붉은토끼풀 (이소플라본)

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis.

1. Phytomedicine. 2007 Feb;14(2-3):153-9. doi: 10.1016/j.phymed.2006.12.009. Epub 2007 Jan 18. Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Coon JT(1), Pittler MH, Ernst E. Author information: (1)Complementary Medicine, Penins

Polyphenol-Related Gut Metabotype Signatures Linked to Quality of Life in Postmenopausal Women: A Randomized, Placebo-Controlled Crossover Trial.

2. Nutrients. 2025 Nov 15;17(22):3572. doi: 10.3390/nu17223572. Polyphenol-Related Gut Metabotype Signatures Linked to Quality of Life in Postmenopausal Women: A Randomized, Placebo-Controlled Crossover Trial. Jarrín-Orozco MP(1), Romo-Vaquero M(1), Carrascosa C(2), Pertegal M(2), Berná J(3), Pu

Isoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomized placebo-controlled trial.

3. Climacteric. 2024 Dec;27(6):548-554. doi: 10.1080/13697137.2024.2393121. Epub 2024 Sep 10. Isoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomized placebo-controlled trial. Yigit E(1), Unsal S(2). Author information

Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial.

4. Nutrients. 2023 Sep 27;15(19):4165. doi: 10.3390/nu15194165. Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial. Villadsen AB(1)(2), Holm-Jacobsen JN(1), Prabhala BK(3), Bundgaard-Nielse

Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

5. Nutrients. 2021 Apr 11;13(4):1258. doi: 10.3390/nu13041258. Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Tri

Effects of red clover on perimenopausal and postmenopausal women's blood lipid profile: A meta-analysis.

6. Climacteric. 2018 Oct;21(5):446-453. doi: 10.1080/13697137.2018.1501673. Effects of red clover on perimenopausal and postmenopausal women's blood lipid profile: A meta-analysis. Luís Â(1), Domingues F(1), Pereira L(2). Author information: (1)a Centro de Investigação em Ciências da Saúde (CICS

Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.

7. Phytomedicine. 2017 Jan 15;24:141-147. doi: 10.1016/j.phymed.2016.12.003. Epub 2016 Dec 12. Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis. Myers SP(1), Vigar V(2). Aut

Soy, red clover, and isoflavones and breast cancer: a systematic review.

8. PLoS One. 2013 Nov 28;8(11):e81968. doi: 10.1371/journal.pone.0081968. eCollection 2013. Soy, red clover, and isoflavones and breast cancer: a systematic review. Fritz H(1), Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, Kennedy D, Cooley K, Wong R, Sagar S, Sabri E, Fergusson D.

Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review.

9. Mol Nutr Food Res. 2009 Sep;53(9):1084-97. doi: 10.1002/mnfr.200800552. Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review. Jacobs A(1), Wegewitz U, Sommerfeld C, Grossklaus R, Lampen A. Author information: (1)Department of Food Safety, Federal Institute

Overall Survival of Glioblastoma Patients Treated With a Combination of 7 Micronutrients: A Nutraceutical Trial.

1. Anticancer Res. 2026 Mar;46(3):1599-1608. doi: 10.21873/anticanres.18055. Overall Survival of Glioblastoma Patients Treated With a Combination of 7 Micronutrients: A Nutraceutical Trial. Rooprai HK(1), Lawrence P(2), Ashkan K(3), Beaney R(4), Pilkington GJ(5), Gullan RW(1). Author information: (1)Department of Neurosurgery, King's College Hospital, London, U.K. (2)Division of Molecular Pathology, The Institute of Cancer Research, Sutton, U.K. (3)Department of Neurosurgery, King's College Hospital, London, U.K.; k.ashkan@nhs.net. (4)Department of Oncology, St Thomas' Hospital, London, U.K. (5)Brain Tumour Research Centre, University of Portsmouth, Portsmouth, U.K. BACKGROUND/AIM: There is increasing evidence for recognition of nutraceuticals as anti-tumour agents in various cancers. Over the years, anecdotal reports and our laboratory-based research have indicated their promising therapeutic potential for the management of glioblastoma. The aim of this study was to assess the effect of a combination of 7 micronutrients on overall survival of these patients. PATIENTS AND METHODS: A Nutraceutical study was conducted at King's College and St Thomas' Hospitals, London. Fifty-three newly diagnosed patients (37 males and 16 females) with glioblastoma were recruited consecutively in this randomised entry, double blind Phase II trial. The treatment (containing chokeberry extract, red grape seed extract, red clover extract, curcumin, selenium, tangeretin and lycopene) was given to two-thirds of the patients for 1 year after neurosurgery. This was consistent with the start date of their concomitant Stupp Protocol chemoradiation therapy. The patients in the placebo group had identical capsules which contained lactose only. RESULTS: Although the Kaplan - Meier analysis showed that the overall survival for the active and placebo groups was 14 and 13 months respectively, the results were not statistically significant (p=0.752). CONCLUSION: This study has limitations but it acts as a proof of principle towards larger studies, as clearly sufficiently powered trials are crucial in determining the nature and size of the treatment effect. Future trials should consider subgroup analysis, with respect to such factors as patient's age at diagnosis, gender, extent of surgery, MGMT mutation and IDH status to identify the optimal responders. Copyright © 2026 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. DOI: 10.21873/anticanres.18055 PMID: 41760279 [Indexed for MEDLINE]

Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis.

2. Phytother Res. 2024 Mar;38(3):1294-1309. doi: 10.1002/ptr.8112. Epub 2024 Jan 8. Efficacy of plant-derived dietary supplements in improving overall menopausal symptoms in women: An updated systematic review and meta-analysis. Oh MR(1), Park JH(2), Park SK(2), Park SH(2). Author information: (1)Clinical Trial Center for Functional Foods, Jeonbuk National University Hospital, Jeonju, Republic of Korea. (2)Food Functionality Research Division, Korea Food Research Institute, Wanju, Republic of Korea. This updated systematic review and meta-analysis aims to confirm the effectiveness of plant-based supplements in improving overall menopausal symptoms and vasomotor symptoms. A systematic review of the literature was conducted by searching the PubMed/MEDLINE, Web of Science, EMBASE, and CENTRAL databases up to June 2022. Randomized placebo-controlled clinical trials that evaluated the effects of dietary supplements on menopausal symptoms were included. Outcome measures included daily hot flash frequency, Kupperman's index, Menopause Rating Scale, and Greene Climacteric Scale. Pooled data were analyzed using a fixed-effects model and expressed as a weighted mean difference with a 95% confidence interval for continuous outcomes. For qualitative assessment, 67 studies were selected. For quantitative assessment, 54 reports were obtained from 61 studies. The study participants were peri- or postmenopausal women aged 38-85, most of whom experienced hot flashes as a menopausal symptom. The investigational products included 28 soy-derived, 6 red clover-derived, and 28 other plant-derived supplements. Qualitative assessment revealed that approximately 76% of the studies were generally of fair or good quality, whereas 24% were of low quality. Meta-analysis results indicated significant improvements in all questionnaire scores, including hot flash frequency, in the dietary supplement group compared with the placebo group. Comprehensive evaluation using different questionnaire tools showed that the various plant-derived dietary supplements can significantly alleviate menopausal symptoms. However, further rigorous studies are needed to determine the association of plant-derived dietary supplements with menopausal health because of the general suboptimal quality and heterogeneous nature of current evidence. © 2024 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd. DOI: 10.1002/ptr.8112 PMID: 38189863 [Indexed for MEDLINE]

Impact of phytoestrogens on treatment of urogenital menopause symptoms: A systematic review of randomized clinical trials.

3. Eur J Obstet Gynecol Reprod Biol. 2021 Jun;261:222-235. doi: 10.1016/j.ejogrb.2021.03.039. Epub 2021 Apr 20. Impact of phytoestrogens on treatment of urogenital menopause symptoms: A systematic review of randomized clinical trials. Abdi F(1), Rahnemaei FA(2), Roozbeh N(3), Pakzad R(4). Author information: (1)Assistant Professor, School of nursing and midwifery, Alborz University of Medical Sciences, Karaj, Iran. (2)Student Research Committee, Nursing and Midwifery Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: f_rahnemaie@yahoo.com. (3)Mother and Child Welfare Research Center, Hormozgan Universiy of Medical Sciences, BandarAbbas, Iran. (4)Faculty of Health, Ilam University of Medical Sciences, Ilam, Iran. OBJECTIVE: Menopause symptoms affect the various dimensions of women's lives and they can lead to reduction of their quality of life. Phytoestrogens can be used as an approach to diminish these symptoms. The aim of this systematic review was to investigate the effect of phytoestrogens on the treatment of urogenital menopause symptoms. STUDY DESIGN: PubMed, EMBASE, Web of Science, Cochrane library,Scopus and ProQuest were systematically searched from 2000-2020. All randomized clinical trials were included. The quality of the selected papers was evaluated by the CONSORT checklist. RESULTS: 33 eligible high-quality papers were reviewed. Various forms of phytoestrogens such as Pueraria Mirifica, fennel, Hop plant(Humuluslupulus L.), Glycine Max (L.) Merr, soy, red clover, black cohosh, ginsing, cimicifugaracemosa, genistein, diadzein, glycitein and isoflavone in the form of oral capsules and pill, food supplement, enriched powder, vaginal gel, cream and suppository could improve menopausal urogenital symptoms. The recovery rate in vaginal use of these phytoestrogens was greater than other consumptions. CONCLUSIONS: After using a variety of phytoestrogens in different forms indicators of urogenital atrophy and urinary disorders improved and women's sexual function improved after treatment. The use of phytoestrogens as a safe, low-risk compared to hormone therapy and almost accessible method for women can relieve urogenital symptoms and promote the sexual satisfaction and quality of life. Copyright © 2021 Elsevier B.V. All rights reserved. DOI: 10.1016/j.ejogrb.2021.03.039 PMID: 33962824 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and Their Associated Anticancer Activity: The Particular Case of Curcumin.

4. Mol Nutr Food Res. 2021 Jun;65(12):e2100163. doi: 10.1002/mnfr.202100163. Epub 2021 May 10. Disposition of Dietary Polyphenols in Breast Cancer Patients' Tumors, and Their Associated Anticancer Activity: The Particular Case of Curcumin. Ávila-Gálvez MÁ(1), González-Sarrías A(1), Martínez-Díaz F(2), Abellán B(3), Martínez-Torrano AJ(2), Fernández-López AJ(3), Giménez-Bastida JA(1), Espín JC(1). Author information: (1)Laboratory of Food & Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, Campus de Espinardo, Murcia, 30100, Spain. (2)Anatomical Pathology Service, Reina Sofía University Hospital, Avda. Intendente Jorge Palacios s/n, Murcia, 30003, Spain. (3)Surgery Service, Reina Sofía University Hospital, Avda. Intendente Jorge Palacios, Murcia, 30003, Spain. SCOPE: Some polyphenol-derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly-diagnosed BC patients and the tissue-occurring metabolites' anticancer activity are evaluated. METHODS AND RESULTS: Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy-confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC-QTOF-MS using targeted metabolomics. Anticancer activity was tested in MCF-7 and MDA-MB-231 BC cells. Mainly phase-II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L-1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L-1 in NT and MT, respectively). Breast tissue-occurring metabolites' antiproliferation was mainly exerted in p53-wild-type MCF-7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone-derived metabolites exerted estrogenic-like activity. CONCLUSION: Curcuminoids could be coadjuvants that might help fight BC upon regular consumption. © 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH. DOI: 10.1002/mnfr.202100163 PMID: 33939887 [Indexed for MEDLINE]

No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women.

5. J Agric Food Chem. 2020 Nov 25;68(47):13929-13939. doi: 10.1021/acs.jafc.0c05856. Epub 2020 Nov 16. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. Chen L(1)(2)(3), Choi J(1), Leonard SW(1), Banuvar S(3), Barengolts E(3), Viana M(3), Chen SN(3), Pauli GF(3), Bolton JL(3), van Breemen RB(1)(2)(3). Author information: (1)Linus Pauling Institute, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United States. (2)College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, United States. (3)UIC/NIH Center for Botanical Dietary Supplements Research, Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois, 833 S. Wood Street, Chicago, Illinois 60612, United States. Extracts of red clover (Trifolium pratense L.), containing estrogenic isoflavones like genistein and daidzein and the proestrogenic isoflavones formononetin and biochanin A, are used by women as dietary supplements for the management of menopausal symptoms. Although marketed as a safer alternative to hormone therapy, red clover isoflavones have been reported to inhibit some cytochrome P450 (CYP) enzymes involved in drug metabolism. To evaluate the potential for clinically relevant drug-red clover interactions, we tested a standardized red clover dietary supplement (120 mg isoflavones per day) for interactions with the pharmacokinetics of four FDA-approved drugs (caffeine, tolbutamide, dextromethorphan, and alprazolam) as probe substrates for the enzymes CYP1A2, CYP2C9, CYP2D6, and CYP3A4/5, respectively. Fifteen peri- and postmenopausal women completed pharmacokinetic studies at baseline and 2 weeks after consuming red clover. The averaged pharmacokinetic profiles of probe substrates in serum showed no significant alterations and no changes in the areas under the curve (AUC) over 96 h. Subgroup analysis based on the demographic characteristics (BMI, menopausal status, race, and age) also showed no differences in AUC for each probe substrate. Analysis of red clover isoflavones in serum showed primarily conjugated metabolites that explain, at least in part, the red clover pharmacokinetic safety profile. DOI: 10.1021/acs.jafc.0c05856 PMCID: PMC8071351 PMID: 33197178 [Indexed for MEDLINE] Conflict of interest statement: Conflict of Interest/Disclosure The authors have no conflicts of interest to disclose.

Effects of isoflavones on breast tissue and the thyroid hormone system in humans: a comprehensive safety evaluation.

6. Arch Toxicol. 2018 Sep;92(9):2703-2748. doi: 10.1007/s00204-018-2279-8. Epub 2018 Aug 21. Effects of isoflavones on breast tissue and the thyroid hormone system in humans: a comprehensive safety evaluation. Hüser S(1), Guth S(1), Joost HG(2), Soukup ST(3), Köhrle J(4), Kreienbrock L(5), Diel P(6), Lachenmeier DW(7), Eisenbrand G(8), Vollmer G(9), Nöthlings U(10), Marko D(11), Mally A(12), Grune T(13), Lehmann L(14), Steinberg P(15)(16), Kulling SE(17). Author information: (1)Institute for Food Toxicology, Senate Commission on Food Safety, University of Veterinary Medicine Hannover, Hannover, Germany. (2)Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Nuthetal, Germany. (3)Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131, Karlsruhe, Germany. (4)Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, CVK, Berlin, Germany. (5)Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Hannover, Germany. (6)Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Cologne, Germany. (7)Chemisches und Veterinäruntersuchungsamt Karlsruhe, Karlsruhe, Germany. (8)Division of Food Chemistry and Toxicology, Molecular Nutrition, Department of Chemistry, Technische Universität Kaiserslautern, Kaiserslautern, Germany. (9)Department of Biology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, Dresden, Germany. (10)Department of Nutrition and Food Sciences, Nutritional Epidemiology, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany. (11)Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Vienna, Austria. (12)Department of Toxicology, University of Würzburg, Würzburg, Germany. (13)Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE), Nuthetal, Germany. (14)Department of Food Chemistry, Institute for Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany. (15)Institute for Food Toxicology, University of Veterinary Medicine Hannover, Hannover, Germany. (16)Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131, Karlsruhe, Germany. (17)Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Haid-und-Neu-Str. 9, 76131, Karlsruhe, Germany. sabine.kulling@mri.bund.de. Isoflavones are secondary plant constituents of certain foods and feeds such as soy, linseeds, and red clover. Furthermore, isoflavone-containing preparations are marketed as food supplements and so-called dietary food for special medical purposes to alleviate health complaints of peri- and postmenopausal women. Based on the bioactivity of isoflavones, especially their hormonal properties, there is an ongoing discussion regarding their potential adverse effects on human health. This review evaluates and summarises the evidence from interventional and observational studies addressing potential unintended effects of isoflavones on the female breast in healthy women as well as in breast cancer patients and on the thyroid hormone system. In addition, evidence from animal and in vitro studies considered relevant in this context was taken into account along with their strengths and limitations. Key factors influencing the biological effects of isoflavones, e.g., bioavailability, plasma and tissue concentrations, metabolism, temporality (pre- vs. postmenopausal women), and duration of isoflavone exposure, were also addressed. Final conclusions on the safety of isoflavones are guided by the aim of precautionary consumer protection. DOI: 10.1007/s00204-018-2279-8 PMCID: PMC6132702 PMID: 30132047 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no conflict of interest.

Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial.

7. Am J Clin Nutr. 2017 Sep;106(3):909-920. doi: 10.3945/ajcn.117.153353. Epub 2017 Aug 2. Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial. Lambert MNT(1), Thybo CB(1), Lykkeboe S(2), Rasmussen LM(3), Frette X(4), Christensen LP(4), Jeppesen PB(5). Author information: (1)Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. (2)Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark. (3)Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; and. (4)Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Odense, Denmark. (5)Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; per.bendix.jeppesen@clin.au.dk. Background: Female age-related estrogen deficiency increases the risk of osteoporosis, which can be effectively treated with the use of hormone replacement therapy. However, hormone replacement therapy is demonstrated to increase cancer risk. Bioavailable isoflavones with selective estrogen receptor affinity show potential to prevent and treat osteoporosis while minimizing or eliminating carcinogenic side effects.Objective: In this study, we sought to determine the beneficial effects of a bioavailable isoflavone and probiotic treatment against postmenopausal osteopenia.Design: We used a novel red clover extract (RCE) rich in isoflavone aglycones and probiotics to concomitantly promote uptake and a favorable intestinal bacterial profile to enhance isoflavone bioavailability. This was a 12-mo, double-blind, parallel design, placebo-controlled, randomized controlled trial of 78 postmenopausal osteopenic women supplemented with calcium (1200 mg/d), magnesium (550 mg/d), and calcitriol (25 μg/d) given either RCE (60 mg isoflavone aglycones/d and probiotics) or a masked placebo [control (CON)].Results: RCE significantly attenuated bone mineral density (BMD) loss at the L2-L4 lumbar spine vertebra (P < 0.05), femoral neck (P < 0.01), and trochanter (P < 0.01) compared with CON (-0.99% and -2.2%; -1.04% and -3.05%; and -0.67% and -2.79, respectively). Plasma concentrations of collagen type 1 cross-linked C-telopeptide was significantly decreased in the RCE group (P < 0.05) compared with CON (-9.40% and -6.76%, respectively). RCE significantly elevated the plasma isoflavone concentration (P < 0.05), the urinary 2-hydroxyestrone (2-OH) to 16α-hydroxyestrone (16α-OH) ratio (P < 0.05), and equol-producer status (P < 0.05) compared with CON. RCE had no significant effect on other bone turnover biomarkers. Self-reported diet and physical activity were consistent and differences were nonsignificant between groups throughout the study. RCE was well tolerated with no adverse events.Conclusions: Twice daily RCE intake over 1 y potently attenuated BMD loss caused by estrogen deficiency, improved bone turnover, promoted a favorable estrogen metabolite profile (2-OH:16α-OH), and stimulated equol production in postmenopausal women with osteopenia. RCE intake combined with supplementation (calcium, magnesium, and calcitriol) was more effective than supplementation alone. This trial was registered at clinicaltrials.gov as NCT02174666. © 2017 American Society for Nutrition. DOI: 10.3945/ajcn.117.153353 PMID: 28768651 [Indexed for MEDLINE]

Combined Red Clover isoflavones and probiotics potently reduce menopausal vasomotor symptoms.

8. PLoS One. 2017 Jun 7;12(6):e0176590. doi: 10.1371/journal.pone.0176590. eCollection 2017. Combined Red Clover isoflavones and probiotics potently reduce menopausal vasomotor symptoms. Lambert MNT(1), Thorup AC(1), Hansen ESS(2), Jeppesen PB(1). Author information: (1)Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. (2)MR Research Centre, Aarhus University Hospital, Skejby, Denmark. BACKGROUND: Natural estrogen decline leads to vasomotor symptoms (VMS). Hormone therapy alleviates symptoms but increases cancer risk. Effective treatments against VMS with minimal cancer risks are needed. We investigate the effects of a highly bioavailable aglycone rich Red Clover isoflavone treatment to alleviate existing menopausal VMS, assessed for the first time by 24hour ambulatory skin conductance (SC). METHODS AND RESULTS: We conducted a parallel, double blind, randomised control trial of 62 peri-menopausal women aged 40-65, reporting ≥ 5 hot flushes/day and follicle stimulating hormone ≥35 IU/L. Participants received either twice daily treatment with bioavailable RC extract (RCE), providing 34 mg/d isoflavones and probiotics, or masked placebo formulation for 12 weeks. The primary outcome was change in daily hot flush frequency (HFF) from baseline to 12 weeks using 24hr SC. Secondary outcomes were change in SC determined hot flush intensity (HFI), self-reported HFF (rHFF) and hot flush severity (rHFS), blood pressure and plasma lipids. A significant decrease in 24hr HFF (P < 0.01) and HFI (P<0.05) was found when comparing change from baseline to 12 months of the RCE (-4.3 HF/24hr, CI -6.8 to -2.3; -12956 μS s-1, CI -20175 to -5737) with placebo (0.79 HF/24hr, CI -1.56 to 3.15; 515 μS s-1, CI -5465 to 6496). rHFF was also significantly reduced (P <0.05)in the RCE (-2.97 HFs/d, CI -4.77 to -1.17) group compared to placebo (0.036 HFs/d, CI -2.42 to 2.49). Other parameters were non-significant. RCE was well tolerated. CONCLUSION: Results suggest that moderate doses of RCE were more effective and superior to placebo in reducing physiological and self-reported VMS. Findings support that objective physiological symptom assessment methods should be used together with self-report measures in future studies on menopausal VMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02028702. DOI: 10.1371/journal.pone.0176590 PMCID: PMC5462345 PMID: 28591133 [Indexed for MEDLINE] Conflict of interest statement: Competing Interests: ML, AT and PBJ are co-inventors on the patent application “PCT/DK2013/050428” for the production of the Red Clover extract used in the present trial as required by US patent authorities. All rights have been assigned to the company Herrens Mark without any kind of compensation, where ML, AT and PBJ have forgone their rights as stipulated by terms and conditions of Aarhus University. Hence, the authors declare no financial or other interests. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Prepartum supplement level and age at weaning: I. Effects on pre- and postpartum beef cow performance and calf performance through weaning.

9. J Anim Sci. 2015 Oct;93(10):4926-35. doi: 10.2527/jas.2014-8564. Prepartum supplement level and age at weaning: I. Effects on pre- and postpartum beef cow performance and calf performance through weaning. Shoup LM, Kloth AC, Wilson TB, González-Peña D, Ireland FA, Rodriguez-Zas S, Felix TL, Shike DW. Objectives were to determine the interaction of prepartum supplement level and age at weaning on cow BW, BCS, milk production, reproduction, and calf performance up to weaning in a fall-calving system over 2 yr. Mature, multiparous, Angus × Simmental cows (yr 1: 326 cows, 9 pastures, BW = 632 ± 67 kg, and BCS = 5.7 ± 0.58; yr 2: 383 cows, 9 pastures, BW = 606 ± 70 kg, and BCS = 5.8 ± 0.74) were used in a split-plot design that included 3 supplement levels-no supplement (NS), low supplement (LS; 2.16 kg∙cow∙d), or high supplement (HS; 8.61 kg∙cow∙d)-and 2 ages at weaning-78 ± 11 d of age (early weaned; EW) or 186 ± 11 d of age (normal weaned; NW). Cows grazed endophyte-infected tall fescue/red clover pastures and were bunk fed supplement (70% dried distillers' grains with solubles and 30% soybean hulls) 103 ± 11 d prepartum to 2 ± 11 d postpartum. Cow BW was greater ( < 0.01) for cows fed HS at precalving (49 ± 11 d prepartum), postcalving (26 ± 11 d postpartum), and postbreeding (81 d after AI) compared with cows fed NS and LS. Prepartum supplementation did not affect ( ≥ 0.62) calf birth BW, percent of calves dead at birth, or percent of cows calving unassisted. Prepartum supplementation tended ( = 0.10) to improve AI conception. Early weaning increased ( ≤ 0.05) AI conception and postbreeding cow BW and BCS compared with cows with NW calves. Neither prepartum supplementation nor age at weaning affected ( ≥ 0.28) overall pregnancy rate. At time of early weaning, BW was increased ( = 0.05) for steers from cows fed LS compared with steers from cows fed NS. Steer BW at time of normal weaning and ADG between early and normal weaning was greater ( < 0.01) for EW steers compared with NW steers. A year × age at weaning interaction occurred ( < 0.01) for ultrasound marbling score at time of normal weaning. In yr 1, marbling was decreased ( = 0.04) for EW steers compared with NW steers; however, in yr 2, marbling was increased ( < 0.01) for EW steers compared with NW steers. In conclusion, there was no interaction between level of supplement during late gestation and age at weaning on cow BW, BCS, milk production, AI conception, and overall pregnancy rate in mature beef cows nor in their steer progeny's BW or ultrasound marbling. Both prepartum supplementation and early weaning improved cow BW, BCS, and reproduction. Minimal effects of dam prepartum supplement level on calf performance up to weaning were observed. Early weaning improved calf growth but had inconsistent effects on ultrasound marbling across years. DOI: 10.2527/jas.2014-8564 PMID: 26523585 [Indexed for MEDLINE]

Therapeutic Potential of Temperate Forage Legumes: A Review.

10. Crit Rev Food Sci Nutr. 2016 Jul 29;56 Suppl 1:S149-61. doi: 10.1080/10408398.2015.1038378. Therapeutic Potential of Temperate Forage Legumes: A Review. Cornara L(1), Xiao J(2)(3), Burlando B(4)(5). Author information: (1)a Dipartimento di Scienze della Terra dell'Ambiente e della Vita , Università degli Studi di Genova , Genova , Italy. (2)b Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau , Taipa , Macau. (3)c College of Food Science, Fujian Agriculture and Forestry University , Fuzhou , Fujian , China. (4)d Dipartimento di Scienze e Innovazione Tecnologica , Università del Piemonte Orientale , Alessandria , Italy. (5)e Istituto di Biofisica, Consiglio Nazionale delle Ricerche , Genova , Italy. The discovery of bioactive molecules from botanical sources is an expanding field, preferentially oriented to plants having a tradition of use in medicine and providing high yields and availability. Temperate forage legumes are Fabaceae species that include worldwide-important crops. These plants possess therapeutic virtues that have not only been used in veterinary and folk medicine, but have also attracted the interest of official medicine. We have examined here Medicago sativa (alfalfa), Trifolium pratense and T. repens (clovers), Melilotus albus and M. officinalis (sweet clovers), Lotus corniculatus (birdsfoot trefoil), Onobrychis viciifolia (sainfoin), Lespedeza capitata (roundhead lespedeza), and Galega officinalis (goat's rue). The phytochemical complexes of these species contain secondary metabolites whose pharmacological potentials deserve investigation. Major classes of compounds include alkaloids and amines, cyanogenic glycosides, flavonoids, coumarins, condensed tannins, and saponins. Some of these phytochemicals have been related to antihypercholesterolemia, antidiabetic, antimenopause, anti-inflammatory, antiedema, anthelmintic, and kidney protective effects. Two widely prescribed drugs have been developed starting from temperate forage legumes, namely, the antithrombotic warfarin, inspired from sweet clover's coumarin, and the antidiabetic metformin, a derivative of sainfoin's guanidine. Available evidence suggests that temperate forage legumes are a potentially important resource for the extraction of active principles to be used as nutraceuticals and pharmaceuticals. DOI: 10.1080/10408398.2015.1038378 PMID: 26507574 [Indexed for MEDLINE]

Muscle antioxidant (vitamin E) and major fatty acid groups, lipid oxidation and retail colour of meat from lambs fed a roughage based diet with flaxseed or algae.

11. Meat Sci. 2016 Jan;111:154-60. doi: 10.1016/j.meatsci.2015.09.007. Epub 2015 Sep 24. Muscle antioxidant (vitamin E) and major fatty acid groups, lipid oxidation and retail colour of meat from lambs fed a roughage based diet with flaxseed or algae. Ponnampalam EN(1), Burnett VF(2), Norng S(2), Hopkins DL(3), Plozza T(2), Jacobs JL(2). Author information: (1)Agriculture Research and Development, DEDJTR, Melbourne, Victoria 3001, Australia. Electronic address: eric.ponnampalam@ecodev.vic.gov.au. (2)Agriculture Research and Development, DEDJTR, Melbourne, Victoria 3001, Australia. (3)NSW Department of Primary Industries, Centre for Red Meat and Sheep Development, PO Box 129, Cowra, NSW 2794, Australia. The effect of feeding flaxseed or algae supplements to lambs on muscle antioxidant potential (vitamin E), major fatty acid groups, lipid oxidation and retail colour was investigated. Lambs (n=120) were randomly allocated to one of 4 dietary treatments according to liveweight and fed the following diets for eight weeks: Annual ryegrass hay [60%]+subterranean clover hay [40%] pellets=Basal diet; Basal diet with flaxseed (10.7%)=Flax; Basal diet with algae (1.8%)=Algae; Basal diet with flaxseed (10.7%) and algae (1.8%)=FlaxAlgae. Flaxseed or algae supplementation significantly affected major fatty acid groups in muscle. The addition of algae (average of Algae and FlaxAlgae) resulted in lower vitamin E concentration in muscle (P<0.003; 1.0 vs 1.3mg/kg of muscle) compared with lambs fed a diet without algae (average of Basal and Flax). Increasing muscle EPA+DHA by algae supplementation significantly increased lipid oxidation, but retail display colour of fresh meat was not affected. Copyright © 2015 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.meatsci.2015.09.007 PMID: 26409038 [Indexed for MEDLINE]

Phytoestrogens for menopausal vasomotor symptoms.

12. Cochrane Database Syst Rev. 2013 Dec 10;2013(12):CD001395. doi: 10.1002/14651858.CD001395.pub4. Phytoestrogens for menopausal vasomotor symptoms. Lethaby A(1), Marjoribanks J, Kronenberg F, Roberts H, Eden J, Brown J. Author information: (1)Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland, New Zealand, 1142. Comment in Evid Based Med. 2014 Oct;19(5):178. doi: 10.1136/ebmed-2014-110000. Update of Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001395. doi: 10.1002/14651858.CD001395.pub3. BACKGROUND: Vasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone therapy has traditionally been used as a highly effective treatment, but concerns about increased risk of some chronic diseases have markedly increased the interest of women in alternative treatments. Some of the most popular of these treatments are foods or supplements enriched with phytoestrogens-plant-derived chemicals that have estrogenic action. OBJECTIVES: To assess the efficacy, safety and acceptability of food products, extracts and dietary supplements containing high levels of phytoestrogens when compared with no treatment, placebo or hormone therapy for the amelioration of vasomotor menopausal symptoms (such as hot flushes and night sweats) in perimenopausal and postmenopausal women. SEARCH METHODS: Searches targeted the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials (29 July 2013), the Cochrane Register of Controlled Trials (CENTRAL; 29 July 2013), MEDLINE (inception to 29 July 2013), EMBASE (inception to 29 July 2013), AMED (1985 to 29 July 2013), PsycINFO (inception to 29 July 2013) and CINAHL (inception to 29 July 2013). Attempts were made to access grey literature by sending letters to pharmaceutical companies and performing searches of ongoing trial registers. Reference lists of included trials were also searched. SELECTION CRITERIA: Studies were included if they were randomised, included perimenopausal or postmenopausal participants with vasomotor symptoms (hot flushes or night sweats), lasted at least 12 weeks and provided interventions such as foods or supplements with high levels of phytoestrogens (not combined with other herbal treatments). Trials that included women who had breast cancer or a history of breast cancer were excluded. DATA COLLECTION AND ANALYSIS: Selection of trials, extraction of data and assessment of quality were undertaken by at least two review authors. Most trials were too dissimilar for their results to be combined in a meta-analysis, so these findings are provided in narrative 'Summary of results' tables. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts, genistein extracts and other types of phytoestrogens. Five trials used Promensil, a red clover extract; results of these trials were combined in a meta-analysis, and summary effect measures were calculated. MAIN RESULTS: A total of 43 randomised controlled trials (4,364 participants) were included in this review. Very few trials provided data suitable for inclusion in a meta-analysis. Among the five trials that yielded data assessing the daily frequency of hot flushes suitable for pooling, no significant difference overall was noted in the incidence of hot flushes between participants taking Promensil (a red clover extract) and those given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to 0.10, I(2) = 31%). No evidence indicated a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08 to 52.38, I(2) = 82%). Four trials that were not combined in meta-analyses suggested that extracts with high (> 30 mg/d) levels of genistein consistently reduced the frequency of hot flushes. Individual results from the remaining trials were compared in broad subgroups such as dietary soy, soy extracts and other types of phytoestrogens that could not be combined. Some of these trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared with placebo, but many trials were small and were determined to be at high risk of bias. A strong placebo effect was noted in most trials, with a reduction in frequency ranging from 1% to 59% with placebo. No indication suggested that discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. Also, no evidence indicated that these treatments caused oestrogenic stimulation of the endometrium or the vagina or other adverse effects when used for up to two years. AUTHORS' CONCLUSIONS: No conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated. DOI: 10.1002/14651858.CD001395.pub4 PMCID: PMC10247921 PMID: 24323914 [Indexed for MEDLINE] Conflict of interest statement: Anne Lethaby provided advice and suggestions to the author of the unpublished Brazilian study (Bicca 2004) that has been included in this review. She is included as an author of that unpublished paper. John Eden is an author of two of the included studies (Knight 1999; Knight 2001).

Effect of concentrate supplementation on feed consumption, nutrient utilization and blood metabolite profile in captive spotted deer (Axis axis) fed oat (Avena sativa) and berseem (Trifolium alexandrinum) fodders based diet.

13. Zoo Biol. 2013 Mar;32(2):195-203. doi: 10.1002/zoo.21058. Epub 2013 Jan 25. Effect of concentrate supplementation on feed consumption, nutrient utilization and blood metabolite profile in captive spotted deer (Axis axis) fed oat (Avena sativa) and berseem (Trifolium alexandrinum) fodders based diet. Suresh C(1), Das A, Katole S, Saini M, Swarup D. Author information: (1)Centre for Wildlife Conservation, Management and Disease Surveillance, Indian Veterinary Research Institute, Izatnagar, India. This experiment was conducted to determine the optimum level of a maize-soybean meal-wheat bran concentrate supplement fed to captive spotted deer fed an oat and berseem fodder-based diet. Twelve adult spotted deer [64-76 kg body weight (BW)] were distributed into three groups of four each and were housed individually. A diet consisting of 5 kg of oat fodder and 5.5 kg of berseem fodder was offered to each one of the experimental animals. The animal in group I received no supplementary concentrate, whereas, those in groups II and III received 0.5 and 1 kg of supplementary concentrate, respectively. A 60 days digestibility trial was conducted with a 5 days collection period on Days 55-59 of the trial. Blood samples were collected from all animals on Day 60 of the experiment. Average daily dry matter intake (DMI) was 1,224, 1,613, and 1,574 g/day in groups I, II, and III, respectively. Dry matter (DM) and organic matter (OM) intake was lowest (P < 0.01) in group I. Intake of P, Cu, and Zn was highest (P < 0.01) in group III, followed by groups II and I. Digestibility of neutral detergent fiber was highest (P < 0.05) in group II. Digestibility of OM and CP was lowest (P < 0.05) in group I. Digestibility of gross energy was highest (P < 0.01) in group III (74.9%), followed by groups II (69.3%) and I (66.2%). Digestible energy (DE) intake (kcal/kg BW(0.75) ) was highest (P < 0.01) in group III (195.4), followed by groups II (180.9) and I (129.8). Initial BW was 72.7, 72.5, and 71.0 kg, whereas, final BW was 71.0, 72.7, and 73.5 kg, in groups I, II and III, respectively. Average daily change in body mass was significantly (P < 0.01) different among the groups. The body mass was lost (-29.2 g/day), maintained (4.1 g/day) and gained (41.6 g/day) in groups I, II, and III, respectively. Blood glucose and cholesterol concentration was highest (P < 0.05) in group III, followed by groups II and I. Serum concentration of Cu and Zn was highest (P < 0.05) in group III, followed by groups II and I. Supplementation of forage only diet with 0.5 kg of concentrate mixture increased intake and digestibility of nutrients, without change in body mass. Animals fed 1 kg of supplementary concentrate received energy in excess of requirements, were consistently gaining body mass and were prone to obesity. Thus, it is a right strategy to supplement forage only diet of captive spotted deer with 0.5 kg of concentrate. © 2013 Wiley Periodicals, Inc. DOI: 10.1002/zoo.21058 PMID: 23349033 [Indexed for MEDLINE]

Gas chromatographic-olfactometric aroma profile and quantitative analysis of volatile carbonyls of grilled beef from different finishing feed systems.

14. J Food Sci. 2012 Jun;77(6):S240-6. doi: 10.1111/j.1750-3841.2012.02720.x. Epub 2012 May 16. Gas chromatographic-olfactometric aroma profile and quantitative analysis of volatile carbonyls of grilled beef from different finishing feed systems. Resconi VC(1), del Mar Campo M, Montossi F, Ferreira V, Sañudo C, Escudero A. Author information: (1)Faculty of Veterinary, Univ of Zaragoza, 50013 Zaragoza, Spain. resconi@unizar.es In this study, the important odor impact volatiles generated in the meat of grilled beef loin muscle were characterized. Animals were finished in 4 different diet systems: T₁, pasture (a mixture of Medicago sativa, Trifolium repens, and Festuca arundinacea); T₂, pasture supplemented with cracked corn grain (offered at 0.6% live weight, LW); T₃, pasture supplemented with cracked corn grain (offered at 1.2% LW); and T₄, concentrate (pellets with 85% corn and 12.8% sunflower, on a dry-matter basis) plus alfalfa hay (both ad libitum). Aroma compounds were assessed by dynamic headspace-solid phase extraction (DHS-SPE) and gas chromatographic-olfactometric (GC-O) analysis. Most odorants were carbonyl compounds, some of them reaching high GC-O scores, especially 1-octen-3-one, (E)-2-octenal, methional, and hexanal. A specific quantitative analysis of ketones and aldehydes was conducted through their derivatization with o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride directly on the headspace trap and analyzed by GC-MS, with the purpose of studying the effect of finishing diet systems. From the 23 carbonyl compounds quantified, 2 were especially affected by the diet system; methional was higher in the treatment based on concentrates, whereas (E,E)-2,4-heptadienal was higher in the treatment based only in pastures. The results are discussed considering previous published productive and quality traits. PRACTICAL APPLICATION: The knowledge of how production factors, such as animal feeding, can affect the flavor of meat is of significant interest toward in achieving a high-quality and differentiated product. The development of more specific and efficient methodologies is necessary to analyze meat aroma compounds, which would be used as routine analysis, that is for product authentication. In the future, the use of this analysis would allow producing and designing specific foods according to different markets. © 2012 Institute of Food Technologists® DOI: 10.1111/j.1750-3841.2012.02720.x PMID: 22591324 [Indexed for MEDLINE]

Taking an integrated approach: managing women with phytoestrogens.

15. Climacteric. 2011 Dec;14 Suppl 2:2-7. doi: 10.3109/13697137.2011.626367. Taking an integrated approach: managing women with phytoestrogens. Panay N(1). Author information: (1)Queen Charlotte's & Chelsea and Chelsea & Westminster Hospitals and Honorary Senior Lecturer, Imperial College London, London, UK. An integrated approach can be employed when counselling women about menopausal management options, where lifestyle, complementary therapies and hormone replacement therapy (HRT) are discussed. Women might opt to use an alternative approach to HRT for a variety of reasons, e.g. fear of side-effects and risks or contraindications to HRT. There are many choices of dietary and herbal approaches for menopausal symptoms, which essentially divide into food supplements and herbal medicines. The choice can often be overwhelming and confusing for the woman. Of concern, the evidence for efficacy and safety of some of these complementary therapies can be extremely limited or non-existent. In order to enable women to make a fully informed choice, it is important that, when a recommendation is made regarding a specific complementary therapy, it should focus on preparations for which a significant dataset exists for efficacy and safety and in which there is ongoing research and development. One of the most extensively studied food supplements has been the phytoestrogenic preparation containing red clover isoflavones. There have been six randomized trials thus far studying the impact on vasomotor symptoms, three of which have shown a significant benefit compared to placebo. There are also data from small randomized and observational trials showing positive outcomes for surrogate markers of osteoporosis and cardiovascular disease. A recent study using validated depression scales has shown that women using red clover isoflavones may also derive psychological benefits. Safety data are reassuring for the endometrium and breast, although further studies would be welcome, particularly in women with significant medical risks. DOI: 10.3109/13697137.2011.626367 PMID: 22074008 [Indexed for MEDLINE]