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Dietary exposure to vegetal estrogens and related compounds and effects on skeletal tissues and lipid metabolism

Objectif

The main objectives of this Concerted Action are to evaluate existing data on dietary exposure to compounds with estrogenic and antiestrogenic effects present in plant food as constituents or contaminants and to identify or develop and then test and disseminate in vitro and in vivo methodologies to analyse the biological effects of such compounds. The Action will concentrate on bone turnover and lipid metabolism as test metabolic systems and will be carried out as joint and parallel laboratory projects.

Existing data on food levels of isoflavonoids, lignans, coumestrol and indoles available from the literature and the participating laboratories will be collected and combined. Particular emphasis will be given to locally produced varieties of legumes and other phytoestrogen containing plant foods. An ingredient table will be developed with the purpose to estimate the intake of isoflavones in the Netherlands, and possibly in other countries where large epidemiological studies on diet and chronic diseases have been conducted. The host factors, such as gut microflora, age, menopausal state, malabsorption syndromes, that might affect phytoestrogen absorption will be examined. The metabolic fate of ingested dietary isoflavones will be analysed by using stable isotopes of the pure compounds and to ascertain factors which may affect the absorption and metabolism. The technical and economic feasibility of production of phytoestrogen enriched foods will be evaluated. Phytoestrogen enriched test products may be evaluated, if their production is considered feasible. Test diets with different content of the different compounds possessing estrogenic action will be designed, based on locally produced varieties phytoestrogen containing plant foods. Specific supplementary strategies will be developed to look at the effects on bone and lipid metabolism, such as a mediterranean style diet or a macrobiotic diet, with or without the addition of synthetic lignans and isoflavonoids.

In vitro cell and organ models will be tested for their capacity to investigate the biological actions of phytoestrogens. The different partners will use different models, so that comparisons can be made on the stability of the system, and the ability to show effects with different compounds and different concentrations. Suitable biomarkers of the action of the compounds of interest will be evaluated, looking at cell growth and differentiation, gene expression, synthesis of mrna of key enzymes and proteins (tracp, cathepsin K, osteocalcin), expression of receptors and cell functions, such as deposition of mineralized matrix, resorption activity. The usefulness and validity of animal models will be examined, so that the conditions when animal experiments are really warranted would be defined and the appropriate protocols developed.

Dietary protocols will be developed by critically analysing the supplementation studies conduced so far and by evaluating the use of in vivo biomarkers of bone and lipid metabolism. Samples from existing studies on the effect of phytoestrogen supplementation of the diet will be analysed to have preliminary information on the relationship between exposure and effect.

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Coordinateur

Istituto Nazionale della Nutrizione
Contribution de l’UE
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Adresse
Via Ardeatina 546
00179 Roma
Italie

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