Lignans and human health

This review focuses on the possible role in human health of the consumption of lignan-rich foods. Most of the plant lignans in human foods are converted by the intestinal microflora in the upper part of the large bowel to enterolactone and enterodiol, called mammalian or enterolignans. The protective role of these compounds, particularly in chronic Western diseases, is discussed. Evidence suggests that fiber- and lignan-rich whole-grain cereals, beans, berries, nuts, and various seeds are the main protective foods. Many factors, in addition to diet, such as intestinal microflora, smoking, antibiotics, and obesity affect circulating lignan levels in the body. Lignan-rich diets may be beneficial, particularly if consumed for life. Experimental evidence in animals has shown clear anticarcinogenic effects of flaxseed or pure lignans in many types of cancer. Many epidemiological results are controversial, partly because the determinants of plasma enterolactone are very different in different countries. The source of the lignans seems to play a role because other factors in the food obviously participate in the protective effects. The results are promising, but much work is still needed in this area of medicine.     

Identification of lignans and phytoestrogens in urine of chimpanzees

It was recently observed that the urinary excretion of animal lignans is low in postmenopausal breast cancer patients compared to normal omnivorous and vegetarian women. In addition, the mean excretion of the isoflavonic phytoestrogen equol tended to be lower. Because nonhuman primates appear to be remarkably resistant to the carcinogenic effect of estrogens, we investigated the possible occurrence of lignans and phytoestrogens in the urine of chimpanzees on their regular diet. Five major diphenols were isolated and identified by capillary gas chromatography and mass spectrometry by comparison with synthesized authentic reference compounds. Three of these compounds, the phytoestrogen equol and its precursor daidzein, the lignan enterolactone, were according to preliminary assays excreted in very large amounts. In addition, the lignan enterodiol and the daidzein metabolite O-desmethylangolensin were identified. It is concluded that the chimpanzee excretes both isoflavonic phytoestrogens and lignans in urine, apparently in high concentrations. It is suggested that these compounds may play a role in the maintenance of the resistance against carcinogenic effects of estrogens, which nonhuman primates possess, because both equol and enterolactone have been shown to have antiestrogenic properties in animals. However, much further work is necessary before the possible biological role of these compounds may be established.     

Gut Microbiota Metabolites of Dietary Lignans and Risk of Type 2 Diabetes: A Prospective Investigation in Two Cohorts of U.S. Women

OBJECTIVETo examine urinary levels of enterolactone and enterodiol, intestinal microbial metabolites of dietary lignans, in relation to type 2 diabetes (T2D) risk.RESULTSIn both cohorts, T2D subjects had significantly lower concentrations of both enterolactone and enterodiol than control subjects. After multivariate adjustment for lifestyle and dietary risk factors of T2D, urinary concentrations of enterolactone were significantly associated with a lower risk of T2D (pooled odds ratio [OR] comparing the extreme quartiles 0.62 [95% CI 0.44, 0.88], P for trend = 0.003). Higher urinary concentrations of enterodiol were also marginally significantly associated with a lower T2D risk (pooled OR comparing extreme quartiles 0.67 [95% CI 0.48, 0.96], P for trend = 0.08). When concentrations of both metabolites were combined to reflect total lignan intake, the OR was 0.70 (95% CI 0.53, 0.92) for each SD increment of total lignan metabolites.CONCLUSIONSThese results indicate that lignan metabolites, especially enterolactone, are associated with a lower risk of T2D in U.S. women. Further studies are needed to replicate these findings and to explore potential mechanisms underlying the observed association.     

Potentially hallucinogenic 5-hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues

Bufotenine and N,N-dimethyltryptamine (DMT) are hallucinogenic dimethylated indolethylamines (DMIAs) formed from serotonin and tryptamine by the enzyme indolethylamine N-methyltransferase (INMT) ubiquitously present in non-neural tissues. In mammals, endogenous bufotenine and DMT have been identified only in human urine. The DMIAs bind effectively to 5HT receptors and their administration causes a variety of autonomic effects, which may reflect their actual physiological function. Endogenous levels of bufotenine and DMT in blood and a number of animal and human tissues were determined using highly sensitive and specific quantitative mass spectrometric techniques. A new finding was the detection of large amounts of bufotenine in stools, which may be an indication of its role in intestinal function. It is suggested that fecal and urinary bufotenine originate from epithelial cells of the intestine and the kidney, respectively, although the possibility of their synthesis by intestinal bacteria cannot be excluded. Only small amounts of the DMIAs were found in somatic or neural tissues and none in blood. This can be explained by rapid catabolism of the DMIAs by mitochondrial monoamino-oxidase or by the fact that the dimethylated products of serotonin and tryptamine are not formed in significant amounts in most mammalian tissues despite the widespread presence of INMT in tissues.     

Capillary gas chromatographic method for the analysis of lignans in human urine

We describe a capillary column gas chromatographic (GC) method for the analysis of lignans in urine. Lignans are excreted as mono-glucuronides which are first extracted on a small reversed-phase cartridge of octadecylsilane bonded silica (Sep-Pak C18) and thereafter isolated by anion exchange chromatography on DEAE-Sephadex A-25, prepared in the acetate form. Lignan mono-glucuronides are enzymatically hydrolysed and re-extracted on a Sep-Pak C18 cartridge. Quantification is carried out by capillary column GC of the trimethylsilyl ether derivatives. The specificity of the method was checked by GC/MS and the intra-assay coefficient of variation (CV) for the two lignans, enterolactone (trans-2,3-bis(3-hydroxybenzyl)butyrolactone) and enterodiol (2.3-bis(3-hydroxybenzyl)butane-1,4-diol) varied between 5 and 8%. Some values for the excretion of these lignans by normal men and women are presented.     

Isotope dilution gas chromatographic-mass spectrometric method for the determination of lignans and isoflavonoids in human urine, including identification of genistein.

We describe an isotope dilution gas chromatographic-mass spectrometric method for the quantitative determination of the lignans enterolactone, enterodiol and matairesinol and the isoflavonoids daidzein, equol, O-desmethylangolensin and genistein in urine. Furthermore we present the gas chromatographic/mass spectrometer identification of genistein. Urine samples were extracted on Sep-Pak cartridges, conjugated fractions were isolated by chromatography on the acetate form of DEAE-Sephadex and deuterated internal standards of all seven compounds were added to the samples before hydrolysis. The hydrolysate was extracted on a Sep-Pak cartridge and following chromatography on the acetate form of QAE-Sephadex two fractions were obtained: Fraction 1 contained equol, enterolactone, enterodiol, matairesinol and all estrogens and fraction 2 contained O-desmethylangolensin, daidzein and genistein. The latter was ready for gas chromatography/mass spectrometry, but the first one was further purified to eliminate the estrogens by chromatography on the carbonate form of QAE-Sephadex. Following silylation, the samples were analyzed by combined capillary column gas chromatography/mass spectrometry in the selective ion monitoring mode. The within-assay imprecision varied from 0.8-15.2% (mean 8.7%) and the between-assay imprecision from 4.1-13.9% (mean 9.3%), depending on compound and concentration level. The mean recovery of authentic standards added to urine extracts before hydrolysis varied from 96.6 to 105.5%. Values obtained from 10 Finnish omnivorous men are presented. Individual values for matairesinol (excretion range 3.3-59.9 nmol/24 h) and genistein (range 21.8-1180 nmol/24 h) in human urine have never been published before.     

Identification of lignans as major components in the phenolic fraction of olive oil

BACKGROUND: Because olive oil is an important component of the Mediterranean diet, it is necessary to establish unequivocal identification of the major potential antioxidant phenolic compounds it contains. METHODS: The major phenolic antioxidants in extra virgin olive oil were isolated and purified. Structural analysis was conducted using several spectroscopic techniques, including mass spectrometry and nuclear magnetic resonance (NMR). In particular, detailed (1)H and (13)C NMR data are presented, and several assignment errors in the literature are corrected. RESULTS: The data show for the first time that the lignans (+)-1-acetoxypinoresinol and (+)-pinoresinol are major components of the phenolic fraction of olive oils. These lignans, which are potent antioxidants, are absent in seed oils and virtually absent in refined virgin oils but are present at concentrations of up to 100 mg/kg (mean +/- SE, 41.53+/-3.93 mg/kg; range, 0.65-99.97 mg/kg) in extra virgin oils. As with the simple phenols and secoiridoids, there is considerable interoil variation in lignan concentrations. Foods containing high amounts of lignan precursors have been found to be protective against breast, colon, and prostate cancer. CONCLUSION: Lignans, as natural components of the diet, may be important modulators of cancer chemopreventive activity.     

Les lignanes phytoestrogènes du lin sont-ils des bienfaiteurs méconnus?

Linseed contains an high lignan content, peculiarly secoisolariciresinol diglucoside (SDG). Antioxydant properties as well as it’s ability to bind estrogen receptors could explain its biological activities and preventive action against cancers and cardiovascular disease. Epidemiological studies have yielded contradictory results on the benefits of SDG. Nevertheless it is worth to note that, although classified as phyoestrogen, no detrimental effect of SDG (such as tumorous cell growth stimulation) has been observed. Our knowledge is increasing in the field of lignan intake and metabolism and further interaction with our metabolism, particularly the sexual hormones one. The recent availability of purified products now allows in vitro studies to better understand the biological activities of lignans.     

The occurrence of lactyl lactate and succinyl lactate in the urine of patients screened for inherited metabolic disease

The gas chromatographic and mass spectrometric identification of lactyl lactate and succinyl lactate, both present in human urine, is described. In the gas chromatogram lactyl lactate (as TMS derivative) presented as two peaks: the L,L- and/or D,D-form as well as the D,L- and/or the L,D-enantiomer. Both L- and D-lactyl succinate were excreted simultaneously. Lactyl lactate was observed in many patients; succinyl lactate only a few times and only together with lactyl lactate. No correlation with (endogenous) urinary lactate could be established. Presumably these compounds are products of the intestinal bacteria.     

Structural features,interaction with the gut microbiota and anti-tumor activity of oligosaccharides

Some oligosaccharides are regarded as biological constituents with benefits to human health in an indirect way. They enter the intestinal tract to be fermented by the gut microbiota, causing changes in the abundance and composition of the gut microbiota and producing fermentation products such as short-chain fatty acids (SCFAs). In this review, the structural features and biological activities of eight common natural oligosaccharides were summarized, including human milk oligosaccharides (HMOS), xylo-oligosaccharides (XOS), arabinoxylo-oligosaccharides (AXOS), isomaltooligosaccharides (IMOS), chitin oligosaccharides (NACOS), mannan-oligosaccharides (MOS), galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS). Furthermore, XOS were selected to explain the anti-tumor mechanism mediated by gut microbiota. The review aims to reveal primary structural features of natural functional oligosaccharides related to the biological activities and also provide an explanation of the anti-tumor activity of functional oligosaccharides mediated by the gut microbiota.

Some oligosaccharides are regarded as biological constituents with benefits to human health in an indirect way.