Effects of consumption of whole grain foods rich in lignans in healthy postmenopausal women with moderate serum cholesterol: a pilot study.

This study aims at investigating the effect of an experimental period of intake of whole grain foods rich in lignans as part of an habitual diet on the plasma and urinary excretion of enterolignans, the biomarkers of lipid metabolism and the immunological and antioxidant status in a group of postmenopausal women with moderate serum cholesterol. A randomized double-blind crossover study was completed on 13 subjects in 12-weeks after protocol approval of an ethical committee. The subjects consumed whole grain foods high in lignans (30 g/d of breakfast cereals or biscuits, etc., 80 g/d of whole grain pasta) or refined grain foods for 4 weeks, separated by a 2-weeks wash-out period. A modest hypocholesterolemic effect (p < 0.05) of the whole grain diet was observed and the intake of whole grain products rich in lignans was also associated with an increase in urinary enterodiol excretion (p < 0.05).

Rye bread intake improves oxidation resistance of LDL in healthy humans.

BACKGROUND: Oxidatively modified LDL particles contribute to atherogenic development and therefore dietary interventions for promoting oxidation resistance of LDL are of interest. The capacity of LDL to resist oxidation can be determined ex vivo by exposing isolated LDL particles to copper ions and measuring the formation of conjugated dienes by spectrophotometry. OBJECTIVE: The aim of this trial was to determine the effect of none versus high intake of rye bread on the oxidation resistance of LDL in healthy humans while otherwise on habitual diet. DESIGN: Sixty-three healthy subjects excluded rye products for one week (baseline), followed by a stepwise addition of rye bread from 99 g/d during the first two weeks to 198 g/d during the following two weeks. Additionally plant sterols were incorporated into the rye bread for half of the subjects to study cholesterol-lowering. The resistance of LDL against copper-induced oxidation was determined at baseline and at the end of the rye-period by monitoring formation of conjugated dienes. RESULTS: We observed a significant increase in the oxidation resistance of LDL, determined as a prolongation of the lag time (P < 0.001) and decrease in the slope of the propagation phase (P = 0.048) from baseline to the end of the rye-period without changes in vitamin E concentration. We observed no significant differences in the oxidation resistance of LDL between subjects who did or did not receive plant sterols. CONCLUSIONS: Rye bread intake improved significantly the oxidation resistance of LDL. Further studies are needed to clarify the protective mechanism(s).

The effect of high-fiber rye bread enriched with nonesterified plant sterols on major serum lipids and apolipoproteins in normocholesterolemic individuals.

BACKGROUND AND AIMS: Plant sterols are naturally occurring cholesterol-lowering compounds which are industrially incorporated in various foods. A novel food carrier is rye bread, the intake of which can be monitored in trials utilizing newly defined plasma biomarkers. Our aim was to determine the effects of plant sterols incorporated into high-fiber rye bread on serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios and lipophilic (pro)vitamins in healthy free-living normocholesterolemic individuals. METHODS AND RESULTS: In this double-blind, dietary intervention trial the subjects (n=68) were randomized to receive a rye bread (9.3g/d fiber) with added plant sterols (2g/d) (active) or without (control). In the second phase of the study the amount of rye bread was doubled providing 18.6g/d fiber and in the active group 4g/d plant sterols. Compliance was monitored utilizing 3-day food diaries and a novel rye fiber-derived biomarker in plasma. Intake of rye bread enriched with 2g/d of plant sterols during two weeks reduced significantly serum total and LDL cholesterol, apoB/apoA1 and total cholesterol/HDL cholesterol ratios by 5.1%, 8.1%, 8.3% and 7.2%, respectively, compared to controls. Correspondingly, the following two-week treatment with 4g/d of plant sterols resulted in 6.5%, 10.4%, 5.5% and 3.7% difference compared to controls, being most pronounced for LDL (0.33 mmol/L). The treatments did not affect lipophilic (pro)vitamin levels. CONCLUSION: Rye bread enriched with 2-4g/d of nonesterified plant sterols beneficially modifies cardiovascular lipid risk factors in normocholesterolemic subjects compared to controls.

Excretion of estrogens, catecholestrogens and phytoestrogens in carriers of BRCA1 gene mutations: effects of metformin.

BRCA1 gene mutation is associated with a combination of excessive aromatase activity/expression, predominantly estrogen receptor-negative phenotypes of tumors, and only scarce information about estrogen contents in body fluids. In the present work, isotope dilution capillary gas chromatography/mass spectrometry was used to study urinary excretion of estrogens, their catechol metabolites, and phytoestrogens in 22 women (11 with BCRA1 gene mutations and 11 without these mutations) in average 5.1+/-0.4 years before surgery for breast cancer. BCRA1 mutation carriers (including 3 premenopausal females) compared with respective controls showed significantly higher urinary estradiol and estrone excretion and a trend to an increased 2-OH-E2 excretion. In the subgroup of untreated postmenopausal women, BCRA1 mutation carriers showed a trend to increased estradiol and estrone excretion and to a higher value of the mean levels of all estrogen metabolites tested. The treatment after the baseline laboratory investigation of 6 women from postmenopausal group with the antidiabetic biguanide metformin for 3 months was associated with decreases in the excretion rates of 4-hydroxyestradiol, 2-methoxyestradiol, and 16-epiestriol and did not influence phytoestrogen excretion. The decrease in 2-methoxyestrogen excretion was more consistent in women without BCRA1 mutations than in BCRA1 mutation carriers. The data suggest the possibility that aromatase complex activation in BCRA1 mutation carriers is combined with increases in both, estrogen metabolism into catecholestrogens and their inactivation by methoxylation, and that metformin may affect both of these pathways.

Dietary lignans and postmenopausal breast cancer risk by oestrogen receptor status: a prospective cohort study of Swedish women.

Among the 51,823 postmenopausal women in the Swedish Mammography Cohort, we investigated breast cancer risk in relation to the FFQ-based estimated lignan intake by oestrogen receptor (ER) and progesterone receptor (PR) subtypes. A significant 17% risk reduction for breast cancer overall in the high lignan quartile was observed, especially among PMH user (P interaction<0.010), but no heterogeneity across ER/PR subtypes.

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

OBJECTIVES: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Urinary phytoestrogen excretion of rats bearing methylnitrosourea-induced mammary carcinoma in response to treatment with 2-methoxyestradiol.

The effect of treating mammary tumor-bearing rats with 2-methoxyestradiol (2-MeE2) on the urinary excretion of 12 phytoestrogens was investigated and compared with the changes in urinary excretion of estradiol metabolites. Alterations of excretion were registered for isoflavonoids, lignans and coumestans. However, due to large variations statistical significant differences were found only for two lignans, i.e. significant increases of enterodiol and matairesinol. Since the single components of phytoestrogens showed diverse alterations, excretions were expressed also by the ratio of total isoflavonoids to total lignans and compared with the estrogen ratios 2-hydroxyestrone to 16alpha-hydroxyestrone and A-ring to D-ring metabolites. The ratio of isoflavonoids to lignans was consistently decreased, whereas both ratios of estradiol metabolites were highly increased. The latter effect is probably due to demethylation of 2-methoxyestrone resulting in high catechol estrogen levels in urine. These results suggest that the high levels of catechol estrogens, produced by 2-MeE2 treatment, may have influenced the urinary excretion pattern of phytoestrogens.

Preliminary antiproliferative effects of some species of Terminalia, Combretum and Pteleopsis collected in Tanzania on some human cancer cell lines.

Methanolic extracts (25 microug/ml) of species belonging to the genera of Combretum, Terminalia and Pteleopsis, collected during a field expedition in Tanzania in 1999, were screened for their antiproliferative and cytotoxic effects against three human cancer cell lines (HeLa, cervical carcinoma; T 24, bladder carcinoma; and MCF 7, breast carcinoma). A leaf extract of Combretum fragrans and a fruit extract of C. zeyheri gave the strongest antiproliferative and cytotoxic effects of all the twenty-four extracts screened in this investigation. In contrast to the highly powerful leaf extract of C. fragrans, the root extract of this species gave no cytotoxic effects against the investigated cancer cell lines at a concentration of 25 microg/ml. The other investigated species of Combretum and Terminalia differed greatly in their cytotoxic potential. Root extracts of Terminalia sambesiaca and T. sericea gave the strongest cytotoxic effects of the five species of Terminalia used in this study. Eight of the twenty-four investigated plant extracts showed pronounced cytotoxic effects (<30% proliferation compared to the control) against the T 24 bladder cancer cells, seven against the HeLa cells and four against the MCF 7 cells.

No effect on adenoma formation in Min mice after moderate amount of flaxseed.

BACKGROUND & AIM: The mammalian lignan enterolactone (ENL) produced from plant lignans, e. g. secoisolariciresinol diglycoside (SDG), may protect against various cancers in humans. The present work aims to evaluate the effect of flaxseed on tumour formation in multiple intestinal neoplasia (Min) mice, a model for colon tumorigenesis. DESIGN: Male and female Min mice were fed either with a non-fibre control diet or the same diet supplemented with 0.5 % (w/w) defatted flaxseed meal. Conversion of SDG to the mammalian lignans enterodiol (END) and ENL in the gut, and plasma ENL, were measured by HPLC with coulometric electrode array detector (CEAD) and timeresolved fluoroimmunoassay, respectively. Wild-type mice were also fed with the experimental diets in order to see whether lignan metabolism is different in Min and wild-type mice. RESULTS: The total number of adenomas or their size in the small intestine was not different in the flaxseed and control groups. The flaxseed group had a tendency for a decreased number of colon adenomas in both genders. Gender and genotype based differences were found in the intestinal ENL levels. When compared to Min females, Min males in the flaxseed group had several fold higher ENL levels in the small intestine (Min males 125 +/- 124.5 nmol/g vs. females 22.8 +/- 16.0 nmol/g, P = 0.048) and caecum (47.6 +/- 31.6 nmol/g vs. females 14.5 +/- 6.6 nmol/g, P = 0.001). Presence of adenomas in the gut influences the intestinal lignan metabolism. Min mice had less intestinal END and ENL as compared with the wild-type mice (P < 0.05). Mean plasma ENL increased 7-fold during the flaxseed feeding (7 nmol/L in control vs. 50 nmol/L in flaxseed group) but no differences between gender and genotype were found. The plasma ENL level did not correlate with adenoma number in the small intestine and colon. CONCLUSION: The number of intestinal adenomas in the Min mouse model is not related to ENL level in plasma nor is it associated with the levels of intestinal lignans. A gender difference in ENL lignan metabolism was found in the gut but not in the plasma.

Circulating enterolactone and risk of breast cancer: a prospective study in New York.

It has been proposed that phyto-oestrogens protect against breast cancer. Lignans are the main class of phyto-oestrogens in Western diets. We conducted a case-control study of breast cancer and serum levels of the main human lignan, enterolactone, nested within a prospective cohort study, the New York University Women's Health Study. Serum samples collected at enrollment and stored at -80 degrees C were used. Among 14 275 participants, 417 incident breast cancer cases were diagnosed a median of 5.1 years after enrollment. Cohort members individually matched to the cases on age, menopausal status at enrollment, serum storage duration and, if premenopausal, day of menstrual cycle were selected as controls. No difference in serum enterolactone was observed between postmenopausal cases (median, 14.3 nmol l(-1)) and controls (14.5 nmol l(-1)), whereas premenopausal cases had higher levels (13.9 nmol l(-1)) than their matched controls (10.9 nmol l(-1), P-value=0.01). In the latter group, the odds ratio for the highest vs the lowest quintile of enterolactone was 1.7 (95% confidence interval (CI), 0.8-3.4; P-value for trend=0.05) and after adjustment for known risk factors for breast cancer was 1.6 (95% CI, 0.7-3.4; P-value for trend=0.13). We observed a moderate positive correlation between serum enterolactone and serum sex hormone-binding globulin in postmenopausal women (r=0.29 in controls (P<0.001) and r=0.14 in cases (P=0.04)), but no correlation with oestrogens or androgens. These results do not support a protective role of circulating lignans, in the range of levels observed, in the development of breast cancer.

Consumption of Lactobacillus acidophilus and Bifidobacterium longum do not alter urinary equol excretion and plasma reproductive hormones in premenopausal women.

OBJECTIVE: To confirm the results of an earlier study showing premenopausal equol excretors to have hormone profiles associated with reduced breast cancer risk, and to investigate whether equol excretion status and plasma hormone concentrations can be influenced by consumption of probiotics. DESIGN: A randomized, single-blinded, placebo-controlled, parallel-arm trial. SUBJECTS: In all, 34 of the initially enrolled 37 subjects completed all requirements. INTERVENTION: All subjects were followed for two full menstrual cycles and the first seven days of a third cycle. During menstrual cycle 1, plasma concentrations of estradiol (E(2)), estrone (E(1)), estrone-sulfate (E(1)-S), testosterone (T), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) were measured on cycle day 2, 3, or 4, and urinary equol measured on day 7 after a 4-day soy challenge. Subjects then received either probiotic capsules (containing Lactobacillus acidophilus and Bifidobacterium longum) or placebo capsules through day 7 of menstrual cycle 3, at which time both the plasma hormone concentrations and the post-soy challenge urinary equol measurements were repeated. RESULTS: During menstrual cycle 1, equol excretors and non-excretors were not significantly different with respect to subject characteristics, diet, or hormone concentrations. Significant inverse correlations were found between E(2) and body mass index (BMI) (P=0.02), SHBG and BMI (P=0.01), DHEA-S and dietary fiber (P=0.04), and A and protein:carbohydrate ratio (P=0.02). Probiotic consumption failed to significantly alter equol excretor status or hormone concentrations during menstrual cycle 3, although there were trends towards decreased concentrations of T (P=0.14) and SHBG (P=0.10) in the probiotic group. CONCLUSIONS: We were unable to verify a previously reported finding of premenopausal equol excretors having plasma hormone concentrations different from those of nonexcretors. Furthermore, a 2-month intervention with probiotic capsules did not significantly alter equol excretion or plasma hormone concentrations.

Highly elevated serum phyto-oestrogen concentrations in patients with diabetic nephropathy.

BACKGROUND AND OBJECTIVES: Phyto-oestrogens, naturally occurring phenolic, hormone-like compounds, have raised considerable interest due to their anticarcinogenic, antiatherogenic and antioxidative potential. Oxidative stress may be one of the key factors in the development of vascular complications in patients with type 1 diabetes. Here, we tested the hypothesis that high concentrations of phyto-oestrogens in serum may be associated with lower occurrence of vascular complications in these patients. SUBJECTS: A total of 400 patients, recruited consecutively from the participant register of the nationwide FinnDiane study of type 1 diabetes and divided into four parallel groups according to the severity of their renal disease with 100 patients to each group: (i) normoalbuminuric patients, (ii) microalbuminuric patients, (iii) macroalbuminuric patients, and (iv) patients with end-stage renal disease (ESRD). MAIN OUTCOME MEASURES: Phyto-oestrogen concentrations in serum (enterolactone, daidzein, genistein and equol) and urine (enterolactone), assessed by time-resolved fluoroimmunoassay. RESULTS: Highly elevated serum concentrations of phyto-oestrogens were measured amongst patients with diabetic nephropathy, and low concentrations amongst patients without diabetic complications. The pattern was similar for all phyto-oestrogens measured, although the increase in mean serum concentrations along with the increasing severity of renal disease was steepest for enterolactone, ranging from 13 nmol L(-1) amongst women and 18 nmol L(-1) amongst men in normoalbuminuric patients to 181 and 206 nmol L(-1) in women and men, respectively, in patients with ESRD (P < 0.001 for both genders between the groups). A strong correlation between serum enterolactone and creatinine concentration was found (r = 0.60, P < 0.001). CONCLUSIONS: The serum concentration of phyto-oestrogens and the severity of diabetic renal disease showed a close positive association, suggesting that phyto-oestrogens are unable to provide any major protective effect, through antioxidative or other mechanisms, on the development of diabetic renal and cardiovascular complications.

Effects of meal frequency and high-fibre rye-bread diet on glucose and lipid metabolism and ileal excretion of energy and sterols in ileostomy subjects.

OBJECTIVE: To investigate the effect of a rye, high-fibre diet (HFD) vs a wheat, low-fibre diet (LFD), meal frequency, nibbling (Nib, seven times a day) or ordinary (Ord, three times a day), and their combined effects on blood glucose, insulin, lipids, urinary C-peptide and ileal excretion of energy, cholesterol and bile acids in humans. DESIGN: LFD period with Nib or Ord meal frequency followed by an HFD diet with Nib or Ord meal frequency in randomized, crossover design. SETTING: Outpatients of ileostomy volunteers were called for an investigation in research word. SUBJECTS: A total of 10 subjects (two female subjects, age 34 and 51 y; eight males, mean age 54.4 y, range 43-65 y) participated in the experiment. All subjects were proctocolectomized for ulcerative colitis (mean 16.0 y, range 8-29 y before the study). INTERVENTION: In total, 10 ileostomy subjects started with LFD for 2 weeks, the first week on either Nib (five subjects) or Ord (five subjects) and the second week on the other meal frequencies, in a crossover design, followed by a wash-out week, and continued with HFD period for 2 weeks in the same meal frequency manner. All foods consumed in both Nib or Ord regimens were identical and a high-fibre rye bread was used in the HFD period and a low-fibre wheat bread in the LFD period. MAIN OUTCOME MEASURES: Day-profiles of blood glucose, insulin and lipids, blood lipids before and after dietary intervention, and excretion of steroids in the effluents and C-peptide in the urine. RESULTS: During the Nib regimen, plasma glucose and insulin peaks were lower at the end of the day with HFD compared with LFD. Urinary C-peptide excretion was significantly higher in the day-time on LFD compared with HFD (LFD-Ord vs HFD-Ord, P < 0.01; LFD-Nib vs HFD-Nib, P < 0.01). Plasma free-cholesterol, total cholesterol, triglycerides and phospholipids were significantly higher (P < 0.05) after LFD than after HFD with the Nib regimen. A higher excretion of energy (P < 0.05) and chenodeoxycholic acid (P < 0.05) were observed with HFD compared with LFD regardless of meal frequency. A higher daily excretion of cholic acid, total bile acids, cholesterol, net cholesterol and net sterols (P < 0.05) was observed on HFD compared with LFD with the Nib regimen. CONCLUSIONS: An HFD decreased insulin secretion measured as a decreased excretion of C-peptide in urine and as decreased plasma insulin peaks at the end of the day during a Nib regimen. The smoother glycaemic responses at the end of the day during a Nib regimen may be a consequence of a second meal phenomenon, possibly related to the nature of dietary fibre complex.

Randomised controlled short-term intervention pilot study on rye bran bread in prostate cancer.

The short-term effects of rye bran bread intake in prostate cancer were investigated. Ten men with conservatively treated prostate cancer were randomised to a daily supplement of 295 g of rye bran bread and eight men to 275 g of wheat bread (control) with similar fibre content for three weeks. Blood samples, ultrasound-guided core biopsies of the prostate, and urine samples were taken. In the rye group, there was a significant increase in plasma enterolactone, and the apoptotic index increased significantly from 2.1% (SD 1.3) to 5.9% (SD 1.8), P<0.005 as measured by a TUNEL index in four cases in the rye group and seven cases in the control group. Besides a significant decrease in weight in both groups, only small changes were observed in plasma concentrations of prostate specific antigen (PSA), circulating sex hormones, excreted oestrogens, insulin-like growth factor (IGF)-I, and in the endothelial fibrinolytical system. High intake of rye bran bread is suggested to increase apoptosis in prostate tumours.

Plasma enterolactone or intestinal Bifidobacterium levels do not explain adenoma formation in multiple intestinal neoplasia (Min) mice fed with two different types of rye-bran fractions.

The study was designed to evaluate whether two types of rye-bran fractions result in distinct bifidogenic effect or enterolactone production in multiple intestinal neoplasia (Min) mice and whether these parameters are associated with intestinal tumorigenesis in this animal model. The experimental diets were a non-fibre diet (control), a rye-bran diet, and diets containing either the soluble extract or the insoluble fraction prepared from rye bran. The main result on adenoma formation in these experiments was the observation that the soluble extract increased number (P=0.012) and size (P=0.008) of adenomas in the distal small intestine when compared with the non-fibre group. All rye-supplemented diets supported similarly the in vivo growth of Bifidobacterium (10(8)-10(9) colony forming units/g) in Min mice, whereas the non-fibre diet lowered intestinal Bifidobacterium below the level of detection. The results show that water solubility does not affect the bifidogenicity of rye bran. Mean plasma enterolactone concentration was highest in the rye-bran group (30.0 nmol/l; P=0.002), which along with the soluble-extract group (16.2 nmol/l; P=0.024) differed significantly from the non-fibre diet group (7.5 nmol/l). Thus, the mice fed with the rye bran were the best enterolactone producers. In conclusion, rye bran and rye fractions influence adenoma formation in Min mice to a varying degree but plasma enterolactone levels or the production of bifidogenic bacteria do not mediate the effect.

Effect of 2-methoxyestradiol on the growth of methyl-nitroso-urea (MNU)-induced rat mammary carcinoma.

The present study investigated the influence of the endogenous estradiol metabolite 2-methoxyestradiol (2ME) on the growth of methyl-nitroso-urea (MNU)-induced mammary carcinoma in the rat. 2ME was administered by means of subcutaneously implanted osmotic pumps for a period of 4 weeks. The dosages of 2ME were 1 and 5mg/kg per day, the control animals received saline. At the low dosage of 2ME a stimulation of tumor growth was observed, whereas at the high dosage an inhibition was found. The urinary excretion of 15 estradiol metabolites revealed that 2ME triggered strong changes in estrogen metabolism in the organism. Our data show that 2ME may elicit both stimulation and inhibition of tumor growth depending on the dosage used, a fact which should be considered in case of therapeutic use.

Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats.

We have investigated the metabolism of isoflavones and lignans in germ-free (GF) rats and rats associated with human faecal bacteria (human flora associated [HFA] rats), in order to provide unequivocal evidence for the role of the gut microflora in the absorption and metabolism of these phytoestrogens. Furthermore, we have investigated whether certain metabolic characteristics (high equol-producing and low equol-producing status) of human intestinal floras can be transferred to GF rats. Germ-free rats fed a soy-isoflavone containing diet excreted large quantities of daidzein and genistein in urine indicating that the gut microflora is not required for the absorption of isoflavones. The isoflavone metabolites equol, O-desmethylangolensin and the lignan enterolactone were not detectable in urine from the GF rats, but were present in HFA rat urine, indicating that they were products of gut microflora activity. Colonization of GF rats with a faecal flora from a human subject with the capacity to convert daidzein to equol, resulted in the rats excreting substantial amounts of the metabolite. In contrast, equol was undetectable in urine of HFA rats associated with a faecal flora from a low equol-producing subject. The results therefore show that the inability of some subjects to produce equol is a consequence of the lack of specific components of the gut microflora.

Phloem fortification in rye bread elevates serum enterolactone level.

OBJECTIVE: To analyse the lignan content of phloem powder enriched rye bread and to study the dose-response relationship of the effect of dietary plant lignans derived from phloem on intestinal production of enterolactone by measuring enterolactone concentration in serum. DESIGN: A randomized double-blind supplementation trial. SUBJECTS: Seventy-five non-smoking men recruited by newspaper advertisements. INTERVENTION: Subjects were randomized to three study groups receiving either rye bread high in phloem (HP, 14% of rye flour substituted with phloem powder), rye bread low in phloem (LP, 7% of rye flour substituted with phloem powder) or placebo rye bread. Participants consumed 70 g of study bread daily for 4 weeks and provided serum samples for enterolactone analysis at baseline and at the end of the intervention. RESULTS: There was a significant increase in serum enterolactone concentration in the LP and HP groups compared with the placebo group (P=0.009 and P=0.003, respectively). Considerable interindividual differences were observed in the response to dietary lignans within the study groups. CONCLUSIONS: Our results indicate that plant lignans attached to insoluble fibre layer in phloem can be further metabolized and converted to enterolactone presumably by the bacteria present in the colon. Phloem powder is useful source of lignans for functional foods aimed to elevate serum enterolactone levels. SPONSORSHIP: Phloem powder and the study breads were provided by Finnpettu Oy and Linkosuo Oy, respectively. The clinical study work was sponsored in part by Oy Jurilab Ltd.

The effect of flaxseed supplementation in processed foods on serum fatty acids and enterolactone.

OBJECTIVE: The purpose was to study the effects of flaxseed supplementation as a part of daily diet on serum lipids, fatty acids and plasma enterolactone. DESIGN: Eighty volunteers participated in this clinical nutrition study which was carried out in a controlled, double-blind and cross-over manner. The subjects were randomized to diet sequences AB or BA. Diet A meals contained 1.3 g/100 g ground flaxseed and 5 g/100 g flaxseed oil. Also 3-4 g/100 of inulin and wheat fiber was added. AB diet with non-supplemented foods served as control. Test subjects were on both diets for 4 weeks separated by a 4-week wash-out period. Fifteen test subjects continued an open part of the study for 4 additional months. INTERVENTIONS: The dietary intake, basic blood values, serum lipids, fatty acids and enterolactone were measured at baseline, after both intervention periods and during the open study, at baseline and after 2 and 4 months. Serum thiocyanate and blood cadmium were controlled after both intervention periods. RESULTS: The percentage of flaxseed supplemented test food out of total dietary intake was 20% of energy. The test food contained significantly higher amounts of fiber, polyunsaturated fatty acids (PUFAs) and especially alpha-linolenic acid than the control food. No significant changes were observed in the basic laboratory values or in blood lipids. There was a significant increase in serum alpha-linolenic acid, eicosapentaenoic acid and docosapentaenoic acid. Serum enterolactone concentration was doubled during flaxseed supplementation. Serum thiocyanate and blood cadmium values did not exceed reference values and there was no difference between the diets. CONCLUSIONS: In this study we were able to show that, by adding ground flaxseed and flaxseed oil to one or two daily meals, it is possible to obtain significant effects on serum levels of enterolactone and alpha-linolenic acid. SPONSORSHIP: The study was sponsored by the National Technology Agency of Finland (Tekes).