Measurement and metabolism of isoflavonoids and lignans in the human male

Morton, Michael S. Scott; Matos-Ferreira, A.; Abranches-Monteiro, Luis; Correia, Rafael Ribeiro; Blacklock, N. J.; Chan, Ping Shing; Chen, Cheng; Lloyd, S. N.; Chieh-ping, Wu; Griffiths, K.

doi:10.1016/s0304-3835(97)04646-6

Cited by 80 publications

(46 citation statements)

References 16 publications

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“…The only previous study in men to show an increase of the serum enterolactone level as a response to dietary supplementation was carried out in four individuals, the supplement being 15 g of flaxseed (Morton et al, 1997). Flaxseed, which contains up to 34% of fat, makes this oil seed a distinct source of lignans as compared with phloem powder, which consists mainly of insoluble fibre and contains almost no fat.…”

Section: Discussionmentioning

confidence: 99%

Phloem fortification in rye bread elevates serum enterolactone level

et al. 2002

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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 ¼ 0.009 and P ¼ 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.

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Section: Discussionmentioning

confidence: 99%

Phloem fortification in rye bread elevates serum enterolactone level

et al. 2002

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“…Poor bioavailability of genistein is a serious concern because most plasma isoflavones are present as conjugated forms, and in vivo plasma concentrations of aglycones (unconjugated isoflavone) are in the range of 0.01 to 0.4 M (Setchell et al, 2001;Busby et al, 2002), significantly less than the IC 50 or EC 50 values of 5 to 50 M commonly reported for its anticancer effects in vitro (Kurzer and Xu, 1997;Birt et al, 2001;Yang et al, 2001). Prostate concentrations of isoflavones (mostly conjugated) have been determined and they are within the same range of the plasma concentrations (Morton et al, 1997;Hong et al, 2002). Genistein is contained in a large number of dietary phytoestrogen products, and its consumption may accelerate as more women seek alternatives to the traditional hormone replacement therapy.…”

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confidence: 97%

Metabolism of Flavonoids via Enteric Recycling: Role of Intestinal Disposition

Chen

Lin²,

Hu³

2002

J Pharmacol Exp Ther

230

251

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The purpose of this study was to determine the importance of intestinal disposition in the first-pass metabolism of flavonoids. A four-site perfused rat intestinal model, rat liver and intestinal microsomes, Caco-2 cell microsomes, and the Caco-2 cell culture model were used. In the four-site model, Ϸ28% of perfused aglycones are absorbed (Ϸ450 nmol/30 min). Both absorption and subsequent excretion of metabolites were rapid and site-dependent (p Ͻ 0.05). Maximal amounts of intestinal conjugates excreted per 30 min were 61 and 150 nmol for genistein and apigenin, respectively. Maximal amounts of biliary conjugates excreted per 30 min were 50 and 30 nmol for genistein and apigenin, respectively. Microsomes, prepared from Caco-2 cells, rat intestine, and rat liver, always glucuronidated apigenin faster than genistein (p Ͻ 0.05). In addition, rat jejunal microsomes glucuronidated both flavonoids faster (p Ͻ 0.05) than rat intestinal microsomes prepared from other regions. When comparing glucuronidation in different organs, jejunal microsomes often but not always glucuronidated both flavonoids faster than liver microsomes. In the Caco-2 model, both flavonoids were rapidly absorbed and rapidly conjugated, and the conjugates were excreted apically and basolaterally. Similar to the four-site perfusion model, apigenin conjugates were excreted much faster than genistein conjugates (Ͼ2.5 times for glucuronic acid, Ͼ4.5 times for sulfate; p Ͻ 0.05). In conclusion, intestinal disposition may be more important than hepatic disposition in the first-pass metabolism of flavonoids such as apigenin. In conjunction with enterohepatic recycling, enteric recycling may be used to explain why flavonoids have poor systemic bioavailabilities.

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“…These in vivo concentrations are significantly less than the IC 50 or EC 50 values (5-50 M) commonly reported for its anticancer effects in vitro (Kurzer and Xu, 1997;Birt et al, 2001;Yang et al, 2001). Similarly, prostate concentrations of isoflavones (mostly conjugated) are also low and found to be within the lower range of the plasma concentrations (Morton et al, 1997;Hong et al, 2002).…”

mentioning

confidence: 64%

Disposition of Flavonoids via Enteric Recycling: Structural Effects and Lack of Correlations between in Vitro and in Situ Metabolic Properties

Wang¹,

Chen²,

Jia³

et al. 2006

Drug Metab Dispos

111

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ABSTRACT:The purpose of this study is to determine the importance of coupling of efflux transporters and metabolic enzymes in the intestinal disposition of six isoflavones (genistein, daidzein, formononetin, glycitein, biochanin A, and prunetin), and to determine how isoflavone structural differences affect the intestinal disposition. A rat intestinal perfusion model was used, together with rat intestinal and liver microsomes. In the intestinal perfusion model, significant absorption and excretion differences were found between isoflavones and their respective glucuronides (p <0.05), with prunetin being the most rapidly absorbed and formononetin glucuronides being the most excreted in the small intestine. In contrast, glucuronides were excreted very little in the colon. In an attempt to account for the differences, we measured the glucuronidation rates of six isoflavones in microsomes prepared from rat intestine and liver. Using multiple regression analysis, intrinsic clearance (CL int ) and other enzyme kinetic parameters (V max and K m ) were determined using appropriate kinetic models based on Akaike's information criterion. The kinetic parameters were dependent on the isoflavone used and the types of microsomes. To determine how metabolite excretion rates are controlled, we plotted excretion rates versus calculated microsomal rates (at 10 M), CL int values, K m values, or V max values, and the results indicated that excretion rates were not controlled by any of the kinetic parameters. In conclusion, coupling of intestinal metabolic enzymes and efflux transporters affects the intestinal disposition of isoflavones, and structural differences of isoflavones, such as having methoxyl groups, significantly influenced their intestinal disposition.

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Measurement and metabolism of isoflavonoids and lignans in the human male

Cited by 80 publications

References 16 publications

Phloem fortification in rye bread elevates serum enterolactone level

Phloem fortification in rye bread elevates serum enterolactone level

Metabolism of Flavonoids via Enteric Recycling: Role of Intestinal Disposition

Disposition of Flavonoids via Enteric Recycling: Structural Effects and Lack of Correlations between in Vitro and in Situ Metabolic Properties

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