Serum Enterolactone Concentrations Research Articles

Lignans intake and enterolactone concentration and prognosis of breast cancer: a systematic review and meta-analysis.

Background: Some literature has studied the relationship between lignans intake and its metabolite, enterolactone, and breast cancer survival, but the results are far from consistent and conclusive. Therefore, we conducted a systematic review and meta-analysis in this situation.Methods: From its inception to August 2020, we conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library databases. This study reported the correlation between lignans intake and serum enterolactone concentrations and prognosis of breast carcinoma. The total hazard ratios (HRs) and 95% confidence interval (95% CI) were estimated, comparing the highest versus the lowest category of lignans intake and serum enterolactone concentrations, using a fixed or random-effects effect model.Results: A total of 6 articles were included in reporting the all-cause mortality (ACM), breast cancer-specific mortality (BCSM), and recurrence of 2668, 1516, and 474 breast cancer patients in 18053 breast cancer patients. In postmenopausal women with breast cancer, lignans intake or enterolactone concentrations were associated with a reduced risk of all-cause mortality (maximum and minimum) (pooled HR = 0.73, 95% CI, 0.58-0.91), as was the association with breast cancer-specific mortality (maximum and minimum) (pooled HR = 0.72, 95% CI, 0.60, 0.87). Stratified analysis showed that exposure type and diagnosis time might be the sources of heterogeneity. In premenopausal women, the relationship seemed to be the opposite, showing an increased risk of all-cause mortality (maximum and minimum) in breast cancer patients (pooled HR = 1.57, 95% CI, 1.11-2.23). No significant association was found between lignans intake or enterolactone concentrations and breast cancer recurrence (pooled HR = 0.91, 95% CI, 0.69, 1.20).Conclusion: This study provides limited evidence that lignans intake and higher serum enterolactone concentrations in postmenopausal women are beneficial to breast cancer patients' prognosis. In premenopausal women, however, the relationship may be reversed.

Serum enterolactone concentrations are low in colon but not in rectal cancer patients

The dietary lignan metabolite, enterolactone, has been suggested to have anti-cancer functions, and high serum enterolactone concentrations have been associated with decreased risk of breast and prostate cancers. We hypothesized that serum enterolactone concentrations as a marker of plant-based foods are associated with decreased risk in colorectal cancer (CRC). We measured serum enterolactone glucuronide and sulfate concentrations by liquid chromatography-tandem mass spectrometry in 115 CRC patients and 76 sex- and age-matched controls and analyzed the results with respect to tumor parameters, clinical parameters, and systemic inflammatory markers. Patients with colon cancer had significant lower serum enterolactone glucuronide and sulfate concentrations than controls (glucuronide: median 3.14 nM vs. 6.32 nM, P < 0.001; sulfate: median 0.13 nM vs. 0.17 nM, P = 0.002), whereas rectal cancer patients had similar enterolactone levels as controls (glucuronide: median 5.39 nM vs. 6.32 nM, P = 0.357; sulfate: median 0.19 nM vs. 0.17 nM, P = 0.452). High serum enterolactone concentrations were associated with low tumor grade, high serum creatinine levels, and concomitant diabetes. In summary, our results suggest that serum enterolactone concentrations are decreased in colon but not in rectal cancer. Further investigations are required to assess whether this reflects an altered lignan metabolism by the colon microbiome.

Low serum enterolactone concentration is associated with low colonicLactobacillus–Enterococcuscounts in men but is not affected by a synbiotic mixture in a randomised, placebo-controlled, double-blind, cross-over intervention study

The aims of the present study were to assess the possible differences in faecal microbiota between men with a low serum enterolactone concentration and those with a high concentration, and to investigate the impact of a synbiotic mixture on serum enterolactone concentration in men with a low concentration. We compared faecal microbiota between ten men with the lowest serum enterolactone concentration and ten men with the highest concentration at recruitment (n 84). Furthermore, we carried out a randomised, double-blind, placebo-controlled, cross-over intervention study (6-week intervention periods and 4-week washout period) to investigate the impact of a synbiotic mixture (two Lactobacillus strains, one Bifidobacterium strain, one Propionibacterium strain and galacto-oligosaccharides (32g/l)) on serum enterolactone concentration in fifty-two men who had a concentration <20nmol/l. Serum sensitive C-reactive protein (CRP) concentration was measured at the end of the first intervention period. Men with a low serum enterolactone concentration when compared with those with a high concentration had less faecal bacteria, especially those belonging to the Lactobacillus-Enterococcus group (median 8·2 (interquartile range 7·8-8·4)log10 colony-forming units/g v. median 8·8 (interquartile range 8·5-8·9)log10 colony-forming units/g, P=0·009). The synbiotic mixture that was used did not have a significant effect on serum enterolactone (synbiotic v. placebo ratio 0·96 (95% CI 0·76, 1·22), P=0·724) or serum sensitive CRP (synbiotic v. placebo ratio 0·99 (95% CI 0·74, 1·33), P=0·954) concentration. Men with a low serum enterolactone concentration harbour less colonic bacteria, especially those belonging to the Lactobacillus-Enterococcus group. A synbiotic mixture does not increase serum enterolactone concentration.

Analysis of prostate cancer association with four single-nucleotide polymorphisms from genome-wide studies and serum phyto-estrogen concentrations

Both genetics and the environment are implicated as risk factors for prostate cancer (PCa). This population-based case-control study evaluated four single-nucleotide polymorphisms (SNPs) previously identified by genome-wide association studies to be associated with increased PCa susceptibility. Potential relationships between serum concentrations of phyto-estrogens and SNPs were also investigated. Four SNPs (rs10993994, rs2660753, rs1016343 and rs6983267) were genotyped in 247 PCa patients, 125 BPH patients and 274 control men recruited in Scotland. Serum concentrations of the phyto-estrogens enterolactone, equol, genistein and daidzein were measured by isotope dilution gas chromatography-mass spectrometry. Increased PCa risk was associated with TT genotype of rs10993994 compared with CC and CT genotypes combined (odds ratio (OR)=1.87; 95% confidence interval (CI), 1.26-2.77). TT homozygotes who had low serum enterolactone concentrations (below median) were more likely to have PCa (OR=2.90; 95% CI, 1.28-6.57) than individuals with CC/CT genotype and high serum enterolactone concentrations (above median). PCa was not associated with the other three SNPs tested. PCa susceptibility was associated with TT genotype of SNP rs10993994 in this cohort of Scottish men and the increased risk of PCa was modified by serum enterolactone concentrations.

Erratum for “Effects of a Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial”

Introduction: Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers. Methods: Forty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed. Results: In pre-menopausal women, treatment supplementation resulted in a significant increase (P , 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend (P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups. Conclusions: Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated. Trial registration: ClinicalTrials.gov registration #NCT01089049.

Flaxseed and Breast Cancer: What Should We Tell Our Patients?

In the United States alone, there are approximately 2.6 million survivors of breast cancer. This population is highly motivated to initiate lifestyle changes in diet and exercise to improve their prognosis. Dietary lignans have been identified as potentially protective against breast cancer via estrogen-dependent and independent anticarcinogenic activity. Lignans are bioactive, non-nutrient, noncaloric phenolic plant compounds that are found in large amounts in flaxseeds and sesame seeds and in small amounts in whole grains, legumes, and certain fruits and vegetables (Table 1). For example, one half cup of whole wheat meal is estimated to provide approximately 325 g lignans, whereas one half cup of flaxseed provides approximately 275,000 g lignans. In humans, lignans are metabolized by the gut microflora into enterolignans; enterolactone is the main metabolite. Therefore, enterolactone concentrations in serum, plasma, and urine have been used as biomarkers of dietary lignans. The article by Buck et al that accompanies this editorial investigates the association of enterolactone with breast cancer outcomes. Specifically, the authors found that among 1,140 patients with breast cancer who were postmenopausal, serum enterolactone concentrations in the highest quartile were associated with an approximate 40% reduced risk of overall mortality (hazard ratio, 0.58; 95% CI, 0.34 to 0.99) and distant disease (hazard ratio, 0.62; 95% CI, 0.35 to 1.09). Although this is the first such study in survivors of breast cancer, these findings are supported by a recent meta-analysis that indicates that enterolactone biomarkers are associated with a statistically significant 28% reduced risk of incident breast cancer. The use of serum enterolactone as an exposure measure offers many advantages in comparison with assessment of dietary intake. Use of a biomarker eliminates the considerable error and bias in dietary self-reporting. In addition, this biomarker bypasses numerous problems that are associated with establishing the lignan content of foods, which can vary substantially within a food according to variety, crop season, location, and processing methods. Finally, the reliability coefficient for serum enterolactone is 0.55, which suggests that this measure provides a reasonably robust estimate of usual exposure. Given this objective evidence that a biomarker of lignan intake improves breast cancer outcomes, should we declare success and recommend that our patients with breast cancer supplement their diet with flaxseed? When considering the study by Buck et al, it is instructive (and sobering) to recall the demise of the carotenoid hypothesis regarding -carotene and chemoprevention of lung cancers. In the 1980s, there was considerable epidemiologic evidence that higher dietary intake of fruits and vegetables and blood levels of -carotene (a marker of fruit and vegetable intake) were associated with a lower risk of epithelial cancers. These epidemiologic studies were bolstered by laboratory research that identified several plausible biologic mechanisms by which -carotene could act to reduce tumor incidence. In response, two large trials were launched to test the effect of -carotene supplements on lung cancer incidence in high-risk populations (eg, smokers). Unexpectedly, both trials found that -carotene supplementation increased the incidence of lung cancers as well as cardiovascular and all-cause mortality. A subsequent review of randomized trials of antioxidant supplements, including 25 trials of -carotene, concluded that use of this supplement increased overall mortality by 7% (relative risk, 1.07; 95% CI, 1.02 to 1.11). These findings reversed the trend toward widespread use of -carotene supplements and fortification of common foods with this compound and likely resulted in many lives saved. A striking observation in both of these trials was that higher baseline serum -carotene concentrations were strongly associated with a reduced risk of lung cancer, although supplementation with -carotene in this same population increased the risk of lung cancer. A number of interpretations of these apparently paradoxical findings have been put forward. For example, it is possible that the physiological effects of relatively low blood concentrations of compounds (such as -carotene or enterolactone) obtained from a mixed diet do not predict the effect of high-dose supplementation, particularly in an Table 1. Major Food Sources of Lignans

A Probiotic Mixture Including Galactooligosaccharides Decreases Fecal β-Glucosidase Activity but Does Not Affect Serum Enterolactone Concentration in Men during a Two-Week Intervention1–3

A high serum concentration of enterolactone, an enterolignan produced by colonic microbiota from precursors in cereals, vegetables, and fruits, is associated with reduced risk of acute coronary events. Probiotics and prebiotics modify colonic metabolism and may affect the serum enterolactone concentration. The effects of a probiotic mixture alone and with galactooligosaccharides (GOS) on serum enterolactone concentration and fecal metabolism were investigated in 18 healthy men. Participants received 3 interventions, each for 2 wk: 1) probiotics [Lactobacillus rhamnosus strains GG (LGG) and LC705, Propionibacterium freudenreichii ssp. shermanii JS, and Bifidobacterium breve Bb99, for a total amount of 2 × 1010 CFU/d]; 2) probiotics and GOS 3.8 g/d; 3) probiotics, GOS, and rye bread (minimum 120 g/d). Serum enterolactone and fecal dry weight, enzyme activities, pH, SCFA, lactic acid bacteria, bifidobacteria, propionibacteria, and the strains LGG and LC705 were determined. The serum enterolactone concentration (nmol/L) tended to be decreased from baseline [mean (95% CI) 18.6 (10.8–26.4)] by probiotics alone [15.2 (7.8–22.7); P = 0.095], was not significantly affected by probiotics with GOS [21.5 (13.2–29.8)], and was increased by probiotics with GOS and rye bread [24.6 (15.4–33.7); P < 0.05]. Probiotics alone did not affect fecal β-glucosidase activity and bifidobacteria, but probiotics with GOS decreased β-glucosidase activity and increased bifidobacteria compared with baseline (P < 0.05) and with probiotics alone (P < 0.01). In conclusion, this probiotic mixture with or without GOS does not significantly affect serum enterolactone concentration. Because probiotics with GOS decreased fecal β-glucosidase activity but not serum enterolactone, the reduced fecal β-glucosidase, within the range of activities measured, does not seem to limit the formation of enterolactone.

Effects of A Breast-Health Herbal Formula Supplement on Estrogen Metabolism in Pre- and Post-Menopausal Women not Taking Hormonal Contraceptives or Supplements: A Randomized Controlled Trial

IntroductionBoth indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers.MethodsForty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed.ResultsIn pre-menopausal women, treatment supplementation resulted in a significant increase (P < 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend (P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups.ConclusionsSupplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated.Trial registrationClinicalTrials.gov registration #NCT01089049.

Flaxseed Ingestion Alters Ratio of Enterolactone Enantiomers in Human Serum

Enterolactone (EL) is an enterolignan found in human subjects. In this pilot study, the enantiomeric ratios of serum EL were determined in serum from healthy adults during consumption of habitual diet, and after an 8-day supplementation with flaxseed (25 g/day). (−)EL dominated in all serum samples collected during habitual diet consumption. However, the ratio of (−)EL and (+)EL enantiomers differed markedly between individuals. Flaxseed ingestion increased significantly the proportion of (+)EL in all subjects. Moreover, a small but significant increase in serum (−)EL concentration was measured. After flaxseed ingestion, (−)EL concentrations correlated with those of (+)EL suggesting that the stereochemistry of the parent plant lignan in flaxseed is not a major determinant of EL formation in human subjects. Comparison of EL concentrations obtained with the validated chromatographic methods (HPLC-MS/MS, HPLC-CEAD, and GC-MS) and the time-resolved fluoroimmunoassay (TR-FIA) revealed that the immunoassay method underestimates human serum EL concentrations after the flaxseed ingestion.

Variation in fasting and non-fasting serum enterolactone concentrations in women of the Malmö Diet and Cancer cohort

The aim of this study was to examine the variation of enterolactone from fasting and non-fasting blood of middle-aged healthy women eating a normal diet to determine the usefulness of a single sample in epidemiological studies. Twenty-six women born between 1940 and 1950 were recruited within the Malmö Diet and Cancer cohort. Three non-fasting and two overnight fasting samples were collected from each individual during a 5-week period. Twenty-one participated in all measurements. Enterolactone concentrations were analyzed by time-resolved fluoroimmunoassay. The within-subject and between-subject variations (coefficient of variations, CV) were estimated to 59 and 89% respectively for fasting samples and 71 and 67% for non-fasting samples. The intraclass correlation coefficients (ICC) were estimated to 0.66 (95% confidence interval (CI) 0.35-0.84) for fasting and 0.48 (95% CI, 0.22-0.72) for non-fasting samples. Although the estimated ICC for blood samples was moderate, it indicates that enterolactone levels of both fasting and non-fasting blood samples should be useful in future projects within the Malmö Diet and Cancer cohort.

Alkylresorcinols from Whole-Grain Wheat and Rye Are Transported in Human Plasma Lipoproteins

Alkylresorcinols with alkyl chains C17:0-C25:0 are abundant in whole-grain wheat and rye. Concentrations in human plasma have been suggested to be biomarkers of dietary whole-grain intake. We measured human plasma, erythrocyte, and lipoprotein alkylresorcinol concentrations and alkylresorcinol homolog distribution, and evaluated the use of plasma alkylresorcinol concentration as a dietary biomarker of whole-grain intake compared with serum enterolactone. A total of 15 subjects (8 women) consumed whole-grain wheat or whole-grain rye crisp bread (∼100 g/d) in a crossover design for 1 wk. The test bread periods were preceded by 1-wk periods of consuming refined wheat bread. Plasma, erythrocyte, lipoprotein alkylresorcinol, and serum enterolactone concentrations were measured before and after each period, and plasma alkylresorcinols and serum enterolactone were measured after habitual diet intake before and 1 wk after the trial. Plasma alkylresorcinols are transported in lipoproteins with VLDL and HDL being the main carriers. AR concentrations in plasma, erythrocytes, and lipoproteins were increased (P < 0.05) by whole-grain wheat bread and even more so with rye crisp bread, although interindividual variation was high. The alkylresorcinol homolog C17:0 to C21:0 ratio in plasma was higher after the whole-grain rye diet period compared with the whole-grain wheat diet period (P < 0.05). Serum enterolactone concentrations were increased significantly by whole-grain rye intake only in men. This is the first report to show that alkylresorcinols in human plasma are mainly transported in lipoproteins. The plasma alkylresorcinol C17:0 to C21:0 ratio reflects intake of whole-grain wheat and rye, and the plasma total alkylresorcinol concentration appears to be a useful biomarker of whole-grain cereal intake.

Serum Enterolactone Concentration and the Risk of Coronary Heart Disease in a Case-Cohort Study of Finnish Male Smokers

The lignan enterolactone produced by the intestinal microflora from dietary precursors has been hypothesized to protect against coronary heart disease. The present study examined the association between serum enterolactone concentration and the risk of coronary heart disease. A prospective case-cohort study was conducted among male smokers randomized to receive a placebo supplement in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1986-1999). Serum enterolactone concentrations were measured by the gas chromatography-mass spectrometry method in serum collected at trial baseline from 340 men diagnosed with nonfatal myocardial infarction (n = 205) or coronary death (n = 135) during follow-up and from the randomly selected subcohort of 420 subjects. The classic risk factors-adjusted rate ratios for all coronary heart disease events in increasing quintiles of enterolactone were 1.00 (referent), 0.85 (95% confidence interval (CI): 0.51, 1.43), 0.59 (95% CI: 0.35, 1.00), 0.69 (95% CI: 0.40, 1.16), and 0.63 (95% CI: 0.33, 1.11), and the p(trend) was 0.07. For the highest versus the lowest quintile of enterolactone, the rate ratios for nonfatal myocardial infarction and coronary death were 0.67 (95% CI: 0.37, 1.23; p(trend) = 0.10) and 0.57 (95% CI: 0.26, 1.25; p(trend) = 0.18), respectively. In conclusion, only weak support for the association between serum enterolactone concentration and coronary heart disease was found.

Dietary Phytoestrogen, Serum Enterolactone and Risk of Prostate Cancer: The Cancer Prostate Sweden Study (Sweden)

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. 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. 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). Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.

A Lignan Complex Isolated from Flaxseed Does Not Affect Plasma Lipid Concentrations or Antioxidant Capacity in Healthy Postmenopausal Women ,

A lignan complex rich in the plant lignan secoisolariciresinol diglucoside (SDG) was isolated from flaxseed. SDG is metabolized by the colonic microflora to the mammalian lignans enterodiol (END) and enterolactone (ENL), and was hypothesized to reduce plasma lipid concentrations and improve antioxidant capacity. The aim of this study was to investigate the effects of a lignan complex, providing 500 mg/d of SDG, on serum concentration and urinary excretion of ENL, plasma lipids, serum lipoprotein oxidation resistance, and markers of antioxidant capacity. Healthy postmenopausal women (n = 22) completed a randomized, double-blind, placebo-controlled, crossover study. Women consumed daily a low-fat muffin, with or without a lignan complex, for 6 wk, separated by a 6-wk washout period. Serum ENL concentration, urinary ENL excretion, plasma concentrations of total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triacylglycerol (TAG), serum lipoprotein oxidation lag time, plasma Trolox-equivalent antioxidant capacity (TEAC), and ferric reducing ability of plasma (FRAP) were measured at the beginning and end of each intervention period. ENL concentrations in serum (P < 0.001) and ENL urinary excretion (P < 0.001) were significantly higher after the lignan complex intervention period compared with placebo. Plasma concentrations of TC, LDL-C, HDL-C, TAG, lipoprotein oxidation lag time, TEAC and FRAP were not affected. Daily consumption for 6 wk of a low-fat muffin enriched with a lignan complex significantly increased serum ENL concentrations and urinary ENL excretion in healthy postmenopausal women, but had no effect on plasma lipid concentrations, serum lipoprotein oxidation resistance, or plasma antioxidant capacity.

No changes in serum enterolactone levels after eight weeks' intake of rye bran products in healthy young men

Background: Enterolactone (ENL) is a mammalian lignan metabolized by the colonic bacterial flora from plant lignan precursors widely distributed in plant foods. Objective: The aim of the study was to identify the point in time at which the onset of an increase in ENL concentration could be observed, and the point in time at which a stable level of ENL concentration was obtained. Design: Sixteen young healthy male volunteers, 25.8±4.0 years of age (mean±SD) and with an average body mass index of 23.4±2.1 kg m-2 completed this 8 week intervention study. Subjects were randomly assigned to two groups receiving 315±10 g of enriched bread and muffin products daily, containing either rye bran, rich in ENL precursors, or Vitacel 600®, a purified cellulose fibre, low in ENL precursors. Eleven fasting blood samples from each subject were taken for analysis of serum ENL concentration. Results: Serum ENL concentration was not affected by the daily supplementation with ry e bran and no significant difference in serum ENL concentration was observed between the groups receiving rye bran or Vitacel products after 8 weeks. A significant decrease in ENL concentration was observed in the Vitacel group after 1 day (p=0.018) and 1 week (p=0.029) of dietary intervention. Conclusions: In an 8 week period no increase in ENL concentration was observed for the rye-bran group and a stable level of ENL concentration was not obtained. The high intake of dietary fibre from the bread products possibly decreased transit time, and thereby reduced microbial fermentation of the plant lignans and absorption of the mammalian lignan ENL. Keywords: dietary fibre; lignan; transit time

No changes in serum enterolactone levels after eight weeks’ intake of ryebran products in healthy young men

Background: Enterolactone (ENL) is a mammalian lignan metabolized by the colonic bacterial flora from plant lignan precursors widely distributed in plant foods. Objective: The aim of the study was to identify the point in time at which the onset of an increase in ENL concentration could be observed, and the point in time at which a stable level of ENL concentration was obtained. Design: Sixteen young healthy male volunteers, 25.8±4.0 years of age (mean±SD) and with an average body mass index of 23.4±2.1 kg m-2 completed this 8 week intervention study. Subjects were randomly assigned to two groups receiving 315±10 g of enriched bread and muffin products daily, containing either rye bran, rich in ENL precursors, or Vitacel 600®, a purified cellulose fibre, low in ENL precursors. Eleven fasting blood samples from each subject were taken for analysis of serum ENL concentration. Results: Serum ENL concentration was not affected by the daily supplementation with ry e bran and no significant difference in serum ENL concentration was observed between the groups receiving rye bran or Vitacel products after 8 weeks. A significant decrease in ENL concentration was observed in the Vitacel group after 1 day (p=0.018) and 1 week (p=0.029) of dietary intervention. Conclusions: In an 8 week period no increase in ENL concentration was observed for the rye-bran group and a stable level of ENL concentration was not obtained. The high intake of dietary fibre from the bread products possibly decreased transit time, and thereby reduced microbial fermentation of the plant lignans and absorption of the mammalian lignan ENL. Keywords: dietary fibre; lignan; transit time

Serum enterolactone levels and the risk of breast cancer in women with palpable cysts

Low levels of lignans, namely enterolactone, have been reported to be associated with an increased risk of breast cancer in the general female population. We assessed, retrospectively, the relationship between serum enterolactone concentrations and the occurrence of breast cancer in women with palpable cysts. The levels of enterolactone in cryopreserved serum aliquots, obtained from 383 women with palpable cysts at the time of their first cyst aspiration, were measured using a time-resolved fluoroimmunoassay (TR-FIA). After a median follow-up time of 6.5 years (range 0.5–12.75 years), 18 women were found to have developed an invasive breast cancer. Median values of serum enterolactone were significantly lower in women who subsequently developed breast cancer: 8.5 nM/l versus 16.0 nM/l: P=0.04. Odd Ratios (OR) for breast cancer were: 0.36 (P=0.03), 0.57 (P=0.3) and 0.38 (P=0.25) for 25th (8 nM/l), 50th (16 nM/l) and 75th (24 nM/l) percentile values, respectively. The receiver operating characteristic (ROC) analysis showed a satisfactory accuracy for enterolactone as a breast cancer risk indicator (area under the curve (AUC)=0.64: P=0.04). Logistic regression analysis confirmed that the enterolactone concentration had a strong protective effect on the breast cancer risk. These findings may have important clinical implications with regard to interventional diet-focused chemo-preventive trials.

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.

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

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. 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. 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. 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.

Whole grain food intake elevates serum enterolactone

Both intake of whole grain and higher levels of serum enterolactone have been related to reduced risk for CHD and some cancers. Because lignans are prevalent in the outer layers of grains, these findings may be related. We carried out a crossover feeding study in which overweight, hyperinsulinaemic, non-diabetic men (n5) and women (n6) ate, in random order, wholegrain foods or refined-grain foods in a diet with 30% energy from fat. The dominant whole grain was wheat, followed by oats and rice. All food was supplied by the investigators and each diet lasted for 6 weeks, with an intervening washout period of 6–9 weeks. Serum enterolactone concentrations were higher when eating the wholegrain than the refined-grain diet by 6·2 (within person SE 1·7) nmol/l (P=0·0008). Most of the increase in serum enterolactone when eating the wholegrain diet occurred within 2 weeks, though the serum enterolactone difference between wholegrain and refined-grain diets continued to increase through 6 weeks. Serum enterolactone concentrations can be raised by eating a diet rich in whole grains.