Disease relevance of Enterolactone

• INTERPRETATION: There is a substantial reduction in breast-cancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens-particularly the isoflavonic phyto-oestrogen equol and the lignan enterolactone [1].
• Risk of cardiovascular disease-related and all-cause death according to serum concentrations of enterolactone: Kuopio Ischaemic Heart Disease Risk Factor Study [2].
• In women, the serum enterolactone concentration was positively and independently associated with consumption of vegetables, subject age, and constipation and was negatively associated with smoking [3].
• Furthermore, female subjects of normal weight had significantly higher serum enterolactone concentrations than did their underweight or obese peers [3].
• No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found [4].

Psychiatry related information on Enterolactone

• Compared with A1A1 carriers with the lowest enterolactone supply, the risk reduction associated with a high enterolactone supply resulted in a comparably decreased breast cancer risk for all genotypes [5].

High impact information on Enterolactone

• Matairesinol is also a plant-derived precursor of the cancer-preventative "mammalian" lignan or "phytoestrogen" enterolactone, formed in the gut following ingestion of high fiber dietary foodstuffs, for example [6].
• Multiple regression analyses showed positive associations in men between the serum enterolactone concentration and constipation, consumption of whole-grain products, and intake of fruit and berries [3].
• BACKGROUND: The mammalian lignans enterolactone and enterodiol are produced in the colon by the action of bacteria on the plant precursor secoisolariciresinol diglycoside, which is found in high concentrations in flaxseed [7].
• Circulating enterolactone and risk of endometrial cancer [8].
• In contrast, enterolactone, dihydrogenistein and formononetin reduced endogenous oxidative DNA damage at 100 microM [9].

Chemical compound and disease context of Enterolactone

• However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61 (0.39-0.98) and 0.57 (0.35-0.92), respectively [10].
• We report the associations of two major phytoestrogens, genistein and enterolactone, with breast cancer risk, using urinary specimens collected 1-9 years before breast cancer was diagnosed [11].
• Unexpectedly, we found that enterolactone and enterodiol, as well as equol, are weak estrogens, and that enterolactone and equol could stimulate the growth of estrogen-dependent breast cancer cell lines [12].

Biological context of Enterolactone

• Enterolactone, a mammalian metabolite of plant lignans, was additionally investigated for modulation of intracellular oxidative stress in NIH 3T3 cells using laser scanning microscopy [9].
• Our present data suggest that low serum enterolactone concentration is associated with enhanced in vivo lipid peroxidation in men [13].
• Mammalian lignans are absorbed by passive diffusion from the large intestine and a substantial fraction of the absorbed mammalian lignans undergoes enterohepatic circulation, resulting in low diurnal variation in plasma levels of enterolactone [14].
• A maximum of 6- to 8-fold induction of QR activity was observed for both enterolactone and genistein, although at high concentrations they showed an adverse effect upon cell growth [15].
• Treatment with enterolactone and enterodiol, alone or in combination, at 0-40 micromol/L resulted in dose- and time-dependent decreases in cell numbers [16].

Anatomical context of Enterolactone

• Rye bread in the diet of pigs enhances the formation of enterolactone and increases its levels in plasma, urine and feces [14].
• 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 [17].
• In two series of experiments we quantified the uptake from the gut of enterolactone in four pigs fitted with catheters in the portal vein and mesenteric artery and with an ultrasonic flow probe attached to the portal vein to monitor the blood flow [14].
• Genistein alone and in combination with the mammalian lignans enterolactone and enterodiol induce estrogenic effects on bone and uterus in a postmenopausal breast cancer mouse model [18].
• 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) [19].

Associations of Enterolactone with other chemical compounds

• Enterodiol and enterolactone excretion varied among subjects in response to flaxseed (3- to 285-fold increase) [20].
• In the in vitro experiment, enterolactone was the major metabolite and 3 intermediates were identified, allowing the elucidation of sesamin metabolism in humans [21].
• After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile [22].
• Phytoestrogen levels (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) in spot urine and serum were analyzed by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry, respectively [23].
• In this first study on phytoestrogen-gene associations in men, we conclude that enterolactone and equol are positively associated with plasma androgen concentrations, and interactions with CYP19 gene may be involved [24].

Gene context of Enterolactone

• 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 [25].
• Plasma enterolactone and breast cancer incidence by estrogen receptor status [26].
• Due to the biphenolic structure of enterolactone, it could act as an antioxidant and through this contribute to cardiovascular health [13].
• We observed a significant modifying effect of CYP17 genotype on plasma enterolactone-associated breast cancer risk (P for interaction < 0.01) [5].
• For instance, the reliability coefficient of the average of three measurements of enterolactone would be 0.79, a level considered acceptable in light of the other sources of error that are present in epidemiological studies (W. Willett, Stat. Med., 8: 1031-1040, 1989) [27].

Analytical, diagnostic and therapeutic context of Enterolactone

• Risk of acute coronary events according to serum concentrations of enterolactone: a prospective population-based case-control study [28].
• DESIGN: Serum enterolactone was measured by using time-resolved fluoroimmunoassay in 2380 Finnish men and women aged 25-64 y who were participating in a cross-sectional national survey in 1997 [3].
• Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53) [8].
• Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum collected at 4 independent cross-sectional population surveys from 206 women with breast cancer diagnosed during follow-up (mean 8.0 years) and from 215 controls frequency-matched to cases by study cohort, 5-year age group and study area [29].
• Single measurements of enterolactone (ENL) used in epidemiologic studies are influenced by intraindividual variation [30].

References