The term phyto-oestrogen encompasses isoflavone compounds, such as genistein and daidzein, found predominantly in soya products and the lignans, such as matairesinol and secoisolariciresinol, found in many fruits, cereals and in flaxseed. There is evidence that they have potential health benefits in man particularly against hormone-dependent diseases such as breast and prostate cancers and osteoporosis. This has led to intense interest in their absorption and biotransformation in man. The metabolism of isoflavones and lignans in animals and man is complex and involves both mammalian and gut microbial processes. Isoflavones are present predominantly as glucosides in most commercially available soya products; there is evidence that they are not absorbed in this form and that their bioavailability requires initial hydrolysis of the sugar moiety by intestinal beta-glucosidases. After absorption, phyto-oestrogens are reconjugated predominantly to glucuronic acid and to a lesser degree to sulphuric acid. Only a small portion of the free aglycone has been detected in blood, demonstrating that the rate of conjugation is high. There is extensive further metabolism of isoflavones (to equol and O-desmethylangolensin) and lignans (to enterodiol and enterolactone) by gut bacteria. In human subjects, even those on controlled diets, there is large interindividual variation in the metabolism of isoflavones and lignans, particularly in the production of the gut bacterial metabolite equol (from daidzein). Factors influencing absorption and metabolism of phyto-oestrogens include diet and gut microflora.

The serum pharmacokinetics of [(13)C]daidzein and [(13)C]genistein were reproducible among healthy women, and genistein was more bioavailable than was daidzein. Pharmacokinetics were unaffected by chronic exposure to soy foods. Urinary isoflavone concentrations correlated poorly with maximal serum concentrations, indicating the limitations of urine measurements as a predictor of systemic bioavailability. The bioavailability of both isoflavones was nonlinear at higher intakes, suggesting that uptake is rate-limiting and saturable.

The precise role that isoflavones play in the health-related effects of soy foods, and their potential for adverse effects are controversial. This may be due in part to a lack of basic knowledge regarding their bioavailability and metabolism, particularly as it relates to the soy source. To date, there is little information concerning possible differences in the bioavailability of isoflavones derived from natural soy foods consumed at physiologically relevant intakes and whether age- or gender-related differences influence that bioavailability. In the current study of healthy adults [premenopausal (n = 21) and postmenopausal (n = 17) women and a group of men (n = 21)], we examined the effect of age, gender, and the food matrix on the bioavailability of isoflavones for both the aglycon and glucoside forms that are naturally present in 3 different soy foods, soy milk, textured vegetable protein, and tempeh. The study was designed as a random crossover trial so that all individuals received each of the 3 foods. The dose of isoflavones administered to each individual as a single bolus dose was 0.44 mg/kg body weight. Pharmacokinetic parameters were normalized to mg of each isoflavone ingested per kilogram body weight to account for differences in daidzein and genistein content between the diets. Serum isoflavone concentrations in all individuals and groups increased rapidly after the ingestion of each soy food; as expected, genistein concentrations exceeded daidzein concentrations in serum. In this small study, gender differences in peak concentrations of daidzein were observed, with higher levels attained in women. Consumption of tempeh (mainly isoflavone aglycon) resulted in higher serum peak levels of both daidzein (P < 0.001) and genistein (P < 0.01) and the associated area under the curve (P < 0.001 and P < 0.03, respectively) compared with textured vegetable protein (predominantly isoflavone glucosides). However, soy milk was absorbed faster and peak levels of isoflavones were attained earlier than with the other soy foods. Only 30% of the subjects were equol producers and no differences in equol production with age or gender were observed.

Urinary isoflavone excretion is used to monitor compliance and examine biological effects. The present study determined if there were alterations in urinary isoflavone excretion following the ingestion of different soya foods and if age and gender potentially modified profiles. Twenty premenopausal women, seventeen post-menopausal women and twenty men received a defined single oral bolus dose (0·44 mg isoflavones/kg body weight) of soya milk, textured vegetable protein (TVP) or tempeh on three separate occasions. Baseline and four consecutive complete 24 h pooled urines were collected during each period. Urinary genistein recovery was influenced by gender and food matrix. For women the urinary genistein recovery was higher following soya-milk consumption compared with TVP (P, 0·05). Tempeh consumption also resulted in an increased urinary genistein recovery relative to soya milk in premenopausal women (P, 0·052). No differences in urinary genistein recoveries between soya foods were observed in the men. Although urinary daidzein excretion was similar across the foods studied and was not affected by age or gender, conversion to its intestinal metabolite, equol, resulted in potential matrix and chemical composition effects; urinary equol excretion was higher (P, 0·01) following tempeh ingestion among equol producers. Together these data suggest that the fractional absorption of genistein is potentially different in men and women and is influenced by the food matrix and chemical composition. Furthermore, the data suggest that the metabolism of daidzein may be altered by the chemical composition of the isoflavones ingested. Further studies are required to examine the effect of higher intake and define the relative influence of these factors in elderly population groups.

The growing interest in the role of phyto-oestrogens in human health has prompted scientists to evaluate the risk : benefit which would result from consuming high levels of these compounds at different stages of the life cycle. These compounds have been shown to exert a wide range of hormonal and non-hormonal activities in animals and in vitro, and these activities suggest plausible mechanisms for potential health effects in human subjects consuming phyto-oestrogen-rich diets. In addition, experimental and epidemiological data are available supporting the concept that phyto-oestrogen-rich diets exert physiological effects in vivo; however, their relative importance to human health remains to be elucidated. Our understanding of factors involved in their absorption and metabolism, including the role of intestinal microflora, is limited, and these factors together with dose-related effects may well be important in determining clinical efficacy.

No sensitive functional index is currently available to assess Cu status in healthy human populations. This study evaluated the effect of Cu supplementation on putative indices of Cu status in twelve women and twelve men, aged between 22 and 45 years, who participated in a double-blind placebo controlled crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu-glycine chelate and 6 mg Cu-glycine chelate, each separated by placebo periods of equal length. Women had significantly higher caeruloplasmin oxidase activity (P < 0·001), caeruloplasmin protein concentration (P < 0·05), and serum diamine oxidase activity (P < 0·01) at baseline than men. Erythrocyte and leucocyte superoxide dismutase activity, leucocyte cytochrome c oxidase activity, and erythrocyte glutathione peroxidase activity did not respond to Cu supplementation. Platelet cytochrome c oxidase activity was significantly higher (P < 0·01), after supplementation with 6 mg Cu-glycine chelate in the total group and in women but did not change in men. Caeruloplasmin oxidase activity was significantly higher (P < 0·05), in men after supplementation with 3 mg Cu-glycine chelate, while caeruloplasmin protein concentration was significantly lower in men after supplementation with 6 mg Cu-glycine chelate (P < 0·05). Serum diamine oxidase activity was significantly higher after all supplementation regimens in the total group and in both men and women (P < 0·01). These results indicate that serum diamine oxidase activity is sensitive to changes in dietary Cu intakes and may also have the potential to evaluate changes in Cu status in healthy adult human subjects.

The objective of the Vegetal Estrogens in Nutrition and the Skeleton (VENUS) project was to evaluate existing data on dietary exposure to compounds with oestrogenic and anti-oestrogenic effects present in plant foods as constituents or contaminants, and to identify and disseminate in vitro and in vivo methodologies to analyse the effects of such compounds on bone. To permit the assessment of exposure to isoflavones in European populations (Italy, the UK, Ireland, The Netherlands), the VENUS database of phyto-oestrogen levels in foods was established. Data on the isoflavone (genistein and daidzein) content of 791 foods, including almost 300 foods commonly consumed in Europe, were collected. Levels of coumestrol, formononetin and biochanin A in a limited number of foods were also included. Lignan levels (secoisolariciresinol and matairesinol) in 158 foods were incorporated into the database, which also contains information on the references sourced for the compositional data, on the analytical methods used by each author and on the number of foods analysed in each reference. The VENUS database was constructed in Microsoft Access 2000, which is widely available as part of Microsoft Office Professional. This paper outlines the procedures used for the selection and evaluation of existing literature data for incorporation into the database. In addition, the design of the database is described, along with the data entry and quality control procedures used in its construction. Limitations of the data are discussed and guidelines for its use are provided.

The object of this study was to determine whether serum diamine oxidase activity could distinguish among adequate, marginal and deficient copper status in rats. Male weanling Sprague-Dawley rats (n = 21) were randomly assigned to one of three dietary regimens, with copper concentrations of 0.52, 1.73 and 6.7 mg/kg diet. On completion of the study, body weights were significantly different among dietary groups, with copper-marginal rats displaying the highest mean weight and copper-deficient rats the lowest. Copper-deficient rats ate significantly less food than the other two groups. Rats fed the three diets had significantly different liver copper concentrations. Liver and heart superoxide dismutase and cytochrome c oxidase activities, and plasma ceruloplasmin and erythrocyte superoxide dismutase activities were significantly lower in the copper-deficient rats than in the other two groups. Plasma diamine oxidase activity was lower in both copper-deficient (0.18 +/- 0.11 U/L) and marginal (0.21 +/- 0.11 U/L) rats compared with copper-adequate rats (3.35 +/- 0.28 U/L). Of the biochemical indices measured, only liver copper concentration (-20%) and plasma diamine oxidase activity (-94%) differed between rats fed copper-marginal and copper-adequate diets. Plasma diamine oxidase activity, therefore, may be a sensitive functional biomarker of suboptimal copper status.