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Biomedical subjects

Herman Adlercreutz

Publications and source records attributed to Herman Adlercreutz.

At least 55 records · Page 3Linked to original sources

Dietary lignins are precursors of mammalian lignans in rats.

The mammalian lignans enterolactone (ENL) and enterodiol, commonly found in human plasma and urine, are phytoestrogens that may contribute to the prevention of breast cancer and coronary heart disease. They are formed by the conversion of dietary precursors such as secoisolariciresinol and matairesinol lignans by the colonic microflora. The identification of lignins, cell-wall polymers structurally related to lignans, as precursors of mammalian lignans is reported here for the first time. In study 1, rats were fed rye or wheat bran (15% diet) for 5 d. Untreated brans and brans extracted with solvents to remove lignans were compared. ENL was estimated in urine samples collected for 24 h by time-resolved fluoroimmunoassay. ENL urinary excretion was reduced from 18.6 to 5.3 nmol/d (n=8; P<0.001) when lignans were removed from rye bran and from 30.5 to 6.2 nmol/d (P<0.001) when they were removed from wheat bran. These results suggest that lignins, embedded in the cell wall and retained in the bran during solvent extraction, account for 26-32% of the ENL formed from cereal brans. In study 2, rats were fed a deuterated synthetic lignin (0.2% diet) together with wheat bran (15%) for 3 d. The detection of deuterated ENL by LC-tandem MS in urine (20 nmol/d) clearly confirms the conversion of lignin into mammalian lignans. More research is warranted to determine the bioavailability of lignins in the human diet.

4-Butyrolactone↗

Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice.

Soybean isoflavones have structures similar to that of estrogen and have received attention as alternatives to hormone replacement therapy for the prevention of postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is metabolized to equol by gut microflora, and the metabolite exhibits a stronger estrogenic activity than daidzein. However, there is no direct evidence that equol affects bone metabolism. In this study, we examined the effect of equol on the inhibition of bone loss in ovariectomized (OVX) mice. Female mice (8 wk old) were assigned to 5 groups as follows: sham-operated (sham), OVX, OVX + 0.1 mg/d equol administration (0.1 Eq), OVX + 0.5 mg/d equol administration (0.5 Eq), and OVX + 0.03 microg/d 17beta-estradiol administration (E(2)). Equol and E(2) were administered s.c., using a mini-osmotic pump. At 4 wk after the intervention, uterine weight was less in the OVX mice than in sham-operated mice (P < 0.05). The weight was maintained in the E(2) group. In contrast, administration of equol at doses used in this study did not affect uterine atrophy in OVX mice. Bone mineral density (BMD) for the whole body in the OVX group measured by dual-energy X-ray absorptiometry was lower than that in the sham group, whereas administration of 0.5 mg/d Eq as well as E(2) maintained the BMD. The BMD of the femur and lumbar spine in the OVX group was also lower than those in the sham group, and treatment with 0.5 mg/d Eq maintained it. Notably, the BMD of the proximal femur in the 0.5 Eq group was the same as that of the sham group. E(2) inhibited bone loss from all regions induced by OVX. These results suggest that equol, a major metabolite of daidzein, inhibits bone loss apparently without estrogenic activity in the reproductive organs of OVX mice.

Animals↗

Phytoestrogens and vitamin D metabolism: a new concept for the prevention and therapy of colorectal, prostate, and mammary carcinomas.

Epidemiologic studies suggest that nutritional phytoestrogens contained in soy are causally related to protection against hormone-dependent cancers. The incidence of colorectal cancer is at least 30% lower in women than in men in the United States. This suggests that estrogen and, conceivably, nutritional phytoestrogens are protective compounds against colorectal cancer for both sexes. Prevention of colorectal, mammary, and prostate cancer may also depend on optimal synthesis of the antimitotic prodifferentiating vitamin D hormonal metabolite 1,25-(OH)(2)-cholecalciferol (1,25-D3). Cytochrome-P450-hydroxylases responsible for synthesis (CYP27B1; 25-D3-1 alpha-hydroxylase) and catabolism (CYP24; 1,25-D3-24-hydroxylase) of 1,25-D3 are not only present in the kidney but are also expressed in human colonocytes, prostate cells, and mammary cells. In addition, levels of CYP27B1, vitamin D receptor, and estrogen receptor-beta (the high-affinity receptor for phytoestrogens) are enhanced early during human colorectal cancer, which suggests an interactive physiological defense against tumor progression. We demonstrate in human mammary and prostate cells concentration-dependent regulation of CYP27B1 and of CYP24 by genistein at 0.05-50 micromol/L. The high concentration of 50 micromol/L is very effective in eliminating CYP24 expression in prostate cancer cells. This high concentration can be achieved in vivo in the prostate by an as-yet-unknown concentrative mechanism. Soy feeding, or more effectively genistein feeding, elevates CYP27B1 and reduces CYP24 expression in the mouse colon. In mice fed low nutritional calcium, CYP24 rises in parallel to enhanced colonic proliferation, and genistein counteracts both. We suggest that nutritional soy or genistein can optimize extrarenal 1,25-D3 synthesis, which could result in growth control and, conceivably, in inhibition of tumor progression.

Animals↗

Plasma phytoestrogens are not altered by probiotic consumption in postmenopausal women with and without a history of breast cancer.

Soy phytoestrogens were suggested to reduce the risk of a number of diseases including breast cancer. Given that these compounds are metabolized by bacteria, alteration of intestinal bacteria and enzymes may affect phytoestrogen metabolism. We hypothesized that probiotics, when consumed with soy protein, would increase plasma isoflavones, as well as equol producer frequency, in postmenopausal women. We further hypothesized that these effects would differ between women who have had breast cancer and women who have not. To test these hypotheses, 20 breast cancer survivors and 20 controls completed four 6-wk treatments in a randomized, crossover design: supplementation with soy protein (S) (26.6 +/- 4.5 g protein, 44.4 +/- 7.5 mg isoflavones/d); soy + probiotics (S+P) (10(9) colony-forming units Lactobacillus acidophilus DDS+1 and Bifidobacterium longum, 15-30 mg fructooligosaccharide/d); milk protein (M) (26.6 +/- 4.5 g protein/d); and milk + probiotics (M+P). Plasma phytoestrogen concentrations did not differ between controls and survivors, although genistein tended to be lower in survivors at baseline (P = 0.15), and during soy (P = 0.16) and milk protein (P = 0.16) consumption. As expected, soy consumption increased plasma phytoestrogen concentrations (P < 0.0001). Plasma phytoestrogen concentrations and the number of equol producers did not differ between the S and S+P diets. At the same time, plasma equol concentrations as well as urinary equol excretion in 2 subjects were more than 7-fold different between the 2 diets. These results indicate that this particular probiotic supplement does not generally affect plasma isoflavones, although the large differences between plasma and urinary equol in some subjects suggest that equol producer status may be modifiable in some individuals.

Biological Availability↗

Effects of soy-derived isoflavones and a high-fat diet on spontaneous mammary tumor development in Tg.NK (MMTV/c-neu) mice.

Phytoestrogens such as isoflavonoids and lignans have been postulated as breast cancer protective constituents in soy and whole-grain cereals. We investigated the ability of isoflavones (IFs) and flaxseed to modulate spontaneous mammary tumor development in female heterozygous Tg.NK (MMTV/c-neu) mice. Two different exposure protocols were applied, either from 4 wk of age onward (postweaning) or during gestation and lactation (perinatal). In the postweaning exposure study, mice were fed IFs or flaxseed in a high-fat diet. In addition, flaxseed in a low-fat diet was tested. Postweaning exposure to IFs and flaxseed tended to accelerate the onset of mammary adenocarcinoma development, although tumor burden at necropsy was not changed significantly. Perinatal IF exposure resulted in enhanced mammary gland differentiation, but palpable mammary tumor onset was not affected. However, tumor burden at necropsy in the perinatal exposure study was significantly increased in the medium- and high-IF dose groups. Comparison of both exposure scenarios revealed a strongly accelerated onset of tumor growth after perinatal high-fat diet exposure compared with the low-fat diet. This study shows that breast cancer-modulating effects of phytoestrogens are dependent both on the background diet and on the timing of exposure in the life cycle.

Adenocarcinoma↗

Liquid chromatography method for plant and mammalian lignans in human urine.

Recently new mammalian lignan precursors were identified but no analysis methods are available for assay of those compounds in human urine. Previously published methods were developed for GC-MS about only two plant lignans were included. Consequently, a method for HPLC equipped with a coulometric electrode array detector was developed to measure plant and mammalian lignans in human urine. The plant lignans, secoisolariciresinol (Seco), matairesinol (Mat), lariciresinol (Lar), pinoresinol (Pin), syringaresinol (Syr) and isolariciresinol (IsoL) were included into the new method together with two mammalian lignans, enterolactone (Enl) and enterodiol (End). Validation of the method demonstrated that it could be applied to normal urine containing low amounts of plant lignans and moderate amounts of mammalian lignans, but the method was also applicable for samples from study subjects in supplementation studies, i.e. sample with very high concentrations of mammalian lignans. The method was found to be a useful tool for studies on plant lignan intake and the activity of micro flora in the metabolism of plant lignans.

Animals↗

Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND: Enterolactone is a plant-derived compound that has been associated with a reduced risk of acute coronary events and cancer. Several studies have suggested that serum enterolactone concentration may play a role as a biomarker of a diet high in fiber and vegetables. Owing to its phenolic structure, enterolactone and its plant lignan precursors, which are converted by intestinal bacteria to enterolactone, are potential antioxidants. METHODS: The associations between serum enterolactone level and the risk of coronary heart disease (CHD)-related, cardiovascular disease (CVD)-related, and all-cause mortality were investigated in the Kuopio Ischaemic Heart Disease Risk Factor Study, which is a prospective population-based study of middle-aged Finnish men. The serum enterolactone concentration and cardiovascular risk factors were determined in 1889 men aged 42 to 60 years. In an average follow-up of 12.2 years, 70 CHD-related, 103 CVD-related, and 242 all-cause deaths occurred in participants free of prior CVD. RESULTS: Multivariate analyses showed significant associations between elevated serum enterolactone concentration and reduced risk of CHD- and CVD-related mortality, but weaker associations in relation to all-cause mortality. In the Cox proportional hazards regression model adjusting for the most potent confounding factors, the risk of CHD-related (P =.03 for trend) and CVD-related (P =.04 for trend) death decreased linearly across quartiles of serum enterolactone concentration. CONCLUSIONS: Our data suggest that a high serum enterolactone level is associated with reduced CHD- and CVD-related mortality in middle-aged Finnish men. These results add to the evidence supporting the importance of whole grain foods, fruits, and vegetables in the prevention of premature death from CVD.

4-Butyrolactone↗

Accumulation of genistein and lipophilic genistein derivatives in lipoproteins during incubation with human plasma in vitro.

Atherosclerosis is initiated by the uptake and retention of oxidized low-density lipoprotein (LDL) into the arterial intima. We have previously shown that dietary isoflavone phytoestrogens inhibit LDL oxidation in vitro. The inhibition could have been caused by undetected isoflavone metabolites associated with lipoproteins. In the present study, we incubated human plasma with [3H]genistein, both with and without the lecithin:cholesterol acyltransferase (LCAT) inhibitor dithionitrobenzoic acid (DTNB). Our results indicated that the 3H-label was attached to both high-density lipoprotein (HDL) and LDL, and that it represented both underivatized genistein and lipophilic derivatives of genistein, part of which were identified as fatty acid monoesters. The latter was demonstrated by the findings that DTNB decreased the HDL and LDL associated radioactivity in the lipophilic fraction isolated by hydrophobic chromatography and that saponification hydrolysis liberated a corresponding part of the 3H-label. Two-dimensional reversed-phase thin-layer chromatography (TLC) demonstrated that a corresponding part of the radioactivity comigrated with genistein monoester standards in the absence of DTNB but was abolished if DTNB had been present in the incubation. In summary, incubation of plasma with [3H]genistein resulted in accumulation of underivatized genistein as well as lipophilic genistein derivatives in lipoproteins. A smaller part of the latter were genistein monoesters, while part remained unidentified. Our results suggest an explanation for the increased oxidation resistance of isolated LDL during intake of soybean isoflavones.

Dithionitrobenzoic Acid↗

Metabolism of the soy isoflavones daidzein, genistein and glycitein in human subjects. Identification of new metabolites having an intact isoflavonoid skeleton.

Epidemiological studies have associated high soy intake with a lowered risk for certain hormone-dependent diseases. Soy and soy foods are rich sources of isoflavones, which have been shown to possess several biological activities. In this study, the metabolism of soy isoflavones daidzein, genistein and glycitein was investigated in human subjects. The aim was to find and identify urinary phase I metabolites of isoflavones, which have an intact isoflavonoid skeleton, and which might possess some bioactivity. Six volunteers included three soy bars per day into their normal western diet for a 2-week period. Daily urine samples were collected before, and after the supplementation period. Urine samples were hydrolyzed with Helix pomatia, extracted with diethyl ether, purified with Sephadex LH-20 chromatography, and analyzed as trimethylsilyl derivatives using gas chromatography-mass spectrometry (GC-MS). The structures of the isoflavone metabolites were identified using authentic reference compounds. The metabolites, for which authentic reference compounds were not available, were identified by the interpretation of mass spectra. Several new isoflavone metabolites were identified, and the presence of previously reported metabolites confirmed. The metabolic pathways of daidzein, genistein and glycitein are presented on the basis of the identification of the metabolites in human urine after soy supplementation.

Adult↗

A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients.

OBJECTIVE: Phytoestrogens are popular in treatment of menopause, although scientific evidence is insufficient as to their efficacy. We studied the effects of daily use of isoflavonoids on climacteric symptoms and quality of life in patients with a history of breast cancer. METHODS: Sixty-two postmenopausal symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for 3 months; the treatment regimens were reversed after a 2-month washout period. Fifty-six women completed the study. Menopausal symptoms were recorded on the Kupperman index and the visual analogue scale, and working capacity and mood changes were assessed via validated questionnaires. In addition, we followed the levels of phytoestrogens, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and sex hormone-binding globulin. Liver enzymes and creatinine were also assessed at each visit. RESULTS: The phytoestrogen regimen raised the circulating levels of phytoestrogens (daidzein, genistein, equol) 19- to 106-fold. The Kupperman index was reduced by 4.2 +/- 9.6 (mean +/- standard deviation) (15.5%) during phytoestrogen use and similarly by 4.0 +/- 8.1 (14.7%) during placebo use (P nonsignificant). The quality of life parameters (working capacity, mood changes) were unaffected by phytoestrogen. In addition, the phytoestrogen regimen caused no changes in FSH, LH, estradiol, or sex hormone-binding globulin. Phytoestrogen treatment was well tolerated and caused no changes in liver enzymes, creatinine, body mass index, or blood pressure. Of the 56 women, 25 (44.6%) preferred the phytoestrogen regimen, 15 preferred the placebo (26.8%), and 16 (28.6%) reported no preference (nonsignificant). CONCLUSION: Pure isoflavonoids did not alleviate subjective menopausal symptoms in breast cancer patients.

Breast Neoplasms↗

Time-resolved fluoroimmunoassay for equol in plasma and urine.

We present a method for the determination of the isoflavan equol in plasma and urine. This estrogenic isoflavan, which is formed by the action of the intestinal microflora, may have higher biological activity than its precursor daidzein. High urinary excretion of equol has been suggested to be associated with a reduction in breast cancer risk. The method is based on time-resolved fluoroimmunoassay, using a europium chelate as a label. After synthesis of 4'-O-carboxymethylequol the compound is coupled to bovine serum albumin (BSA), then used as antigen to immunize rabbits. The tracer with the europium chelate is synthesized using the same 4'-O-derivative of equol. After enzymatic hydrolysis (urine) or enzymatic hydrolysis and ether extraction (plasma) the immunoassay is carried out. The antiserum cross-reacted to variable extent with some isoflavonoids. For the plasma method the cross-reactivity does not seem to influence the results, which were highly specific. The overestimation of the values using the urine method (164%) compared to the results obtained by a gas chromatography-mass spectrometry (GC-MS) method is probably due to some influence of the matrix on the signal, and interference of structurally related compounds. It is suggested that plasma assays are used but if urine samples are measured a formula has to be used to correct the values making them comparable to the GC-MS results. The correlation coefficients between the time-resolved fluoroimmunoassay (TR-FIA) methods and GC-MS methods were high; r-values for the plasma and urine method, were 0.98 and 0.91, respectively. The intra-assay coefficient of variation (CV%) for the TR-FIA plasma and urine results at three different concentrations vary between 5.5-6.5 and 3.4-6.9, respectively. The inter-assay CV% varies between 5.4-9.7 and 7.4-7.7, respectively. The working ranges of the plasma and urine assay are 1.27-512 and 1.9-512nmol/l, respectively.

Animals↗

Phyto-oestrogen database of foods and average intake in Finland.

Information on phyto-oestrogen intake in various populations has been scanty until now, primarily because data on the content of these compounds in foods were lacking. We report here on expansion of the Finnish National Food Composition Database (Fineli) with values for the plant lignans matairesinol and secoisolariciresinol and the isoflavones daidzein and genistein. The values, expressed as aglycones, were based on food analyses (mainly GC-MS) or imputed from analytical data for 180 foods for lignans and 160 foods for isoflavones; additionally, over 1000 values were derived from the recipe database of Fineli. Average intake of these phyto-oestrogens was calculated using food consumption data of the National Dietary Survey FINDIET 1997, which was carried out in a random sample of the adult population in five areas in Finland. The dietary data were collected by 24 h recall =2862). The mean lignan intake was 434 (standard deviation (SD) 1575) microg/d and the mean isoflavone intake was 788 (SD 673) microg/d. Women had a higher lignan density (microg lignans/MJ) in their diet than men (P<0.05). Men had a higher mean daily isoflavone intake, 902 (SD 368) microg, than women, 668 (SD 963) microg (P<0.05). The sources of lignans were many: seeds, cereals, fruit, berries and vegetables. The main sources of isoflavones appeared to be processed meat products/sausages containing soya as an ingredient, and legumes as such. The average intake of lignans and isoflavones in Finland seems to be low, but intake varies throughout the population.

Adult↗

Process-induced changes on bioactive compounds in whole grain rye.

Manufacturing of healthy wholegrain foods demands knowledge of process-induced changes in macro-, micro- and non-nutrients. The high content of dietary fibre is a challenge in relation to good product texture and sensory quality. The stability and bioavailability of bioactive compounds have a marked influence on the health effects of cereal foods. It was confirmed that sterols, folates, tocopherols and tocotrienols, alkylresorcinols, lignans, phenolic acids and total phenolics are concentrated in the bran layers of the rye grain, and are only present at low levels in the flour endosperm. The levels of folate and easily-extractable phenolic compounds increase in germination and sourdough baking, but there are negligible changes in the levels of sterols, lignans and alk(en)ylresorcinols. The levels of tocopherols and tocotrienols are reduced during the sourdough fermentation. In conclusion, many of the bioactive compounds in wholegrain rye are stable during food processing, and their levels can even be increased with suitable processing.

Dietary Fiber↗

Rye, lignans and human health.

Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

Cardiovascular Diseases↗

Rye bread in the diet of pigs enhances the formation of enterolactone and increases its levels in plasma, urine and feces.

To obtain new insight into the quantitative and qualitative metabolism of rye and wheat lignans, we performed three series of experiments with catheterized pigs. Two diets with similar levels of dietary fiber and macronutrients but with contrasting levels of plant lignans (isolariciresinol, lariciresinol, matairesinol, pinoresinol, secoisolariciresinol and syringaresinol) were prepared from rye (high in lignans) and wheat (low in lignans) soft and crisp breads. In two series of experiments we quantified the uptake from the gut of enterolactone in four pigs fitted with catheters in the portal vein and mesenteric artery and with an ultrasonic flow probe attached to the portal vein to monitor the blood flow. In a third study with six pigs, we quantified the bioavailability of the plant lignans that can be converted to enterolactone (lariciresinol, matairesinol, pinoresinol, secoisolariciresinol and syringaresinol) and the concentration in the peripheral blood. Plant and mammalian lignans in diets and stool were analyzed by isotope dilution gas chromatography-mass spectrometry and enterolactone in plasma and urine determined by time-resolved fluoroimmunoassay. There was a significantly higher formation of enterolactone in pigs fed the rye diet, and higher fecal and urinary excretion and circulating levels of mammalian lignans than in pigs fed the wheat diet. The conversion of mammalian lignan precursors to enterolactone was 48% with the wheat diet and 60% with the rye diet. Mammalian lignans are absorbed by passive diffusion from the large intestine and a substantial fraction of the absorbed mammalian lignans undergoes enterohepatic circulation, resulting in low diurnal variation in plasma levels of enterolactone.

4-Butyrolactone↗

Intake of lignans is associated with serum enterolactone concentration in Finnish men and women.

The mammalian lignans (a form of phytoestrogens), metabolically derived by the intestinal microflora from dietary precursors, may have several health benefits. Information concerning their dietary sources and bioavailability is scarce. We assessed lignan intake via a 24-h dietary recall (n = 2852) and determined serum enterolactone (EL) concentration (n = 1784) in 25- to 64-y-old Finnish men and women participating in a national survey in 1997. Mean intake of lignans [sum of matairesinol (MAT) and secoisolariciresinol (SECO)] in men and women was 173 microg/d (19 microg/MJ) and 151 microg/d (23 microg/MJ), respectively. SECO made up over two thirds of the total lignan intake. The major sources of SECO were fruit, berries and cereals, whereas MAT derived almost exclusively from cereals. Lignan intake was positively associated with serum EL concentration (r = 0.19, P < 0.0001), i.e., the mean EL concentration in the highest quintile of lignan intake was 50% higher than that in the lowest quintile. We conclude that lignans are common components of the Finnish diet, although the mean daily intake is low (<0.2 mg). The main dietary sources of lignans, i.e., whole grain, vegetables and fruits, are foods commonly associated with lower risk of cardiovascular diseases and cancer. Serum EL concentration is a feasible biomarker of lignan intake.

4-Butyrolactone↗

Lignan precursors from flaxseed or rye bran do not protect against the development of intestinal neoplasia in ApcMin mice.

Phytoestrogens, like isoflavonoids and lignans, have been postulated as possible colorectal cancer protective constituents. To investigate this hypothesis, two high-fiber sources rich in lignan precursors, i.e., rye bran and flaxseed, were tested for their ability to modulate intestinal tumor development in ApcMin mice. Test diets consisted of a control diet (a Western-style diet, adjusted for fiber and/or phytate content) supplemented with 5% flaxseed or 30% rye bran. Chemical analysis of diets and blood samples confirmed the enhanced systemic exposure of mice fed the test diets to the major lignan precursors, i.e., secoisolariciresinol and matairesinol. No statistically significant difference was observed in the incidence and multiplicity of small intestinal and colon tumors at terminal sacrifice between mice fed the control diet or the diet supplemented with 5% flaxseed. With the rye bran diet a statistically significant enhancement of the number of small intestinal tumors in female mice was observed. The number of colon tumors, however, was comparable between the control and rye bran-fed mice of either sex. Furthermore, no activating point mutations in the K-ras oncogene nor positive immunohistochemical staining for the p53 gene were observed in a set of 48 colon tumors. In conclusion, our results demonstrate that increased intake of lignan precursors from flaxseed or rye bran, administered in a Western-style diet, does not protect against intestinal tumor development in an appropriate animal model for intestinal neoplasia such as the ApcMin mice.

Animals↗

Soy isoflavones: a safety review.

Soy isoflavones have been a component of the diet of certain populations for centuries. The consumption of soy generally has been considered beneficial, with a potentially protective effect against a number of chronic diseases; because of their estrogenic activity, however, negative effects of isoflavones have been postulated. This review examines the literature associated with the safety of soy isoflavones, including dietary soy isoflavone exposure data of populations with high soy intakes, human studies in which soy protein or isoflavones were provided, and toxicologic studies investigating the potential genotoxicity, carcinogenicity, and reproductive and developmental toxicity of soy isoflavones. Whereas results in some studies are limited or conflicting, when viewed in its entirety, the current literature supports the safety of isoflavones as typically consumed in diets based on soy or containing soy products.

Animals↗