Skip to main content

Advertisement

SpringerLink
Log in

Isoflavonhaltige Nahrungsergänzungsmittel

Isoflavone-containing dietary supplements

  • Leitthema
  • Published:
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

Isoflavone (IF) sind Inhaltsstoffe von Soja und anderen Leguminosen mit schwacher estrogener Wirkung. Sie werden in angereicherter Form als Nahrungsergänzungsmittel (NEM) angeboten, häufig mit Auslobung einer Wirkung gegen Wechseljahresbeschwerden. Der Beitrag gibt eine Übersicht über Vorkommen und Verstoffwechselung, beschreibt die Marktlage und fasst die Datenlage zur Wirksamkeit und Sicherheit von IF bzw. IF-haltigen NEM (IF-NEM) zusammen. Die biologische Wirkung von IF wird v. a. der Aktivierung der Estrogenrezeptoren zugeschrieben. Studien zum Einfluss auf endogene Estrogenspiegel in Frauen zeigen keine einheitlichen Ergebnisse. Die Europäische Behörde für Lebensmittelsicherheit (EFSA) hat bisher alle beantragten Health Claims für IF abgelehnt, da wissenschaftlich gesicherte Belege für die postulierten Wirkungen fehlen. Laut aktueller Risikobewertung der EFSA ergaben die ausgewerteten Humanstudien keine Hinweise auf adverse Effekte durch IF-NEM in den Zielorganen Brustdrüse, Uterus und Schilddrüse bei gesunden postmenopausalen Frauen. Die Bewertung erlaubt jedoch keine allgemeingültigen Aussagen zur Sicherheit von IF-NEM. Untersuchungen in Tiermodellen sind aufgrund von Unterschieden in der Verstoffwechselung von IF, im biologischen Entwicklungsstadium zum Zeitpunkt der Exposition und in der zeitlich begrenzten Aufnahme von IF in bestimmten Lebensphasen nur eingeschränkt auf den Menschen übertragbar.

Fazit: Keine der beworbenen Wirkungen für IF konnte bislang zweifelsfrei nachgewiesen werden. Mögliche unerwünschte Wirkungen können auf Basis der vorliegenden Daten nicht völlig ausgeschlossen werden. Dies gilt vor allem für Frauen mit noch nicht erkannten Erkrankungen wie (prä-)kanzerogenen Veränderungen in der Brust.

Abstract

Isoflavones (IFs) from soy and other legumes have weak estrogenic properties. Isolated IFs are available as dietary supplements and advertised to alleviate symptoms of menopause. The present chapter provides an overview of the occurrence, the chemical structure of IFs and their metabolites, the market situation and reviews the current evidence on the efficacy and safety of IF-containing dietary supplements.

The biological effectiveness of IFs is attributable to the activation of the estrogen receptor (ER). Studies on the influence of IFs on endogenous estrogen levels in women show inconsistent results. So far, the European Food Safety Authority (EFSA) has rejected all submitted health claims for IFs due to insufficient scientific evidence for any of the postulated health effects. Based on the results of their recent risk assessment, the EFSA concluded that the available human studies did not support the hypothesis of adverse effects of isolated IFs on the human mammary gland, uterus or thyroid in healthy postmenopausal women. However, the assessment does not allow a general statement on the safety of IF-containing dietary supplements. Studies in animal models are often not comparable with the complex interactions in humans due to differences in the metabolism of IFs, in the developmental stage at time of consumption and in the temporarily restricted uptake of IFs during certain stages of life.

Conclusion: So far, for none of the advertised functions is unequivocal scientific evidence available. On the basis of available data, potential unwanted side effects cannot be fully excluded. This holds particularly true for women with undiagnosed diseases, especially for those with undetected precancerous lesions in the mammary gland.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. EFSA Panel on Food Additives and Nutrient Sources added to Food (2015) Risk assessment for peri- and post-menopausal women taking food supplements containing isolated isoflavones. EFSA J 13:4246

    Article  Google Scholar 

  2. Nagata C (2010) Factors to consider in the association between soy isoflavone intake and breast cancer risk. J Epidemiol 20:83–89

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sitte P, Weiler E, Kadereit J, Bresinsky A, Körner C (2002) Straßburger – Lehrbuch der Botanik. Spektrum Akademischer Verlag, Heidelberg

    Google Scholar 

  4. U.S. Department of Agriculture, Agricultural Research Service – USDA (2008) Database for the Isoflavone Content of Selected Foods. Release 2.0 – 2008, Nutrient Data Laboratory Web site. http://www.ars.usda.gov/Services/docs.htm?docid=6382. Zugegriffen: 09. Jan 2017

    Google Scholar 

  5. Lang K, Lindemann A, Hauser F, Göttfert M (2008) The genistein stimulon of Bradyrhizobium japonicum. Mol Genet Genomics 279:203–211

    Article  CAS  PubMed  Google Scholar 

  6. Graham TL, Graham MY, Subramanian S, Yu O (2007) RNAi silencing of genes for elicitation or biosynthesis of 5‑Deoxyisoflavonoids suppresses race-specific resistance and hypersensitive cell death in phytophthora sojae infected tissues. Plant Physiol 144:728–740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mortensen A, Kulling SE, Schwartz H et al (2009) Analytical and compositional aspects of isoflavones in food and their biological effects. Mol Nutr Food Res 53:S266–S309

    Article  PubMed  Google Scholar 

  8. Klein MA, Nahin RL, Messina MJ et al (2010) Guidance from an NIH Workshop on designing, implementing, and reporting clinical studies of soy interventions. J Nutr 140:1192 S–1204 S

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hosoda K, Furuta T, Ishii K (2011) Metabolism and disposition of isoflavone conjugated metabolites in humans after ingestion of kinako. Drug Metab Dispos 39:1762–1767

    Article  CAS  PubMed  Google Scholar 

  10. Soukup ST, Helppi J, Müller DR et al (2016) Phase II metabolism of the soy isoflavones genistein and daidzein in humans, rats and mice: a cross-species and sex comparison. Arch Toxicol 90(6):1335–1347

    Article  CAS  PubMed  Google Scholar 

  11. Kuiper GG, Carlsson B, Grandien K et al (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:863–870

    CAS  Google Scholar 

  12. Kuiper GGJM, Lemmen JG, Carlsson B et al (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 139:4252–4263

    CAS  Google Scholar 

  13. Reiter E, Beck V, Medjakovic S, Mueller M, Jungbauer A (2009) Comparison of hormonal activity of isoflavone-containing supplements used to treat menopausal complaints. Menopause 16:1049–1060

    Article  PubMed  Google Scholar 

  14. Blei T, Soukup ST, Schmalbach K et al (2015) Dose-dependent effects of isoflavone exposure during early lifetime on the rat mammary gland: studies on estrogen sensitivity, isoflavone metabolism, and DNA methylation. Mol Nutr Food Res 59:270–283

    Article  CAS  PubMed  Google Scholar 

  15. Kinjo J, Tsuchihashi R, Morito K et al (2004) Interactions of phytoestrogens with estrogen receptors alpha and beta (III). Estrogenic activities of soy isoflavone aglycones and their metabolites isolated from human urine. Biol Pharm Bull 27:185–188

    Article  CAS  PubMed  Google Scholar 

  16. Pugazhendhi D, Watson KA, Mills S, Botting N, Pope GS, Darbre PD (2008) Effect of sulphation on the oestrogen agonist activity of the phytoestrogens genistein and daidzein in MCF-7 human breast cancer cells. J Endocrinol 197:503–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hillisch A, Peters O, Kosemund D et al (2004) Dissecting physiological roles of estrogen receptor alpha and beta with potent selective ligands from structure-based design. Mol Endocrinol 18:1599–1609

    Article  CAS  PubMed  Google Scholar 

  18. OECD (2007) Test no. 440: uterotrophic bioassay in rodents. OECD, Paris

    Book  Google Scholar 

  19. Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME (2013) Challenges to the measurement of estradiol: an endocrine society position statement. J Clin Endocrinol Metab 98:1376–1387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Key TJ, Chen J, Wang DY, Pike MC, Boreham J (1990) Sex hormones in women in rural China and in Britain. Br J Cancer 62:631–636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hooper L, Ryder JJ, Kurzer MS et al (2009) Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis. Hum Reprod Update 15:423–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Key TJ, Appleby PN, Reeves GK et al (2011) Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 105:709–722

    Article  CAS  PubMed  Google Scholar 

  23. The Endogenous Hormones and Breast Cancer Collaborative Group (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616

    Article  Google Scholar 

  24. Keinan-Boker L, Peeters P, Mulligan A et al (2002) Soy product consumption in 10 European countries: the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr 5:1217–1226

    Article  CAS  PubMed  Google Scholar 

  25. Messina M, Nagata C, Wu AH (2006) Estimated asian adult soy protein and isoflavone intakes. Nutr Cancer 55:1–12

    Article  CAS  PubMed  Google Scholar 

  26. EFSA Panel on Dietetic Products, Nutrition and Allergies – NDA (2012) Scientific Opinion on the substantiation of health claims related to soy isoflavones and maintenance of bone mineral density (ID 1655) and reduction of vasomotor symptoms associated with menopause (ID 1654, 1704, 2140, 3093, 3154, 3590) (further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 10:2847

    Article  Google Scholar 

  27. Panel on Dietetic Products, Nutrition and Allergies (2010) Scientific opinion on the substantiation of health claims related to pantothenic acid and mental performance (ID 58), reduction of tiredness and fatigue (ID 63), adrenal function (ID 204) and maintenance of normal skin (ID 2878) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 8:1759

    Article  Google Scholar 

  28. Panel on Dietetic Products, Nutrition and Allergies (2009) Scientific opinion on the substantiation of health claims related to vitamin B6 and protein and glycogen metabolism (ID 65, 70, 71), function of the nervous system (ID 66), red blood cell formation (ID 67, 72, 186), function of the immune system (ID 68), regulation of hormonal activity (ID 69) and mental performance (ID 185) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 7:1225

    Article  Google Scholar 

  29. Panel on Dietetic Products, Nutrition and Allergies (2009) Scientific opinion on the substantiation of health claims related to calcium and maintenance of bones and teeth (ID 224, 230, 231, 354, 3099), muscle function and neurotransmission (ID 226, 227, 230, 235), blood coagulation (ID 230, 236), energy-yielding metabolism (ID 234), function of digestive enzymes (ID 355), and maintenance of normal blood pressure (ID 225, 385, 1419) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J 7:1210

    Article  Google Scholar 

  30. Rüfer CE, Bub A, Moseneder J, Winterhalter P, Sturtz M, Kulling SE (2008) Pharmacokinetics of the soybean isoflavone daidzein in its aglycone and glucoside form: a randomized, double-blind, crossover study. Am J Clin Nutr 87:1314–1323

    PubMed  Google Scholar 

  31. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (2003) Phytoestrogens and health. http://cot.food.gov.uk/sites/default/files/cot/phytoreport0503.pdf. Zugegriffen: 14 Aug 2016

    Google Scholar 

  32. DFG-Senatskommission zur gesundheitlichen Bewertung von Lebensmitteln (2006) Isoflavone als Phytoestrogene in Nahrungsergänzungsmitteln und diätetischen Lebensmitteln für besondere medizinische Zwecke

    Google Scholar 

  33. Bundesinstitut für Risikobewertung (2007) Isolierte Isoflavone sind nicht ohne Risiko. Aktualisierte Stellungnahme Nr. 039/2007 des BfR. http://www.bfr.bund.de/cm/343/isolierte_isoflavone_sind_nicht_ohne_risiko.pdf (Erstellt: 29 Okt 2007). Zugegriffen: 14 Aug 2016

    Google Scholar 

  34. Lee S‑A, Shu X‑O, Li H et al (2009) Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women’s Health Study. Am J Clin Nutr 89:1920–1926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nagata C, Mizoue T, Tanaka K et al (2014) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol 44:282–295

    Article  PubMed  Google Scholar 

  36. Shu X, Zheng Y, Cai H et al (2009) Soy food intake and breast cancer survival. JAMA 302:2437–2443

    Article  PubMed  PubMed Central  Google Scholar 

  37. Nechuta SJ, Caan BJ, Chen WY et al (2012) Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women. Am J Clin Nutr 96:123–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shike M, Doane AS, Russo L et al (2014) The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study. J Natl Cancer Inst 106(9):dju189

    Article  PubMed  PubMed Central  Google Scholar 

  39. Möller FJ, Pemp D, Soukup ST et al (2016) Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats. Arch Toxicol 90(8):1907–1916

    Article  PubMed  Google Scholar 

  40. Martinson HA, Lyons TR, Giles ED, Borges VF, Schedin P (2013) Developmental windows of breast cancer risk provide opportunities for targeted chemoprevention. Exp Cell Res 319:1671–1678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pudenz M, Roth K, Gerhauser C (2014) Impact of soy isoflavones on the epigenome in cancer prevention. Nutrients 6:4218–4272

    Article  PubMed  PubMed Central  Google Scholar 

  42. Keiler AM, Bernhardt R, Scharnweber D, Jarry H, Vollmer G, Zierau O (2013) Comparison of estrogenic responses in bone and uterus depending on the parity status in Lewis rats. J Steroid Biochem Mol Biol 133:101–109

    Article  CAS  PubMed  Google Scholar 

  43. Manning HC, Buck JR, Cook RS (2016) Mouse models of breast cancer: platforms for discovering precision imaging diagnostics and future cancer medicine. J Nucl Med 57:60 S–68 S

    Article  PubMed  Google Scholar 

  44. Dabydeen SA, Furth PA (2014) Genetically engineered ERα-positive breast cancer mouse models. Endocr Relat Cancer 21:R195–R208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Russo J (2015) Significance of rat mammary tumors for human risk assessment. Toxicol Pathol 43:145–170

    Article  CAS  PubMed  Google Scholar 

  46. Novel Foods Expert Committee of the Food Safety Commission (2006) Fundamental concepts in the safety assessment of foods containing soy Isoflavones for the purpose of specified health use. Cabinet office, government of japan food safety commission (original: Japanese, provisional translation). https://www.fsc.go.jp/english/evaluationreports/newfoods_sphealth/soy_isoflavones.pdf. Zugegriffen: 09 Jan 2017

    Google Scholar 

  47. Bundesinstitut für Risikobewertung (2015) Nahrungsergänzungsmittel mit isolierten Isoflavonen: Bei Einnahme in und nach den Wechseljahren Orientierungswerte für Dosierung und Anwendungsdauer einhalten. Mitteilung Nr. 043/2015 des BfR vom 16. November 2015. http://www.bfr.bund.de/cm/343/nahrungsergaenzungsmittel-mit-isolierten-isoflavonen-bei-einnahme-in-und-nach-den-wechseljahren-orientierungswerte-fuer-dosierung-und-anwendungsdauer-einhalten.pdf. Zugegriffen: 29 Jul 2016

    Google Scholar 

Download references

Danksagung

C. Gerhäuser, S. Kulling, L. Lehmann und G. Vollmer danken der Deutschen Forschungsgemeinschaft (DFG) für die finanzielle Förderung im Rahmen des Verbundprojektes PAK 634: IsoCross „Isoflavones: Cross-species comparison on metabolism, estrogen sensitivity, epigenetics, and carcinogenesis“ (Fördernummern GE 1049/5-1; KU 1079/9-1; LE 1329/10–1; VO 410/12-1).

Author information

Authors and Affiliations

  1. Institut für Pharmazie und Lebensmittelchemie, Julius-Maximilians-Universität Würzburg, Würzburg, Deutschland

    Leane Lehmann

  2. Institut für Sicherheit und Qualität bei Obst und Gemüse, Max Rubner-Institut, Karlsruhe, Deutschland

    Sebastian T. Soukup &  Sabine E. Kulling

  3. Epigenomik und Krebsrisikofaktoren, Deutsches Krebsforschungszentrum, Heidelberg, Deutschland

    Clarissa Gerhäuser

  4. Institut für Zoologie, Technische Universität Dresden, Dresden, Deutschland

    Günter Vollmer

Authors
  1. Leane Lehmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastian T. Soukup
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Clarissa Gerhäuser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Günter Vollmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sabine E. Kulling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sabine E. Kulling.

Ethics declarations

Interessenkonflikt

L. Lehmann, S.T. Soukup, C. Gerhäuser, G. Vollmer und S.E. Kulling geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lehmann, L., Soukup, S.T., Gerhäuser, C. et al. Isoflavonhaltige Nahrungsergänzungsmittel. Bundesgesundheitsbl 60, 305–313 (2017). https://doi.org/10.1007/s00103-016-2497-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00103-016-2497-2

Schlüsselwörter

Keywords

Search

Navigation