| | - Lorraine Brennan
- 1UCD School of Agriculture and Food Science, UCD Institute of Food and Health, UCD, Belfield, Dublin 4, Ireland
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13
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Rizzo G, Baroni L. Soy, Soy Foods and Their Role in Vegetarian Diets. Nutrients 2018; 10:E43. [PMID: 29304010 PMCID: PMC5793271 DOI: 10.3390/nu10010043] [Citation(s) in RCA: 216] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 11/30/2017] [Accepted: 01/03/2018] [Indexed: 02/07/2023] Open
Abstract
Soy is a basic food ingredient of traditional Asian cuisine used for thousands of years. In Western countries, soybeans have been introduced about a hundred years ago and recently they are mainly used for surrogate foods production. Soy and soy foods are common nutritional solutions for vegetarians, due to their high protein content and versatility in the production of meat analogues and milk substitutes. However, there are some doubts about the potential effects on health, such as the effectiveness on cardiovascular risk reduction or, conversely, on the possible disruption of thyroid function and sexual hormones. The soy components that have stimulated the most research interest are isoflavones, which are polyphenols with estrogenic properties highly contained in soybeans. In this review, we discuss the characteristics of soy and soy foods, focusing on their nutrient content, including phytoestrogens and other bioactive substances that are noteworthy for vegetarians, the largest soy consumers in the Western countries. The safety of use will also be discussed, given the growing trend in adoption of vegetarian styles and the new soy-based foods availability.
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Affiliation(s)
| | - Luciana Baroni
- Primary Care Unit, Northern District, Local Health Unit 2, 31100 Treviso, Italy.
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14
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Phytoestrogen Concentrations in Human Urine as Biomarkers for Dietary Phytoestrogen Intake in Mexican Women. Nutrients 2017; 9:nu9101078. [PMID: 28961176 PMCID: PMC5691695 DOI: 10.3390/nu9101078] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 09/07/2017] [Accepted: 09/13/2017] [Indexed: 01/11/2023] Open
Abstract
There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (r = 0.460, p < 0.001), lignans (r = 0.550, p < 0.0001), flavonoids (r = 0.240, p < 0.05), and total phytoestrogens (r = 0.410, p < 0.001) were correlated to their urinary levels. Total phytoestrogen intakes estimated by the FFQ showed higher correlations to urinary levels (r = 0.730, p < 0.0001). Urinary phytoestrogens may be useful as biomarkers of phytoestrogen intake, and as a tool for evaluating the relationship of intake and disease risk in Mexican women.
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15
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Messina M, Badger TM. Health effects of isoflavones misrepresented. Food Chem 2017; 225:289-292. [DOI: 10.1016/j.foodchem.2017.01.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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16
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Genistein as antioxidant and antibrowning agents in in vivo and in vitro: A review. Biomed Pharmacother 2016; 82:379-92. [DOI: 10.1016/j.biopha.2016.05.023] [Citation(s) in RCA: 79] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 05/13/2016] [Accepted: 05/16/2016] [Indexed: 12/16/2022] Open
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Xiao X, Liu Z, Wang R, Wang J, Zhang S, Cai X, Wu K, Bergan RC, Xu L, Fan D. Genistein suppresses FLT4 and inhibits human colorectal cancer metastasis. Oncotarget 2016; 6:3225-39. [PMID: 25605009 PMCID: PMC4413649 DOI: 10.18632/oncotarget.3064] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 12/13/2014] [Indexed: 01/06/2023] Open
Abstract
Dietary consumption of genistein, found in soy, has been associated with a potentially protective role in colorectal cancer (CRC) development and progression. Herein we demonstrate that genistein will inhibit human CRC cell invasion and migration, that it does so at non-cytotoxic concentrations and we demonstrate this in multiple human CRC cell lines. After orthotopic implantation of human CRC tumors into mice, oral genistein did not inhibit tumor growth, but did inhibit distant metastasis formation, and was non-toxic to mice. Using a qPCR array, we screened for genistein-induced changes in gene expression, followed by Western blot confirmation, demonstrating that genistein downregulated matrix metalloproteinase 2 and Fms-Related Tyrosine Kinase 4 (FLT4; vascular endothelial growth factor receptor 3). After demonstrating that genistein suppressed neo-angiogenesis in mouse tumors, we examined FLT4 expression in primary CRC and adjacent normal colonic tissue from 60 human subjects, demonstrating that increased FLT4 significantly correlates with increased stage and decreased survival. In summary, we demonstrate for the first time that genistein inhibits human CRC metastasis at dietary, non-toxic, doses. FLT4 is identified as a marker of metastatic disease, and as a response marker for small molecule therapeutics that inhibit CRC metastasis.
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Affiliation(s)
- Xiao Xiao
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Zhiguo Liu
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Rui Wang
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Jiayin Wang
- The Genome Institute, Washington University in St. Louis, St. Louis, MO, USA
| | - Song Zhang
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Xiqiang Cai
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Raymond C Bergan
- Department of Medicine, Robert H. Lurie Cancer Center and Center for Drug Discovery and Chemical Biology of Northwestern University, Chicago, IL, USA
| | - Li Xu
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China
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18
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Fraser GE, Jaceldo-Siegl K, Henning SM, Fan J, Knutsen SF, Haddad EH, Sabaté J, Beeson WL, Bennett H. Biomarkers of Dietary Intake Are Correlated with Corresponding Measures from Repeated Dietary Recalls and Food-Frequency Questionnaires in the Adventist Health Study-2. J Nutr 2016; 146:586-94. [PMID: 26843587 PMCID: PMC4763486 DOI: 10.3945/jn.115.225508] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 12/29/2015] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Accurate assessment of diet in study populations is still a challenge. Some statistical strategies that use biomarkers of dietary intake attempt to compensate for the biasing effects of reporting errors. OBJECTIVE The objective was to correlate biomarkers of dietary intake with 2 direct measures of dietary intake. METHODS Subjects provided repeated 24-h dietary recalls and 2 food-frequency questionnaires (FFQs) separated by ∼3 y. Correlations between biomarkers and reported dietary intakes as measured by the recalls and FFQs were de-attenuated for within-person variability. The Adventist Health Study-2 (AHS-2) has a large database of biomarkers of dietary intake (blood, urine, adipose tissue) from a calibration study (909 analytic subjects) representing the cohort. Participants were black and non-black Adventists in the United States and Canada. RESULTS Dietary items with higher-valued de-attenuated correlations (≥0.50) between biomarkers and recalls included some fatty acids (FAs), the non-fish meats, fruit (non-black subjects), some carotenoids, vitamin B-12 (non-black subjects), and vitamin E. Moderately valued correlations (0.30-0.49) were found for very long chain ω-3 (n-3) FAs, some carotenoids, folate, isoflavones, cruciferous vegetables, fruit (black subjects), and calcium. The highest correlation values in non-black and black subjects were 0.69 (urinary 1-methyl-histidine and meat consumption) and 0.72 (adipose and dietary 18:2 ω-6), respectively. Correlations comparing biomarkers with recalls were generally similar for black and non-black subjects, but correlations between biomarkers and the FFQ were slightly lower than corresponding recall correlations. Correlations between biomarkers and a single FFQ estimate (the usual cohort situation) were generally much lower. CONCLUSIONS Many biomarkers that have relatively high-valued correlations with dietary intake were identified and were usually of similar value in black and non-black subjects. These may be used to correct effects of dietary measurement errors in the AHS-2 cohort, and in some cases they also provide evidence supporting the validity of the dietary data.
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Affiliation(s)
- Gary E Fraser
- Adventist Health Study and,Center for Nutrition, Healthy Lifestyle and Disease Prevention, Loma Linda University, Loma Linda, CA; and
| | - Karen Jaceldo-Siegl
- Adventist Health Study and Center for Nutrition, Healthy Lifestyle and Disease Prevention, Loma Linda University, Loma Linda, CA; and
| | - Susanne M Henning
- UCLA Center for Human Nutrition, School of Medicine, Los Angeles, CA
| | | | - Synnove F Knutsen
- Adventist Health Study and,Center for Nutrition, Healthy Lifestyle and Disease Prevention, Loma Linda University, Loma Linda, CA; and
| | - Ella H Haddad
- Center for Nutrition, Healthy Lifestyle and Disease Prevention, Loma Linda University, Loma Linda, CA; and
| | - Joan Sabaté
- Adventist Health Study and,Center for Nutrition, Healthy Lifestyle and Disease Prevention, Loma Linda University, Loma Linda, CA; and
| | - W Lawrence Beeson
- Adventist Health Study and,Center for Nutrition, Healthy Lifestyle and Disease Prevention, Loma Linda University, Loma Linda, CA; and
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19
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Biomarkers of Dietary Polyphenols in Cancer Studies: Current Evidence and Beyond. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:732302. [PMID: 26180594 PMCID: PMC4477246 DOI: 10.1155/2015/732302] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 01/06/2015] [Indexed: 12/13/2022]
Abstract
Polyphenols, commonly contained in fruits and vegetables, have long been associated with a protective role against multiple diseases and adverse health effects. Generally, in vitro and animal experiments have provided strong positive evidence, whereas evidence from in vivo and human epidemiological studies is not strong enough. Most epidemiological studies to date use food frequency questionnaire based dietary intake estimations, which inevitably incur imprecision. Biomarkers of polyphenol have the potential to complement and enhance current studies. This review performed a literature search of all epidemiological studies or controlled clinical/intervention trials which employed biomarkers of exposure for polyphenols to help assess their anticarcinogenic role, using studies on green tea polyphenols as a study model. Currently, studies on this topic are still limited; breast cancer and prostate cancer were the only widely studied cancer types. Isoflavone is the only widely studied polyphenol. In addition to associations between polyphenols and cancer risks, factors such as host genetic susceptibility, epigenetic modification, and gut microbiome patterns may also impact on the protective roles of polyphenols. More evidence should be collected by utilizing biomarkers of exposure for polyphenols in future epidemiological studies before a clear conclusion can be made.
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20
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Talaei M, Pan A. Role of phytoestrogens in prevention and management of type 2 diabetes. World J Diabetes 2015; 6:271-283. [PMID: 25789108 PMCID: PMC4360420 DOI: 10.4239/wjd.v6.i2.271] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2014] [Revised: 11/04/2014] [Accepted: 12/17/2014] [Indexed: 02/05/2023] Open
Abstract
Type 2 diabetes (T2D) has become a major public health threat across the globe. It has been widely acknowledged that diet plays an important role in the development and management of T2D. Phytoestrogens are polyphenols that are structurally similar to endogenous estrogen and have weak estrogenic properties. Emerging evidence from pre-clinical models has suggested that phytoestrogens may have anti-diabetic function via both estrogen-dependent and estrogen-independent pathways. In the current review, we have summarized the evidence linking two major types of phytoestrogens, isoflavones and lignans, and T2D from epidemiological studies and clinical trials. The cross-sectional and prospective cohort studies have reported inconsistent results, which may due to the large variations in different populations and measurement errors in dietary intakes. Long-term intervention studies
using isoflavone supplements have reported potential beneficial effects on glycemic parameters in postmenopausal women, while results from short-term small-size clinical trials are conflicting. Taken together, the current evidence from different study designs is complex and inconsistent. Although the widespread use of phytoestrogens could not be recommended yet, habitual consumption of phytoestrogens, particularly their intact food sources like soy and whole flaxseed, could be considered as a component of overall healthy dietary pattern for prevention and management of T2D.
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21
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Pudenz M, Roth K, Gerhauser C. Impact of soy isoflavones on the epigenome in cancer prevention. Nutrients 2014; 6:4218-72. [PMID: 25322458 PMCID: PMC4210915 DOI: 10.3390/nu6104218] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 08/25/2014] [Accepted: 08/27/2014] [Indexed: 12/21/2022] Open
Abstract
Isoflavones (IF) such as genistein are cancer preventive phytochemicals found in soy and other legumes. Epidemiological studies point to a reduced risk for hormone‑dependent cancers in populations following a typical Asian diet rich in soy products. IF act as phytoestrogens and prevent tumorigenesis in rodent models by a broad spectrum of bioactivities. During the past 10 years, IF were shown to target all major epigenetic mechanisms regulating gene expression, including DNA methylation, histone modifications controlling chromatin accessibility, and non-coding RNAs. These effects have been suggested to contribute to cancer preventive potential in in vitro and in vivo studies, affecting several key processes such as DNA repair, cell signaling cascades including Wnt-signaling, induction of apoptosis, cell cycle progression, cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), metastasis formation and development of drug-resistance. We here summarize the state-of-the-art of IF affecting the epigenome in major hormone-dependent, urogenital, and gastrointestinal tumor types and in in vivo studies on anti-cancer treatment or developmental aspects, and short-term intervention studies in adults. These data, while often requiring replication, suggest that epigenetic gene regulation represents an important novel target of IF and should be taken into consideration when evaluating the cancer preventive potential of IF in humans.
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Affiliation(s)
- Maria Pudenz
- Division Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
| | - Kevin Roth
- Division Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
| | - Clarissa Gerhauser
- Division Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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Pampaloni B, Palmini G, Mavilia C, Zonefrati R, Tanini A, Brandi ML. In vitro effects of polyphenols on colorectal cancer cells. World J Gastrointest Oncol 2014; 6:289-300. [PMID: 25132926 PMCID: PMC4133796 DOI: 10.4251/wjgo.v6.i8.289] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 05/30/2014] [Accepted: 06/27/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To investigate the effects of quercetin and genistein on colon cancer cell proliferation and their estrogen receptor β (ERβ) expression.
METHODS: Colon cancer cells were stably transfected with a mammalian expression vector to overexpress ERβ (HCT8-β8-expressing cells) or a control vector (HCT8-pSV2neo-expressing cells). The proliferation of these cells was examined after treatment with quercetin or genistein (5-100 μmol/L), or 10 nmol/L 17β-estradiol (17β-E2). Cell viability was examined by acridine orange staining following treatments for 48 or 144 h. Effects of quercetin and genistein on ERβ transcriptional transactivation were examined by luciferase activity in HCT8-β8-expressing cells transiently transfected with a pEREtkLUC reporter vector. In addition, the regulation of ERβ transcription by phytoestrogens and 17β-E2 was examined by quantitative polymerase chain reaction.
RESULTS: Proliferation of HCT8-β8-expressing cells was not reduced low doses (5 μmol/L) of quercetin and genistein, while it was reduced at 25-50 μmol/L with an effect similar to 10 nmol/L 17β-E2. Treatment with doses of phytoestrogens ≥ 75 μmol/L completely blocked cell growth and reduced overall cell counts, however no effects at any dose were observed in HCT8-pSV2neo-expressing cells. These results were supported by viability staining that revealed acridine orange-stained lysosomes with high doses or extended treatment periods. Genistein and quercetin (50 μmol/L) significantly increased ER-responsive luciferase activity similar to 10 nmol/L 17β-E2 (P < 0.05). Furthermore, genistein and quercetin (50 μmol/L), as well as 10 nmol/L 17β-E2 significantly increased ERβ mRNA levels in HCT8-β8-expressing cells (P < 0.05). In addition, treatment of HCT8-pSV2neo-expressing cells with 50 µmol/L quercetin or 10 nmol/L 17β-E2 significantly increased ERβ mRNA levels compared to untreated controls (P < 0.05), though the absolute levels were much lower than in HCT8-β8-expressing cells.
CONCLUSION: The antitumorigenic effects of the phytoestrogenic compounds quercetin and genistein on colon cancers cells occur through ERβ activity and expression.
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Morimoto Y, Beckford F, Franke AA, Maskarinec G. Urinary isoflavonoid excretion as a biomarker of dietary soy intake during two randomized soy trials. Asia Pac J Clin Nutr 2014; 23:205-9. [PMID: 24901088 DOI: 10.6133/apjcn.2014.23.2.19] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
We evaluated urinary isoflavonoid excretion as a biomarker of dietary isoflavone intake during two randomized soy trials (13-24 months) among 256 premenopausal women with a total of 1,385 repeated urine samples. Participants consumed a high-soy diet (2 servings/day) and a low-soy diet (<3 servings/week), completed 7 unannounced 24-hour dietary recalls, and donated repeated urine samples, which were analyzed for isoflavonoid excretion by liquid chromatography methods. We computed Spearman correlation coefficients and applied logistic regression to estimate the area under the curve. Median overall daily dietary isoflavone intakes at baseline, during low- and high-soy diet were 2.3, 0.2, and 60.4 mg aglycone equivalents, respectively. The corresponding urinary isoflavonoid excretion values were 0.4, 1.0, and 32.4 nmol/mg creatinine. Across diets, urinary isoflavonoid excretion was significantly associated with dietary isoflavone intake (rs=0.51, AUC=0.85; p<0.0001) but not within diet periods (rs=0.05-0.06, AUC=0.565-0.573). Urinary isoflavonoid excretion is an excellent biomarker to discriminate between low- and high-soy diets across populations, but the association with dietary isoflavone intake is weak when the range of soy intake is small.
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Affiliation(s)
- Yukiko Morimoto
- University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA.
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Zamora-Ros R, Touillaud M, Rothwell JA, Romieu I, Scalbert A. Measuring exposure to the polyphenol metabolome in observational epidemiologic studies: current tools and applications and their limits. Am J Clin Nutr 2014; 100:11-26. [PMID: 24787490 PMCID: PMC4144095 DOI: 10.3945/ajcn.113.077743] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Accepted: 03/25/2014] [Indexed: 12/13/2022] Open
Abstract
Much experimental evidence supports a protective role of dietary polyphenols against chronic diseases such as cardiovascular diseases, diabetes, and cancer. However, results from observational epidemiologic studies are still limited and are often inconsistent. This is largely explained by the difficulties encountered in the estimation of exposure to the polyphenol metabolome, which is composed of ~500 polyphenols distributed across a wide variety of foods and characterized by diverse biological properties. Exposure to the polyphenol metabolome in epidemiologic studies can be assessed by the use of detailed dietary questionnaires or the measurement of biomarkers of polyphenol intake. The questionnaire approach has been greatly facilitated by the use of new databases on polyphenol composition but is limited by bias as a result of self-reporting. The use of polyphenol biomarkers holds much promise for objective estimation of polyphenol exposure in future metabolome-wide association studies. These approaches are reviewed and their advantages and limitations discussed by using examples of epidemiologic studies on polyphenols and cancer. The current improvement in these techniques, along with greater emphasis on the intake of individual polyphenols rather than polyphenols considered collectively, will help unravel the role of these major food bioactive constituents in disease prevention.
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Affiliation(s)
- Raul Zamora-Ros
- From the Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (RZ-R, JAR, IR, and AS); the Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (RZ-R); and the Cancer and Environment Unit, Centre Léon Bérard, Lyon, France (MT)
| | - Marina Touillaud
- From the Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (RZ-R, JAR, IR, and AS); the Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (RZ-R); and the Cancer and Environment Unit, Centre Léon Bérard, Lyon, France (MT)
| | - Joseph A Rothwell
- From the Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (RZ-R, JAR, IR, and AS); the Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (RZ-R); and the Cancer and Environment Unit, Centre Léon Bérard, Lyon, France (MT)
| | - Isabelle Romieu
- From the Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (RZ-R, JAR, IR, and AS); the Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (RZ-R); and the Cancer and Environment Unit, Centre Léon Bérard, Lyon, France (MT)
| | - Augustin Scalbert
- From the Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (RZ-R, JAR, IR, and AS); the Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (RZ-R); and the Cancer and Environment Unit, Centre Léon Bérard, Lyon, France (MT)
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Thomas AJ, Ismail R, Taylor-Swanson L, Cray L, Schnall JG, Mitchell ES, Woods NF. Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: a systematic review. Maturitas 2014; 78:263-76. [PMID: 24951101 DOI: 10.1016/j.maturitas.2014.05.007] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Accepted: 05/15/2014] [Indexed: 11/18/2022]
Abstract
AIMS Review controlled clinical trials of isoflavones and amino acid preparation effects on hot flashes and at least one other symptom including mood, sleep, pain, and cognitive function that women report during the menopausal transition and early postmenopause. METHODS An experienced reference librarian searched PubMed/Medline, CINAHL Plus, PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, AMED, and Alt-Health Watch for English-language randomized controlled trials between 2004 and July 2011. Seventeen trials of isoflavones and amino acid effects on hot flashes and one additional symptom were identified. RESULTS In five trials of soy isoflavone preparations, two (6g soy germ extract and 25 g soy protein in soy nuts) significantly decreased hot flashes, but no other symptoms. In the seven trials of other isoflavones, six significantly reduced hot flashes; in addition, red clover (80 mg) significantly reduced mood symptoms; Rexflavone (350 mg) for women with Kupperman Index>20 significantly reduced sleep symptoms; two trials had significant reductions for pain: isoflavone powder (90 mg) and red clover (80 mg). The only trial in this systematic review that significantly reduced cognitive symptoms was red clover (80 mg). In one trial, red clover isoflavone (80 mg/day) significantly relieved hot flashes, mood, pain, and cognitive symptoms. Amino acids yielded no significant results. Equol supplements of 30 mg/day for non-Equol producing women significantly reduced mood symptoms in one trial. The magnolia bark extract combination significantly reduced hot flashes, mood, and sleep symptoms. CONCLUSIONS Isoflavone trials yielded significant reductions on hot flashes and co-occurring symptoms during the menopausal transition and postmenopause, but studies require replication with larger sample sizes and attention to measurement of outcomes.
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Affiliation(s)
| | - Rita Ismail
- University of Washington School of Nursing, United States and Ministry of Health, Republic of Indonesia, United States
| | | | - Lori Cray
- College of Nursing, Seattle University, United States
| | - Janet G Schnall
- Health Sciences Library, University of Washington, United States
| | | | - Nancy Fugate Woods
- Biobehavioral Nursing and Health Systems, University of Washington, United States
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Gardana C, Canzi E, Simonetti P. R(-)-O-desmethylangolensin is the main enantiomeric form of daidzein metabolite produced by human in vitro and in vivo. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 953-954:30-7. [PMID: 24561352 DOI: 10.1016/j.jchromb.2014.01.048] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Revised: 01/21/2014] [Accepted: 01/29/2014] [Indexed: 11/19/2022]
Abstract
After ingestion, human intestinal bacteria transform daidzein into dihydrodaidzein, which can be further metabolised to O-desmethylangolensin. This metabolite, unlike daidzein, has a chiral centre and can therefore occur as two distinct enantiomers; however, it is unclear which enantiomer is present in humans. The aim of this study was to define in vitro and in vivo the structure of O-desmethylangolensin and then to evaluate its pharmacokinetic parameters. Daidzein metabolism was preliminarily investigated in anaerobic batch cultures inoculated with mixed faecal bacteria from O-desmethylangolensin producer volunteers. The transformation was monitored by liquid chromatography-mass spectrometry and a chiral column was used to distinguish dihydrodaidzein and O-desmethylangolensin enantiomers. These were purified, analysed by circular dichroism and the results established R(-)-O-desmethylangolensin as the main product (enantiomer excess 91%). However, both dihydrodaidzein enantiomers were detected. Similar results were obtained by in vivo trials. The in vitro formation of O-desmethylangolensin seems to be directly correlated with the number of transforming microorganisms. This correlation was found in vivo for tmax but not for other pharmacokinetic indexes. The pharmacokinetics of daidzein, dihydrodaidzein and O-desmethylangolensin were then evaluated in 11 healthy adult O-desmethylangolensin producers after the single administration of soy milk containing 100mg daidzein. The conjugated forms of daidzein, dihydrodaidzein and O-desmethylangolensin represent more than 90 and 95% of the plasmatic and urinary forms, respectively. The Cmax, tmax and half-life of O-desmethylangolensin in plasma were 62±53nM, 28±11 and 15±6h, respectively. Relevant inter-individual variations were observed as indicated by the high standard deviations.
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Affiliation(s)
- Claudio Gardana
- Università degli Studi di Milano - Department of Food, Environmental and Nutritional Sciences - DeFENS, Division of Human Nutrition - Via Celoria 2, 20133 Milan, Italy.
| | - Enrica Canzi
- Università degli Studi di Milano - Department of Food, Environmental and Nutritional Sciences - DeFENS, Division of Microbiology - Via Celoria 2, 20133 Milan, Italy
| | - Paolo Simonetti
- Università degli Studi di Milano - Department of Food, Environmental and Nutritional Sciences - DeFENS, Division of Human Nutrition - Via Celoria 2, 20133 Milan, Italy
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Franke AA, Custer LJ. Application of HPLC coupled with ultraviolet-photodiode array detection for the analysis of phytoestrogens in biological samples. J Med Food 2013; 2:119-23. [PMID: 19281361 DOI: 10.1089/jmf.1999.2.119] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
HPLC/PDA methodology was developed for phytoestrogen analysis in human blood, urine, and breast milk. Applications of this technique in four different observational studies showed that urinary excretion rates of isoflavonoids reflects soy consumption reliably. A case-control study in Shanghai showed a decrease in risk to develop breast cancer for women with high urinary isoflavone excretion. These findings support a potential breast cancer preventive effect achieved by soy consumption in populations that eat soy foods habitually.
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Affiliation(s)
- A A Franke
- Cancer Research Center of Hawaii, Cancer Etiology, Honolulu, HI, USA
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28
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Swann R, Perkins KA, Velentzis LS, Ciria C, Dutton SJ, Mulligan AA, Woodside JV, Cantwell MM, Leathem AJ, Robertson CE, Dwek MV. The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption. Maturitas 2013; 75:232-40. [PMID: 23664318 DOI: 10.1016/j.maturitas.2013.03.018] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2013] [Revised: 03/28/2013] [Accepted: 03/30/2013] [Indexed: 11/12/2022]
Abstract
DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed.
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Affiliation(s)
- Ruth Swann
- Departments of Molecular and Applied Biosciences and Human and Health Sciences, University of Westminster, 115 New Cavendish St., London, UK
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Zhang X, Gao YT, Yang G, Li H, Cai Q, Xiang YB, Ji BT, Franke AA, Zheng W, Shu XO. Urinary isoflavonoids and risk of coronary heart disease. Int J Epidemiol 2012; 41:1367-75. [PMID: 22927214 PMCID: PMC3465770 DOI: 10.1093/ije/dys130] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2012] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Whether soy food consumption may protect against coronary heart disease (CHD) remains controversial. No previous study has used biomarkers of soy intake in assessing the relationship between soy consumption and CHD. Biomarkers that reflect both intake and metabolism may be more informative than self-reports of dietary intake. METHODS We examined associations of urinary isoflavonoids, a biomarker of soy or soy isoflavone intake, with risk of CHD in a case-control study nested within two prospective cohort studies of Chinese adults in Shanghai. Cases were defined as subjects with no history of CHD at baseline who developed incident CHD during follow-up. Control subjects were randomly selected from those who remained free of CHD and matched to cases by sex, age, date and time of sample collection and antibiotic use. Baseline urinary isoflavonoids (daidzein, genistein, glycitein, equol, O-desmethylangolensin, dihydrodaidzein and dihydrogenistein) were compared between cases (n = 377) and control subjects (n = 753). Conditional logistic regression was used to evaluate the associations. RESULTS Total urinary isoflavonoids were not associated with CHD in either women or men. However, urinary equol excretion showed a significant inverse association with CHD in women. The adjusted odds ratios (95% confidence intervals) for CHD across increasing quartiles of equol levels in women were 1 (reference), 0.61 (0.32, 1.15), 0.51 (0.26, 0.98) and 0.46 (0.24, 0.89) (P = 0.02 for trend). CONCLUSIONS Our study suggests for the first time that equol, a bioactive metabolite of soy isoflavone daidzein, may be inversely associated with risk of CHD in women.
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Affiliation(s)
- Xianglan Zhang
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37203-1738, USA.
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Zamora-Ros R, Rabassa M, Llorach R, González CA, Andres-Lacueva C. Application of dietary phenolic biomarkers in epidemiology: past, present, and future. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:6648-6657. [PMID: 22296234 DOI: 10.1021/jf204742e] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Phenolics are a large group of plant compounds that have been associated with protective health effects against several chronic diseases due to their potential antioxidant, anti-inflammatory, and anticarcinogenic properties. Consequently, in nutritional epidemiology it is essential to make an accurate assessment of phenolic exposure to evaluate their protective activities against human diseases. Self-reported questionnaires and biomarkers are the two main methods used for estimating dietary phenolics. Despite the limitations of self-reported methods, they are still an acceptable and useful measure. Meanwhile, nutritional biomarkers provide an alternative, more accurate measure, but they are expensive, and to date there are few validated biomarkers of phenolic intake. Nowadays, new analytical techniques, using both targeted and untargeted metabolomic approaches, play an important part in the rapid increase in the understanding of phenolic bioavailability and, consequently, have provided new potential biomarkers in small trials. In the near future, these dietary biomarkers should be tested in large epidemiological studies. Furthermore, the use of two independent measures-questionnaires and biomarkers-together provides a more thorough analysis of true phenolic exposure. Indeed, the challenge in the long term is to combine the information from biomarkers and self-reported questionnaires to clarify the relationship between dietary phenolics and disease.
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Affiliation(s)
- Raul Zamora-Ros
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology , IDIBELL, Barcelona, Spain
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Franke AA, Lai JF, Pagano I, Morimoto Y, Maskarinec G. Equol production changes over time in pre-menopausal women. Br J Nutr 2012; 107:1201-6. [PMID: 21920062 PMCID: PMC3319310 DOI: 10.1017/s0007114511004223] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Equol (EQ) is a metabolite produced by gut bacteria through the chemical reduction of the soya isoflavone daidzein (DE), but only by 30-60% of the population. EQ is believed to provide benefits derived from soya intake and its production is widely viewed as a relatively stable phenomenon. In a randomised, cross-over intervention with soya foods, seventy-nine pre-menopausal women were challenged with a high-soya and a low-soya diet each for 6 months, separated by a 1-month washout period. Overnight urine was collected at three time points during each diet period and analysed for DE and EQ by liquid chromatography tandem MS. Remaining an EQ producer (EP) or non-producer (NP) or changing towards an EP or NP was assessed using an EQ:DE ratio of ≥0·018 combined with a DE threshold of ≥2 nmol/mg creatinine as a cut-off point. We observed 19 and 24% EP during the low-soya and high-soya diet periods, respectively, and found that 6-11% of our subjects changed EQ status 'within' each study period (on an average of 1·2 times), while 16% changed 'between' the two diet periods. The present finding challenges the widely held conviction that EQ production within an individual remains stable over time. The precise factors contributing to changes in EQ status, however, remain elusive and warrant further investigation.
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Affiliation(s)
- Adrian A Franke
- University of Hawaii Cancer Center, Clinical Sciences Program, 1236 Lauhala Street, Honolulu, HI 96813, USA.
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Yuan B, Zhen H, Jin Y, Xu L, Jiang X, Sun S, Li C, Xu H. Absorption and plasma disposition of genistin differ from those of genistein in healthy women. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:1428-36. [PMID: 22256777 DOI: 10.1021/jf204421c] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
The chemical forms in which isoflavones appear in food or supplements seem to play an important role in their absorption efficiency. However, the influence of the chemical form of isoflavones on their plasma disposition has never been reported, although the metabolites of isoflavones circulating in the blood may have biological activity themselves. The purpose of the study was to investigate the pharmacokinetic profiles of genistein (GEN) and its phase II metabolites in the plasma and urine of healthy young women after multiple doses of pure aglycone and glucoside forms of GEN. Genistein-7-glucuronide (G-7-G), 4'-glucuronide (G-4'-G), 7-sulfate (G-7-S), 4'-sulfate (G-4'-S), 4',7-diglucuronide (G-4',7-diG), and 7-glucuronide-4'-sulfate (G-7-G-4'-S) besides unconjugated GEN were observed in human plasma after ingestion of GEN and its glucoside. Among these metabolites, G-4',7-diG and G-7-G-4'-S were the major ones, comprising both about 30% of the total amount of GEN in plasma. Compared with the aglycone, the amount of total GEN in vivo and those of G-4',7-diG and G-7-G-4'-S were increased after the glucoside intake. No difference was observed in urinary excretion between the aglycone and the glucoside. Overall, the absorption and plasma disposition of GEN were affected by the glucoside form.
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Affiliation(s)
- Bo Yuan
- Department of Pharmaceutical Analysis, Pharmacy School, Shenyang Pharmaceutical University, Shenyang 110016, China
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33
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de Luis DA, Aller R. Efecto del consumo de soja sobre la masa ósea en mujeres menopáusicas. Med Clin (Barc) 2012; 138:60-1. [DOI: 10.1016/j.medcli.2011.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2011] [Revised: 07/25/2011] [Accepted: 09/06/2011] [Indexed: 11/25/2022]
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Su Y, Chen LJ, He JR, Yuan XJ, Cen YL, Su FX, Tang LY, Zhang AH, Chen WQ, Lin Y, Wang SM, Ren ZF. Urinary rubidium in breast cancers. Clin Chim Acta 2011; 412:2305-9. [DOI: 10.1016/j.cca.2011.08.035] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Revised: 08/02/2011] [Accepted: 08/24/2011] [Indexed: 01/05/2023]
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Franke AA, Lai JF, Halm BM, Pagano I, Kono N, Mack WJ, Hodis HN. Equol production changes over time in postmenopausal women. J Nutr Biochem 2011; 23:573-9. [PMID: 21775122 DOI: 10.1016/j.jnutbio.2011.03.002] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Revised: 02/24/2011] [Accepted: 03/02/2011] [Indexed: 10/17/2022]
Abstract
Equol (EQ) is produced by intestinal bacteria from the soy isoflavone daidzein (DE) in 30%-60% of the population and is believed to provide benefits from soy intake. A robust EQ status definition is lacking, and it is uncertain whether EQ is formed consistently within an individual and ceases upon oral antibiotic treatment. In a randomized, double-blind, placebo-controlled soy intervention trial with 350 postmenopausal women, DE and EQ were analyzed by liquid chromatography/tandem mass spectrometry at baseline and every 6 months over 2.5 years in overnight urine, spot urine and plasma. Equol production changes and status (remaining an EQ producer or nonproducer or changing towards an EQ producer or nonproducer) were assessed. Equol status was determined most dependably by overnight urine applying as cutoff a ratio of EQ/DE≥0.018 with a DE threshold ≥2 nmol/mg creatinine: the soy and placebo groups had approximately 30% consistent EQ producers during the study, but 14% and 35%, respectively, changed EQ status (mean 1.4-1.7 times), while 27% and 17%, respectively, had antibiotic treatment (P<.01 for inverse association). No significant trend in change of EQ production or status was observed when overnight urine was limited to collections closest to before and after antibiotic treatment. Similarly, antibiotic type or class, duration, dose or time between antibiotic treatment and overnight urine collection showed no consistent influence on EQ production. Equol production can markedly change intraindividually over 2.5 years, and antibiotic treatment impacts it inconsistently. Factors other than antibiotic treatment must be considered as causes for EQ production changes.
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Affiliation(s)
- Adrian A Franke
- Cancer Research Center of Hawaii, Clinical Sciences Program, University of Hawaii, Honolulu, HI 96813, USA.
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36
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Napora JK, Short RG, Muller DC, Carlson OD, Odetunde JO, Xu X, Carducci M, Travison TG, Maggio M, Egan JM, Basaria S. High-dose isoflavones do not improve metabolic and inflammatory parameters in androgen-deprived men with prostate cancer. JOURNAL OF ANDROLOGY 2011; 32:40-8. [PMID: 20798386 PMCID: PMC3005077 DOI: 10.2164/jandrol.110.010983] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for prostate cancer (PCa) results in complications such as diabetes and metabolic syndrome that predispose to cardiovascular disease. Because phytoestrogens have been associated with an improvement in metabolic parameters, we evaluated their role in men undergoing ADT. Our objective was to evaluate the effects of high-dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT. This was a randomized, double-blind, placebo-controlled, 12-week pilot study. Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The study was conducted at a tertiary care center in the United States. Thirty-three men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot study. Mean age in the 2 groups was 69 years and the majority of men were Caucasians. Mean duration of ADT in both groups was approximately 2 years (P = .70). The 2 groups were well matched at baseline. After 12 weeks of intervention, there was no significant difference in either metabolic or inflammatory parameters between the 2 groups. We found that high-dose isoflavones over a course of 12 weeks do not improve metabolic or inflammatory parameters in androgen-deprived men.
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Affiliation(s)
- Joshua K. Napora
- National Institute of Health, National Institute on Aging, Laboratory of Clinical Investigation, Diabetes Section
| | - Ryan G. Short
- National Institute of Health, National Institute on Aging, Laboratory of Clinical Investigation, Diabetes Section
| | - Denis C. Muller
- National Institute of Health, National Institute on Aging, Laboratory of Clinical Investigation, Diabetes Section
| | - Olga D. Carlson
- National Institute of Health, National Institute on Aging, Laboratory of Clinical Investigation, Diabetes Section
| | - Juliana O. Odetunde
- National Institute of Health, National Institute on Aging, Laboratory of Clinical Investigation, Diabetes Section
| | - Xiaoqiang Xu
- Department of Medicine, Johns Hopkins University School of Medicine
| | - Michael Carducci
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
| | - Thomas G. Travison
- Division of Endocrinology & Metabolism, Boston University School of Medicine
| | | | - Josephine M. Egan
- National Institute of Health, National Institute on Aging, Laboratory of Clinical Investigation, Diabetes Section
| | - Shehzad Basaria
- Division of Endocrinology & Metabolism, Boston University School of Medicine
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Jackson MD, McFarlane-Anderson ND, Simon GA, Bennett FI, Walker SP. Urinary phytoestrogens and risk of prostate cancer in Jamaican men. Cancer Causes Control 2010; 21:2249-57. [DOI: 10.1007/s10552-010-9648-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2010] [Accepted: 09/21/2010] [Indexed: 02/06/2023]
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Overnight urinary excretion of isoflavones as an indicator for dietary isoflavone intake in Korean girls of pubertal age. Br J Nutr 2010; 104:709-15. [DOI: 10.1017/s0007114510000978] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Little is known about the bioavailability of isoflavones in children. Previous studies have shown that children excrete more isoflavone in urine compared with adults. Thus we examined the relationship between usual dietary isoflavone intake and the urinary excretion of isoflavonoids in Korean girls of pubertal age. Twelve girls each were selected from the lowest and the highest quartiles of isoflavone intake among 252 Korean girls aged 8–11 years. Age, BMI and sexual maturation stage were matched between the two groups. Dietary intakes for 3 d by diet record and overnight urine samples were collected at baseline and at 6 and 12 months. Total and individual isoflavone (daidzein, genistein and glycitein) intakes were calculated from diet records. The parent isoflavone compounds (daidzein, genistein and glycitein) and their metabolites (equol,O-desmethylangolensin (O-DMA), dihydrodaidzein and dihydrogenistein) present in the urine samples were analysed using liquid chromatography–MS. Intake levels of total and individual isoflavone compounds were significantly higher in the high isoflavone (HI) group than the levels in the low isoflavone (LI) group (P < 0·05). Urinary excretion of all isoflavone parent compounds was significantly higher in the HI group than in the LI group (P < 0·0001). Among isoflavone metabolites, onlyO-DMA and total metabolites were significantly different (P < 0·05). Total isoflavone intake was highly correlated with the urinary excretion of total parent compounds (r0·68;P < 0·01), parent compounds plus their metabolites (r0·66–0·69;P < 0·01) and total isoflavonoids (r0·72;P < 0·0001). In conclusion, overnight urinary excretion of total isoflavonoids is a reliable biomarker of usual isoflavone intake in Korean girls of pubertal age.
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Luo J, Gao YT, Chow WH, Shu XO, Li H, Yang G, Cai Q, Rothman N, Cai H, Shrubsole MJ, Franke AA, Zheng W, Dai Q. Urinary polyphenols and breast cancer risk: results from the Shanghai Women's Health Study. Breast Cancer Res Treat 2010; 120:693-702. [PMID: 19653095 PMCID: PMC2842475 DOI: 10.1007/s10549-009-0487-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2009] [Accepted: 07/18/2009] [Indexed: 12/27/2022]
Abstract
Polyphenols, the most abundant dietary antioxidants, also possess many other anticarcinogenic activities. Urinary metabolites of polyphenols could complement dietary assessment of the bioavailability of these nutrients. We conducted a study of 353 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 40-70 years at baseline. Liquid chromatography photo-diode array electrospray mass spectrometry was used to measure tea polyphenols (epicatechin, epigallocatechin, and their metabolites) and flavonols (e.g., quercetin and kaempferol). Multivariate conditional logistic regression analyses were used to assess associations between breast cancer risk and urinary excretion rates of polyphenols. Urinary excretion of tea polyphenols increased with increasing tea leaves consumed among controls, but not among breast cancer cases. Compared with cases, controls had higher levels of urinary total polyphenols and tea polyphenols, particularly epicatechin. In contrast, we did not find any dose-response relationship between urinary polyphenols and breast cancer risk. Urinary excretion of epicatechin was inversely associated with breast cancer risk [odds ratio (OR) and 95% confidence interval (CI) of 0.59 (0.39-0.88) for the intermediate tertile]. In spline regression, we found an overall dose-response relationship between epicatechin level and risk of breast cancer, although it was not apparent in low and middle urinary excretion range. In conclusion, high epicatechin may be related to a reduced risk of breast cancer. Further studies are warranted to confirm our findings.
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Affiliation(s)
- Jianfeng Luo
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
- Department of Health Statistics and Social Medicine, School of Public Health, Fudan University, Shanghai 200032, China
| | - Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Wong-Ho Chow
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland
| | - Xiao-Ou Shu
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
| | - Honglan Li
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Gong Yang
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
| | - Qiuyin Cai
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
| | - Nathaniel Rothman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland
| | - Hui Cai
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
| | - Martha J. Shrubsole
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
| | - Adrian A Franke
- Cancer Research Center of Hawaii, University of Hawaii, 1236 Lauhala Street, Honolulu, Hawaii 96813
| | - Wei Zheng
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
| | - Qi Dai
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine
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Cassidy A. Dietary phyto-oestrogens: molecular mechanisms, bioavailability and importance to menopausal health. Nutr Res Rev 2009; 18:183-201. [PMID: 19079904 DOI: 10.1079/nrr2005102] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Following the high-profile studies on hormone replacement therapy which provided little evidence in support of the drug therapy improving future health, there remains a growing demand for dietary solutions for maintaining health and preventing disease as women age. Although interest in the relative importance of phyto-oestrogens to human health has increased dramatically over the last decade, the effective dose for health benefits and hypothetical issues on safety remain to be resolved. Plausible mechanisms and epidemiological data are available to support the concept that phyto-oestrogen-rich diets exert physiological effects, but optimal doses and sources of these compounds have still not been elucidated for specific health benefits. In addition, much of the current mechanistic data are difficult to interpret as the experiments have incorporated levels of phyto-oestrogens that may not be achievable in vivo and have to date only used aglycones and glycosides of the pure compounds rather than examining the biological effects of gut and liver metabolites. The present review will concentrate on the isoflavone subclass of phyto-oestrogens, as, to date, these compounds have received most attention from both a commercial and research perspective.
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Affiliation(s)
- Aedín Cassidy
- School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.
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Setchell KDR, Zhao X, Shoaf SE, Ragland K. The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women. J Nutr 2009; 139:2037-43. [PMID: 19776178 DOI: 10.3945/jn.109.110874] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
The soy isoflavone metabolite, S-(-)equol, has selective affinity for estrogen receptor (ER)beta and also antagonizes in vivo the action of dihydrotestosterone. It is therefore of interest as a potential new therapeutic agent in hormone-dependent conditions and is under development as a nutraceutical. Our objective in this study was to define the pharmacokinetics of natural S-(-)equol after administration of SE5-OH, a newly developed S-(-)equol supplement made by incubation of the equol-producing bacterium Lactococcus garvieae with soy germ isoflavones. In a single-center, open-label, randomized, 2-period crossover design study, the pharmacokinetics of S-(-)equol administered as single-bolus oral doses of 10 and 30 mg in the form of SE5-OH tablets was determined in 12 healthy postmenopausal women. S-(-)equol was measured in plasma and urine collected at timed intervals over a 48-h period postdosing using tandem MS. Equol-producer status was also determined after a soymilk challenge conducted after the pharmacokinetic sampling was complete. S-(-)equol was rapidly absorbed after oral administration and attained high plasma concentrations, with a plasma elimination half-life of 8 h. The maximum plasma concentration/dose, area under the plasma concentration-time curve from time 0 to infinity/dose, and the fraction of dose excreted in urine (%f(e,u)) were similar for the 2 doses, indicating a dose-proportional response in total S-(-)equol pharmacokinetics. The systemic bioavailability of S-(-)equol was very high, as the %f(e,u) was 82% for both doses, which is greater than published data for the soy isoflavones daidzein and genistein. Three participants were determined to be equol-producers, representing a 25% frequency, and equol-producer status had no effect on natural S-(-)equol pharmacokinetics.
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Affiliation(s)
- Kenneth D R Setchell
- Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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Setchell KD, Zhao X, Jha P, Heubi JE, Brown NM. The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers. Am J Clin Nutr 2009; 90:1029-37. [PMID: 19710188 PMCID: PMC2744624 DOI: 10.3945/ajcn.2009.27981] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2009] [Accepted: 07/28/2009] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND The nonsteroidal estrogen equol occurs as diastereoisomers, S-(-)equol and R-(+)equol, both of which have significant biological actions. S-(-)equol, the naturally occurring enantiomer produced by 20-30% of adults consuming soy foods, has selective affinity for estrogen receptor-beta, whereas both enantiomers modulate androgen action. Little is known about the pharmacokinetics of the diastereoisomers, despite current interest in developing equol as a nutraceutical or pharmaceutical agent. OBJECTIVE The objective was to compare the pharmacokinetics of S-(-)equol and R-(+)equol by using [13C] stable-isotope-labeled tracers to facilitate the optimization of clinical studies aimed at evaluating the potential of these diastereoisomers in the prevention and treatment of estrogen- and androgen-dependent conditions. DESIGN A randomized, crossover, open-label study in 12 healthy adults (6 men and 6 women) compared the plasma and urinary pharmacokinetics of orally administered enantiomeric pure forms of S-(-)[2-13C]equol, R-(+)[2-13C]equol, and the racemic mixture. Plasma and urinary [13C]R-equol and [13C]S-equol concentrations were measured by tandem mass spectrometry. RESULTS Plasma [13C]equol concentration appearance and disappearance curves showed that both enantiomers were rapidly absorbed, attained high circulating concentrations, and had a similar terminal elimination half-life of 7-8 h. The systemic bioavailability and fractional absorption of R-(+)[2-13C]equol were higher than those of S-(-)[2-13C]equol or the racemate. The pharmacokinetics of racemic (+/-)[2-13C]equol were different from those of the individual enantiomers: slower absorption, lower peak plasma concentrations, and lower systemic bioavailability. CONCLUSIONS The high bioavailability of both diastereoisomers contrasts with previous findings for the soy isoflavones daidzein and genistein, both of which have relatively poor bioavailability, and suggests that low doses of equol taken twice daily may be sufficient to achieve biological effects.
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Affiliation(s)
- Kenneth Dr Setchell
- Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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Park SY, Wilkens LR, Franke AA, Le Marchand L, Kakazu KK, Goodman MT, Murphy SP, Henderson BE, Kolonel LN. Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort. Br J Cancer 2009; 101:185-91. [PMID: 19536097 PMCID: PMC2713708 DOI: 10.1038/sj.bjc.6605137] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2009] [Revised: 05/20/2009] [Accepted: 05/20/2009] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries. METHODS This case-control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status. RESULTS The median excretion of daidzein was 0.173 nmol mg(-1) creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31-0.98, P(trend)=0.03) and seemed to apply to localized (P(trend)=0.08) as well as advanced or high-grade cancer (P(trend)=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk. CONCLUSION Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.
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Affiliation(s)
- S-Y Park
- Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA.
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Chun OK, Chung SJ, Song WO. Urinary isoflavones and their metabolites validate the dietary isoflavone intakes in US adults. ACTA ACUST UNITED AC 2009; 109:245-54. [PMID: 19167951 DOI: 10.1016/j.jada.2008.10.055] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2007] [Accepted: 07/24/2008] [Indexed: 01/22/2023]
Abstract
BACKGROUND Isoflavones are derived from dietary sources and considered to promote health by preventing the onset of such chronic diseases as cardiovascular disease, cancer, and osteoporosis. Valid and reliable estimation of isoflavone intake is a prerequisite to establishing biological functions of isoflavones on health risks. OBJECTIVE This study aimed to validate the approach of estimating dietary isoflavone intake with respective urinary isoflavone concentrations in US adults. DESIGN Data from the US Department of Agriculture isoflavone database and dietary recalls of 2,908 US adults with urinary isoflavone data in the 1999-2002 National Health and Nutrition Examination Survey were used. RESULTS Dietary isoflavone was consumed by only 35% of adults in a day with an average intake of 3.1 mg/day, which resulted in a mean intake of 1.0 mg/day for all US adults. The isoflavone intakes were from genistein (55%), diadzein (35%), glycitein (7%), biochanin A (2%), and formononetin (2%). Both daily total and energy adjusted isoflavone intake differed by race/ethnicity subgroups (P<0.05) and was associated positively with income (P<0.01) and inversely with body mass index (P<0.05). Geometric mean urinary isoflavone concentration was 5.0 ng/mL among isoflavone consumers and the urinary genistein and daidzein excretion correlated with their isoflavone intake levels (P<0.01). CONCLUSIONS In large population-based studies, estimated dietary isoflavone intake can be validated by urinary isoflavones. Further studies are needed at an individual level to validate dietary isoflavone intake by urinary isoflavone concentration.
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Affiliation(s)
- Ock Kyoung Chun
- Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269-4017, USA.
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Charles C, Yuskavage J, Carlson O, John M, Tagalicud AS, Maggio M, Muller DC, Egan J, Basaria S. Effects of high-dose isoflavones on metabolic and inflammatory markers in healthy postmenopausal women. Menopause 2009; 16:395-400. [PMID: 18981951 PMCID: PMC2695501 DOI: 10.1097/gme.0b013e3181857979] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVE After menopause, women experience changes in body composition, especially an increase in fat mass. In addition, advancing age, decreased physical activity, and increased inflammation may predispose them to develop type 2 diabetes. Isoflavones have been shown to improve metabolic parameters in postmenopausal women. However, the effect of isoflavones on adipokines/cytokines remains unclear. The purpose of this study was to evaluate the effect of high-dose isoflavones on inflammatory and metabolic markers in postmenopausal women. METHODS We measured glucose, insulin, and adipokines/cytokines in 75 healthy postmenopausal women who were randomized to receive 20 g of soy protein with 160 mg of total isoflavones (64 mg genistein, 63 mg daidzein, and 34 mg glycitein) or 20 g of soy protein placebo for 12 weeks. Women taking estrogen discontinued therapy at least 3 months before the study. The supplements were given in a powder form and consumed once daily with milk or other beverages. RESULTS Mean ages in the placebo and active groups were similar (P = 0.4). Average time since menopause was 9 years, and two thirds of the women underwent natural menopause. There was no significant difference in body mass index at baseline between the groups (placebo, 25.1 kg/m; active, 26 kg/m) and it did not change significantly during the study. At baseline, the placebo group had significantly higher levels of tumor necrosis factor alpha (P < 0.0001); otherwise, there was no difference in any other parameter. After 12 weeks of treatment, there were significant positive changes in tumor necrosis factor alpha levels within the placebo group (P < 0.0001) and adiponectin levels within the isoflavone group (P = 0.03). Comparison of pre-post change between the groups showed a small but significant increase in serum adiponectin levels in the isoflavone group (P = 0.03) compared with the placebo group. No significant changes were seen in any other parameter between the two groups. CONCLUSIONS Healthy, normal-weight postmenopausal women may not experience improvement in metabolic parameters when given high-dose isoflavones despite an increase in serum adiponectin levels. The role of isoflavones in obese and insulin-resistant postmenopausal women needs exploration.
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Affiliation(s)
- Cornelia Charles
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Julia Yuskavage
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Olga Carlson
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Majnu John
- Department of Internal Medicine, Division of Endocrinology & Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Arlene S. Tagalicud
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Marcello Maggio
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Denis C. Muller
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Josephine Egan
- Laboratory of Clinical Investigation, Diabetes Section, National Institute on Aging, Baltimore, MD
| | - Shehzad Basaria
- Department of Internal Medicine, Division of Endocrinology & Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD
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Stubert J, Gerber B. Isoflavones - Mechanism of Action and Impact on Breast Cancer Risk. Breast Care (Basel) 2009; 4:22-29. [PMID: 20877680 DOI: 10.1159/000200980] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Isoflavones are plant-derived substances with weak es-trogenic effects. Asian populations are high consumers of soy products which are rich in isoflavones. The lower breast cancer incidence in Asian women compared with Western women has been associated with the possibility of a preventive isoflavone effect on cancer risk. The aim of this review is to give an overview of current research data on the influence of isoflavones on the risk of primary breast cancer development as well as the risk of recurrence in breast cancer patients. Despite inconsistencies in the available data, an inverse correlation between isoflavone intake and risk of breast cancer is likely. However, a negative impact on breast cancer disease, especially on hormone receptor-positive tumors, cannot be excluded at present.
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Affiliation(s)
- Johannes Stubert
- Department of Obstetrics and Gynecology, University of Rostock, Germany
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Tseng M, Olufade T, Kurzer MS, Wahala K, Fang CY, van der Schouw YT, Daly MB. Food frequency questionnaires and overnight urines are valid indicators of daidzein and genistein intake in U.S. women relative to multiple 24-h urine samples. Nutr Cancer 2009; 60:619-26. [PMID: 18791925 DOI: 10.1080/01635580801993751] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Data regarding convenient, valid methods for measuring U.S. isoflavone intake are limited. We evaluated a soy food questionnaire (SFQ), the Willett food frequency questionnaire (FFQ), and overnight urine samples relative to excretion in 24-h urine samples. We also described intake among women in a high-risk program for breast or ovarian cancer. Between April 2002 and June 2003, 451 women aged 30 to 50 yr with a family history of breast or ovarian cancer completed the SFQ and FFQ. Of them, 27 provided four 24-h and overnight urine specimens. In these women, 24-h sample measures were correlated with SFQ estimates of daidzein (Spearman r = .48) and genistein (r = .54) intake, moderately correlated with the Willett FFQ (daidzein r = .38, genistein r = .33), and strongly correlated with overnight urine excretion (daidzein r = .84, genistein r = 0.93). Among all 451 SFQ respondents, mean (median) daidzein and genistein intakes were 2.8 (0.24) and 3.9 (0.30) mg/day. Primary sources of both were soymilk, soy nuts, and tofu. We conclude that targeted soy food questionnaires, comprehensive FFQs, and multiple overnight urines are all reasonable options for assessing isoflavone intake in epidemiologic studies.
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Affiliation(s)
- Marilyn Tseng
- Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19130, USA.
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Basaria S, Wisniewski A, Dupree K, Bruno T, Song MY, Yao F, Ojumu A, John M, Dobs AS. Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women. J Endocrinol Invest 2009; 32:150-5. [PMID: 19411814 DOI: 10.1007/bf03345705] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
CONTEXT Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer. Isoflavones, a class of plant estrogens, have structural similarities to estradiol. Hence, isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects. OBJECTIVE To evaluate the effect of high-dose isoflavones on self-reported quality of life (QOL), cognition, lipoproteins and androgen status in post-menopausal women. DESIGN AND SUBJECTS Double-blind, randomized, placebo-controlled, 12-week trial of 93 healthy, ambulatory, post-menopausal women (mean age 56 yr). The study was conducted at a tertiary care center in the United States. INTERVENTION Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). Both soy and the placebo were provided in the form of a powder to be mixed with beverages. MAIN OUTCOME MEASURES QOL was judged by the Menopause-specific Quality of Life (MENQOL) questionnaire while cognitive function was assessed with standard instruments. Total, free, and bioavailable testosterone, gonadotropins, SHBG, and fasting lipids were measured. RESULTS Eighty-four women (90%) completed the study (active=38, placebo=46). There was a significant improvement in all 4 QOL subscales (vasomotor, psychosexual, physical, and sexual) among the women taking isoflavones, while no changes were seen in the placebo group. No significant changes in cognition, serum androgens or plasma lipids were seen within any of the groups. However, at the end of the study, a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups. CONCLUSION High-dose isoflavones is associated with improved QOL among women who have become menopausal recently. Hence, the timing of isoflavone supplementation with regards to the onset of menopause appears to be important. The use of isoflavones, as an alternative to estrogen therapy, may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms.
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Affiliation(s)
- S Basaria
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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Kim MH, Han JH, Kim SU. Isoflavone Daidzein: Chemistry and Bacterial Metabolism. ACTA ACUST UNITED AC 2008. [DOI: 10.3839/jabc.2008.040] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Pan A, Franco OH, Ye J, Demark-Wahnefried W, Ye X, Yu Z, Li H, Lin X. Soy protein intake has sex-specific effects on the risk of metabolic syndrome in middle-aged and elderly Chinese. J Nutr 2008; 138:2413-21. [PMID: 19022966 DOI: 10.3945/jn.108.097519] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Soy protein intake has been postulated to improve lipid profiles, glucose homeostasis, and blood pressure. However, data linking soy protein intake and metabolic syndrome (MetS) are limited. We evaluated the association between soy protein intake and the risk of MetS and its components among middle-aged and elderly Chinese. A cross-sectional study was conducted among 2811 Chinese men and women aged 50-70 y, who were free of diagnosed cardiovascular diseases and cancers. Dietary data, including soy protein intake, was collected using a 74-item FFQ. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. We used multivariate logistical regression models to quantify these associations. The median level of soy protein intake was 7.82 g/d (7.64 g/d in men and 8.02 g/d in women). Overall, the association of soy protein intake and the risk of MetS differed between men and women (P for interaction = 0.008). In men, the adjusted odds ratio comparing the extreme quartiles was 1.64 (95% CI: 0.95-2.81; P-trend = 0.077), whereas for women, it was 0.66 (95% CI: 0.42-1.03; P-trend = 0.138). Soy protein intake was positively associated with hyperglycemia (P-trend = 0.005) in men, whereas it was inversely associated with elevated blood pressure (P-trend = 0.049). It was not associated with any component in women. In conclusion, habitual soy protein intake may have sex-dependent effects on risk of MetS in middle-aged and elderly Chinese.
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Affiliation(s)
- An Pan
- Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China
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