Article

Role of dietary lignans in the reduction of breast cancer risk

Functional Foods Forum, University of Turku, Turku, Finland.
Molecular Nutrition & Food Research (Impact Factor: 4.6). 07/2007; 51(7):857-66. DOI: 10.1002/mnfr.200600240
Source: PubMed

ABSTRACT

Lignans are a large group of fiber-associated phenolic compounds widely distributed in edible plants. Some of the ingested plant lignans are converted by intestinal microbiota to enterolignans, enterodiol (END) and enterolactone (ENL), the latter of which has been thought to be the major biologically active lignan, and suggested to be associated with low risk of breast cancer. In line with this, administration of plant lignans which are further metabolized to ENL, or ENL as such, have been shown to inhibit or delay the growth of experimental mammary cancer. The mechanism of anticarcinogenic action of ENL is not yet fully understood, but there is intriguing evidence for ENL as a modulator of estrogen signaling. These findings have generated interest in the use of lignans as components of breast cancer risk reducing functional foods. Identification of target groups, who would benefit most, is of pivotal importance. Therefore, further identification and validation of relevant biomarkers, which can be used as indicators of lignan or ENL action and breast cancer risk reduction at different stages of the disease, are of importance.

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    • "The various anticarcinogenic mechanisms of phenolic compounds have been reviewed by Yang et al. (2001). Furthermore, olive oil is rich in lignans (Owen et al., 2000; Bendini, 2007) and it is assumed that foods containing high amounts of lignans appeared to protect against breast cancer via their anti-estrogenic effects (Saarinen et al., 2007). In addition, in cell experiments, oleuropein and hydroxytyrosol have been shown to induce cell death of MCF- 7 human breast cancer cells (Han et al., 2009). "
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    ABSTRACT: Olive oil is a key component of the Mediterranean diet which is recognized to contribute to its health benefits. Recent prospective studies point towards a protective effect from an olive oil-rich diet in relation to the incidence of cardiovascular diseases and an improvement of cardiometabolic markers such as blood pressure, glycaemia and dyslipidemia, notably by reducing LDL cholesterol and LDL oxidation. The role of minor phenolic fraction was evidenced in intervention trials where lipid profiles showed greater improvement in participants receiving olive oil with higher phenolic content. The phenolic fraction of olive oil is composed of simple phenols (hydroxytyrosol), phenolic secoiridoids (oleuropein aglycone), lignans (pinoresinol), flavonoids and hydroxyisochromans. All these compounds have diverse biological activities that are described in the present review, supporting the protective effects of olive oil against degenerative diseases found in large cohorts monitored in Southern European countries.
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    • "Pinosylvin and its derivatives have considerable antimicrobial activities and cytotoxicity against a murine hepatic carcinoma cell line (Välimaa et al. 2007). Lignans, another important group of phenolic compounds, have been reported to possess antioxidant, antitumor, and healthpromoting properties and even have potential for cancer prevention (Nishibe 1997; Ford et al. 1999; Kitts et al. 1999; Ward 1999; Saarinen et al. 2007). Wood, especially knotwood (KW) of Scots pine, is an abundant source of stilbenes and lignans, mainly nortrachelogenin (NTG) (Willför et al. 2003b; Pietarinen et al. 2006). "
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    ABSTRACT: The extraction conditions have been evaluated concerning the recovery of specific polyphenols from Scots pine (Pinus sylvestris) knots by means of an accelerated solvent extractor. The composition of the extracts was determined by gas chromatography, gas chromatography-mass spectrometry, and high-performance size-exclusion chromatography. The main phenolic compounds are the stilbenes pinosylvin and its monomethyl ether and the lignan nortrachelogenin (NTG), and their amounts vary a lot from sample to sample. The sequential extraction with a nonpolar solvent as a first step for removing the lipophilic compounds was the most efficient approach for the recovery of both pinosylvins and NTG. For food applications, hot water and 85% aqueous ethanol were good solvents for the production of the substances in focus. An industrial knotwood sample from a pulp mill was sequentially extracted with cyclohexane and ethanol/water (95:5) in a large-scale Soxhlet equipment. The results show that the industrial production of pinosylvins and NTG from knots is feasible.
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    • "HMRlignan (Linnea SA, Switzerland), an extract derived from this plant, is a pure lignan in the aglycone form. In humans, dietary lignans are converted by enteric bacteria to enterolactone (ENL) and enterodiol and have been shown in vitro as well as in rat studies to preferentially bind alpha-estrogen receptors and demonstrate weak estrogenic activity [1,4]. The effects of these plant-derived compounds are primarily mediated through 2 estrogen receptors, ER-α and ER-β, which affect transcription of genes involved in cell growth, proliferation, and differentiation [5]. "
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    ABSTRACT: Objective 7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors. Methods A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 post-menopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity. Results Pharmacokinetic studies demonstrated 7-HMR Cmax = 757.08 ng/ml at 1 hour and ENL Cmax = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study. Conclusion The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population.
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