Biomedical subjects

Herman Adlercreutz

Publications and source records attributed to Herman Adlercreutz.

At least 37 records · Page 2Linked to original sources

PubMed2005

A semiquantitative food frequency questionnaire is a valid indicator of the usual intake of phytoestrogens by south Asian women in the UK relative to multiple 24-h dietary recalls and multiple plasma samples.

We investigated the relative validity of an interview-administered FFQ to estimate phytoestrogen intake among South Asian women in the UK. A population-based sample of 108 healthy South Asian women completed random repeated monthly 24-h recalls [with a subsample (n = 58) also providing multiple plasma samples] over a period of 1 y followed by administration of the FFQ. The FFQ produced slightly higher estimates of phytoestrogen intake than the 24-h recalls, but the percentage of women classified into the same +/- 1 quartile by the 2 methods was high for all phytoestrogens (from 81 to 94%) with only a small percentage (<5%) being misclassified into extreme opposite quartiles. Energy-adjusted Spearman correlations coefficients between the estimates obtained by the FFQ and the 24-h recalls were 0.55 for genistein, 0.60 for daidzein, 0.70 for secoisolariciresinol, and 0.63 for matairesinol (all P < 0.001). Spearman correlation coefficients between the FFQ estimates and plasma levels were 0.21 (P = 0.12) for genistein, 0.32 (P = 0.02) for daidzein and 0.10 (P = 0.43) for enterolactone; the corresponding values for the 24-h recalls compared with plasma levels were 0.43 (P < 0.001), 0.40 (P = 0.002), and 0.08 (P = 0.50), respectively. The method of triads was used to estimate the validity coefficients (VCs) between the estimates provided by each assessment method and "true intake." The FFQ had the highest VC for lignans (0.91 vs. 0.73 for 24-h recalls and 0.11 for plasma samples) and satisfactory VCs for both genistein (0.46 vs. 0.95 and 0.45, respectively) and daidzein (0.67 vs. 0.83 and 0.45, respectively). This FFQ is thus a relatively valid tool with which to estimate phytoestrogen intake among South Asian women in the UK.

Asia, Southeastern↗

PubMed2005

Whole-grain rye bread consumption by women correlates with plasma alkylresorcinols and increases their concentration compared with low-fiber wheat bread.

Whole-grain rye and wheat products are rich in lignans, the precursors of enterolactone (ENL) and alkylresorcinols (ARs), which are phenolic lipids. In this crossover trial, we examined the effect of whole-grain rye bread compared with low-fiber wheat bread on plasma AR levels. Women (n = 39) aged 59 +/- 0.94 y (mean +/- SEM) were advised to consume rye (214 +/- 7.1 g/d) or wheat (178 +/- 6.5 g/d) bread (20% of total daily energy intake) in random order for 8 wk. The test periods were separated by an 8-wk washout period. ARs with different homologues and ENL were measured in plasma collected at the beginning (habitual diet) and end of the test bread periods. AR concentrations were higher (P < 0.001) after the rye bread (352 +/- 24.7 nmol/L) and habitual diet (97.7 +/- 12.1 and 88.3 +/- 8.7 nmol/L) periods than after the wheat bread period (36.6 +/- 4.2 nmol/L). Plasma AR concentrations were correlated with intake of rye bread (r = 0.34, P = 0.037), and with insoluble fiber from the whole diet during the rye (r = 0.39, P = 0.013) and wheat (r = 0.32, P = 0.047) bread periods. The plasma AR 17:0/21:0 ratio differed after the rye (0.84 +/- 0.04) and wheat (0.53 +/- 0.08) bread diet periods (P < 0.001). These data strongly suggest that plasma ARs could be used as specific biomarkers for whole-grain rye intake, and their homologue pattern could be used as an indicator of the bread type consumed.

Bread↗

PubMed2005

The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption.

Some epidemiologic studies reported an association between a low ratio of urinary 2-hydroxyestrogens (2-hydroxyestradiol + 2-hydroxyestrone) to 16alpha-hydroxyestrone (2:16OHE(1)) and increased breast cancer risk. Some studies show that soy consumption increases this ratio, and it is suggested that this effect may reduce breast cancer risk. We hypothesized that consumption of probiotic bacteria would alter fecal bacteria and enzymes involved in soy isoflavone metabolism, thereby increasing isoflavone bioavailability and enhancing the beneficial effects of soy on estrogen metabolism. Breast cancer survivors (n = 20) and controls (n = 20) were given 4 treatments for 6 wk each, separated by 2-wk washout periods, in a randomized, crossover design: soy protein (26.6 +/- 4.5 g protein/d containing 44.4 +/- 7.5 mg isoflavones/d); soy protein + probiotics (10(9) colony-forming units Lactobacillus acidophilus DDS(R)+1 & Bifidobacterium longum, 15-30 mg fructooligosaccharide/d); milk protein (26.6 +/- 4.5 g protein/d); and milk protein + probiotics. Survivors tended to have a lower baseline urine 2:16OHE(1) ratio than controls (P = 0.10). In the group as a whole, soy consumption tended to increase urinary 2-hydroxyestrogens (P = 0.07) and 16alpha-hydroxyestrone (P = 0.11) but had no effect on the urinary 2:16OHE(1) ratio. When subjects were divided into groups by plasma concentrations and urinary levels of the daidzein metabolite equol, soy increased urinary 2-hydroxyestrogens (P = 0.01) and the 2:16OHE(1) ratio (P = 0.04) only in subjects with high plasma equol concentrations. None of these results were influenced by probiotic consumption. These results are consistent with studies that found lower urine 2:16OHE(1) ratios in women with breast cancer and suggest that soy consumption increases this ratio only in women who are equol producers.

Bifidobacterium↗

PubMed2005

Dietary sesamin is converted to enterolactone in humans.

Sesamin, a major sesame seed lignan, has many biological actions. The specific mechanisms for most of these actions as well as the full metabolic pathway of sesamin in humans are unclear. Two experiments were carried out to determine whether postprandial plasma enterolactone is related to sesamin concentration in sesame seeds and whether enterolactone is the major product of the in vitro fermentation of sesamin. Four subjects (3 women, 1 man) were given a single dose of sesame seeds after they consumed a low-lignan diet for 1 wk. Blood was collected at baseline and at time intervals after intake and plasma was analyzed for plant and mammalian lignan concentrations. Additionally, pure sesamin standard was incubated in vitro with human fecal inoculum to mimic the fermentation process in human gut. We calculated individual pharmacokinetic variables and found high interindividual variation in the plasma plant lignan concentrations. The mammalian lignan appearance rate in plasma shows that sesamin is a major precursor of enterolactone in vivo. In the in vitro experiment, enterolactone was the major metabolite and 3 intermediates were identified, allowing the elucidation of sesamin metabolism in humans. Enterolactone was the major metabolite of sesamin both in vivo and in vitro. The abundance of sesamin in sesame seeds indicates that they are a major food source of enterolactone precursors.

4-Butyrolactone↗

PubMed2005

Plasma levels of enterolactone and percentage mammographic density among postmenopausal women.

AIMS: Certain phytoestrogens, such as lignans, may protect against developing breast cancer. Enterolactone is a lignan metabolite produced by the intestinal flora from dietary precursors such as whole grains, vegetables, and fruits. Enterolactone has been shown to have weak estrogenic and antiestrogenic properties. We decided to examine the association between plasma levels of enterolactone and mammographic density, a biomarker for breast cancer risk. METHODS: We included data from postmenopausal women ages 55 and older who participated in a cross-sectional mammogram study in Tromsø, Norway. Mammograms, plasma enterolactone measurements, as well as information on anthropometric and hormonal/reproduction factors were available on 616 women. We assessed mammographic density using a previously validated computer-assisted method. We estimated correlation coefficients and conducted multiple regression analyses. RESULTS: Mean mammographic density increased slightly across quartiles of enterolactone; the women in the highest quartile had, on average, 3.1% (absolute difference) higher percentage mammographic density compared with the lowest quartile (P(trend) < 0.01). After adjustment for age, body mass index, number of full-term pregnancies, age at first birth, and use of postmenopausal hormone therapy, the mean difference in density was reduced to 2.0% (P(trend) = 0.05). Results were similar when restricted to the 454 current hormone nonusers. The fully adjusted statistical model explained 28.3% of the total variability in mammographic percentage density, with body mass index contributing 18.2% and enterolactone only 0.9%. CONCLUSION: In our study, higher levels of enterolactone were associated with slightly higher percentage mammographic density. Our results suggest that if higher enterolactone levels reduce the risk of developing breast cancer in postmenopausal women, then this effect is not through lowering mammographic density.

4-Butyrolactone↗

PubMed2005

Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.

Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

Animals↗

PubMed2005

Hormonal response to diets high in soy or animal protein without and with isoflavones in moderately hypercholesterolemic subjects.

Consumption of soy protein has been associated with altered risk of developing endocrine-regulated cancers. This study was designed to assess the independent effect of soy relative to animal protein and soy-derived isoflavones on circulating estrogen and androgen concentrations in postmenopausal women and older men. Forty-two subjects (> 50 yr) with low-density lipoprotein cholesterol levels of > or = 3.36 mmol/l were fed each of 4 diets in randomized order for 6 wk/phase. All food and drink were provided. Diets contained 25 g soy or common sources of animal protein/4.2 MJ containing trace or 50 mg isoflavones/4.2 MJ. At the end of each diet phase, concentrations of estrone sulfate, estrone, estradiol, testosterone, androstendione, dihydrotestosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were measured. In postmenopausal women, concentrations of estrone were higher and its precursor, dehydroepiandrosterone, lower after consuming the soy compared with animal protein diets (P = 0.0396 and 0.0374, respectively). There was no significant effect of isoflavones on any of the hormones measured. In older men, dehydroepiandrosterone sulfate concentrations were lower after consuming the isoflavone (P = 0.0106) and higher after soy, compared with the animal protein diets (P = 0.0118). These data suggest that relatively large amounts of soy protein or soy-derived isoflavones had modest and limited sex-specific effects on circulating hormone levels.

Androgens↗

PubMed2004

Identification of urinary metabolites of the red clover isoflavones formononetin and biochanin A in human subjects.

Dietary supplements manufactured from red clover are widely marketed to provide the beneficial health effects of isoflavones without changing the original diet. In this study the metabolism of formononetin and biochanin A, the principal isoflavones of red clover, was studied in human subjects. Seven women ingested four red clover dietary supplements, and the metabolites of the isoflavones were identified in their urine samples. The structures of trimethylsilyl derivatives of the metabolites were established by GC-MS. New reduced metabolites of formononetin (dihydroformononetin and angolensin) and biochanin A (dihydrobiochanin A and 6'-hydroxyangolensin) were identified in urine samples using authentic reference compounds. Possible metabolic pathways are presented for the red clover isoflavones formononetin and biochanin A.

Adult↗

PubMed2004

Immunoassay for biochanin A.

Two variants of immunoassay for the determination of biochanin A (5,7-dihydroxy 4'-methoxy isoflavone), i.e., a radioimmunoassay (RIA) and an indirect ELISA, have been developed and evaluated. Both methods employ the same rabbit antiserum to a 7-O-carboxymethyl-5-hydroxy-4'-methoxyisoflavone-bovine serum albumin (BSA) conjugate. A 125I-labeled hapten-tyrosine methyl ester (TME) conjugate was used as a radioligand for the RIA. The indirect ELISA uses immunogen-coated microtitration plates and a peroxidase-labeled antirabbit Ig antibody. Both methods are specific for biochanin A with a comparable sensitivity (3.1 pg/tube for RIA; 5.3 pg/well for ELISA); however, their sensitivity to individual cross-reactants differs. The main cross-reactants are sissotrin (the cross-reactivity 15.7% for RIA; 120% for ELISA), 5-hydroxy, 4',7-dimethoxy isoflavone (51.5% for RIA; 46.5% for ELISA), prunetin (4.5% for RIA; 5.0% for ELISA), genistein (0.8% for RIA; 2.8% for ELISA) and formononetin (0.4% for RIA; 0.3% for ELISA). These methods were used for the analysis of biochanin A in alfalfa and in several nonleguminous plants.

Animals↗

PubMed2004

Determination of lignans in human plasma by liquid chromatography with coulometric electrode array detection.

The presence of mammalian lignans, mainly enterolactone, in human plasma has been related to lower incidence of certain cancers and cardiovascular disease. The plant lignans secoisolariciresinol and matairesinol have been reported to be precursors of mammalian lignans, but recently other plant lignans relatively abundant in the diet have also been identified as precursors. To evaluate the importance and contribution of these new dietary precursors to the mammalian lignan formation in vivo, metabolic studies in human subjects must be carried out. For this purpose a method based on high-performance liquid chromatography using coulometric electrode array detection for the simultaneous determination of nine plant lignans and two mammalian lignans in human plasma was developed, validated, and shown to fulfill the reliability criteria.

Animals↗

PubMed2004

Plant lignans in soy-based health supplements.

The presence of plant lignans in 14 different soy-based health supplements is reported here for the first time together with the analysis of the isoflavone content, for which these products are commercialized. Six plant lignans, i.e., secoisolariciresinol, matairesinol, syringaresinol, lariciresinol, isolariciresinol, and pinoresinol, have been identified and quantified by gas chromatography-mass spectrometry, and a positive correlation has been found between the levels of plant lignans and the levels of isoflavones in the different products. Additional quantification of plant lignans and isoflavones in soybeans has been carried out, and results are provided to allow the comparison of the average levels in soybeans and soy-based supplements.

Dietary Supplements↗

PubMed2004

Studies of the in vitro intestinal metabolism of isoflavones aid in the identification of their urinary metabolites.

Soy isoflavones have recently gained considerable interest due to their possible health benefits. However, detailed studies on the metabolism of isoflavones are lacking. The aims of the investigation presented here were (1) to study the in vitro intestinal metabolism of isoflavones and their hydroxylated analogues 3'-OH-daidzein, 6-OH-daidzein, 8-OH-daidzein, and 3'-OH-genistein and (2) to characterize the structures of some earlier identified urinary metabolites of soy isoflavones, for which no authentic reference compounds have been available. Isoflavone standards (1-2 mg) were fermented with human fecal flora (16.7%) for 24 h. Metabolites formed during the fermentation were tentatively identified by interpretation of the mass spectra of trimethylsilylated compounds obtained by GC-MS. Compounds having hydroxyl groups at 5-position (i.e., genistein and 3'-OH-genistein) were completely converted to metabolites that could not be detected by the methods used in this study. The metabolism of daidzein and its hydroxylated analogues, 3'-OH-daidzein, 6-OH-daidzein, and 8-OH-daidzein, occurred to a much lesser extent. Minor amounts of reduced metabolites (i.e., isoflavanones and alpha-methyldeoxybenzoins) of these compounds were tentatively identified in fermentation extracts. The retention times and the mass spectra of reduced isoflavone metabolites, obtained from in vitro fermentations of pure compounds, were utilized to identify unknown urinary metabolites of soy isoflavones. Four novel isoflavone metabolites were identified in human urine collected after soy supplementation: 3' '-OH-O-desmethylangolensin, 3',4',7-trihydroxyisoflavanone, 4',7,8-trihydroxyisoflavanone, and 4',6,7-trihydroxyisoflavanone.

Feces↗

PubMed2004

Androgen receptor expression in the rat prostate is down-regulated by dietary phytoestrogens.

BACKGROUND: It is well established that the growth of the prostate gland is a hormone-dependent phenomenon involving both androgenic and estrogenic control. Proliferation of prostate cells is, at least in part, under control of estrogen receptor beta (ER-beta). Phytoestrogens bind ER-beta with high affinity and therefore may have antiproliferative effects in the prostate. METHODS: The prostates of male Long-Evans rats fed a diet high in phytoestrogens (Phyto-600) or very low levels of phytoestrogens (Phyto-free) were analyzed to determine the impact of dietary phytoestrogens on prostate weight and androgen receptor (AR) expression in the prostate. RESULTS: Dietary phytoestrogens significantly decreased post-pubertal prostate weight gain in Phyto-600 vs Phyto-free fed males. Additionally, dietary phytoestrogens (Phyto-600) decreased AR expression in the prostate as determined by in situ hybridization. CONCLUSIONS: Soy phytoestrogens, present in diet, alter prostate growth presumably by binding ER-beta and subsequently reducing AR expression within the prostate.

Administration, Oral↗

PubMed2004

Serum enterolactone concentration is not associated with breast cancer risk in a nested case-control study.

The lignan enterolactone produced by the intestinal microflora from dietary precursors has been hypothesized to protect against hormone-dependent cancers. We conducted a nested case-control study to examine the relationship between serum enterolactone concentration and risk of breast cancer. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum collected at 4 independent cross-sectional population surveys from 206 women with breast cancer diagnosed during follow-up (mean 8.0 years) and from 215 controls frequency-matched to cases by study cohort, 5-year age group and study area. Mean serum enterolactone concentration (nmol/l) did not significantly differ between case and control subjects [25.2 (SD 22.2) vs. 24.0 (SD 21.3), respectively]. Odds ratios for breast cancer risk estimated by conditional logistic regression for increasing concentration of enterolactone in quartiles were 1.00 (referent), 1.67 (95% CI 0.95-2.95), 1.71 (95% CI 0.96-3.06) and 1.30 (95% CI 0.73-2.31), and p for trend was 0.48. Our findings do not support the hypothesis that high serum enterolactone concentration is associated with reduced risk of breast cancer.

4-Butyrolactone↗

PubMed2004

Phytoestrogens, cancer and coronary heart disease.

Recent results obtained in collaboration with many other groups with regard to phytoestrogens (isoflavones and lignans) and breast cancer, prostate cancer and cardiovascular disease are presented and discussed in light of new developments in the field. Both isoflavones and lignans may be protective with regard to these diseases, but we do not yet understand some of the controversial results obtained. In this short communication the possible mechanisms of disease prevention were not discussed.

Anticarcinogenic Agents↗

PubMed2004

Prospective study of plasma enterolactone and prostate cancer risk (Sweden).

OBJECTIVES: Enterolactone, a phytoestrogen produced by the intestinal microflora from precursors in plant foods, has been postulated to protect against hormone-dependent cancers. We studied the association between plasma enterolactone and risk of prostate cancer. METHODS: In the Northern Sweden Health and Disease Cohort, enterolactone concentrations were measured by time-resolved fluoroimmunoassay in plasma taken from 265 men who were diagnosed with prostate cancer at a mean time of 5 years after blood collection, and in plasma from 525 control men, matched for age and date of blood collection. RESULTS: There was no significant association between quartiles of plasma enterolactone and risk of prostate cancer. Odds ratios for prostate cancer, estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles were 1.00 (referent), 0.81 (95% confidence interval 0.52-1.27), 1.03 (0.67-1.58), and 1.22 (0.80-1.86). Adjustments for body mass index (BMI), smoking status and stratification for age, lag time, storage time and tumour characteristics did not materially alter risk estimates. Men with very low enterolactone levels, however, had significantly higher risk of prostate cancer, odds ratio for bottom decile versus all other deciles was 1.68 (1.03-2.74). CONCLUSIONS: Our results do not support the hypothesis that enterolactone formed from dietary lignans protects against prostate cancer.

4-Butyrolactone↗

PubMed2004

Estrogen-inducible uterine flavonoid binding sites: is it time to reconsider?

Epidemiological data support the beneficial effect of plant flavonoids on human health including anti-inflammatory and cancer preventing actions. The phytoestrogen flavonoids might interfere with estrogen action. The possible relations between the steroid- and the flavonoid-signalling in animal and plant cells have been addressed in numerous studies in the past decade. In search for possible sites of conjunction between these phenomena the post-receptor targets must not be disregarded. The estrogen-inducible type II estrogen binding sites of rat uteri have first been reported 25 years ago by Clark and coworkers [Biochem. Biophys. Res. Commun. 81 (1978) 1]. These sites are known to bind catecholic flavonoids with considerable affinity. Behaviour of the tyrosinase-like enzymatic activity associated with these sites appeared reminiscent to the recently described dopachrome oxidase or tautomerase activity exhibited by the cytokine macrophage migration inhibitory factor (MIF) inasmuch as it also accepts a broad range of catecholic melanogenic precursors. Therefore we assessed, whether the known type II ligand flavonoids interfere with the MIF tautomerase. We report here, that luteolin and quercetin have a biphasic effect on the enol-keto conversion of phenylpyruvate mediated by MIF tautomerase. We also demonstrate the presence of MIF immunoreactivity by Western blotting in rat uterine nuclear extracts prepared according to the method that yields high type II binding activity. These data support the possible participation of MIF in type II estrogen binding phenomena.

Animals↗

PubMed2004

Phytoestrogen tissue levels in benign prostatic hyperplasia and prostate cancer and their association with prostatic diseases.

OBJECTIVES: To compare phytoestrogen tissue levels in men with small-volume benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa). METHODS: Prostatic tissue samples of men consuming a Western diet who underwent surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees C. In the tissue samples, the enterolactone and genistein levels were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared the tissue levels in patients with BPH and PCa and studied the impact of enterolactone and genistein on prostate volume. RESULTS: The enterolactone tissue levels were comparable in patients with BPH and PCa and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0 ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight) compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023). CONCLUSIONS: Our data suggest an involvement of genistein in the pathogenesis of BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.

4-Butyrolactone↗