Biomedical subjects

Herman Adlercreutz

Publications and source records attributed to Herman Adlercreutz.

At least 19 recordsLinked to original sources

PubMed2006

Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary fatty acids and life stage-specific exposure to phytoestrogens.

Breast cancer is a major public health problem among women worldwide. Phytoestrogens and dietary fat composition are being investigated to elucidate the role of nutrition in breast cancer risk. Both epidemiological and rodent studies suggest that the chemopreventive effect of phytoestrogens depends on timing of exposure. We investigated spontaneous mammary tumor development in female heterozygous MMTV/c-neu (Tg.NK) mice upon isoflavone exposure on background diets rich in either n-6 or n-3 polyunsaturated fatty acids (PUFAs). Three different exposure protocols were used, either from conception to weaning, or from weaning onwards, or lifelong. Mice fed diets high in n-3 PUFAs developed mammary tumors 15 weeks later than mice fed n-6 PUFA diets. In the latter mice, isoflavone exposure from weaning onwards resulted in a significant decrease in tumor incidence and a delay in tumor onset. Therefore, the effects of phytoestrogen exposure on tumor formation appear to depend on the composition of the background diet and on the timing of exposure within the life cycle.

Animals↗

PubMed2006

Circulating enterolactone and risk of endometrial cancer.

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.

4-Butyrolactone↗

PubMed2006

Secoisolariciresinol and matairesinol of sea buckthorn (Hippophaë rhamnoides L.) berries of different subspecies and harvesting times.

Sea buckthorn (Hippophaë rhamnoides) seeds, berries, and berry fractions are often used as sources of bioactive ingredients for health products. The aim of the present study was to analyze lignans in these fractions of sea buckthorn. Secoisolariciresinol and matairesinol in seeds, fruit pulp/peel, and whole berries of sea buckthorn of three subspecies were analyzed by isotope dilution gas chromatography-mass spectrometry. The total content of the two lignans secoisolariciresinol and matairesinol varied widely from 8 to 139 microg/100 g in fresh berries and from 51 to 319 microg/100 g in dry berries. The content of secoisolariciresinol varied in the range of 34-313 microg/100 g of dry mass in the fruit pulp/peel and 93-355 microg/100 g in dry seeds. The content of matairesinol fell within the range of 3-25 microg/100 g in dry pulp/peel and 1-13 microg/kg in dry seeds. Wild H. rhamnoides ssp. sinensis contained a significantly higher total level of secoisolariciresinol and matairesinol in dry seeds, dry berries, and fresh berries compared with wild ssp. rhamnoides (253 vs 135 microg/100 g, P < 0.01, in seeds; 224 vs 153 microg/100 g, P < 0.05, in dry berries; 71 vs 29 g/100 g, P < 0.01, in fresh berries) and the cultivar of ssp. mongolica (253 vs 112 microg/100 g in seeds, 71 vs 9 microg/100 g in fresh berries). Harvesting dates had a significant influence on the content of the two lignans in seeds, fruit pulp/peel, and whole berries. This is the first report of lignans in sea buckthorn.

Butylene Glycols↗

PubMed2006

Effect of sesamin on serum cholesterol and triglycerides levels in LDL receptor-deficient mice.

BACKGROUND: Sesamin, a major lignan from sesame seeds has been associated with cholesterol reduction in previous reports, but recent studies suggested differences in the response to sesamin intake depending on the model studied as well as the nature of the sesamin preparation used. AIM: The effect of pure sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor-knockout mice under cholesterol fed condition. DESIGN: Animals were randomly assigned to 4 groups, fed an atherogenic diet containing stanol ester, sesamin, combination of stanol ester and sesamin or a control diet with no additions. RESULTS: The control group showed an almost 3-fold increase in serum cholesterol levels due to the atherogenic diet but no effect was seen for triglyceride levels. Stanol ester alone or together with sesamin significantly attenuated the elevation of the cholesterol levels. CONCLUSION: Sesamin alone did not affect the elevation of the diet-induced cholesterol level and it did not enhance the effect of stanol ester.

Animals↗

PubMed2006

The effects of short-term oral phytoestrogen supplementation on the hypothalamic-pituitary-testicular axis in prostate cancer patients.

BACKGROUND: Here we evaluate the effects of oral phytoestrogen supplementation on hypothalamic-pituitary-testicular (HPT) axis in CaP patients. METHODS: We recruited 40 men about to undergo radical prostatectomy for CaP to receive either 240 mg of clover phytoestrogens or placebo daily for 2 weeks. Serum hormone levels were measured before and after treatment. In addition, recombinant cell bioassay was used to measure serum androgen bioactivity (ABA). RESULTS: Phytoestrogen treatment increased serum LH from mean of 3.4-5.2 IU, P = 0.03. Concomitantly, non-significant trend towards decline in serum T, cfT and ABA values was noted. However, mean serum LH/T ratio was upregulated from 0.20 to 0.48 IU/nM, P = 0.004, suggesting compensated hypogonadism. During the course of treatment, serum concentration of equol correlated strongly with the concomitant decrease in ABA (r = -0.586, P = 0.022). CONCLUSIONS: Phytoestrogen treatment interferes with HPT axis in CaP patients by inducing testicular resistance to LH and compensated hypogonadism.

Administration, Oral↗

PubMed2006

Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation.

BACKGROUND: Phytoestrogens have been suggested to reduce the risk of prostate cancer (CaP), but no data exists on how oral phytoestrogen supplementation influences phytoestrogen concentrations in prostate tissue. METHODS: Forty men with CaP, assigned for radical prostatectomy, received 240 mg of clover phytoestrogens or placebo daily for a 2-week period before their operation in a prospective and randomized study. Phytoestrogens were measured in plasma and prostate tissue by time-resolved fluoroimmunoassay (TR-FIA). RESULTS: All patients had low baseline phytoestrogen concentrations and only 35% had a detectable plasma concentration of equol. Oral supplementation with phytoestrogens induced a statistically significant (P<0.001) 23- and 7-fold increase in prostate tissue concentrations of the phytoestrogens genistein and daidzein, respectively. Supplemented patients demonstrated prostate tissue genistein and daidzein concentrations that were over twofold higher than their plasma. Interestingly, even though the placebo group did not receive phytoestrogen challenge, they also demonstrated twofold prostate tissue genistein and daidzein concentrations compared to their plasma values, suggesting that the prostate can concentrate available phytoestrogens. In addition, after the supplementation, 90% of the supplemented patients had a detectable plasma equol concentration. CONCLUSIONS: We conclude that prostate tissue can concentrate genistein and daidzein. Significant elevation of intraprostatic genistein and daidzein concentrations can be achieved with a short-term dietary phytoestrogen supplementation.

Administration, Oral↗

PubMed2006

Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden).

OBJECTIVE: Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer. METHODS: In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer. RESULTS: High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57-0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15-0.55), 0.63 (95% CI: 0.35-1.14) and 0.74 (95% CI: 0.41-1.32). CONCLUSIONS: Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.

4-Butyrolactone↗

PubMed2006

Kinetics of the appearance of cereal alkylresorcinols in pig plasma.

Alkylresorcinols (AR) are phenolic lipids found in high amounts in wholegrain wheat and rye. They may be important as bioactive components and/or biomarkers of wholegrain wheat and rye intake. AR absorption was studied with pigs during a habitual diet and after a single meal of AR-rich diet. In study 1, four pigs were fed wholegrain rye (RD) and white wheat bread (WD) for 1 week in a cross-over design. Arterial and venous AR concentrations were determined over 540 min after feeding on days 5 and 7. In study 2, four pigs were fed a synthetic, starch-based diet for 5 d, and arterial and venous AR concentrations were determined over 960 min after feeding a single meal of RD. In study 1, plasma AR concentrations after consuming RD peaked at 120 min, remained elevated between 120 and 420 min, and were re-elevated on refeeding at 480 min. In study 2, AR appeared in the plasma after 60 min, peaked at 180-240 min, and remained elevated after 960 min. The apparent elimination half-life was 3.93 h, and the maximum plasma concentration was 666 (sem 35) nmol/l. Arterial and venous plasma AR concentrations were similar, suggesting that AR are absorbed via the lymphatic system. AR concentrations in pig plasma increase rapidly after a meal containing AR, and persist in plasma for at least 5 d, indicating that AR may be a useful biomarker of wholegrain wheat and rye intake.

Animal Feed↗

PubMed2006

Phyto-oestrogen intake and plasma concentrations in South Asian and native British women resident in England.

Phyto-oestrogens, naturally occurring hormone-like chemicals in plant food, may play a protective role against hormone-related chronic diseases. South Asian migrants in the UK have a lower incidence of hormone-related cancer than their hosts but the extent to which this difference may be due to phytoestrogen intake is not known. The aim was to compare habitual phytoestrogen intake in first-generation South Asian migrant women and native British women. South Asian (n 221) and native British women (n 50) were recruited from general practitioner lists and were asked to provide monthly 24 h recalls for a period of 1 year. An enhanced phytoestrogen database was compiled using data from a literature search and unpublished data. A sub-sample of South Asian women (n 100) and the native British women (n 40) also provided blood samples every 3 months during the 1-year period. The median daily intakes (microg/d) of isoflavones (184.2 v. 333.9) and lignans (110.8 v. 148.8) were significantly lower in South Asians than in the native British (P<0.001, P=0.04 respectively). There were no significant differences in mean plasma isoflavone levels (nmol/l) but plasma enterolactone was significantly lower in the South Asians (13.9 (SD 17.5) v. 28.5 (SD 23.3), P<0.001). The main sources of phytoestrogens were bread and vegetables in both ethnic groups. Habitual phytoestrogen intake in South Asian and native British women was below 1 mg/d and was higher in the native British diet. The present study does not support the hypothesis that differences in phytoestrogen intake, or in circulating levels, could explain differences in hormone-related cancer risks between these two populations.

Adult↗

PubMed2006

Human plasma kinetics and relative bioavailability of alkylresorcinols after intake of rye bran.

Alkylresorcinols (ARs) are phenolic lipids present in whole grain and bran of wheat and rye. Chemically, they comprise 1,3- dihydroxy-5-alkylbenzene homologs with odd-numbered, mainly saturated hydrocarbon side chains in the range of 17-25 carbon atoms. ARs are evaluated both for physiological effects and for their potential use as biomarkers of whole-grain wheat and rye intake. In this study, plasma kinetics and relative bioavailability of ARs in humans were investigated after a single intake of rye bran 120 g (190 mg ARs). The shapes of plasma concentration time curves were similar in the subjects (n = 6) with 2 peaks at approximately 2.8 and 6.5 h and maximum concentrations (mean +/- SEM) of 1253 +/- 125 and 3365 +/- 309 nmol/L, respectively. The relative bioavailability of different homologs increased with increasing length of the AR side chain (r = 0.97, P < 0.001), indicating differences in metabolism. The apparent half-lives were rather short, approximately 5 h for all homologs, which suggests that the AR concentration in plasma could be used as a short- to medium-term biomarker of regular intake of whole-grain wheat and rye.

Absorption↗

PubMed2006

Prostatic phyto-oestrogen tissue levels in different Austrian regions.

INTRODUCTION: A number of studies suggest that the low incidence of prostate cancer as well as benign prostatic enlargement in Asia depends on the extended consumption of phyto-oestrogens in these parts of the world. In most Asian men, phyto-oestrogen levels are multiple higher compared to Austrian (European) men. The aim of our study was to evaluate, according to the East-West decline, whether there were significant differences within the Austrian population. We compared prostate phyto-oestrogen tissue levels of men living in three different geographical regions of Austria. We further compared men living in rural and urban environments. MATERIAL AND METHODS: Prostatic tissue samples of 103 men undergoing surgery for benign prostatic hyperplasia or prostate cancer were collected and frozen at -40 degrees C. In tissue samples, enterolactone (representative for lignans) and genistein levels (representative for isoflavones) were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared tissue levels of men living in rural and urban environments and different geographical regions of Austria. RESULTS: Prostatic enterolactone tissue levels were similar in men living in an urban (median 19.1 ng/g dry weight, range 1.5-76.4) or rural environment (median 15.7 range 0.6-140.6) p = 0.99. The respective values for genistein were 20.5 ng/g dry weight (range 4.6-47.4) and 9.3 (range 0.1-156.7) p = 0.77. Furthermore, enterolactone (p = 0.1) and genistein (p = 0.65) levels were similar in three different geographic regions in Austria. CONCLUSION: No significant differences regarding genistein and enterolactone were found between our study populations. However, we found a wide variation between individual patients.

Austria↗

PubMed2005

Quantification of lignans in food using isotope dilution gas chromatography/mass spectrometry.

The optimization and validation of a protocol for the quantification of six dietary lignans, i.e., secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, medioresinol, and syringaresinol, in food are presented. The method incorporates isotope dilution to ensure correct accuracy and precision, introducing the utilization of individual stable 13C3-labeled lignans. To demonstrate the potential of this new method, preliminary results of the levels of dietary lignans in selected foods are presented. It is concluded that the method fulfils the reliability criteria and can be applied to the analysis of the most common lignans in human food, being an essential asset to establish the intake of lignans in a determined population and their relation with disease prevention.

Carbon Isotopes↗

PubMed2005

Determination of plasma genistein fatty acid esters following administration of genistein or genistein 4'7-O-dioleate in monkeys.

Soy-derived isoflavone phytoestrogens, such as genistein (4',5,7-trihydroxyisoflavone), have been shown to protect low-density lipoprotein from oxidation. In addition, human plasma was previously shown to be capable of converting genistein into lipophilic fatty acid esters that accumulate in lipoproteins in vitro. We developed a method for the quantitation of genistein fatty acid esters in plasma. Furthermore, the method was utilized to measure genistein ester concentrations in monkey plasma following administration of genistein or genistein 4',7-O-dioleate. After extraction from plasma, genistein fatty acid esters were separated from unesterified genistein by Sephadex LH-20 column chromatography. The genistein ester fraction was hydrolyzed by saponification and purified by a second chromatography on Sephadex LH-20. The hydrolyzed genistein esters were measured by time-resolved fluoroimmunoassay. Adult female rhesus monkeys (n=10) received a subcutaneous injection of genistein (24 mg, n=2) or genistein 4',7-O-dioleate (71 mg, n=3) or an oral dose of genistein (24 mg, n=2) or genistein 4',7-O-dioleate (71 mg, n=3). Plasma was collected at 4, 8, and 24 h post-dosing. Following subcutaneous administration of genistein 4',7-O-dioleate, the plasma concentrations of genistein esters became elevated in two out of three monkeys with 8-h values exceeding 7.5 nmol/L and 24-h values above 12 nmol/L. Other treatments resulted in lower plasma values ranging between 2.7 and 6.1 nmol/L. The lower limit of detection for the method was 1.44 nmol/L. Subcutaneously administered genistein 4',7-O-dioleate was also converted to water-soluble conjugates, but oral administration did not elevate plasma genistein fatty acid ester levels. The results suggest that it may be possible to introduce intact genistein ester molecules into plasma by parenteral but not oral administration.

Administration, Oral↗

PubMed2005

An isotope dilution gas chromatographic-mass spectrometric method for the simultaneous assay of estrogens and phytoestrogens in urine.

The metabolism of endogenous estrogens is complicated and certain metabolic patterns may reflect an individual risk of estrogen-dependent diseases such as breast cancer. Since the 1960s we have been constantly involved in developing estrogen profiling methods, in the beginning using gas chromatography and later gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode (SIM) and finally utilizing isotope dilution (ID-GC-MS-SIM). The addition of the dietary phytoestrogens to the profile rendered the method even more complicated. The present work presents the final estrogen profile method for 15 endogenous estrogens, four lignans, seven isoflavonoids and coumestrol in one small urine sample (1/150th of a 24 h human urine sample, minimum 2.5-5 ml) with complete validation including investigations as to the precision, sensitivity, accuracy and specificity. The method does not include the minimal amounts of unconjugated estrogens in urine. It may also be used for animal (e.g. rat and mouse) urine using a minimum of 2 ml of usually pooled sample. Despite its complexity it was found to fulfill the reliability criteria, resulting in highly specific and accurate results.

Estrogens↗

PubMed2005

Estrogen A-ring structure and antioxidative effect on lipoproteins.

The oxidative modification of lipoprotein particles is an important step in atherogenesis. Estrogens are known to be powerful antioxidants independently of their binding to the estrogen receptors and the hormonal functions. We explored the structural determinants for the antioxidant activity of a large number of estrogen derivatives (n=43) in an aqueous lipoprotein solution in vitro by monitoring formation of conjugated dienes. Our results indicate that estrogen derivatives with an unsubstituted A-ring phenolic hydroxyl group with one or two adjacent methoxy groups provide strongest antioxidant protection of low density lipoprotein (LDL) and high density lipoprotein (HDL). The electron donating methoxy groups may enhance the antioxidant effect by weakening the phenolic OH bond and providing stability to the formed phenoxyl radical. With some exceptions, compounds completely lacking unsubstituted hydroxyl groups in the A-ring exhibited no antioxidant effect, e.g. the most hydrophilic "tetrol" compound with three unsubstituted A-ring hydroxyl groups had no antioxidant effect. Moreover, additional hydroxyl groups in the B-, C- or D-ring seemed to weaken the antioxidant effect. Accordingly, both the presence of unsubstituted hydroxyl groups and adjacent substituents, as well as the lipophilicity of the derivatives determine the antioxidant activity of estrogen derivatives in aqueous lipoprotein solutions.

Antioxidants↗

PubMed2005

Whole-grain rye and wheat alkylresorcinols are incorporated into human erythrocyte membranes.

Alkylresorcinols (AR), a group of phenolic lipids, exist in the human diet in whole-grain rye and wheat. They are absorbed by humans and have been quantified in plasma. In this 2-week study we assessed AR incorporation into human erythrocyte membranes. Nine subjects attended the study; four avoided whole-grain products for 1 week and then included whole-grain rye and wheat bread in the diet for the second week, four included whole-grain rye and wheat products in the diet during the whole follow-up and one followed a gluten-free diet. Plasma and erythrocyte membrane AR were analysed after weeks 1 and 2. Erythrocyte membrane AR concentrations increased an average of 231 nmol/l of packed erythrocytes (P=0.036) after consumption of whole-grain rye and wheat products. Plasma AR levels increased an average of 175 nmol/l (P=0.058). When intake of whole-grain products was constant, erythrocyte membrane and plasma AR levels remained stable. Long-chain AR were incorporated into erythrocyte membranes in a higher proportion compared to shorter-chain AR. This preliminary study shows that AR are incorporated into human erythrocyte membranes in vivo.

Bread↗

PubMed2005

Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice.

Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.

Actins↗

PubMed2005

Short-term soy and probiotic supplementation does not markedly affect concentrations of reproductive hormones in postmenopausal women with and without histories of breast cancer.

BACKGROUND: Observational studies suggest that dietary isoflavones reduce breast cancer risk, and this may be caused in part by effects on endogenous hormone concentrations. Because intestinal bacteria metabolize isoflavones, it was hypothesized that consumption of probiotic bacteria would enhance the biologic effects of isoflavones, including effects on endogenous hormones. DESIGN: Twenty (20) postmenopausal breast cancer survivors and 20 healthy postmenopausal women completed four 42-day diet periods in a randomized, crossover design. They received one of the following: isolated soy protein; isolated milk protein; soy + probiotic capsules; or milk + probiotic capsules. Each protein supplement provided 0.38 g protein/(kg body weight/day) (26.6 +/- 4.5 g protein/day) and soy protein provided 0.64 mg isoflavones/(kg body weight/day) (44.4 +/- 7.5 mg isoflavones/day). Probiotic capsules provided 10(9) colony-forming units Lactobacillus acidophilus (strain DDS-1), Bifidobacterium longum, and 15-20 mg fructo-oligosaccharide. MEASURES: Plasma samples were collected at baseline and after each diet for analysis of estrogens, follicle-stimulating hormone (FSH), androgens, and sex hormone?binding globulin (SHBG). RESULTS: Hormone levels were not affected by soy, probiotic supplements, or equol producer status, and neither cancer status nor equol producer status altered the effects of soy or probiotics. Furthermore probiotics did not alter the effects of soy consumption. Soy protein tended to decrease SHBG compared to milk protein diets (p = 0.05), although both proteins significantly decreased SHBG relative to baseline (p = 0.0001 and p = 0.03). CONCLUSIONS: These data suggest that short-term, moderate consumption of isoflavone-containing soy protein and consumption of these particular probiotic capsules do not significantly alter reproductive hormone concentrations in breast cancer survivors or controls, regardless of equol producer status.

Administration, Oral↗