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  • Simões, Catarina (Helsingin yliopisto, 2013)
    The establishment of microbial populations in the gastrointestinal (GI)-tract is a complex process, involving microbial and host interactions eventually resulting in a dense and stable population. Recently, the identification of microbial species from fecal samples has become more accurate with the use of 16S RNA gene-based methods. However, although these molecular-based detection methods have apparent benefits over culture-based techniques, they involve potential pitfalls that should be taken into consideration when studying the fecal microbiota, such as the storage conditions and deoxyribonucleic acid (DNA)-extraction. Therefore, the effects of different storage conditions and DNA-extraction protocols on fecal samples were evaluated in this study. Whereas the DNA-extraction protocol did not affect the numbers of Bac-teroides spp., the abundance of this group showed a significant decrease after one week s storage at -20°C. Furthermore, the numbers of predominant bacteria, Eubacterium rectale group, Clostridium leptum group, bifidobacteria and Atopobium group, were significantly higher in samples stored at -70°C after mechanical DNA-extraction than after enzymatic DNA-extraction as detected with real-time PCR (qPCR). These results indicate that rigorous mechanical lysis leads to the detection of higher bacterial numbers from human fecal samples than enzymatic DNA-extraction. Therefore, the use of different DNA-extraction protocols may partly ex-plain contradictory results reported in previous studies. The composition of the human intestinal microbiota is influenced by host-specific factors such as age, genetics and physical and chemical conditions encountered in the GI-tract. On the other hand, it is modulated by environmental factors with impact on the host during the lifespan, such as diet. The impact of diet on the gut microbiota has usually been assessed by subjecting people to the same controlled diet, and thereafter following the shifts in the microbiota. In the present study, the habitual dietary intake of monozygotic twins was associated with the fecal microbiota com-position, which was analysed using qPCR and Denaturing Gradient Gel Electrophoresis (DGGE). The effect of diet on the numbers of the bacteria was described using a hierarchical linear mixed model that included the twin individuals, stratified by body mass index, and their families as random effects. The abundance and diversity of the bacterial groups studied did not differ between normal weight, overweight, and obese individuals with the techniques used. However, intakes of energy, monounsaturated fat, (n-3) polyunsaturated fat, (n-6) polyunsaturated fat and soluble fibre had significant associations with the fecal bacterial numbers. In addition, co-twins with identical energy intakes had more similar numbers and DGGE-profile diversities of Bacteroides spp. than co-twins with different intakes. Moreover, co-twins who ingested the same amounts of saturated fat had very similar DGGE-profiles of Bacteroides spp., whereas co-twins with similar consumption of fibre had very low bifidobacterial DGGE-profile similarity. Thereafter, the impact of the energy intake on the fecal microbiota of a group of 16 obese individuals was assessed during a 12 month intervention, which consisted of a 6 week very low energy diet (VLED) and thereafter a follow-up period of 5, 8 and 12 months. The diet plan was combined with exercise and lifestyle counseling. Fecal samples were analyzed using qPCR, DGGE and fluorescent in situ hybridization. The effect of the energy restricted diet on the fecal bacterial numbers was described using a linear mixed model that accounted for repeated measurements in the same individual. The VLED period affected the major fecal microbial groups; in particular bifidobacteria decreased compared to the baseline numbers. Furthermore, the change in numbers of the fecal bacterial groups studied, followed the dietary intake and not the weight changes during the 12 months. Methanogens were detected in 56% of the participants at every sampling time point, regardless of the change in dietary intake. In addition, weight loss was associated with a decrease in Lactobacillus group bacteria. These findings confirm that the diet and energetic intake play an important role in modulation of the fecal microbiota. Finally, the potential of utilising the information on expression levels of selected stress genes in assessing the quality of probiotic products was evaluated. For this purpose, reverse transcription-qPCR methods were developed to study the expres-sion of clpL1 and clpL2 stress genes in Lactobacillus rhamnosus VTT E-97800 cells after exposure to processing-related stress conditions or to freeze-drying. Heat treatments were performed with L. rhamnosus VTT E-97800 in laboratory scale, whereas acid treatments were performed both in laboratory and fermenter scale. RNA was extracted from fresh cells and freeze-dried powders. clpL1 and clpL2 transcripts were analysed by qPCR using SYBR Green I. clpL1 was induced in L. rhamnosus VTT E-97800 cells exposed to 50°C and to a much lesser extent in cells exposed to 47°C. No induction was observed for clpL2 during either acid or heat treatment in any of the conditions applied. RNA isolation from freeze-dried powders was unsuccessful, although several attempts were made with high quality products. These results suggest that developing quality indicators for probiotic prod-ucts based on differences in the expression of stress genes will be a challenging task, since rather harsh conditions are apparently needed to detect differences in the gene expression. In addition, the unsuccessful RNA isolation from freeze-dried pow-ders hampers the applicability of this technique in the quality control of probiotic products.
  • Pere, Anna-Kaisa (Helsingin yliopisto, 2008)
    Cyclosporine-A (CsA) is widely used after organ transplantation to prevent rejection and in the treatment of autoimmune diseases. Hypertension and nephrotoxicity are common side-effects of CsA. Studies in patients on the prevention of the side-effects of CsA are difficult to conduct because the patients often receive a combination of different drugs thus making study of the side-effects of a single drug impossible. A challenge in experimental studies has been the lack of an animal model in which the side-effects concomitantly occur. Epidemiological data show an association between sodium (Na) intake and blood pressure. There is also evidence on low dietary intake of magnesium (Mg) and potassium (K) and high blood pressure. Our study was designed to develop an experimental model to study the side-effects of CsA in spontaneously hypertensive rats (SHR). On high dietary sodium, CsA caused hypertension, left ventricular hypertrophy (LVH), narrowing of the coronary arteries, small myocardial infarctions, and proteinuria, reduced creatinine clearance and histopathological renal injury in SHR. Loss of Mg into the urine caused by CsA resulted in Mg depletion in the tissues. Renal excretion of dopamine was reduced and the renin-angiotensin-aldosterone system was activated. We investigated the effects of dietary Mg and/or K and the calcium antagonist drug, isradipine, on the prevention of CsA toxicity. Dietary supplementation of Mg alone or in combination with K prevented from the deleterious pathophysiological and histopathological changes in the kidneys and the heart. K alone had little effect. Isradipine protected better than Mg from LVH, but the combination of isradipine and Mg was the most effective. Isradipine did not, however, protect against Mg loss. In our animal model, the combination of high dietary Na and treatment with CsA accelerated the development of the cardiovascular and renal changes clinically known as the side-effects of CsA. Dietary supplementation of Mg and K and reduction of Na intake and the calcium antagonist drug isradipine prevent from the deleterious effects of CsA.
  • Bogl, Leonie-Helen (Helsingin yliopisto, 2014)
    Background: Energy-dense food and low physical activity have been blamed for the dramatic rise in the prevalence of obesity and related metabolic disorders. However, few dietary and physical activity factors have been consistently associated with obesity in observational studies. Self-reported behaviors are prone to misreporting, which may partly explain the inconsistency of previous results. Nutritional biomarkers provide an objective approach to measure habitual intake, but valid biomarkers are not available for all types of dietary exposures. Aims: The aims of this dissertation were to 1) validate self-reported dietary intake and physical activity by using objective co-twin comparison assessments (I) and the doubly labeled water (DLW) technique (II); 2) determine whether eating and physical activity behaviors are associated with body mass index (BMI) and waist circumference (WC) (I, II); 3) examine whether acquired obesity (IV) and dietary factors (III, V) are associated with serum lipoprotein profiles. Materials and methods: The following participants were recruited from the FinnTwin12 and FinnTwin16 studies, two population-based studies on young adult Finnish twins: 1) 713 monozygotic (MZ) and 698 dizygotic (DZ) twin pairs of the same sex who filled in food-frequency questionnaires (FFQ) and co-twin comparison questions (I); 2) 14 MZ twin pairs discordant (BMI difference more than 3kg/m2) and 10 pairs concordant for obesity who provided 3-day food and activity diaries, eating behavior questionnaires, co-twin comparison questions and total energy expenditure (TEE) measurements determined by DLW (II); 3) 15 obesity-discordant and 9 concordant MZ twin pairs who completed 3-day food diaries, physical activity questionnaires and measurements of subcutaneous adipose tissue, visceral adipose tissue and liver fat by magnetic resonance imaging and spectroscopy and of serum lipid determinations by ultracentrifugation, gradient gel electrophoresis and enzymatic techniques (III, IV); 4) 663 twin individuals who provided FFQs and nuclear magnetic resonance spectroscopy-derived measurements of serum lipoproteins and serum docosahexaenoic acid (DHA) as an objective biomarker of DHA intake (V). Results: In both zygosity groups, the co-twins for whom both twin pair members concordantly answered that the identified twin eats more (overall), or eats more fatty foods, or eats more sweet and fatty delicacies, or eats faster, or selects food less according to healthiness or makes less active choices in daily life had significantly higher BMIs and WCs than their twin siblings. Eating more (overall), eating more sweet and fatty delicacies and exercising less remained significant predictors of intrapair differences in BMI and WC independent of each other as evaluated by multivariate regression analysis. Co-twin comparison questions on snacking, fatty foods, sweet and fatty delicacies and healthy foods corresponded well with self-reported food intake in the FFQs. Twin pairs who differed in the overall amount of food they consumed had the largest intrapair differences in BMI (MZ: 1.9 ± 0.1, DZ: 2.9 ± 0.2 kg/m2) and WC (MZ: 5.5 ± 0.6, DZ: 7.5 ± 0.7 cm). However, there were no differences in self-reported intake between these pairs (I). Analysis of obesity-discordant MZ twin pairs confirmed these results, as most pairs agreed that the heavier twins ate more (overall), snacked more and exercised less than the leaner co-twins. Eating behaviors such as eating too much, striving to be thin and body dissatisfaction were more frequently reported by obese co-twins than their lean counterparts. Total energy intake did not differ between the obese and lean co-twins and few differences were found in the 3-day food diary data. Underreporting of actual energy intake was significant for the obese (24.7% of TEE) but not for the lean co-twins (8.4% of TEE) (II). Obesity-discordant pairs differed significantly in their serum lipoprotein profiles, and the acquired accumulation of liver fat was particularly associated with increased concentrations of atherogenic lipids, including low-density lipoprotein (LDL-C) and Apolipoprotein B (ApoB), while physical activity was related to reduced concentrations of atherogenic lipids (IV). Omega-3 polyunsaturated fatty acid intake, as evaluated by self-reporting and serum measurements of DHA, was significantly related to a shift in the serum high-density lipoprotein (HDL) subclass distribution toward larger HDL particle size (III, V). In addition, serum DHA was positively associated with serum LDL particle diameter and negatively associated with triglyceride (TG) concentrations, medium and large very-low density lipoprotein (VLDL) particle concentrations and VLDL particle diameter. A high-fat, high-sucrose, low fiber dietary pattern (labeled junk food ) was positively associated with TG concentrations, a shift in the subclass distribution of VLDL toward larger particles and LDL toward smaller particles, and an increased concentration of small HDL particles in the serum (V). The associations were independent of adiposity and other lifestyle factors, and most were independent of the potential confounding effects of genotype and early environmental factors shared by twins. Conclusions: By using mutual responses of twin pairs, this study provides compelling evidence that acquired eating and physical patterns are important determinants of obesity, but they may be overlooked in population studies that use self-reported data due considerable misreporting of actual energy intakes and exercise behavior by obese subjects. Habitual physical activity and fish intake were related to a favorable serum lipoprotein profile, whereas a high-fat, high-sucrose, low-fiber dietary pattern and accumulation of liver fat associated with an unfavorable serum lipoprotein profile. These results emphasize a healthy lifestyle, in particular reduced portion sizes of energy-dense, nutrient poor foods and regular physical activity as the cornerstone of preventing obesity and lipid disturbances in young adults.
  • Stenman, Lotta (Helsingin yliopisto, 2013)
    Gut barrier function is impaired in several disorders such as inflammatory bowel diseases, diabetes and steatohepatitis. It is suspected that this is related to increased permeability to bacterial endotoxins from the lumen through the gut epithelium. Recent studies have shown a link between high-fat diet and endotoxemia, but the underlying mechanisms are unknown. One possible explanation is the contribution of other luminal substances, such as bile acids. Fat ingestion induces bile flow to the duodenum to facilitate the absorption of fat. At high concentrations, bile acids especially very hydrophobic bile acids are cytotoxic. The aim of this study was to investigate whether dietary fat or obesity causes barrier dysfunction, and whether bile acids play a role in its pathogenesis. The role of bile acid hydrophobicity in their capability of inducing barrier dysfunction was given special attention. The effects of dietary fat and obesity on gut barrier function were investigated in the diet induced obesity and ob/ob -mouse models. Fecal bile acids were quantified and profiles calculated from these mice. The effects of bile acids on intestinal permeability were studied in an in vivo feeding trial with deoxycholic acid and in vitro in an Ussing chamber. In vitro, tissue preparations were incubated with deoxycholic acid and/or ursodeoxycholic acid - two bile acids greatly different in their hydrophobicity. Gut barrier function was impaired by a high-saturated fat diet in mice, but not in genetically obese mice that were fed normal low-fat chow. Barrier dysfunction by dietary fat was especially prominent in jejunum and colon - no significant difference was seen in the permeability of duodenum or ileum. Fecal bile acid hydrophobicity was increased only by dietary fat, not by genetic obesity, and was positively correlated with intestinal permeability. Deoxycholic acid alone increased gut permeability both in vivo and in vitro. The effect was more evident in colonic than jejunal tissue preparations, and the mechanism seemed not to be inflammation-dependent. Barrier impairment was reduced by the hydrophilic ursodeoxycholic acid, which was also reflected as improved tissue morphology. Deoxycholic acid -induced barrier dysfunction seemed to be aggravated by translocated lipopolysaccharides. The present results suggest that dietary fat, but not obesity itself, impairs gut barrier function. The data imply that luminal bile acids are one mechanism for barrier impairment, with hydrophobic bile acids initiating tissue disruption and lipopolysaccharides likely playing the role of a second hit.
  • Niinistö, Sari (Unigrafia, 2014)
    The aim of the present study was to evaluate the associations between the maternal intakes of fatty acids, vitamin D, and their respective dietary sources during pregnancy or lactation, as well as the child s fatty acid status, and the risk of type 1 diabetes. The present study is a prospective cohort belonging to the nutrition part of the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP). The cohort comprised children at increased genetic risk for type 1 diabetes (n=6069) born at the Oulu and Tampere University Hospitals between the years 1997 and 2004. Maternal diet was assessed with a validated food frequency questionnaire during the 8th month of pregnancy and the 3rd month of lactation. The children were monitored for the appearance of autoantibodies associated with type 1 diabetes and for the development of clinical type 1 diabetes, at intervals between 3 and 12 months. The associations between the maternal intakes of fatty acids, vitamin D, as well as their respective food sources and the endpoints, were analyzed by the piecewise linear log-hazard survival model and Cox proportional hazard analyses. The associations between the children s serum fatty acid composition and the risk of type 1 diabetes were studied in a nested case-control study design that included 108 children with preclinical type 1 diabetes and 216 matched controls. The total serum fatty acid composition was analyzed by gas chromatography from samples that were taken from the children between the ages of 1 and 6 years. Conditional logistic regression was applied in the statistical analysis. After adjustment for putative confounders, neither the maternal intake of fatty acids during pregnancy and lactation nor the intake of vitamin D during pregnancy, showed any association with the development of type 1 diabetes. The maternal use of fresh milk and cheese, and the intake of protein from fresh milk during pregnancy, were associated with a lower risk of clinical type 1 diabetes. The maternal total consumption of red meat and meat products, particularly processed meat, during lactation was associated with an increased risk of type 1 diabetes. The child s serum profile of milk-associated fatty acids at, or closest to, the time of seroconversion, was associated with a higher risk of preclinical type 1 diabetes. Findings give one of the first indications that prenatal exposure to certain dairy foods may affect immune regulation, and our results on the milk-associated fatty acid biomarkers confirm the previous findings that the child s own direct cow s milk exposure is associated with autoimmunity in children with increased genetic risk of type 1 diabetes. These results thus indicate that milk and meat products in particular, are interesting topics for future studies on potential nutritional risk and protective factors for type 1 diabetes.
  • Karppinen, Sirpa (Helsingin yliopisto, 2003)
  • Konttinen, Hanna (Helsingin yliopisto, 2012)
    In post-industrialised societies, food is more plentiful, accessible and palatable than ever before and technological development has reduced the need for physical activity. Consequently, the prevalence of obesity is increasing, which is problematic as obesity is related to a number of diseases. Various psychological and social factors have an important influence on dietary habits and the development of obesity in the current food-rich and sedentary environments. The present study concentrates on the associations of emotional and cognitive factors with dietary intake and obesity as well as on the role these factors play in socioeconomic disparities in diet. Many people cognitively restrict their food intake to prevent weight gain or to lose weight, but research on whether restrained eating is a useful weight control strategy has produced conflicting findings. With respect to emotional factors, the evidence is accumulating that depressive symptoms are related to less healthy dietary intake and obesity, but the mechanisms explaining these associations remain unclear. Furthermore, it is not fully understood why socioeconomically disadvantaged individuals tend to have unhealthier dietary habits and the motives underlying food choices (e.g., price and health) could be relevant in this respect. The specific aims of the study were to examine 1) whether obesity status and dieting history moderate the associations of restrained eating with overeating tendencies, self-control and obesity indicators; 2) whether the associations of depressive symptoms with unhealthier dietary intake and obesity are attributable to a tendency for emotional eating and a low level of physical activity self-efficacy; and 3) whether the absolute or relative importance of food choice motives (health, pleasure, convenience, price, familiarity and ethicality) contribute to the socioeconomic disparities in dietary habits. The study was based on a large population-based sample of Finnish adults: the participants were men (N=2325) and women (N=2699) aged 25-74 who took part in the DILGOM (Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome) sub-study of the National FINRISK Study 2007. The participants weight, height, waist circumference and body fat percentage were measured in a health examination. Psychological eating styles (the Three-Factor Eating Questionnaire-R18), food choice motives (a shortened version of the Food Choice Questionnaire), depressive symptoms (the Center for Epidemiological Studies Depression Scale) and self-control (the Brief Self-Control Scale) were measured with pre-existing questionnaires. A validated food frequency questionnaire was used to assess the average consumption of sweet and non-sweet energy-dense foods and vegetables/fruit. Self-reported total years of education and gross household income were used as indicators of socioeconomic position. The results indicated that 1) restrained eating was related to a lower body mass index, waist circumference, emotional eating and uncontrolled eating, and to a higher self-control in obese participants and current/past dieters. In contrast, the associations were the opposite in normal weight individuals and those who had never dieted. Thus, restrained eating may be related to better weight control among obese individuals and those with dieting experiences, while among others it may function as an indicator of problems with eating and an attempt to solve them. 2) Emotional eating and depressive symptoms were both related to less healthy dietary intake, and the greater consumption of energy-dense sweet foods among participants with elevated depressive symptoms was attributable to the susceptibility for emotional eating. In addition, emotional eating and physical activity self-efficacy were both important in explaining the positive association between depressive symptoms and obesity. 3) The lower vegetable/fruit intake and higher energy-dense food intake among individuals with a low socioeconomic position were partly explained by the higher priority they placed on price and familiarity and the lower priority they gave to health motives in their daily food choices. In conclusion, although policy interventions to change the obesogenic nature of the current environment are definitely needed, knowledge of the factors that hinder or facilitate people s ability to cope with the food-rich environment is also necessary. This study implies that more emphasis should be placed on various psychological and social factors in weight control programmes and interventions.
  • Paronen, Johanna (Helsingin yliopisto, 2001)
  • Misikangas, Marjo (Helsingin yliopisto, 2007)
    Colorectal cancer is among the major cancers and one of the leading causes of cancer-related deaths in Western societies. Its occurrence is strongly affected by environmental factors such as diet. Thus, for preventative strategies it is vitally important to understand the mechanisms that stimulate adenoma growth and development towards accelerated malignancy or, in contrast, attenuate them to remain in quiescence for periods as long as decades. The main objective of this study was to investigate whether diet is able to modulate β-catenin signalling related to the promotion or prevention of intestinal tumourigenesis in an animal model of colon cancer, the Min/+ mouse. A series of dietary experiments with Min/+ mice were performed where fructo-oligosaccharide inulin was used for tumour promotion and four berries, bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), cloudberry (Rubus chamaemorus) and white currant (Ribes x pallidum), were used for tumour prevention. The adenomas (Apc-/-) and surrounding normal-appearing mucosa (Apc+/-) were investigated separately due to their mutational and functional differences. Tumour promotive and preventive diets had opposite effects on β-catenin signalling in the adenomas that was related to the different adenoma growth effects of dietary inulin and berries. The levels of nuclear β-catenin and cyclin D1 combined with size of the adenomas in the treatment groups suggests that diets induced differences in the cancerous process. Adenomas progressing to malignant carcinomas are most likely found in the sub-groups having the highest levels of β-catenin. On the other hand, adenomas staying quiescent for a long period of time are most probably found in the cloudberry or white currant diet groups. The levels of membranous E-cadherin and β-catenin increased as the adenomas in the inulin diet group grew, which could be a result of the overall increase in the protein levels of the cell. Therefore, the increasing levels of membranous β-catenin in Min/+ mice adenomas would be undesirable, due to the simultaneous increase in oncogenic nuclear β-catenin. We propose that the decreased amount of membranous β-catenin in benign adenomas of berry groups also means a decrease in the nuclear pool of β-catenin. Tumour promotion, but not the tumour prevention, influenced β-catenin signalling already in the normal appearing mucosa. Inulin-induced tumour promotion was related to β-catenin signalling in Min/+ mice, and in WT mice changes were also visible. The preventative effects of berries in the initiation phase were not mediated by β-catenin signalling. Our results suggest that, in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should be considered when evaluating preventative dietary strategies.
  • Itkonen, Suvi (Helsingin yliopisto, 2015)
    Phosphorus (P) intake in Western countries exceeds the nutritional recommendations 2- to 3-fold, and the increased use of food additive phosphates (FAPs) in the food industry has augmented total P (TP) intake; an estimated 10-50% of TP intake comes from additives. However, in food composition databases, the amounts of FAPs may have not been taken into account. Difficulties in measuring true P intake occur also because bioavailability of P differs between foodstuffs; inorganic P from additives is absorbed better in the intestine than natural, organic P. The harmfulness of high P intake to kidney patients has been known for years, and dietary P restriction is used in the treatment of the disease to avoid vascular calcification, which occurs due to calcium-phosphate deposition in the vascular vessel wall. However, recently, concerns have been raised about the role of elevated serum phosphate concentrations in cardiovascular health in the general population, but data on dietary P is scarce. This thesis aims to offer new insights into the potential health risks related to high dietary P intake in Finland by providing knowledge on the bioavailability of P in foodstuffs, and on the association of high dietary P intake with cardiovascular disease risk factors in the general population. In Study I, a new method was developed for analysis of in vitro digestible P (DP), indicating bioavailable and absorbable P. DP and TP contents of certain differently processed cereals were analyzed. The calculated uncertainty of the new analysis method had little effect on the DP contents in the samples. Soured cereals contained more DP than unsoured cereals, and the long processing time increased the amounts of DP. In Study II, the DP contents of selected plant-based foodstuffs with or without FAPs were determined by the analysis method developed in Study I. The analyzed plant-based products contained varying amounts of P, but most P was not digestible, except in FAP-containing foodstuffs (cola drinks and baking powder-leavened muffins). In Study III, the associations between TP intake, P density of the diet (TP intake related to energy intake), FAP intake, and a risk factor of cardiovascular disease, carotid intima-media thickness were investigated in a middle-aged Finnish population (n=546). Linear associations among P density of the diet, FAP intake, and carotid intima-media thickness were found when all subjects were included in the analysis, and between FAP intake and carotid intima-media thickness in females (n=370). However, among males (n=176) no significant associations were found. In conclusion, results of this thesis reinforce the previous understanding about the importance of the source of P when assessing P intake in a population. The plant-based foodstuffs generally contain low amounts of DP, but the FAP-containing plant-based products have relatively higher DP contents than FAP-free products. The method developed for the analysis of DP is reliable but requires validation against an in vivo method before these results can be generalized. Albeit high dietary P intake (P density of the diet and FAP intake) was associated with a cardiovascular disease risk factor, carotid intima-media thickness, due to the cross-sectional design of the study, no causal relationships can be inferred. Thus, the potential adverse effects of highly absorbable FAPs should be further investigated both in intervention and in follow-up studies before final conclusions about the harmfulness of high P intake for the general population can be drawn. To find this out, data on use of FAPs in the food industry and updated information on P contents in foodstuffs are also needed.
  • Karp, Heini (Helsingin yliopisto, 2013)
    A high P intake is deleterious to chronic kidney disease (CKD) patients, but based on more recent data, it has also been associated with an increased risk of osteoporosis and cardiovascular diseases in the general population. In addition to several natural sources of P (especially dairy products, meats, whole grains, legumes, and eggs), the use of P additives in the food industry is common and further increases P intake. In this thesis, P contents of foods were analysed and the effects of different P sources on mineral metabolism were compared in healthy young female subjects. In Studies I and II, the objective was to measure both total phosphorus (TP) and in vitro digestible phosphorus (DP) contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The results suggest that the absorbability of P may differ substantially among different foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives. Among foods of animal origin, the highest TP and DP contents were found in processed and hard cheeses; the lowest, in milk and cottage cheese. Studies III and IV were controlled intervention studies in healthy young women. Each subject served as her own control, and the order of the study sessions was randomized. Markers of mineral metabolism from blood and urine samples were measured. In Study III, acute effects of dietary P from three different food sources (meat, cheese and whole grains) and a phosphate supplement on calcium (Ca) and bone metabolism were investigated. Only the phosphate supplement increased serum parathyroid hormone (S-PTH) concentration compared with the control session. Relative to the control session, meat increased markers of both bone formation and bone resorption. Cheese decreased S-PTH and bone resorption. These data suggest that the metabolic response was different for different foods. The purpose of Study IV was to determine whether the effects of mono- and polyphosphate salts (MP and PP, respectively) used as additives differ on markers of Ca and P metabolism in young women. In both MP and PP sessions, serum phosphate, urinary phosphate, and S-PTH increased relative to the control session. PP decreased urinary Ca more than did MP. The results suggest that PP binds Ca in the intestine better than does MP. In the long run, increased S-PTH, caused by either an MP or PP salt, could have negative effects on bone metabolism. In summary, the studies support the previous understanding of differences in P absorbability and mineral metabolism. This is relevant regarding the diets of CKD patients, but may also have a wider relevance if the significance of high P intake in the aetiology of cardiovascular diseases and osteoporosis is confirmed.
  • Marttinen, Maija (Helsingin yliopisto, 2014)
    Plant sterols and stanols (collectively named as phytosterols) are plant-derived dietary compounds. The intake of natural phytosterols from a habitual Western diet varies between 150 to 400 mg/d. Phytosterols are added to functional foods for their serum cholesterol-lowering effect and their intake increases greatly when phytosterol enriched functional foods are consumed. Phytosterols reduce the absorption of dietary and biliary cholesterol from the intestine, leading to increased concentrations of cholesterol excreted in the feces. Increased fecal cholesterol may act as a carcinogen in the intestinal lumen. The focus of this thesis was to study the effect of plant sterols and stanols on the tumor formation in the ApcMin mouse, an experimental model of colon cancer. The ApcMin carries an inherited mutation in the Apc tumor-suppressor gene, which eventually leads to the development of adenomas in the intestine. Mice were fed a control diet or a 0.8% (w/w) plant sterol/ stanol diet. Commercial foods enriched with plant sterols or stanols were used to compose the experimental diets. The impact of phytosterol feeding on cell signaling pathways involved in intestinal tumorigenesis and the changes in sterol metabolism were studied in the intestinal mucosa of ApcMin mouse. The final part of this work assesses the intake of phytosterols from enrichment among Finnish men and women from the FINDIET 2007 Survey. Both plant sterols and plant stanols increased the number of adenomas in the small intestine of ApcMin mice. Plant stanol feeding increased the number of intestinal tumors in both genders, whereas plant sterol feeding increased the number of tumors more pronouncedly in female mice. Wnt- β-catenin and Egfr signaling were up-regulated in the intestinal mucosa of plant stanol fed ApcMin mice when compared with control mice. Plant sterol and stanol feeding increased fecal cholesterol concentration that positively associated with the number of intestinal adenomas. Significant changes in the composition of intestinal sterols were observed after plant sterol and stanol feeding. It appears that plant sterol feeding affects genders differently, and estrogen signaling may play a role in intestinal tumorigenesis in female ApcMin mice after plant sterol feeding. Overall, the mice responded in a different manner to plant sterol and plant stanol feeding in intestinal sterol handling, cell signaling, and tumor development. Finally, this thesis shows that according to the FINDIET 2007 Survey the intake of phytosterols from enrichment can go beyond the advised intake; for 20% of those using phytosterol enriched products the intake of phytosterols was more than 3 g/d. The consistency or duration of the consumption of phytosterol enriched products was not determined in this work. The results show that phytosterols at high intakes are harmful in the intestine of tumor-prone mice. Whether phytosterols from enrichment affect human intestinal health warrants for further research.
  • Huurinainen, Outi (2009)
    Microbiota inhabiting the colon fermentate carbohydrates, proteins and endogenous substrates to volatile fatty acids (VFA) and produce energy for the microbial growth. Because all species of bacteria ferment some component of the digesta and produce various VFAs, alterations in microflora may modify these fermentative end products. Thus, measuring the amount and type of VFA produced gives an instrument which reflects changes in the bacterial microbiota of the intestine. This study set out to explain the connections between diet composition and the formation of VFAs. The general hypothesis was that different food compositions cause differences in the VFA profile, and this may have systemic effect on animal health. Graeco Latin Square design study with 5 healthy Beagles was performed, feeding high protein (diet A, starch 54 g/kg, crude protein 609 g/kg), high carbohydrate (diet B, starch 438 g/kg, crude protein 194 g/kg), and a balanced commercial (diet C, starch 277 g/kg, crude protein 264 g/kg) diets for three weeks each. The diet C was used also for the baseline. VFA, fecal dry matter and fecal consistency score were assessed. All dogs had formed feces during diets B and C but diarrhea during diet A, leading to significant differences in fecal consistency score between the diets (p < 0.0001). The results indicate that alterations in diet had a large influence on the amount and quality of VFAs produced. Mixed-effect model analysis shows that the diets had a statistically significant (p<0.05) influence on all of the VFAs produced excluding butyric acid. The most significant changes from the baseline diet were seen with the high protein diet. Compared to the baseline diet, valeric acid production increased 24-fold, isobutyric acid by 79.5% and isovaleric acid by 42.4%. Production of propionic acid decreased by 43.3%, acetic acid by 25.0%, and butyric acid by 10.2%. In previous studies similar changes in VFA profile have been coupled with various intestinal diseases as well as inhibition in biotin absorption. Furthermore, this might have an influence on inflammatory response at the cellular level. Thus, changes in VFA profile may have an influence at least on the local intestinal health. The total amount of fatty acids decreased on both experimental diets. It seems that having moderate protein and carbohydate levels in the diet is a virtue and more is not necessarily better. This study provides additions to existing understanding of the relationship between diet composition and the formation of VFAs in the intestine. The findings suggest that observing the alterations in VFA levels formed in the intestine and therefore present in feces, may provide an instrument to indirectly observe changes in the bacterial microbiota of the intestine. Thus, there is a need to find the link between the changes in VFA profiles and colonic microbiota, and bacterial diversity in feces by using molecular methods. Having this greater level of understanding would lead to more robust insights into the role of intestinal microbiota in animal health, and to potential advances in the prevention and curing of related diseases. Paksusuolen mikrobit fermentoivat hiilihydraatteja, proteiineja ja sisäsyntyisiä substraatteja haihtuviksi rasvahapoiksi ja energiaksi, jota mikrobit käyttävät aineenvaihduntaansa. Tämän tutkimuksen tavoitteena oli selittää dieetin koostumuksen ja haihtuvien rasvahappojen välinen yhteys. Yleinen tutkimushypoteesi oli, että muutokset ruoan koostumuksessa aiheuttavat muutoksia myös haihtuvien rasvahappojen pitoisuuksiin, millä saattaa olla vaikutusta eläimen yleiseen terveydentilaan. Kokeellinen tutkimus (kreikkalais-latinalainen neliö) tehtiin syöttämällä viidelle terveelle Beagle-rotuiselle koiralle korkeaproteiinista (dieetti A, tärkkelys 54g/kg, raakaproteiini 609g/kg), korkeahiilihydraattista (dieetti B, tärkkelys 438g/kg, raakaproteiini 194g/kg) sekä tasapainotettua kaupallista ruokaa (dieetti C, tärkkelys 277g/kg, raakaproteiini 264g/kg) kolmen viikon ajan kutakin. C dieettiä syötettiin myös “baseline” aikana. Haihtuvat rasvahapot, ulosteen kuiva-aineen määrä sekä koostumus mitattiin. Ulosteen koostumus oli hyvä B ja C dieettien aikana, mutta dieetti A aiheutti kaikille koirille ripulin johtaen merkitseviin eroihin ulosteen koostumuksessa (p < 0.0001). Tulosten mukaan muutokset ruoan koostumuksessa vaikuttivat suuresti haihtuvien rasvahappojen määrään ja koostumukseen. Dieeteillä oli tilastollisesti merkitsevä vaikutus kaikkien muiden paitsi voihapon tuottoon. Suurimmat muutokset tavattiin korkeaproteiinisen dieetin aikana. Verrattuna lähtökohtaan valeriaanahapon tuotto muuttui 24-kertaiseksi, isovoihapon tuotto lisääntyi 79.5% ja isovaleriaanahapon 42.4%. Propionihapon tuotto sen sijaan laski 43.3%, etikkahapon 25.0% ja voihapon 10.2%. Aiemmissa tutkimuksissa vastaavanlaiset muutokset haihtuvien rasvahappojen koostumuksessa on yhdistetty useisiin eri suolistosairauksiin sekä biotiinin imeytymisen häiriintymiseen. Lisäksi tämänkaltaisilla muutoksilla saattaa olla yhteys solutasolla tapahtuvaan immuunipuolustukseen. Näin ollen havaituilla muutoksilla saattaa olla vaikutusta ainakin paikallisesti suoliston terveyteen. Haihtuvien rasvahappojen kokonaismäärä väheni molempien kokeellisten dieettien aikana. Näyttäisi siltä että kohtuus on hyve myös dieetin proteiinien ja hiilihydraattien suhteen eikä enemmän ole välttämättä parempi. Tämä tutkimus toi lisää tietoa dieetin koostumuksen ja haihtuvien rasvahappojen tuoton välisestä yhteydestä. Tulokset viittavat siihen että tutkimalla haihtuvien rasvahappojen muodostumista suolistossa määrittämällä kyseisten aineiden pitoisuus ulosteissa, voidaan epäsuorasti saada tietoa mikrobiston muutoksista suolistossa. Näin ollen lisätutkimuksia molekulaarisia menetelmiä käyttäen tarvitaan, jotta voitaisiin löytää yhteys haihtuvien rasvahappojen pitoisuuden ja suoliston mikrobien välille. Näin ymmärrettäisiin paremmin suolistomikrobiston merkitys eläimen terveydelle ja voitaisiin paremmin ennaltaehkäistä ja hoitaa suolistomikrobien epätasapainotiloihin liittyviä sairauksia.
  • Kangas, Suvi (2013)
    Background: Cancer is the leading cause of death worldwide, claiming 7.6 million lives a year. Five behavioural factors have been recognised to be responsible for 30 % of the disease burden. Among them is low fruit and vegetable consumption. Fruit and vegetable consumption has been inversely associated with cancer risk but the mechanisms behind this effect are still largely debated. Dietary antioxidants present in large quantities in plant foods have been hypothesised to contribute to this protection. Objective: The aim of this study was to investigate the relationship between dietary total antioxidant capacity (TAC) and overall cancer incidence. This was done applying a new antioxidant measurement that reflects the whole set of direct antioxidant reducers (vitamin C, alpha-tocopherol, carotenoids and flavonoids) present in diet. The average TAC intake levels of the participants were assessed and the main dietary contributors to the TAC scores were examined. Subjects: Study subjects included 67 634 middle aged French women participating in an on-going prospective cohort study called E3N. Their dietary assessment was made between June 1993 and July 1995 using a semi-quantitative food frequency questionnaire able to quantitatively and qualitatively assess the average daily intake of 208 different foods, recipes and beverages. Cancer cases were self-reported and validated against medical records. The follow up of the participants ended in May 2008. Methods: Four different total antioxidant capacity scores were created using two different TAC methods, the ferric reducing ability parameter (FRAP) and the total radical-trapping antioxidant parameter (TRAP), and including or excluding coffee from the dietary TAC calculation. Coffee exclusion was justified with the fact that it is the largest contributor to the dietary TAC intake, and because of its association with some negative lifestyle behaviours, it can act as a confounder even if adjustments are made. Statistical analyses for cancer risk according to dietary TAC intake were made using Cox proportional hazards model adjusting for energy intake without alcohol, tobacco smoking, alcohol intake, BMI, physical activity level, educational background, region of residence and family history of cancer. Results: When coffee was included in the dietary TAC scores a significant but modest increase in cancer risk was observed towards higher TAC intakes (p for trend < 0.05 for both FRAP and TRAP). On the contrary, when coffee was excluded from the TAC scores a significant although modest decrease in overall cancer risk was observed (p for trend = 0.016 for both FRAP and TRAP without coffee). In the indexes where coffee was included in the score it contributed up to 43 % and 76 % of total FRAP and TRAP scores respectively. After coffee the main contributors to dietary TAC intake were tea, wine, fruits, vegetables, fruit juice and chocolate. The mean daily intake of TAC was 20.5 mmol of FRAP and 20.2 TE of TRAP in the scores including coffee. When coffee was excluded from the scores, the mean intake levels dropped to 9.4 mmol and 4.9 TE. Conclusion: Dietary total antioxidant capacity was associated with a statistically significant but modest decrease in cancer incidence when intake of coffee, the main TAC source, was not taken into account. Coffee seems to be acting as a confounding factor since when it was included in the TAC scores, there was a small but statistically significant positive association with cancer risk. For future studies it would be crucial to standardise the TAC methods so that comparisons between studies could be made. On the other hand in vitro nature of the TAC methods should be kept in mind; a fact that challenges the interpretation of the results from the biological perspective.
  • Männistö, Satu (Helsingin yliopisto, 1999)
  • Rajakangas-Tolsa, Johanna (Helsingin yliopisto, 2008)
    The incidence of colon cancer is high in Western societies, and in Finland it is among the three most common cancer types in both females and males. Environmental factors, including diet, affect colon cancer development. During the last few years, a vast amount of new, functional foods have been introduced to the consumers. Several products are already available that are marketed as promoting intestinal health. To be able to reliably call a dietary compound a chemopreventive substance it is of fundamental importance to understand the mechanism by which it affects tumour formation and the integrity of the epithelial cells. In this thesis, three different dietary compounds were studied in an experimental model of colon cancer. Inulin is a non-digestible fibre found naturally in chicory roots, artichokes and onions, amongst others. Nowadays it is widely used as an added dietary fibre in several food products. Conjugated linoleic acid (CLA) is a conjugated form of the fatty acid linoleic acid. CLA is formed by bacterial fermentation of linoleic acid in the rumen of cows and other ruminants. Concomitantly, it can naturally be found in milk and meat of ruminants. White currant is a colourless berry low in phenolic compounds that are believed to prevent cancer formation. Contrary to what was expected, inulin and the conjugated linoleic acid isomer trans-10, cis-12, were tumour growth promoting dietary constituents when fed to Min mice. Both diets decreased the NF-kappaB levels in the mucosa, but physiological adenoma development did not affect NF-kappaB. Diet altered beta-catenin and p53 signalling in the adenomas, confirming their involvement in adenoma growth. White currant, on the other hand, was chemopreventive, despite its low contents of phenolic compounds. The chemopreventive effect was accompanied by increased p53 levels in the mucosa, and decreased beta-catenin and NF-kappaB levels in the adenoma. This could explain the reduced adenoma number and size. The results underline the importance of carefully testing new dietary compounds in different settings to reliably confirm their health benefits. In this study two compounds that are consumed and believed to add to our health proved to be cancer promotive. A berry with low phenolic contents, on the other hand, was chemopreventive.
  • Salonen, Saija (1971)
  • Dolfus, Gero (2009)
    In this thesis, I analyze how differences in redistributive tax schedules alone and together with wage differences arising from industry-specific shocks form migration incentives. I do so with the help of a theoretical model in which there are two countries that are identical except that in only one of them income is redistributed. The citizens of these two countries maximize their expected lifetime utility by investing in education and deciding on migration. Allowing for migration increases the investment in human capital by the citizens who initially live in the redistributive country and want to emigrate, while those who wish to emigrate from the country without redistribution may lower their educational effort. Moreover, migration influences the composition of the population of the redistributive country which, in turn, changes the size of the tax revenue and may reduce or increase the flat-rate benefit. Comparing the individuals' utility before and after migration is allowed reveals that integrating labor markets may result in a Pareto improvement.
  • Jansson, Julia (2008)
    Pro gradu –tutkielmani sijoittuu poliisihistorian alaan ja liittyy sekä kriminologiaan että kansainvälisiin suhteisiin. Tutkielma käsittelee terrorismin ja anarkismin vastaista poliisiyhteistyötä. Työssä analysoidaan Rooman kansainvälisen anarkismin vastaisen konferenssin (International Anti-Anarchist Conference of Rome) päätöksiä vuodelta 1898 sekä Interpolin (the International Criminal Police Organization – Interpol) päätöslauselmia vuodelta 1998. Nämä ovat työni primaarilähteet. Lisäksi tarkastelen myös muita Interpolin vuoden 1951 jälkeen tekemiä terrorismiin liittyviä päätöslauselmia. Työssäni tutkin päätöslauselmia ja vertailen niiden tapoja käsitellä ja määritellä terrorismia. Työn lähtökohta on Richard Bach Jensenin ajatus siitä, että Interpol on itse asiassa anarkismin vastaisen konferenssin seuraaja. Tämän takia päätöslauselmia on hedelmällistä verrata keskenään. Interpolin suhtautuminen terrorismiin muuttui huomattavasti vuonna 1998, minkä takia juuri tämä vuosi on valittu tutkimuksen kohteeksi. Tähän saakka Interpol oli pitänyt tärkeimpänä ohjenuoranaan peruskirjansa kolmatta artiklaa, joka kieltää organisaatiota puuttumasta poliittisiin, sotilaallisiin, uskonnollisiin tai rotuun liittyviin asioihin. Terrorismia pidettiin näihin asioihin kuuluvana. Vuoden 1998 jälkeen terrorismi kuitenkin katsottiin osaksi kansainvälistä rikollisuutta, eli asiaksi, jota vastaan Interpolin tulee taistella. Sekä Rooman anarkismin vastaisen konferenssin että Interpolin päätöslauselmissa (anarkistinen) terrorismi epäpolitisoitiin, eli määriteltiin rikolliseksi. Tutkielma pyrkii kuvaamaan sitä, miten epäpolitisointi näkyy päätöslauselmissa sekä hahmottelemaan sille mahdollisia syitä. Yhtenä epäpolitisoinnin tärkeimmistä syistä voidaan pitää anarkismin ja terrorismin poliittista luonnetta, jonka takia kansainväliselle poliisiyhteistyölle on ollut vaikea rakentaa pohjaa. Epäpolitisoinnin avulla ongelma on voitu kiertää, koska teot on erotettu niiden motiiveista. Tällä tavalla niitä on voitu käsitellä tekoina, joita jokainen maa pitää rikollisina, kuten tuhopolttoina tai murhina. Vuosina 1898 ja 1998 molemmat toimijat, sekä Rooman anarkismin vastainen konferenssi että Interpol, kohtasivat samankaltaisen uhan ja reagoivat siihen samalla tavoin. Terrorismin luonteen muutos lisäsi tarvetta tiiviimmälle kansainväliselle yhteistyölle, minkä epäpolitisointi mahdollisti. Lisäksi yhteiskunnalliset olot ja poliisin byrokratisoituminen vaikuttivat anarkismin vastaisen konferenssin ja Interpolin toimintatavan muutoksiin.