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PubMed2006

Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen Elderly Study.

BACKGROUND: Plant lignans are converted to enterolignans that have antioxidant and weak estrogen-like activities, and therefore they may lower cardiovascular disease and cancer risks. OBJECTIVE: We investigated whether the intakes of 4 plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol) were inversely associated with coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality. DESIGN: The Zutphen Elderly Study is a prospective cohort study in which 570 men aged 64-84 y were followed for 15 y. We recently developed a database and used it to estimate the dietary intakes of 4 plant lignans. Lignan intake was related to mortality with the use of Cox proportional hazards analysis. RESULTS: The median total lignan intake in 1985 was 977 microg/d. Tea, vegetables, bread, coffee, fruit, and wine were the major sources of lignan. The total lignan intake was not related to mortality. However, the intake of matairesinol was inversely associated with CHD, CVD, and all-cause mortality (P </= 0.05 for all) and cancer (P = 0.06). Multivariate-adjusted rate ratios (95% CI) per 1-SD increase in intake were 0.72 (0.53, 0.98) for CHD, 0.83 (0.69, 1.00) for CVD, 0.86 (0.76, 0.97) for all-cause mortality, and 0.81 (0.65, 1.00) for cancer. CONCLUSIONS: Total lignan intake was not associated with mortality. The intake of matairesinol was inversely associated with mortality due to CHD, CVD, cancer, and all causes. We cannot exclude the possibility that the inverse association between matairesinol intake and mortality is due to an associated factor, such as wine consumption.

Aged↗

PubMed2005

Whole sesame seed is as rich a source of mammalian lignan precursors as whole flaxseed.

The mammalian lignans enterolactone and enterodiol, which are produced by the microflora in the colon of humans and animals from precursors in foods, have been suggested to have potential anticancer effects. This study determined the production of mammalian lignans from precursors in food bars containing 25 g unground whole flaxseed (FB), sesame seed (SB), or their combination (FSB; 12.5 g each). In a randomized crossover study, healthy postmenopausal women supplemented their diets with the bars for 4 wk each separated by 4-wk washout periods, and urinary mammalian lignan excretion was measured at baseline and after 4 wk as a marker of mammalian lignan production. Results showed an increase with all treatments (65.1-81.0 mumol/day; P < 0.0001), which did not differ among treatments. Lignan excretion with the whole flaxseed was similar to results of other studies using ground flaxseed. An unidentified lignan metabolite was detected after consumption of SB and FSB but not of FB. Thus, we demonstrated for the first time that 1) precursors from unground whole flaxseed and sesame seed are converted by the bacterial flora in the colon to mammalian lignans and 2) sesame seed, alone and in combination with flaxseed, produces mammalian lignans equivalent to those obtained from flaxseed alone.

4-Butyrolactone↗

PubMed1999

Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake.

Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure to these compounds in human populations and to determine which components of a mixed diet contribute to the exposure. Typically, urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However, other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein, O-desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected for 3 days from 49 male and 49 female volunteers (age, 18-37 years) reporting a wide range of habitual V&F intakes. Dietary intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein (r = 0.40; P = 0.0001), O-desmethylangolensin (r = 0.37; P = 0.0002), daidzein (r = 034; P = 0.0007), and the sum of isoflavonoids (r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary contributors to isoflavone intake; however, additional "hidden sources" of soy may also contribute to exposure. In contrast, a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone, and matairesinol, was associated with intake of total F (r = 0.27; P = 0.008), total V&F (r = 0.25; P = 0.01), soyfoods (r = 0.28; P = 0.006), and dietary fiber (r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in "high" compared with "low" V&F consumers. Compared with the "low" V&F group, the "high" group consumed diets that were, on average, higher in fiber and carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary patterns.

Adolescent↗

PubMed2004

Dietary lignan intakes and risk of pre- and postmenopausal breast cancer.

Lignans are plant compounds metabolized in the mammalian gut to produce the phytoestrogens enterolactone and enterodiol. Because estrogens have been linked to breast cancer etiology, lignans could affect breast cancer risk through modulation of endogenous estrogen metabolism or competitive inhibition with estrogen receptors. We examined breast cancer risk and dietary lignan intake in a population-based case-control study of 1,122 women with primary, incident, histologically confirmed breast cancer and 2,036 controls frequency matched to cases on age and county of residence as part of the Western New York Exposures and Breast Cancer (WEB) Study. Diet was assessed with a self-administered 104-item food frequency questionnaire and other relevant data were collected by detailed in-person interviews. Lignans were expressed as the sum of the dietary precursors secoisolariciresinol and matairesinol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, adjusting for age, total energy and other breast cancer risk factors. Premenopausal women in the highest quartile of dietary lignan intake had reduced breast cancer risk (OR = 0.66; 95% CI = 0.44-0.98). No association was observed between lignan intakes and postmenopausal breast cancer. Our results suggest that dietary lignans may be important in the etiology of breast cancer, particularly among premenopausal women.

Adult↗

PubMed1998

The metabolism and n-6/n-3 ratio of essential fatty acids in rats: effect of dietary arachidonic acid and a mixture of sesame lignans (sesamin and episesamin).

In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum TG level as compared to the AO group. In addition, the AOS diet significantly increased the acetoacetate level, but reduced the beta-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification.

Animals↗

PubMed1994

Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells.

Anti leukemic-cell efficacy of 28 naturally occurring and synthetic flavonoids and 11 naturally occurring lignans on human promyelocytic leukemic cell line HL-60 were examined using MTT assay methods. Differences between anti cell-proliferative activity and cytotoxicity of these compounds were compared with those of 4 clinical anti-cancer agents. Eight of the 28 flavonoids and 4 of the 11 lignans showed considerable suppressive effects on HL-60 cell growth with IC50s ranging from 10-940 ng/ml. Among these compounds, genistein, honokiol, machilin A, matairesinol, and arctigenin had the strongest effects with IC50s less than 100 ng/ml, which were almost equivalent to the effects of current anti-cancer agents. The flavonoid genistein and the lignans, however, showed little or no cytotoxicity against HL-60 cells as assessed by dye exclusion tests (LC50s > 2,900 ng/ml), whereas the regular anti-cancer agents had potent cytotoxicity. All of the flavonoids and lignans, except for machilin A and arctigenin, were less effective against growth of human T lymphocytic leukemia cell line MOLT-4. In addition, the flavonoid and the lignans showed little or no inhibiting activity on mitogen-induced blastogenesis of human peripheral-blood lymphocytes. The lignans and genistein were strongly suppressive against incorporations of [3H]thymidine, [3H]uridine, and [3H]leucine into HL-60 cells. These results showed that some of the naturally occurring flavonoids and lignans inhibited HL-60 cell growth with a non-toxic mechanism, possibly via cessation of DNA, RNA, and/or protein synthesis of the leukemic cells.

Antineoplastic Agents↗

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↗

PubMed2002

Effect of lignans isolated from Hernandia nymphaeifolia on estrogenic compounds-induced calcium mobilization in human neutrophils.

The effect of five lignans isolated from Hernandia nymphaeifolia on estrogenic compounds (17beta-estradiol, tamoxifen and clomiphene)-induced Ca(2+) mobilization in human neutrophils was investigated. The five lignans were epi-yangambin, epi-magnolin, epi-aschantin, deoxypodophyllotoxin and yatein. In Ca(2+)-containing medium, the lignans (50-100 microM) inhibited 10 microM 17beta-estradiol- and 5 microM tamoxifen-induced increases in intracellular free Ca(2+) levels ([Ca(2+)](i)) without changing 25 microM clomiphene-induced [Ca(2+)](i) increase. 17beta-estradiol and tamoxifen increased [Ca(2+)](i) by causing Ca(2+) influx and Ca(2+) release because their responses were partly reduced by removing extracellular Ca(2+). In contrast, clomiphene solely induced Ca(2+) release. The effect of the lignans on these two Ca(2+) movement pathways underlying 17beta-estradiol- and tamoxifen-induced [Ca(2+)](i) increases was explored. All the lignans (50-100 microM) inhibited 10 microM 17beta-estradiol-and 5 microM tamoxifen-induced Ca(2+) release, and 17beta-estradiol-induced Ca(2+) influx. However, only 100 microM epi-aschantin was able to reduce tamoxifen-induced Ca(2+) influx while the other lignans had no effect. Collectively, this study shows that the lignans altered estrogenic compounds-induced Ca(2+) signaling in human neutrophils in a multiple manner.

Calcium↗

PubMed2003

Effect of flaxseed and wheat bran on serum hormones and lignan excretion in premenopausal women.

OBJECTIVE: To examine the effects of flaxseed consumption (a lignan-rich plant food) alone and in combination with wheat bran on serum hormones and urinary lignan excretion in premenopausal women. METHODS: Sixteen subjects were studied for four feeding treatments lasting two menstrual cycles each in a randomized, crossover design. During each treatment, subjects consumed their habitual diets supplemented with baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Serum samples collected during the mid-luteal phase of the second menstrual cycle of each diet treatment were analyzed for serum hormones and sex hormone binding globulin. Urine samples collected during the same time period were analyzed for urinary lignan excretion. RESULTS: There were no changes in serum hormone concentrations or sex hormone binding globulin on any of the treatments. Urinary lignan excretion significantly increased on diet treatments that included flaxseed, but inclusion of wheat bran did not significantly alter lignan excretion. CONCLUSIONS: Urinary lignan excretion increased with flaxseed consumption, but serum hormones did not change in this group of premenopausal women. Consumption of wheat bran with flaxseed did not alter urinary lignan excretion associated with flaxseed consumption.

Adult↗

PubMed2001

Exposure to flaxseed and its purified lignan reduces bone strength in young but not older male rats.

Flaxseed is the richest source of the plant lignan secoisolariciresinol diglycoside (SDG), which is converted to the two major mammalian lignans, enterodiol (ED) and enterolactone (EL), by colonic bacteria. Because both ED and EL can produce biological effects similar to estrogen, exposure to lignans during early stages of development may adversely alter the normal development of bone in males since bone is a hormone-sensitive tissue. To determine whether early exposure to flaxseed or its lignan compromised the acquisition of bone mass or reduced bone strength, male offspring were exposed to one of three diets during lactation only (birth through postnatal day [PND] 21) via mother's milk or continuously from the start of lactation through to adolescence (PND 50) or young adulthood (PND 132). The diets were a basal diet (BD) that was devoid of phytoestrogens, BD containing 10% flaxseed, or BD containing the equivalent quantity of SDG present in a 10% flaxseed diet. To assess bone quantity, the bone mineral content (BMC) and bone mineral density (BMD) of femurs were assessed by dual-energy x-ray absorptiometry. Since the biomechanical properties of bone are indicators of the microarchitecture and thus bone quality, the biomechanical strength of femurs was assessed by three-point bending. At PND 50, ultimate bending stress and Young's modulus, measures of bone strength, were reduced among rats that received the 10% flaxseed diet from PND 0 through PND 50, while there were no marked differences in bone size, BMC, or BMD among groups. Interestingly, this effect does not appear to be due to the lignan in flaxseed, as continuous exposure to the diet containing the equivalent quantity of lignan (10 S diet) did not alter any measures of bone strength. In contrast to PND 50, bone strength did not differ among groups at PND 132, indicating that the compromise in bone strength was not sustained into early adulthood. Bone size, BMC, and BMD continued to be similar among treatment groups at PND 132. In conclusion, exposing male rats to a diet containing 10% flaxseed or an equivalent quantity of lignan either during lactation only or through to early adulthood is safe with respect to bone health, as measures of bone mass and strength were similar to control rats.

Age Factors↗

PubMed2006

Lignan and isoflavone excretion in relation to uterine fibroids: a case-control study of young to middle-aged women in the United States.

BACKGROUND: Uterine fibroids are hormonally responsive; estradiol and progesterone stimulate their growth, and gonadotrophin-releasing hormone agonists shrink them. Phytoestrogens, including isoflavones and lignans, can act as weak estrogens or antiestrogens. OBJECTIVE: The objective of this case-control study was to evaluate the relation between uterine fibroid risk and phytoestrogen exposure. DESIGN: Two overnight urine collections (48 h apart) from 170 uterine fibroid cases and 173 controls were analyzed for isoflavonoids (ie, daidzein, genistein, equol, and O-desmethylangolensin) and lignans (enterodiol and enterolactone). Logistic regression was used to determine associations between the mean excretion of the 2 collections and the risk of uterine fibroids. RESULTS: Unadjusted isoflavone excretion did not differ significantly between cases and controls (2.33 +/- 5.82 and 2.60 +/- 5.90 nmol/mg Cr, respectively; P = 0.68), but cases excreted significantly less lignans than did controls (2.86 +/- 3.45 and 4.57 +/- 6.67 nmol/mg Cr, respectively; P < 0.01). The trend for a reduced risk of uterine fibroids with increasing quartiles of lignan excretion was significant (odds ratio for highest versus lowest quartile = 0.31; 95% CI: 0.17, 0.58; P for trend < 0.01). When adjusted for age, BMI, race, family history of uterine fibroids, and isoflavone excretion, this trend remained but was attenuated (P = 0.07). CONCLUSIONS: Our findings suggest a modest inverse association between lignan excretion and uterine fibroid risk. Whether this relation represents an effect of lignans per se or of other constituents of lignan-containing foods on the development of uterine fibroids remains to be determined. No association was found between isoflavone excretion and uterine fibroids; however, the intake of soy foods, the primary source of isoflavones, was low in this population.

Adult↗

PubMed2002

The risk of breast cancer associated with dietary lignans differs by CYP17 genotype in women.

Lignans are plant compounds metabolized in the gut to produce the phytoestrogens enterolactone and enterodiol. Reduced breast cancer risks associated with higher urinary lignan excretion may be related to competitive inhibition of endogenous estrogens. Evidence exists that associations with reproductive risk factors for breast cancer differ according to cytochrome P450c17alpha (CYP17) genotype. Genetic variability in estrogen metabolism could affect lignan metabolism thereby modifying risk associations. We examined breast cancer risk, dietary lignans and CYP17 genotype among 207 women with primary, incident, histologically confirmed breast cancer and 188 controls frequency matched to cases by age and county of residence. Self-reported frequency of intake of 170 foods and beverages during the 2 y before the interview and other relevant data were collected by detailed in-person interviews. Dietary lignan intake was expressed as the sum of enterolactone and enterodiol production from foods. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education and other breast cancer risk factors. Women in the highest tertile of dietary lignans tended to have reduced breast cancer risk (OR 0.45, 95% CI 0.20-1.01 and OR 0.59, 95% CI 0.28-1.27, pre- and postmenopausal women, respectively). Substantially reduced risks in the highest tertile of lignans were observed for premenopausal women with at least one A2 allele (OR 0.12, 95% CI 0.03-0.50). Our results suggest that CYP17 genotype may be important in modifying the effect on breast cancer risk of exogenous estrogens, particularly for premenopausal women.

4-Butyrolactone↗

PubMed2003

Isoflavonoid and lignan phytoestrogens as dietary biomarkers.

Isoflavones and lignans are biologically active plant-food constituents that have potential chemopreventive properties. Quantitation of isoflavones and lignans in humans is necessary to establish the benefits and risks of exposure to these compounds in populations and to determine which components of a mixed diet contribute to the exposure. Isoflavones and lignans are metabolized by colonic bacteria to more biologically active metabolites; thus both the parent compounds and the metabolites are measured routinely. Isoflavonoids (genistein, daidzein, dihydrodaidzein, O-desmethylangolensin and equol) and lignans (enterolactone, enterodiol, matairesinol and secoisolariciresinol) can be quantified in various body fluids. Typically, high concentrations of isoflavonoids in urine and serum are associated with soy consumption, and high concentrations of lignans are associated primarily with intake of whole grains and other fiber-containing plant foods. Controlled feeding studies and nutritional epidemiologic studies demonstrate a linear dose response between dietary intake and urinary excretion of isoflavones. Lignan excretion is associated positively with dietary fiber intake as well as with diets that are on average higher in fiber and carbohydrate and lower in fat; thus lignans have also been proposed as a marker of healthier dietary patterns. The complex interactions between the colonic environment and the external and internal factors that modulate it contribute to significant variation in serum and urinary phytoestrogen levels among individuals. Understanding these sources of variation is important to be able to use these measures effectively as dietary biomarkers.

Biomarkers↗

PubMed2004

Dietary lignins are precursors of mammalian lignans in rats.

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

4-Butyrolactone↗

PubMed2006

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.

4-Butyrolactone↗

PubMed2006

Daily consumption for six weeks of a lignan complex isolated from flaxseed does not affect endothelial function in healthy postmenopausal women.

The occurrence of menopause is associated with an increased risk of cardiovascular events, and this has partly been attributed to the decline in circulating levels of estrogen. 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 and enterolactone and is hypothesized to be cardioprotective due to their structural similarity to estrogen. The aim of this study was to investigate the effect of a lignan complex, providing 500 mg/d of SDG, on markers of endothelial function. 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. Flow-mediated, endothelium-dependent vasodilatation (FMD) and nitroglycerine-mediated, endothelium-independent vasodilatation were measured at the end of each intervention period. The sum of Plasma nitrite and nitrate (NOx), endothelin-1 (ET-1), and asymmetric dimethylarginine (ADMA) were measured at the beginning and end of each intervention period. FMD was 3.6 +/- 0.9% (mean +/- SEM) after the lignan complex intervention period compared with 3.9 +/- 0.7% after the placebo period (P = 0.72). Plasma concentrations of NOx, ET-1, and ADMA were not affected. We conclude that daily consumption for 6 wk of a low-fat muffin enriched with a lignan complex had no effect on endothelial function in healthy postmenopausal women.

4-Butyrolactone↗

PubMed2000

A novel treatment for lupus nephritis: lignan precursor derived from flax.

BACKGROUND: Flaxseed has renoprotective effects in animal and human lupus nephritis. We have recently extracted the lignan precursor (secoisolariresinol diglucoside) (SDG) to determine if this more palatable derivative of flaxseed would exert renoprotection similar to the whole flaxseed in the aggressive MRL/lpr lupus mouse model. METHODS: 131 MRL/lpr mice were randomly assigned to saline gavage, 600, 1,200 and 4,800 microg lignan gavage groups. At 7 weeks, 6 animals underwent platelet aggregating factor (PAF) lethal challenge and 40 were studied with urine collection to determine the levels of secoisolariresinol, enterodiol and enterolactone in the gavaged animals. A baseline study of 10 saline gavaged animals took place at 6 weeks. 25 animals in the saline gavage, 600 and 1200 microg lignan groups were studied at 14 and 22 weeks for GFR, spleen lymphocyte S-phase and organ weight studies. RESULTS: Metabolic studies indicated that secoisolariresinol is the major metabolite absorbed and the lowest lignan dose provides a lengthening in survival for the PAF lethal challenge. Body weight, fluid and water intake studies demonstrated that the lignan was well tolerated. Changes in proteinuria, GFR and renal size showed a time- and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in the S-phase demonstrated modest dose-dependent reductions in the lignan gavaged groups. CONCLUSION: SDG was converted in the gut to secoisolariresinol, which was absorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidenced, in a dose-dependent fashion, by a significant delay in the onset of proteinuria with preservation in GFR and renal size. This study suggests that SDG may have a therapeutic role in lupus nephritis.

4-Butyrolactone↗

PubMed2005

Dietary lignans: potential role in cancer prevention.

Recent in vitro, animal, and epidemiological studies suggest that dietary lignans may be chemopreventive, potentially through anti-estrogenic, anti-angiogenic, pro- apoptotic, and anti-oxidant mechanisms. In this article, we review lignan food sources and metabolism, proposed anti-carcinogenic mechanisms, and the evidence for a role of lignans in breast, colon, and prostate cancer prevention from animal and epidemiologic literature. Although a number of in vitro and animal studies support a role for lignan-rich foods and purified lignans in the modulation of cancer events of the breast, prostate, and colon, epidemiological studies, sparse and often retrospective in nature, offer inconsistent findings. The most support for a role of lignans in cancer is observed for premenopausal breast cancer. Additional epidemiological studies that use a prospective design and well-developed food databases and questionnaires are needed to adequately evaluate the role of lignans in cancer prevention.

Animals↗