19.1.2 Sojalecithin

Lecithin, auch als E322 bekannt, ist eine fettähnliche Substanz und wird mehreren Funktionsklassen – unter anderem den Emulgatoren – zugeordnet. Zudem findet Lecithin jedoch auch als Nahrungsergänzungsmittel an sich Verwendung. Während es im Rahmen des Einsatzes in Säuglingsanfangs- und -folgenahrung einer Höchstmengenbeschränkung unterliegt, gilt dies nicht für die übrigen Lebens- und Nahrungsergänzungsmittel. Liposomale und mizellierte Formulierungen, aber auch Präparate zur intravenösen Anwendung, sind besonders auf den Einsatz von Lecithin angewiesen.

Chemisch gesehen handelt es sich bei Lecithin um Phospholipide, die aus Fettsäurediestern von Glycerol, Phosphorsäure und Cholin bestehen. Die Gewinnung erfolgt häufig aus Sojabohnen, Raps, Erdnüssen, Sonnenblumenkernen, aber auch Hühnerei. Qualitativ gibt es daher sowohl beim Ursprung als auch der Herstellung große Unterschiede. Insbesondere die Gewinnung aus gentechnisch veränderten Pflanzen, was insbesondere bei Soja und Raps häufig vorkommt, ist bei der Herstellung von Lecithin ein großes Thema (siehe auch Kapitel 12). Zudem kann die Schadstoffbelastung des Ursprungsmaterials mit Pestiziden und anderen Chemikalien auch für das Endprodukt von Bedeutung sein (siehe auch Kapitel 4). Gerade bei der Weiterverarbeitung von Soja spielen zudem Lösungsmittel, speziell N-Hexan, eine Rolle (siehe Kapitel 11). Schlecht aufgereinigte Produkte können durchaus gesundheitsabträgliche Rückstände schädlicher Lösungsmittel enthalten. Um ein möglichst hochwertiges, unbelastetes und gentechnikfreies Produkt zu erhalten, sollte man Hersteller, welche die Rohmaterialien aus regionaler Quelle beziehen, bevorzugen. Durch die Kennzeichnung gemäß Öko-Verordnung (EU) ist die Herkunft des Emulgators aus gentechnisch modifizierten Pflanzen weitest möglich ausgeschlossen.

Unabhängig von den Qualitätsunterschieden gibt es auch Untersuchungen zu möglichen Gesundheitsbeeinträchtigungen durch das Lecithin selbst:

Studienergebnisse zeigen, dass sehr hohe täglich aufgenommene Mengen Sojalecithin (15 g pro Tag) Auswirkungen auf die Darmgesundheit haben können. So erhöhte Sojalecithin die Fettsäureabsorption im Darm, führte zu Veränderungen im Darmmikrobiom und beeinträchtigte die Darmschleimhautbarriere. Die erhöhte Permeabilität der Darmschleimhaut fördert nicht nur die Aufnahme von Wirkstoffen, sondern kann auch das Eindringen von Bakterien aus dem Darm in den Blutkreislauf verstärken. Dies führt letztendlich zu einem Zustand unterschwelliger Entzündung und einem erhöhten Risiko für entzündliche Darmerkrankung. (499)

Obwohl solch hohe Mengen Lecithin über die Nahrung, Arzneimittel und Nahrungsergänzungsmittel nicht aufgenommen werden, zeigen Praxiserfahrungen, dass selbst geringe Mengen Lecithin bei empfindlichen Personen schwer verträglich sein können. Dies könnte jedoch auch auf allergische Reaktionen zurückzuführen sein: Obwohl Sojalecithin als hypoallergen gilt, konnten im Rahmen einer Studie IgE-bindende Proteine nachgewiesen werden, was Sojalecithin als verstecktes Allergen klassifiziert. (500)

Für eine Übersicht der Emulgatoren in Nahrungs(ergänzungsmitteln) siehe Kapitel 19.

Exkurs: Erhöhter Konsum von Soja

Insgesamt ist der vermehrte Verzehr sojahaltiger Lebensmittel immer wieder aufgrund verschiedener Themen in der Kritik: Es geht hier vor allem um die im Soja enthaltenen Isoflavone und deren Einflussnahme auf die Schilddrüse, deren Wirkung als Phytoöstrogene und die Förderung verschiedener Krebsformen:

Isoflavone sind in der Lage, die Aktivität von Enzymen zu hemmen, die für die Synthese von Schilddrüsenhormonen sowie für deren Inaktivierung und Elimination unverzichtbar sind. Auch die Wiedergewinnung von Jod in der menschlichen Schilddrüse wird gedrosselt. In einer britischen Studie wurde festgestellt, dass insbesondere Menschen mit einer bereits bestehenden subklinischen Schilddrüsenunterfunktion durch eine geringe Isoflavonexposition von 16 mg pro Tag von einer subklinischen zu einer manifesten Hypothyreose übergehen können. 

Überdies gleichen Isoflavone, die auch als Phytoöstrogene bezeichnet werden, dem menschlichen Östrogen chemisch sehr stark. Durch ihre Fähigkeit, sich an den Östrogenrezeptor zu binden, entfalten sie sowohl östrogen-nachahmende als auch östrogen-blockierende Effekte. Östrogen-blockierende Effekte sind so zu erklären, dass Isoflavone den körpereigenen Östrogenrezeptor besetzen und das natürliche Östrogen damit verdrängen. Gleichzeitig besitzen Isoflavone aber eine geringere östrogene Wirkung, sodass sich hier eher ein anti-östrogener Effekt ergibt.  Diese anti-östrogene Wirkung spielt vor allem eine Rolle bei jüngeren Frauen, wenn der Östrogenspiegel noch hoch ist. Bei Frauen nach den Wechseljahren ist der Östrogenspiegel niedrig, sodass die Isoflavone an den Rezeptoren östrogene Effekte erzeugen können. Aufgrund dieser östrogenen Wirkung kommen Isoflavone auch in isolierter Form als Ersatz für die Hormontherapie bei Wechseljahrsbeschwerden als Nahrungsergänzungsmittel zum Einsatz. Interessant ist auch, dass abhängig von der Kolonflora im Dickdarm nicht resorbierte Isoflavone zu Metaboliten mit einer höheren Östrogenpotenz umgewandelt werden, wie beispielsweise das Isoflavon Daidzein zu Equol Four hitherto undescribed Clostridium strains capable of cleaving the C ring of quercetin, kaempferol, and naringenin at C-3-C-4 were isolated from the fecal flora of humans. None of the strains cleaved catechin. C-ring fission occurred when the substrate was either in solution or in suspension. Mixed cultures of flavonoid-hydrolyzing bacteria, flavonoid-cleaving bacteria, and Escherichia coli, which was used to provide the anaerobic environment, rapidly metabolized rutin to 3,4-dihydroxyphenylacetic acid, indicating that the intestinal half-life of the biologically active aglycone is short. The cleaving strains shared many phenotypic characteristics, including their inability to ferment sugars, but they differed sufficiently to indicate that they represent different species. The metabolic fate of the dietary isoflavones daidzein and genistein was investigated in human volunteers challenged with soya. Urinary diphenols, isolated by partition chromatography on Sephadex LH-20, were characterized and identified by profile capillary gas chromatography (GC) and electron ionization mass spectrometry (GC-EIMS) analysis of the trimethylsilyl ether (TMS) derivatives. Novel isoflavonic phytoestrogens found in the urine of volunteers were those of tetrahydrodaidzein, dihydrogenistein, 6'-hydroxy-O-demethylangolesin and 2-dehydro-O-demethylangolensin. Other known diphenols identified were those of equal, dehydrodaidzein, O-demethylangolensin, daidzein, genistein, glycitein, and the lignan enterolactone. Two other urinary isomers with a fragmentation pattern closely resembling that of the persilylated TMS ethers of cis/trans-isomers of tetrahydrodaidzein, were characterized based on the elucidation of fragments associated with the loss of a non-phenolic-OTMS functional group in ring-C. These are fragments presented in the persilylated mass spectra of isoflavan-4-ols and isoflav-3-ene-4-ols, demonstrated here by a combination of simple and tandem mass spectrometry study of the deuterated persilylated TMS ethers of dihydrodaidzein. In a similar study we also present the data on the structural identification and fragment elucidation of the keto/enol tautomers of the TMS ether derivatives of the dihydro derivatives of daidzein and genistein, observed in the urine of volunteers and considered probable products of the derivatization process. Finally, the GC and GC-MS data of two unknown isoflavonoids and that of a lignan-like compound are presented together with those of dihydrodaidzein, dihydrogenistein, tetrahydrodaidzein and 2-dehydro-O-demethylangolensin. The latter four were obtained here as products of small scale chemical synthesis in a preliminary study on the tentative identification of urinary isoflavonoids in human volunteers challenged with soya. Es ist möglich, dass diese Unterscheidung zwischen Personen, die zu einer solchen Metabolisierung fähig sind und solchen, deren Darmflora eine Umwandlung verhindert, unterschiedlich auf verschiedene Mengen an Isoflavonen reagieren. Neuere Untersuchungen weisen darauf hin, dass etwa 30 % der Erwachsenen zur intestinalen Konversion von Daidzein zu Equol befähigt sind. Plasma levels of the lignans enterodiol and enterolactone, and also the isoflavonic phyto-oestrogens daidzein, equol and genistein, are reported for postmenopausal Australian women consuming a traditional diet supplemented with linseed, soya flour or clover sprouts. Analysis was performed by gas chromatography-mass spectrometry, after enzymatic hydrolysis and ion-exchange chromatography. Following linseed supplementation, combined levels of enterolactone and enterodiol reached 500 ng/ml, whereas after soya flour or clover sprouts the respective concentrations of equol, daidzein and genistein reached 43, 312 and 148 ng/ml. Not all subjects were able to produce equol from daidzein. The possible relationship and role of these weak dietary oestrogens as restraining factors in the development of hormone-dependent cancers in Asian populations is discussed. The precise role that isoflavones play in the health-related effects of soy foods, and their potential for adverse effects are controversial. This may be due in part to a lack of basic knowledge regarding their bioavailability and metabolism, particularly as it relates to the soy source. To date, there is little information concerning possible differences in the bioavailability of isoflavones derived from natural soy foods consumed at physiologically relevant intakes and whether age- or gender-related differences influence that bioavailability. In the current study of healthy adults [premenopausal (n = 21) and postmenopausal (n = 17) women and a group of men (n = 21)], we examined the effect of age, gender, and the food matrix on the bioavailability of isoflavones for both the aglycon and glucoside forms that are naturally present in 3 different soy foods, soy milk, textured vegetable protein, and tempeh. The study was designed as a random crossover trial so that all individuals received each of the 3 foods. The dose of isoflavones administered to each individual as a single bolus dose was 0.44 mg/kg body weight. Pharmacokinetic parameters were normalized to mg of each isoflavone ingested per kilogram body weight to account for differences in daidzein and genistein content between the diets. Serum isoflavone concentrations in all individuals and groups increased rapidly after the ingestion of each soy food; as expected, genistein concentrations exceeded daidzein concentrations in serum. In this small study, gender differences in peak concentrations of daidzein were observed, with higher levels attained in women. Consumption of tempeh (mainly isoflavone aglycon) resulted in higher serum peak levels of both daidzein (P < 0.001) and genistein (P < 0.01) and the associated area under the curve (P < 0.001 and P < 0.03, respectively) compared with textured vegetable protein (predominantly isoflavone glucosides). However, soy milk was absorbed faster and peak levels of isoflavones were attained earlier than with the other soy foods. Only 30% of the subjects were equol producers and no differences in equol production with age or gender were observed.

Fortsetzung Exkurs: Erhöhter Konsum von Soja

Lange wurde gestritten, ob Isoflavone das Risiko für die Ausbildung von hormonabhängigen Tumoren wie unter anderem Brustkrebs eher erhöhen oder senken. Für beide Positionen gibt es zahlreiche Hinweise. Es liegt eine Reihe epidemiologischer Studien aus dem asiatischen Raum vor, die für einen protektiven Effekt durch einen hohen Sojakonsum sprechen, welche auch durch manche Tierversuchsstudien gestützt werden. BACKGROUND: Soybeans are reported to have cancer inhibitory effects, probably due to their isoflavones. Soybean hypocotyls are embryo buds of soybeans and contain a higher amount of isoflavones and other factors than soybeans themselves.\nMATERIALS AND METHODS: The effects of soybean protein and soybean hypocotyls as diets on the development of N-methyl-n-nitrosourea (MNU) induced tumors were examined in female F344 rats. For this trial, 120 animals were used and at 6 weeks of age, groups of 30 animals were fed diets containing casein, soy protein isolate (SPI), 1.5% soybean hypocotyls and 5% soybean hypocotyls. Three weeks later all the animals except the control animals received a first dose (37.5 mg/kg body weight) of MNU by tail vein injection. At 29 weeks of age the animals received a second MNU dose (50 mg/kg body weight). Testing was performed 42 weeks after the first MNU dose.\nRESULTS: Analysis of cumulative palpable tumor incidence indicated that final tumor development of the SPI diet group and the hypocotyl diet groups was less than that of the casein diet group. Tumors were detected in one or more sites from 9 out of 24 rats in the casein diet group, 5 of 20 rats in SPI diet group, 6 out of 24 rats in the 1.5% hypocotyl diet group and 6 out of 23 rats in the 5% hypocotyl diet group. Pairwise comparisons indicated that the formation of tumors during the experiment was significantly less rapid in the SPI diet group and the hypocotyl diet groups than the casein group. No difference in tumor promotion was observed between the SPI diet group and the soybean hypocotyl diet groups.\nCONCLUSION: Our results suggest that dietary soybeans and soybean hypocotyls are capable of suppressing tumor promotion. A study was conducted to determine the protective effects of two common dietary proteins, soy protein isolate (soy) and bovine whey, against chemically induced mammary tumors in female Sprague Dawley rats. Rats were fed AIN-93G diets having casein, soy, or whey as the sole protein source. Rats within the same dietary groups were mated to obtain the F1 and F2 generations. At age 50 days, F1 (experiment A) or F2 (experiment B) female offspring (> or =19 rats/group) were p.o. gavaged with 80 mg/kg 7,12-dimethylbenz(a)anthracene, and mammary glands were evaluated when 100% of the casein-fed group developed at least one palpable tumor. Rats grew well on all three diets, but casein-fed rats gained slightly more body weight than soy- or whey-fed rats (P < 0.05). Vaginal opening occurred 1 day earlier in soy-fed rats than in casein- or whey-fed rats, but no other differences in reproductive and developmental parameters were observed between groups. When 50% of the casein-fed rats had at least one mammary tumor, lower tumor incidences (24-34%) were observed in the soy-fed (P < 0.009) and whey-fed groups (P < 0.001). When 100% of the casein-fed rats had at least one tumor, soy-fed rats had a lower tumor incidence (77%) in experiment B (P < 0.002), but not in experiment A (P < 0.12), and there were no differences in tumor multiplicity. Whey-fed rats had lower mammary tumor incidence (54-62%; P < 0.002) and multiplicity (P < 0.007) than casein-fed rats in both experiments. Our results indicate that diets rich in soy reduce the incidence of chemically induced mammary tumors by approximately 20%. Furthermore, whey appears to be at least twice as effective as soy in reducing both tumor incidence and multiplicity.","container-title":"Cancer Epidemiology, Biomarkers & Prevention: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. We examined the effects of soybeans, a soy product (miso) and biochanin A, an isoflavone derivative, on N-nitroso-N-methylurea (MNU)-induced rat mammary carcinogenesis. Seven-week-old female CD/Crj rats received a single i.v. dose (40 mg/kg body weight) of MNU. After administration of MNU, rats were fed diet containing 0% (control), 2% or 10% soybeans, or 10% miso as a soy-supplemented diet, or 10 or 50 mg/kg biochanin A. All rats were observed for 18 weeks after MNU administration. At 18 weeks, the multiplicity (mean tumors/rat) of palpable mammary tumors was significantly decreased in the 10% soybean (1.1) and 10% miso (1.2) diet groups compared to the control (2.2) (P<0.05, respectively). In the biochanin A-supplemented diet groups, the incidence (percentage of rats with tumors) was significantly decreased in the 50 mg/kg (32%) diet group compared to the control (80%) (P<0.01), and the multiplicity was significantly decreased in both the 10 mg/kg (0.7) and 50 mg/kg (0.5) diet groups compared to the control (2.2) (P<0.01 and P<0.001, respectively). The proliferative cell nuclear antigen labeling index of mammary tumors was significantly decreased in both biochanin A-supplemented diet groups compared to the control. The present results indicate that soybeans, miso, and biochanin A are useful for the prevention of mammary cancer. BACKGROUND: Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women.\nMETHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intake and breast cancer risk for pre- and/or post-menopausal women, calculated pooled odds ratios and their 95% confidence intervals of pre- and post-menopausal women respectively, and further explored soy isoflavone-breast cancer association on the basis of considering different study regions and designs. Summary results suggested that soy isoflavone intake has a protective effect against breast cancer for both pre- and post-menopausal women. However, they are influenced by study design and region. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavone's protective effect exist in both pre- and post-menopausal women (OR = 0.59, 95%CI: 0.48-0.69 for premenopausal women; OR = 0.59, 95%CI: 0.44-0.74 for postmenopausal women). However, there are some differences between the results pooled from different study designs for women in Asian countries (test for consistency, P = 0.04). Pooled OR of studies on postmenopausal women in Western countries suggested that soy isoflavone intake has a marginally significant protective effect (OR = 0.92; 95%CI: 0.83 ∼ 1.00), but further analyses stratifying by study design found no statistically significant association.\nCONCLUSIONS: We meta-analyzed more and newer research results, and separated women according to menopausal status to explore soy isoflavone-breast cancer association. We founded that soy isoflavone intake could lower the risk of breast cancer for both pre- and post-menopausal women in Asian countries. However, for women in Western countries, pre- or post-menopausal, there is no evidence to suggest an association between intake of soy isoflavone and breast cancer. BACKGROUND: High intake of soy foods has been proposed to contribute to the low breast cancer risk in Asian countries. However, results of epidemiologic studies of this association are highly variable, and experimental data suggest that soy constituents can be estrogenic and potentially risk enhancing. Thus, rigorous evaluation of available epidemiologic data is necessary before appropriate recommendations can be made, especially for women at high risk of breast cancer or those who have survived the disease.\nMETHODS: We performed a meta-analysis of 18 epidemiologic studies (12 case-control and six cohort or nested case-control) published from 1978 through 2004 that examined soy exposure and breast cancer risk. Pooled relative risk estimates were based on either the original soy exposure measure defined in each study or on an estimate of daily soy protein intake.\nRESULTS: Risk estimates, levels and measures of soy exposure, and control for confounding factors varied considerably across studies. In a pooled analysis, among all women, high soy intake was modestly associated with reduced breast cancer risk (odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.75 to 0.99); the association was not statistically significant among women in Asian countries (OR = 0.89, 95% CI = 0.71 to 1.12). Among the 10 studies that stratified by menopausal status the inverse association between soy exposure and breast cancer risk was somewhat stronger in premenopausal women (OR = 0.70, 95% CI = 0.58 to 0.85) than in postmenopausal women (OR = 0.77, 95% CI = 0.60 to 0.98); however, eight studies did not provide menopause-specific results, six of which did not support an association. When exposure was analyzed by soy protein intake in grams per day, a statistically significant association with breast cancer risk was seen only among premenopausal women (OR = 0.94, 95% CI = 0.92 to 0.97).\nCONCLUSIONS: Soy intake may be associated with a small reduction in breast cancer risk. However, this result should be interpreted with caution due to potential exposure misclassification, confounding, and lack of a dose response. Given these caveats and results of some experimental studies that suggest adverse effects from soy constituents, recommendations for high-dose isoflavone supplementation to prevent breast cancer or prevent its recurrence are premature. Soy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG-2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women. Genistein, found in soy products, is a phytochemical with several biological activities. In the current study, our research focused on the estrogenic and proliferation-inducing activity of genistein. We have demonstrated that genistein enhanced the proliferation of estrogen-dependent human breast cancer (MCF-7) cells in vitro at concentrations as low as 10 nM, with a concentration of 100 nM achieving proliferative effects similar to those of 1 nM estradiol. Expression of the estrogen-responsive gene pS2 was also induced in MCF-7 cells in response to treatment with a concentration of genistein as low as 1 microM. At higher concentrations (above 20 microM), genistein inhibits MCF-7 cell growth. In vivo, we have shown that dietary treatment with genistein (750 ppm) for 5 days enhanced mammary gland growth in 28-day-old ovariectomized athymic mice, indicating that genistein acts as an estrogen in normal mammary tissue. To evaluate whether the estrogenic effects observed in vitro with MCF-7 cells could be reproduced in vivo, MCF-7 cells were implanted s.c. in ovariectomized athymic mice, and the growth of the estrogen-dependent tumors was measured weekly. Negative control animals received the American Institute of Nutrition (AIN)-93G diet, the positive control group received a new s.c. estradiol (2 mg) pellet plus the AIN-93G diet, and the third group received genistein at 750 ppm in the AIN-93G diet. Tumors were larger in the genistein (750 ppm)-treated group than they were in the negative control group, demonstrating that dietary genistein was able to enhance the growth of MCF-7 cell tumors in vivo. Increased uterine weights were also observed in the genistein-treated groups. In summary, genistein can act as an estrogen agonist in vivo and in vitro, resulting in the proliferation of cultured human breast cancer cells (MCF-7) and the induction of pS2 gene expression. Here we present new information that dietary genistein stimulates mammary gland growth and enhances the growth of MCF-7 cell tumors in ovariectomized athymic mice. Bei den epidemiologischen Studien wird auch zu bedenken gegeben, dass diese den Jodkonsum nicht als Störvariable erfasst haben. So könnte der Zusammenhang zwischen hohem Sojakonsum und einer geringeren Auftretenshäufigkeit von Brustkrebs ebenfalls durch eine bessere Jodversorgung im asiatischen Raum vermittelt sein. 

Die American Cancer Society und das American Institute for Cancer Research vertreten die Auffassung, dass Sojalebensmittel von Frauen mit Brustkrebs verzehrt werden können. Cancer survivors are often highly motivated to seek information about food choices, physical activity, and dietary supplements to improve their treatment outcomes, quality of life, and overall survival. To address these concerns, the American Cancer Society (ACS) convened a group of experts in nutrition, physical activity, and cancer survivorship to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer. This report summarizes their findings and is intended to present health care providers with the best possible information with which to help cancer survivors and their families make informed choices related to nutrition and physical activity. The report discusses nutrition and physical activity guidelines during the continuum of cancer care, briefly highlighting important issues during cancer treatment and for patients with advanced cancer, but focusing largely on the needs of the population of individuals who are disease free or who have stable disease following their recovery from treatment. It also discusses select nutrition and physical activity issues such as body weight, food choices, food safety, and dietary supplements; issues related to selected cancer sites; and common questions about diet, physical activity, and cancer survivorship. Current research on soy and breast cancer suggests that moderate levels of soy are safe for survivors, allaying early concerns from animal studies. Der Informationsdienst des deutschen Krebsforschungszentrums hält eine Isoflavonmenge von 25 bis 50 g auch für Brustkrebspatientinnen und Brustkrebsüberlebende für unbedenklich. Dies entspricht etwa 100 bis 200 g Tofu oder 250 bis 500 ml Sojamilch. Auch eine antihormonelle Therapie mit Tamoxifen oder Aromataseinhibitoren spricht nicht gegen den Verzehr von Soja. Sojaisoflavone ähneln in ihrer Struktur dem weiblichen Sexualhormon Östrogen. Daher stellen Patientinnen immer mal wieder die Frage, ob Sojaprodukte bei Brustkrebs die Wahrscheinlichkeit für einen Rückfall erhöhen könnten. 

Von Nahrungsergänzungsmitteln mit isolierten Isoflavonen rät das Bundesinstitut für Risikobewertung bei Frauen mit oder nach einer hormonabhängigen Brustkrebserkrankung aber ab. 

Auch bei bereits bestehenden Brustkrebs-Diagnosen gibt es widersprüchliche Aussagen: einige Studien zeigen stimulierende Effekte auf das Burstkrebswachstum, andere wiederum keine Auswirkung. Many laboratory-based studies have shown that soy can suppress breast cancer proliferation. However, given the recent controversy generated by animal experiments that soy may under certain conditions stimulate breast cancer growth, we decided to carry out a pilot clinical trial in order to elucidate any interaction(s) between short-term isoflavone supplement administration and breast cancer growth. After a core-needle biopsy established the diagnosis of breast cancer, 17 patients were administered soy isoflavone tablets for two weeks. This surgically based study provided the unique opportunity to make objective observations based on human breast cancer tissues and blood obtained prior to and after isoflavone supplement treatment in the same patient. Twenty-six historical control cases with similar characteristics to the experimental patients were selected for comparison. We observed that the apoptosis/mitosis ratios in isoflavone-treated cancer specimens were not significantly different from those of control untreated cancer specimens. Furthermore, there appeared to be a statistically nonsignificant trend towards cancer growth inhibition in the isoflavone treatment group, as manifested by higher apoptosis/mitosis ratios compared with those from the control untreated group. Ex vivo/in vitro assays using serum from breast cancer patients prior to and at the conclusion of soy treatment reveal no significant proliferative changes on both breast cancer cells and endothelial cells. We concluded that the effect of soy on breast cancer deserves further studies in larger clinical trials. There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways.\nMETHODS: Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry.\nRESULTS: Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression (two-sided Student's t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student's t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3.\nCONCLUSIONS: Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Prospektive epidemiologische Studien zeigen jedoch wiederum einen Zusammenhang zwischen dem Sojakonsum und einer Lebensverlängerung bei Patienten mit einer Brustkrebs-Diagnose. Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis.\nMETHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event).\nRESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93).\nCONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed. The intake of soy isoflavones among women with breast cancer has become a public health concern, because these compounds have weak estrogenic effects. There is little clinical evidence about their safety for patients with breast cancer who are receiving adjuvant endocrine therapy.\nMETHODS: For patients who underwent surgery for breast cancer between August 2002 and July 2003 and who were receiving adjuvant endocrine therapy, we examined associations between dietary intake of soy isoflavones and recurrence of breast cancer and death. We measured dietary intake of soy isoflavones at baseline using a validated food frequency questionnaire. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by means of multivariable Cox proportional hazards regression models. We further stratified the analyses by hormonal receptor status and endocrine therapy.\nRESULTS: The median follow-up period for the 524 patients in this study was 5.1 years. Among premenopausal patients, the overall death rate (30.6%) was not related to intake of soy isoflavones (HR = 1.05, 95% CI 0.78-1.71 for the highest quartile [> 42.3 mg/day] v. the lowest quartile [< 15.2 mg/day], p for trend = 0.87). Relative to post-menopausal patients in the lowest quartile of soy isoflavone intake, the risk of recurrence for post-menopausal patients in the highest quartile was significantly lower (HR = 0.67, 95% CI 0.54-0.85, p for trend = 0.02). Inverse associations were observed in patients with estrogen and progesterone receptor positive disease and those receiving anastrozole therapy.\nINTERPRETATION: High dietary intake of soy isoflavones was associated with lower risk of recurrence among post-menopausal patients with breast cancer positive for estrogen and progesterone receptor and those who were receiving anastrozole as endocrine therapy. Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. A cohort of 1,954 female breast cancer survivors, diagnosed during 1997-2000, was prospectively followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed entry Cox proportional hazards models. Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = 0.08 for daidzein, P = 0.06 for glycetin) and among tamoxifen users (P = 0.10 for daidzein, P = 0.05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1,453 vs. <7.7 microg/day; HR, 0.48; 95% CI, 0.21-0.79, P = 0.008). Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors. Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis.\nMETHODS: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model.\nRESULTS: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death.\nCONCLUSION: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis.\nIMPACT: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer.