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At just 46% in 2017, the vaccination percentage for HPV (human papillomavirus) is low in the Netherlands. This dissertation describes the development and evaluation of an online intervention with tailored advice on the HPV vaccine. We developed a website that provided mothers with personal and interactive guidance to help them decide whether or not to vaccinate their daughters against HPV. The intervention helped mothers make a more informed decision and made them more willing to vaccinate their daughters. Next year, the intervention will be included in the national education programme for HPV vaccination. The online intervention may have a considerable social impact, as it can reach a large target group at relatively low costs.

Absorption of toxic substances via the skin is an important phenomenon in the assessment of the risk of exposure to these substances. People are exposed to a variety of substances and products via the skin, either directly or indirectly, while at work, at home or in public space. Pesticides, organic solvents and metalworking fluids are seen to be important contributors to adverse health effects due to occupational exposure via the skin. In daily life, cosmetics, clothing and household products are the most relevant commodities with respect to exposure via the skin. Given the importance of skin exposure in the assessment of the risk of toxic substances, the objective of this thesis was to further develop, evaluate and improve methods for including skin absorption data this assessment. In this thesis, four factors influencing dermal absorption, namely dermal loading (chapters 3 and 6), irritative/corrosive potential (chapters 3 and 4), frequency of exposure (chapters 3, 4 and 5) and the vehicle used (chapter 5), were investigated in more detail. Furthermore, a model to extrapolate infinite dose absorption data to finite dose conditions, baptized Dermal Absorption Model for Extrapolation (DAME), was developed and tested. I n chapter 2 of this thesis, the relationship between relative dermal absorption and dermal loading was investigated. Hundred-and-thirty-eight dermal publicly available absorption experiments with 98 substances were evaluated. The results obtained revealed that dermal loading ranged mostly between 0.001 and 10 mg/cm2. In 87 experiments (63%), an inverse relationship was observed between relative dermal absorption and dermal loading. On average, relative absorption at high dermal loading was 33 times lower than at low dermal loading. Known skin irritating and volatile substances less frequently showed an inverse relationship between dermal loading and relative absorption. It was concluded that when using relative dermal absorption in regulatory risk assessment, its value should be determined at or extrapolated to dermal loadings relevant for the exposure conditions being evaluated. I n chapter 3 of this thesis, a literature search was presented with the aim to investigate whether neglecting the effects of repeated exposure may lead to an incorrect estimate of dermal absorption. The results demonstrated that the effect of repeated versus single exposure does not demonstrate a unique trend. Nevertheless, an increase in daily absorption was frequently observed upon repeated daily exposure. The little information available mostly concerned pharmaceuticals. However, consumers and workers may be repeatedly exposed to other types of chemicals, like disinfectants and cleaning products, which often contain biocidal active substances that may decrease the barrier function of the skin, especially after repeated exposure. These biocidal products, therefore, may present a safety risk that is not covered by the current risk assessment practice since absorption data are usually obtained by single exposure experiments. Consequently, it was decided to investigate the importance of this issue for biocide safety evaluation. As the literature search revealed that hardly any data on absorption upon repeated dermal exposure to biocides are available, it was concluded that data need to be generated by testing. To cover the entire range of biocidal products in such testing, a representative series of biocidal substances should be tested, making in vitro testing of dermal absorption the preferred choice over in vivo testing. Based on an inventory made, it appeared that the 16 product types represented among the biocidal products authorised in the Netherlands could be clustered into 6 more or less homogeneous categories based on similarity in active substances. This result could facilitate experimental testing by providing a basis for selection of a limited number of representative compounds to be evaluated. I n chapter 4 of this thesis, the importance of the effect of repeated dermal exposure on skin permeability for biocide safety evaluation was investigated, using a selection of nine representative biocides from the inventory made in chapter 3. The in vitro dermal penetration of tritiated water and [14C]propoxur was chosen as a measure of the permeability and integrity of human abdominal skin after single and repeated exposure. The results indicated that single and repeated exposure to specific biocidal products (e.g. the quaternary ammonium chlorides DDAC and ADBAC) may significantly increase skin permeability, especially when the compounds are applied at high concentrations, while a substance like formaldehyde may reduce skin permeability under specific conditions. I n chapter 5 of this thesis, the in vitro dermal absorption kinetics of the quaternary ammonium compound didecyldimethylammonium chloride (DDAC) during single and repeated exposure was studied in more detail. In addition, the influence of biocidal formulations on the absorption of DDAC was investigated, because it was expected that formulation characteristics may be another factor influencing its dermal absorption. The analysis of biocidal products on the Dutch market, reported in chapter 3, indicated that DDAC is often used in combination with other active ingredients. DDAC was most frequently combined with formaldehyde, glutaraldehyde and/or alkyldimethylbenzyl­ammo­nium chloride (ADBAC). Consequently, commercial formulations containing one or more of these additional active ingredients were selected, in addition to one formulation containing only DDAC as an active ingredient. The selected commercial formulations tended to reduce skin penetration of DDAC. This was most pronounced with the formulation containing the highest concentration of formaldehyde (196 mg/mL) and glutaraldehyde (106 mg/mL), which reduced the flux of DDAC across the skin by 95%. The reduction caused by the only tested formulation containing no other active ingredients than DDAC, and thus incorporating no aldehydes, was smallest, and did not reach statistical significance. I n chapter 6 of this thesis, a simple in silico model to predict finite dose dermal absorption from infinite dose data (kp and lag time) and the stratum corneum/water partition coefficient (KSC,W) was developed. This model was tentatively called Dermal Absorption Model for Extrapolation (DAME). As dermal exposure may occur under a large variety of conditions leading to quite different rates of absorption, such a predictive model using simple experimental or physicochemical inputs provides a cost-effective means to estimate dermal absorption under different conditions. To evaluate the DAME, a series of in vitro dermal absorption experiments was performed under both infinite and finite dose conditions using a variety of different substances. The kp’s and lag times determined in the infinite dose experiments were entered into DAME to predict relative dermal absorption value under finite dose conditions. For six substances, the predicted relative dermal absorption under finite dose conditions was not statistically different from the measured value. For all other substances, measured absorption was overpredicted by DAME, but most of the overpredicted values were still lower than 100%, the European default absorption value for the tested compounds. In conclusion, our finite dose prediction model (DAME) provides a useful and cost-effective estimate of in vitro dermal absorption, to be used in risk assessment for non-volatile substances dissolved in water at non-irritating concentrations. I n chapter 7 of this thesis, the results of the research reported in chapters 2 to 6 were put into perspective, the pitfalls and promises emanating from them discussed and general conclusions drawn. The possible influence of vehicles on absorption and the possible impact of irritative or corrosive vehicles or chemicals on the skin barrier have been demonstrated in this thesis. An in silico predictive model tentatively called DAME was developed, which enables the user to evaluate a variety of dermal exposure scenarios with limited experimental data (kp and lag time) and easy to obtain physicochemical properties (MW and log KOW). The predictions of our experiments reported in chapter 6 were compared to those of the Finite Dose Skin Permeation (FDSP) model published on the internet by the US Centers for Disease Control and Prevention (CDC). DAME outperformed FDSP (R2 of the correlation predicted/measured potential absorption 0.64 and 0.12, respectively). At present, the applicability domain of DAME is limited to non-volatile substances dissolved in aqueous solvents. However, in future the model will be adapted to include volatile substances as well. Altogether, it is concluded that dermal exposure can be an important factor in risks posed by chemicals and should be taken into account in risk assessment. The methods to actually do this are still open for further improvement to better account for the various factors influencing skin penetration and to develop adequate combinations of in vitro and in silico models that can accurately predict human dermal absorption.

In this thesis, prospective studies on fruit and vegetable consumption in relation to epithelial cancer risk were described. The main research question was whether higher intakes were related to lower risks of epithelial cancers, mainly of lung cancer.In the Seven Countries Study, at the population level, consumption of fruits, vegetables and total plant foods was not related to colorectal cancer risk, whereas a difference of 10 g/d of fiber intake was associated with a 33% lower risk. Average population consumption of fruit was inversely and of refined grains positively related to population stomach cancer risk. Low consumption of fruits was however strongly correlated with high refined grain consumption.Fruit but not vegetable consumption was inversely associated with 25-year lung cancer mortality among European smoking men. This association was confined to heavy cigarette smokers. In Dutch men and women aged 20-59, vegetable consumption was inversely associated with lung cancer incidence, particularly of adenocarcinomas. Fruit consumption was not related to lung cancer after adjustment for smoking.Adherence to the dietary guidelines for fruits and vegetables was inversely associated with cancer incidence in Dutch elderly men. Consumption of the recommended amount of fruit was related to a 38% lower risk, while vegetables were not associated. Variety in vegetable intake was however inversely related to total and non-lung epithelial cancer.Plasma carotenoid concentrations were only crude indicators of usual vegetable and fruit intake in Dutch men and women aged 20-59. Plasmaβ-cryptoxanthin indicated fruit intake and total intake of vegetables, fruits and juices, whereas lutein was a marker for vegetable intake. Concentrations of carotenoids coul d not differ between all four quartiles of intake.During 1987/88-1997/98, the mean fruit and vegetable consumption (excluding juices) decreased with 34 g/d (12%) in Dutch men and 23 g/d (8%) in Dutch women. The consumption was lowest and decreased most in those aged 19-35 with a low level of education. Using a computer simulation model, the maximum theoretically reduction in cancer incidence, i.e., when all would consume the recommended 400 grams daily, was estimated to be 14 to 22% for this group.Valid assessment of fruit and mainly of vegetable intake, residual confounding by smoking and enough power of the study are major methodological concerns. In recent cohort studies weaker associations were observed compared to earlier risk estimates. Taken all evidence together, an inverse association between fruit and vegetable intake and cancer of the lung, stomach and colon/rectum is still indicated. There is not enough evidence yet to point at specific fruits and vegetables or plant compounds as responsible actors.

To produce a complete and balanced dog diet it is necessary to know the nutritional needs of the dog as well as the availability of nutrients from the diet. Petfood manufacturers are restricted in performing (invasive) studies with animals for ethical reasons. Therefore, it is necessary to search for in vitro alternatives to these studies as explained in Chapter 1. Based on a literature study on the physiology of the GI tract of the healthy, adult dog (Chapter 2), the dynamic in vitro model for human subjects, pigs and calves, as described by Minekus (1995), was modified to mimic the physiological conditions of the dog. The model is named FIDO ( f unctional gastro i ntestinal do g model).The aim of the study was to develop the in vitro model simulating the GI tract of the dog. The model should simulate the physiological conditions in the GI tract of the dog as closely as possible. In that way luminal processes as well as physical and chemical properties of diets could be investigated. This thesis describes the developmental experiments, the validation experiments in comparison to dog studies as well as application studies.Validation of the modelTechnical validationThe study started with an extended literature review on the physiology of the stomach and small intestine of the healthy, adult dog with a special emphasis on those parameters which are relevant for the development of the dog model (Chapter 2). With respect to digestion of food, such parameters as transit times, pH values, concentrations of electrolytes and activities of enzymes are important to mimic physiological conditions as closely as possible. Data found in the literature were translated to a computer program to simulate these parameters in FIDO. The features of the model are described in Chapters 2 to 7. Based on the simulation of the physiology of the dog dry and canned dog foods were used to test the technical possibilities of the model. After some technical modifications to the gastric compartment and the pre-filters connected to the jejunal and ileal compartments, a study was performed to test the effect of particle size of dry dog food on gastric emptying. Particles≤3 mm emptied more slowly than particles≤1 mm. The effect of transit time on the availability for absorption of nitrogen and calcium of canned dog food was also investigated. Like in vivo , in FIDO less nitrogen and calcium were available for absorption with faster transit times (Chapter 3).Validation in vitro versus in vivoValidation of the model in comparison to the in vivo situation was the next step in the development of the dog model (Chapter 4). Ileal protein digestibility and availability for absorption of nitrogen of eight different dry dog foods were tested in the model. The results were compared with data found in vivo with ileally cannulated dogs, performed at the University of Illinois. The experiments proved to be very reproducible and the results found in FIDO are similar to those found in vivo in the dogs.Based on these findings and those of former experiments simulating pigs, calves and human beings, it can be concluded that the model is a suitable tool as an alternative to animal experiments in nutritional research.Application of the modelThe validation study (Chapter 3) showed a low availability for absorption of calcium in the model. Based on these results it was decided to study calcium and phosphorus availability from three commercially available canned dog foods (Chapter 4). Effects of addition of calcium-phosphorus supplements or the enzyme phytase and the effect of a lower pH in the small intestine were also included in this study. A human standard breakfast was used as a control diet, because this diet had a high calcium availability under human conditions in the diet.The results showed that the canned dog foods had a low availability for absorption for calcium (maximum 21%) and phosphorus (maximum 44%). Differences in relative availability of calcium and phosphorus were found among these diets, which can probably be explained by the source of these minerals. Also the low availability of these minerals can be attributable to the source. Another possible explanation of the low availability are the (saturated) fatty acids in the diet, which can form calcium soaps in the model.The advantage of FIDO is that the availability for absorption of calcium and other nutrients can be studied without the influence of the physiological status of the animal. The real amount absorbed by the animal, however, cannot be studied. Absorption by the animal depends on its needs and the absorption is hence dependent on two different mechanisms: passive and active absorption. To get more insight into the absorption of calcium through the intestinal wall of the dog, experiments were performed with Great Danes (8 and 20 weeks of age; in cooperation with the Veterinary Faculty of Utrecht University), FIDO and intestinal segments (Chapter 7). The effect of vitamin D was taken into account in this study by studying two levels in the diet. The three different methods ( in vivo , FIDO and intestinal segments) are complementary and can be used to get a better understanding of the regulation of calcium absorption in the dog.In Chapter 6 experiments are described to investigate the effect of gelling agents on the digestibility and availability for absorption of nutrients ('chunks in gravy' products). Three different (combinations of) gelling agents added to the gravy were used in this study in different concentrations (0.2% and 0.5%): carrageenan plus guar gum, carrageenan plus locust bean meal, and wheat starch. A diet without gelling agent was used as a control diet. Neither the gelling agent nor the concentration had any effect on digestibility of proteins and carbohydrates, availability for absorption of calcium and phosphorus, viscosity or buffering capacity in the intestinal content. From the results it can be concluded that addition of the gelling agents used does not affect the nutritional quality of the diets at the low concentrations tested.ConclusionsThe dynamic in vitro model of the GI tract of dogs simulates the physiological parameters very accurately and reproducibly. Transit time of food has an effect on digestibility and availability for absorption, just like in dogs. Also ileal protein digestibility in the model is similar to the data found in vivo . It is possible to investigate specific questions regarding dog food in this model (e.g. the effect of gelling agents on digestibility). Another important aspect is the fact that the experiments in FIDO can be performed under highly standardized condition, in contrast to in vivo studies in which biological variance among animals plays a role. This comes to expression in the reproducibility and sensitivity of the results from FIDO compared to results of in vivo studies.The dynamic in vitro model of the gastrointestinal tract of the dog is a suitable alternative to in vivo studies with respect to digestibility and availability for absorption of nutrients from different types of dog food, such as canned and dry dog foods.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (eNS) that affects eNS myelin which isolates nerve axons and allows saltatory pulse conduction. It is the most important chronic disabling neurological disease in young adults, with a mean age of onset around 30 years. It has a prevalence of approximately I per 1000 in Western European countries and it affects women versus men at a ratio of 1.5 to I (Sadovnick and Ebers, 1993). Although the cause and pathogenesis of MS are unknown, it is generally believed that MS is an autoimmune disease in which environmental factors as well as genetic factors are involved. Studies with monozygotic twins reveal an MS concordance rate of 20-30%, ·whereas this is 3-5% for dizygotic twins (reviewed by Ebers and Sadovnick, 1994). This high concordance rate is a strong argument in favor of a genetic basis of MS, but can also be used as an argument for an environmental involvement in MS. The role of environmental factors in MS is supported by the presence of geographic gradients in the distribution of the disease. The general pattern is that MS prevalence rises with increasing distance from the equator. The nature of these environmental factors is unknown. Dietary factors, climate variation and infectious agents have all been postulated to be involved in MS, but there is no definitive proof for involvement in MS of any of these factors. Especially herpes viruses have gained interest the last few years (Dalgleish, 1997). The notion that MS is a multifactorial disease is strengthened by the fact that the clinical course of MS is highly variable for each individual patient, and can be divided into four categories (Lublin and Reingold, 1996). The first category is relapsingremitting disease, in which discrete attacks are alternated with periods in which a patient returns to the pre-attack base line. In the relapsing-progressive form of MS, the patients do not return to base-line level in between attacks and disability increases in these patients. In chronic-progressive disease, the disease progresses without periods of stability. The uncommon fourth form is characterized by a progressive relapsing course of MS.

The main goal of prevention and health care for elderly people is optimizing 'quality of life'. Frail older persons have limited reserves and are therefore at an increased risk of a decline in health, which may lead to dependency and disability. This thesis focuses on the health-related effects of physical exercise and nutrient dense foods among non-institutionalized frail older people. First, criteria for identification of frailty were investigated using prospective cohort data. It was concluded that physical inactivity in combination with weight loss seems a practical and inexpensive screening criterion to identify functionally vulnerable persons among non-institutionalized elderly. Second, the results of a 17-weeks randomized controlled trial on a specific exercise and nutritional program in 217 frail, independently-living elderly (aged 67-96) are presented.The exercise program proved of benefit for functional status and immune response. Performance on 7 functional tests had significantly improved (+8%) in trained compared to non-trained subjects (-8%). The beneficial effect on the sum score of 7 fitness tests was also significant but smaller. Cellular immune response was measured by the delayed-type hypersensitivity skin test response against 7 recall antigens. The number of positive responses declined in non-exercising subjects (-26%) compared to an unchanged responsiveness among exercising subjects. Effects on self-rated disabilities, psychological well-being and self-rated health could not be demonstrated. Seventeen weeks of consumption of micronutrient enriched foods at physiological doses (25-100% of the RDA) did not affect functional status, cellular immune response or psychological well-being.In conclusion, exercise programs can be developed which are effective in preventing, slowing down or reversing the age-related decline in physical functioning and cellular immune response. Moreover, subjects highly appreciated the exercise program and the majority favored continuing program participation.ISBN:90-5808-125-7

This thesis reports the background, design and results of a multi-centre study on the relationship between diet-derived antioxidants and the risk of acute myocardial infarction (MI) in men. Levels ofα-tocopherol andβ-carotene in adipose tissue and of selenium in toenails were compared between almost 700 patients with first MI and a similar number of control subjects, recruited in 8 European countries and Israel. The concentration ofβ-carotene in adipose tissue, expressed in quintiles of the distribution in controls, was inversely associated with the risk of MI (p for trend 0.001), independently of other risk factors. This association was strongest in current cigarette smokers and in subjects with a high proportion of polyunsaturated fatty acids in the adipose tissue. The risk of MI was not related toα-tocopherol in adipose tissue. In persons with low vitamin E levels, low toenail selenium was associated with a 2.5-fold increased risk of MI, compared to high selenium levels. An additional study among 85 healthy, non-smoking volunteers, aged 50-70, showed only a modest correlation of adipose tissue concentrations with dietary intake ofα-tocopherol andβ-carotene assessed by a food frequency questionnaire.Randomized controlled trials with varying doses and combinations of antioxidant nutrients should clarify whether the observed associations are causal. Until then, supplement use is not recommended, but a generous consumption of fruits and vegetables may be encouraged.

Contains fulltext : mmubn000001_160089344.pdf (Publisher’s version ) (Open Access) Promotores : J. Noordhoek, P. Henderson en F. Jongeneelen 131 p.

Minerals and trace elements play essential roles in numerous biochemical and physiological processes in animals and man. A deficiency, an overdose or imbalances between minerals or trace elements will exert a negative effect on health. Generally, it is not the ingested dose of minerals and trace elements that is important to maintain balance, but rather the amount that is bioavailable (available for biological and biochemical processes in the organism). Several food components are able to form soluble or insoluble complexes with minerals and trace elements under gastrointestinal conditions. These food components thereby increase or decrease the availability for absorption in the small intestine, and thus the bioavailability of minerals and trace elements, Due to the complexity of food products, however, the relative contributions of food components to the bioavailability of minerals and trace elements are often not clear.Although in vivo experiments are the best way to study the bioavailability of minerals and trace elements, in vitro methods offer an appealing alternative because they are relatively simple, rapid and inexpensive. Therefore, there is a great need in human nutrition and animal nutrition for an in vitro method which predicts the bioavailability of minerals and trace elements in vivo.Part I describes the scope and the objectives (Chapter 1), and the experimental approach (Chapter 2) of the research presented in this thesis. The objectives were twofold:- to develop an in vitro method for the prediction of the bioavailability of calcium, magnesium, iron, copper and zinc- to investigate the effects of phytic acid, dietary fibre and other food components on the in vitro availability of calcium, magnesium, iron, copper and zinc.To meet these objectives a multidisciplinary approach was followed.Part II discusses several aspects of dietary fibre.In Chapter 3 a literature review of the definitions and terminology of dietary fibre is presented. Although the term "dietary fibre" is now widely accepted, there is still some confusion concerning its definition.Chapter 4 presents a literature review of methods for the analysis of dietary fibre. As such methods are based on a definition of dietary fibre, it is important that there is consensus regarding the type of components that should be included in the definition. An advantage of a definition based on chemically defined components is that it allows for a specific analytical determination of dietary fibre components.In Chapter 5 a comparison of different methods for the analysis of dietary fibre is presented. The ADF, NDF, Hellendoorn, AOAC and Englyst methods are compared with respect to the amount and the composition of the dietary fibre analysed. Although different methods for the analysis of dietary fibre can yield comparable integral values, the NSP (non-starch polysaccharides) composition of the dietary fibre residues may differ greatly. It is shown that modern methods such as the AOAC and Englyst methods give more accurate determinations of dietary fibre than older methods such as the ADF/NDF method and Hellendoorn's method. Methods in which the NSP are determined (such as the Englyst method) are to be preferred because a well defined group of dietary fibre components are determined. Moreover, the gas chromatographic procedures give insight into the types of NSP present.Part III concerns the analysis of phytic acid (myoinositol hexakis(dihydrogen)phosphate).A literature review of methods for the analysis of phytic acid is presented in Chapter 6. According to the literature, few methods for the analysis of phytic acid are specific because of interferences from lower inositol phosphates, inorganic phosphates and metal ions. Currently, methods based on anion-exchange chromatography with postcolumn derivatization and methods based on phosphorus-31 NMR show the best results.In Chapter 7 an improved method for the determination of phytic acid is presented. The method is based on an anion-exchange chromatographic procedure with postcolumn derivatization in which EDTA treatment of the samples is incorporated to eliminate interferences from metal ions. The improved method is compared with a HPLC method without EDTA treatment and with a method using small single-use ionexchange columns. It is shown that elimination of the interference of metal ions by means of EDTA treatment in the anion- exchange chromatographic procedure allows for a more specific determination of phytic acid.Part IV deals with in vitro methods for the prediction of the bioavailability of Ca, Mg, Fe, Cu and Zn.Chapter 8 presents a literature review of in vitro methods for the estimation of the bioavailability and its correlation with bioavailability in vivo. According to the literature, the most promising in vitro methods are based on equilibrium dialysis under simulated physiological conditions, in which the dialysability of minerals and trace elements is taken as a measure for their bioavailability.In Chapter 9 a continuous in vitro method for the estimation of the bioavailability of Ca, Mg, Fe, Cu and Zn is described. In this in vitro method dialysable components (including minerals and trace elements) are continuously removed from the pancreatic digestion mixture. The in vitro method based on continuous dialysis is compared with the in vitro method based on equilibrium dialysis with respect to the dialysability of Ca, Mg, Fe, Cu and Zn from eight types of bread. The continuous in vitro method generally results in higher dialysabilities of minerals and trace elements than the equilibrium in vitro method. The relevance of this effect for prediction of the bioavailability in vivo needs further investigation.The in vitro method with continuous dialysis and the in vitro method with equilibrium dialysis were validated for their usefulness as predictors of the bioavailability of Ca, Mg, Fe, Cu and Zn in an in vivo experiment with piglets. This study is presented in Chapter 10. It is shown that although both in vitro methods show a discrepancy between the absolute values of the availability determined in vitro and the bioavailability determined in vivo, they reflect quite well the effects of differences in food composition on the bioavailability in vivo. Therefore it is concluded that the in vitro methods can be used for a relative prediction of the bioavailability of minerals and trace elements and thus may be very useful in providing preliminary or additional information to in vivo experiments.Part V discusses the influence of food components on the availability of minerals and trace elements.Chapter 11 is a literature review of the influence of dietary fibre, phytic acid and other food components on the availability of Ca, Mg, Fe, Cu and Zn. This concise review shows that the bioavailability of minerals and trace elements is a very complex issue because it may be influenced by a variety of dietary components. Therefore, the influence of dietary fibre, phytic acid and other dietary components on the bioavailability of minerals and trace elements should not be studied separately but in the whole food matrix.Chapter 12 describes a mathematical model to investigate the relative influences of food components on the in vitro availability of Ca, Mg, Fe, Cu and Zn. The mathematical model is based on chemical theoretical assumptions and optimized with respect to the model structure and the numerical model parameters. It is shown that the mathematical model describes and predicts the in vitro availability of Ca, Mg, Fe and Zn quite well on the basis of the concentrations of two or three food components. The mathematical model proves also valuable for obtaining insight into the relative influences of food components on the in vitro availability of minerals and trace elements. According to the mathematical description of the in vitro availability, phytic acid has a strong negative effect on the availability of Ca, Fe and Zn, and a less pronounced effect on the availability of Mg. Arabinose-containing components decrease the availability of Ca and Fe. Oxalic acid has a negative influence on the availability of Ca, Mg and Zn. Ascorbic acid increases the availability of Fe, while citric acid has a positive influence on the availability of Ca, Mg and Zn. It is shown that food components with a positive influence on availability can counteract the effects of food components with a negative influence.Because in vitro methods are rapid and relatively inexpensive, and mathematical models provide insight into the relative influences of food components, the combination of in vivo experiments, in vitro experiments and mathematical modelling is a powerful approach to obtain a better understanding of the, mechanisms and important factors involved in the bioavailability of minerals and trace elements.The studies presented in this thesis investigated the bioavailability of minerals and trace elements from different points of view. In Part VI the most relevant points of discussion (Chapter 13) and conclusions (Chapter 14) are presented.

Contains fulltext : mmubn000001_151922241.pdf (Publisher’s version ) (Open Access) Promotores : L. van de Putte en M. Jonker 115 p.