Doctor of Philosophy / Department of Human Nutrition / Weiqun Wang / Weight control via dietary caloric restriction and/or exercise has been demonstrated for cancer prevention. However, the underlying mechanisms are not clear. Previous studies in our lab showed that IGF-1 and IGF-1-dependent signaling were reduced by weight control. To confirm the requirement of IGF-1 reduction for cancer prevention, we restored IGF-1 in the exercised mice, which partially reversed the reduction of TPA-induced PI3K expression and PI3K-related 38:4 PI substrate. To explore the overall mechanistic impact, we further studied the effect of weight control on the profiles of lipid, gene and protein expression in TPA treated skin tissues. The mice were randomly assigned into 4 groups: ad libitum-fed sedentary control (control), ad libitum-fed exercise (AL+Exe), exercise but pair-fed at the amount of control (PF+Exe), and 20% of dietary calorie restriction (DCR). At the end of 10 weeks, the mice were treated with TPA topically for two hours. The body weights were significantly reduced in DCR and PF+Exe but not AL+Exe mice when compared with the control. Plasma and skin tissue triacylglycerides were significantly decreased in PF+Exe and DCR groups but not AL+Exe. Similar impact was found for the diacylglyceride profile in both plasma and skin tissue accordingly. Using Affymetrix microarray, 784, 223, and 152 probe sets were respectively found significantly changed by DCR, PF+Exe, and AL+Exe. PF+Exe and DCR showed similar impact on signaling pathways-related gene expression as analyzed by GenMAPP. Of the total 86 proteins identified by 2D-DIGE proteomics, 20 proteins were significantly changed by DCR. Overall, our results showed weight control via DCR or pair-fed exercise rather than exercise with ad libitum feeding significantly reduced body weight and body fat, resulting in reduction of IGF-1 and IGF-1-induced signaling such as PI3K and PI-related pathway. The overall impact upon lipid profiling and gene and protein expression by weight loss suggests many other mechanistic targets. Although we could not ambitiously clarify all the changes were related to anticancer mechanisms in the scope of this study, understanding of the relationship between weight control and TPA-induced skin cancer risk as well as IGF-1-dependent signaling pathways may reveal intrinsic mechanisms and provide novel approaches to prevent cancer in the future studies.

Doctor of Philosophy / Department of Human Nutrition / Valentina M. Remig / The frequency of dietary supplement use has increased in recent years, especially among older adults. National studies estimated 60-65% of older adults were using at least one dietary supplement, typically a multi-vitamin, multi-mineral (MVMM) supplement. Dietary supplement use has been reported to improve the micronutrient intakes of older adults. The current research study focused on the use of dietary supplements, dietary intakes, and impact of vitamin/mineral (VM) supplements on the nutrient intakes of older Kansans. Volunteer subjects, 60+ years of age, were recruited from 35 senior centers across Kansas. Subjects completed a questionnaire asking for demographic information, current health status, and dietary supplement use. Dietary supplement use was verified for 319 subjects. Two subsequent 24-hour diet recalls were completed by 312 subjects. The sample population was primarily white, non-Hispanic females. Nearly 86% of participants used at least one dietary supplement; most commonly MVMM, calcium, vitamin D, and fish oil. Dietary intake analyses compared intakes of dietary supplement (DS) users to non-dietary supplement (NDS) users. DS subjects consumed significantly higher dietary intakes of carbohydrate, fiber, vitamin A, and zinc than NDS subjects. The NDS group consumed undesirably higher intakes of total fat, saturated fat, and sodium. These results support previous findings that DS users consume healthier diets. The impact of VM supplement use on micronutrient intake compared only the intakes of subjects using VM supplements (n=263) to the Dietary Reference Intakes (DRI). Subjects were most likely to have inadequate dietary intakes of vitamin D, calcium, vitamin E, and magnesium. All micronutrient intakes were improved with the inclusion of VM supplements; most improved were vitamin E, folic acid, vitamin D, vitamin B6, and calcium. Despite supplementation, nearly half of subjects still exhibited low intakes of vitamin D, calcium, and magnesium. Supplementation did not consistently exceed the Tolerable Upper Limit established by the DRIs for most nutrients. In conclusion, dietary supplement use was very common in the sample population, DS subjects had generally healthier diets, and VM supplement use improved micronutrient intake without contributing to concern for toxicity.

Doctor of Philosophy / Department of Human Nutrition / Mark D. Haub / Background: Mixed Martial Arts (MMA) is a growing sport that places competitors into specific weight classes to level the competition field. Athletes “cut weight” to compete in a weight class lower than their “walk around” weight. Techniques for cutting weight include dehydration, starvation and exercise in hot environments jeopardizing health and performance. Higher-protein diets (HPD) have been shown to improve weight loss by increasing satiety, thermogenesis, decreasing total energy intake, and maintain lean mass during periods of energy deficiency, such as weight loss. Research regarding the impact of HPD on performance is limited and conflicting. Specific Aims: The central hypothesis for this study was: HPD diets will elicit greater weight loss and enhance body composition compare to tradition low-fat diets in non-obese, active individuals. The three specific aims of this study are: 1) examine the effects of HPD on weight loss, 2) evaluate the impact of HPD of athletic performance, and 3) determine the effectiveness of HPD for accelerated weight loss. Methods: Military personnel participating in the Combatives program were recruited. Participants were assigned a HPD (40% CHO, 30% PRO, 30% fat), traditional low-fat, high-carbohydrate diet (65% CHO, 15% PRO, 20% fat), or an ad libitum diet for 12-day to 6-weeks depending on their training program. Fields tests for pre- and post-intervention measures of performance included: vertical jump and leg power index to measure explosive power, 600 meter shuttle run for anaerobic capacity and 1.5 mile run for aerobic capacity. Pre- and post-intervention of weight and body composition were determined using dual energy x-ray absorptiometry. Diet analysis software was used to determine nutrient intakes during the study. SPSS statistical software was used to determine descriptive statistics, paired t-tests, Pearson’s Correlations and one-way ANOVA. Results & Conclusions: Due to the unanticipated high rate of dropout, statistical significance was difficult to determine, however, there was a trend for the HPD to elicit fat-free mass retention and it not negatively impact performance. Discrepancies in energy and nutrient intake made dietary comparison difficult. Future studies with larger samples and greater dietary control are needed to further evaluate the research goals of this study.

Doctor of Philosophy / Department of Human Nutrition / Edgar Chambers IV / Food consumption continues to be an area of focus for nutrition, health, and consumer research. Eating adequate amounts of fruits and vegetables, appropriate levels of dairy products, increasing whole grains, and switching to lean meat and fish all are associated with managing weight and reducing the risk of chronic diseases including cancer, diabetes, hypertension, and cardiovascular disease. Research has shown that food consumption rates vary across segments of the U.S. population depending on several socio-demographics including race/ethnicity, gender, and age. The purpose of this research was to examine consumption of various foods including fruits and vegetables, dairy products, selected types of grain and starchy vegetable foods, and meat and legume products based on race and ethnicity, age, and gender using 24-hour recall dietary data from survey years 2003-2006 of the National Health and Nutrition Examination Survey (NHANES) conducted by the Centers for Disease Control and the United States Department of Agriculture. The 2003-2006 NHANES 24-hour dietary recall data, known as What We Eat In America, were used for analysis of food consumption. Two non-consecutive days of 24-hour dietary recall and demographic information were analyzed to assess consumption patterns of participants who: 1) were at least two years of age, 2) had complete and satisfactory dietary recall data, and 3) were members of a selected racial/ethnic group. The sample size was 17, 885 males and females: 4,994 African Americans (non-Hispanic); 7,525 Whites (non- Hispanic); and 5,366 Hispanics (Mexican American and other Hispanics). Individual Foods Files (IFF), containing foods coded for each individual, were accessed via the NHANES website to use for the consumption comparison analysis. There were food files for each of the two recall days of each survey year, 2003-2004 and 2005-2006. These findings indicate that there are racial/ethnic, age, and gender differences in the consumption of various foods. Fruits, vegetables, and dairy products were only consumed by 70-80% of the sample populations. Only 18-42% of the respondents reported eating whole grain breads, legumes, nuts, and seeds. However, meat and meat product consumption was reported by more than 75% of the sample. African Americans consumed fewer fruits, vegetables, whole grains, and dairy products compared to Whites and Hispanics. African Americans had a tendency to consume culturally relevant items such as greens, sweet potatoes, grits, and chicken. Children consumed more French fries, frankfurters, peanut butter, macaroni and cheese, and hamburgers than adults. Consumption rates among males and females depended on race/ethnicity. However, within a racial/ethnic group, gender consumption differences were minimal. This research demonstrates that the types of foods eaten for all groups of food products vary by racial and ethnic population, and age or gender subgroups. African Americans' fruit and vegetable consumption trends are distinct in many cases. This research serves as a current baseline for future research exploring the relationship of dietary intake and race and ethnicity. Given that African Americans have higher incidences of chronic diseases, there is a need to continue to develop culturally sensitive dietary counseling and intervention programs. Furthermore, this study highlights areas of opportunities to expand research involving African Americans from a sensory, business and promotional perspective capitalizing on the diversity of food habits.

Master of Science / Department of Human Nutrition / Mark D. Haub / Purpose: Physical activity (PA) and resistant starch (RS) beneficially affect metabolic health. However, their combined effects on gut health are poorly understood. The purpose of this thesis was to investigate the combined effects of PA and RS via breath hydrogen production and blood glucose responses and directly learn about the research process. Methods: Twenty subjects with no reported symptoms of metabolic diseases participated in this thesis project. Subjects wore accelerometers to determine PA status, and were then stratified into two groups: less active or more active. Once enrolled and stratified into groups based on PA assessment, subjects came to the laboratory on two more occasions to eat a standardized energy dense test meal with a lemonade beverage. The beverage contained different doses (5 g or 25 g) of RS type 4. On each test day, breath hydrogen was collected at baseline through the sixth hour at hour intervals through the fourth hour. Between hours four and six, the breath samples were collected every 30 minutes. Blood glucose samples were collected at baseline before the meal and then 15, 30, 45, 60, 90, and 120 minutes after beginning to eat the meal. Results: The incremental areas under the curve for glucose were not different between PA groups or RS dose (p>0.05). The area under the curve values for breath hydrogen were not different (p>0.05) between groups or doses of PA and RS, respectively. Conclusion: These results indicate that acute assessments of gut fermentation in generally healthy participants, as assessed by postprandial breath hydrogen production, requires more than six hours of assessment to determine differences between treatments and levels of physical activity.

Le but de cette étude consiste à démontrer l’impact positif d’une supplémentation en glutamine chez des nageurs élites, afin d’améliorer le statut immunitaire et d’évaluer si les changements plasmatiques de la glutamine peuvent expliquer l’incidence d’infections des voies respiratoires (IVRS). En parallèle, ce projet évalue si les apports alimentaires influencent la glutamine plasmatique et l’incidence d’IVRS. L’étude s’est effectuée auprès de 14 athlètes élites (8 hommes, 6 femmes). Chaque athlète a participé aux deux conditions expérimentales : un supplément de glutamine et une solution placebo isocalorique. Les périodes de supplémentation se déroulaient sur sept jours, incluant trois journées consécutives de compétition. Le profil hématologique, après les compétitions, montre qu’un supplément de glutamine n’améliore pas significativement la concentration plasmatique en glutamine ni les niveaux de cytokines comparativement à une solution placebo. Bien que les résultats soient semblables sous les deux conditions, les niveaux post-compétition ont tendance à être supérieurs aux valeurs pré-supplémentation, lorsqu’un apport exogène en glutamine est fourni à l’organisme alors que les concentrations plasmatiques de glutamine tendent à diminuer lorsqu’une solution placebo est administrée (p=0.067). L'incidence d’IVRS ne peut être expliquée par une faible concentration plasmatique de glutamine ni par un apport exogène de glutamine. On observe cependant une augmentation d’IVRS suite aux compétitions, soient de 8 athlètes pour le groupe placebo contre 3 au groupe glutamine. Les athlètes atteints d'IVRS semblent consommer moins d'énergie totale (kcal) et de protéines que les athlètes sains (p=0.060). Les résultats obtenus ne démontrent pas qu’une supplémentation en glutamine améliore le profil immunitaire et ne prévienne l’incidence d’IVRS, mais ils soulèvent l’hypothèse qu’un apport exogène en glutamine stabilise les niveaux plasmatiques de glutamine, permettant aux athlètes de poursuivre leurs entraînements et de récupérer efficacement. / The purposes of this study were to determine the positive impacts of glutamine supplementation upon immune system status and to determine whether changes in plasma glutamine relate to the appearance of upper respiratory tract infections (URTI) in elite swimmers. Furthermore, this study evaluated dietary intakes and its influence on immune parameters and URTI incidence. Fourteen athletes (8 men, 6 women) took part of the study. Each athlete participated in both experimental conditions: glutamine supplement and an isocaloric solution placebo. The supplementation period lasted seven day, including three consecutive competing days. Post competing hematologic profils of swimmers show that glutamine supplement does not significantly improve plasma glutamine neither cytokines levels, compared to a placebo solution. Even if plasma glutamine concentrations are similar with both conditions, the post competiting levels tend to be higher than pre competing values, when glutamine is supplemented. Futhermore, plasma glutamine levels show a decreasing trend under control conditions (p=0.060). In this study, URTI can not be explained by low plasma glutamine or supplemented glutamine. However, URTI incidence is higher after competitions, where 8 athletes showed symptoms (control group) and 3 only in the experimental group. Athletes with URTI seem to consume less energy and proteins than healthy athletes (p=0.060). These data does not suggest that glutamine supplementation improves immune function or prevents URTI in highly trained swimmers during competition. However, results support the hypothesis that exogenous glutamine stabilizes plasma glutamine levels, allowing athletes to tolerate training workload and recover properly.

La vitamine K fait l’objet d’un intérêt croissant en regard du rôle qu’elle peut jouer dans la santé humaine hormis celui bien établi dans la coagulation sanguine. De plus en plus d’études expérimentales lui confèrent des fonctions dans le système nerveux central, particulièrement dans la synthèse des sphingolipides, l’activation de la protéine vitamine K-dépendante Gas6 et la protection contre les dommages oxydatifs. Toutefois, il demeure beaucoup moins bien établi si la perturbation de ces fonctions peut conduire à des déficits cognitifs. L’objectif principal de cette thèse est de vérifier l’hypothèse selon laquelle le statut vitaminique K des personnes âgées en santé est un déterminant de la performance cognitive. En vue de la réalisation de cet objectif, une meilleure compréhension des indicateurs du statut vitaminique K s’avérait nécessaire. Chacune des études présentées vise donc un objectif spécifique : 1) évaluer le nombre de rappels alimentaires de 24 heures non consécutifs nécessaire pour mesurer l’apport habituel de vitamine K des personnes âgées; 2) évaluer la valeur d’une seule mesure de la concentration sérique de vitamine K comme marqueur de l’exposition à long terme; et 3) examiner l’association entre le statut vitaminique K et la performance cognitive des personnes âgées en santé de la cohorte québécoise NuAge. Trois dimensions cognitives ont été évaluées soient la mémoire épisodique verbale et non-verbale, les fonctions exécutives et la vitesse de traitement de l’information. Cette thèse présente la première étude appuyant l’hypothèse d’un rôle de la vitamine K dans la cognition chez les personnes âgées. Spécifiquement, la concentration sérique de vitamine K a été associée positivement à la performance en mémoire épisodique verbale, et plus particulièrement au processus de consolidation de la trace mnésique. En accord avec les travaux chez l’animal et l’action de la protéine Gas6 dans l’hippocampe, un rôle spécifique de la vitamine K à l’étape de consolidation est biologiquement plausible. Aucune association significative n’a été observée avec les fonctions exécutives et la vitesse de traitement de l’information. Parallèlement, il a été démontré qu’une mesure unique de la concentration sérique de vitamine K constitue une mesure adéquate de l’exposition à long terme à la vitamine K. De même, il a été établi que six à 13 rappels alimentaires de 24 heures sont nécessaires pour estimer précisément l’apport de vitamine K des personnes âgées en santé. Collectivement, les résultats de ces deux études fournissent des informations précieuses aux chercheurs permettant une meilleure interprétation des études existantes et une meilleure planification des études futures. Les résultats de cette thèse constituent une avancée importante dans la compréhension du rôle potentiel de la vitamine K dans le système nerveux central et renforce la nécessité qu’elle soit considérée en tant que facteur nutritionnel du vieillissement cognitif, en particulier chez les personnes traitées par un antagoniste de la vitamine K. / There is an increasing interest in the potential roles of vitamin K in human health aside from the one well established in blood clotting. Notably, a growing number of experimental studies show that vitamin K has biological functions in the central nervous system, particularly in the synthesis of sphingolipids, the activation of the vitamin K-dependent protein Gas6, and the prevention of oxidative damage. However, it remains uncertain whether the disruption of these functions can lead to cognitive deficits. The main objective of this thesis is to test the hypothesis that vitamin K status is a determinant of cognitive performance in healthy older adults. In order to achieve this goal, a better understanding of vitamin K status indicators was needed. Accordingly, three studies are presented each aiming at a specific objective: 1) estimate the number of non-consecutive 24-hour dietary recalls needed to assess usual vitamin K intake; 2) determine whether a single measurement of serum vitamin K concentration is an adequate indicator of long-term vitamin K exposure; and 3) examine the association between vitamin K status and cognitive performance in healthy older adults from the Québec NuAge Study. Three cognitive domains were assessed namely verbal and non-verbal episodic memory, executive functions, and speed of processing. This thesis presents the first study providing support for a role of vitamin K in cognition in older adults. Specifically, serum vitamin K concentration was positively associated with performance in verbal episodic memory, particularly in the consolidation process of the memory trace. Consistent with rodent studies and the action of the protein Gas6 in the hippocampus, a specific role of vitamin K in memory consolidation is biologically plausible. No significant association was observed with executive functions and speed of processing. Additionally, it was established that a single measurement of serum vitamin K concentration is adequate for assessing long-term vitamin K exposure in healthy older adults. Similarly, it was determined that six to 13 24-hour dietary recalls are needed to accurately assess usual vitamin K intake. Collectively, both studies provide valuable information to researchers for better interpretation of existing studies and planning future ones. Results from this thesis constitute an important step in the understanding of the potential role of vitamin K in the central nervous system, emphasizing the need to consider this micronutrient as a nutritional factor of cognitive aging, especially among those treated with vitamin K antagonists.

Doctor of Philosophy / Department of Human Nutrition / Mark D. Haub / Objective: The objective was to compare the postprandial glycemic and insulinemic responses to nutrition bars containing either cross-linked RS type 4 (RS4[subscript]XL) or standard wheat starch in normoglycemic adults (n=13; age= 27±5 yr; BMI=25±3 kg/m²). Methods: Volunteers completed three trials during which they consumed a glucose beverage (GLU), a puffed wheat control bar (PWB), and a bar containing RS4[subscript]XL matched for available carbohydrate content. Serial blood samples were collected over two hours and glucose and insulin concentrations were determined and the incremental area under the curve (iAUC) was calculated. Results: The RS4[subscript]XL peak glucose and insulin concentrations were lower than the GLU and PWB (p<0.05). The iAUC for glucose and insulin were lower following ingestion of RS4[subscript]XL compared with the GLU and PWB trials. Conclusions: These data illustrate, for the first time, that directly substituting standard starch with RS4[subscript]XL, while matched for available carbohydrates, attenuated postprandial glucose and insulin levels in humans. It remains to be determined whether this response was due to the dietary fiber and/or resistant starch aspects of the RS4[subscript]XL bar. Keywords: insulin sensitivity, diabetes, dietary fiber, prebiotic, glycemic index

Doctor of Philosophy / Department of Human Nutrition / David A. Dzewaltowski / David A. Dzewaltowski / Insufficient physical activity, excessive sedentary behavior and insufficient fruit and vegetable consumption may contribute to childhood obesity. Parents and other adults provide social and physical environments, and build children’s skills for these healthful behaviors. The purpose of this dissertation was to examine parent and adult practices that contribute to the prevention of obesity in children. Chapter one reviewed the literature examining the influence of parent and adult practices on the development of young children’s eating and activity self-regulation skills. Recently, studies have provided evidence that children who lack self-regulation skills are more likely to be overweight. However, there is a gap in the literature addressing practices necessary to foster young children’s self-regulation. Thus, a need exists to identify parent and adult practices that foster the development of children’s eating and activity self-regulation skills. Chapter two described the development, validity and reliability of a self-report measure of parenting practices that may foster children’s self-regulation skills. Parents of overweight/obese children use less parenting practices that foster self-reflection of screen time than parents of normal weight children. Chapter three described the development and evaluation of an intervention designed to develop children’s self-regulation skills to ask parents for healthful home environments. The 12-week intervention was delivered to children and their parents through training child care providers. Children’s self-regulation for asking for healthy foods and activities increased after intervention, as well as increases in child eating and physical activity behaviors. In addition to parents, other adults can impact children’s environments to increase energy expenditure. Chapter four examined the influence of adult leader participation compared to no leader participation among children participating in active games. Results showed no effect of leader participation on children’s physical activity. It may be that adult participation could not increase physical activity because the children were already exhibiting high levels of moderate-to-vigorous physical activity. This dissertation provides preliminary evidence that parent/adult practices play a key role in the development of healthy eating and physical activity in children. Future research is necessary to identify the most important parent/adult practices that can be targeted by interventions to provide healthful options and build children’s skills to promote healthful behavior to prevent obesity.

Doctor of Philosophy / Department of Human Nutrition / Mark D. Haub / Mark D. Haub / Psychological problems and human error are leading causes of death and disability among military service members. Strategies to improve the psychological health and cognitive performance of those in the military are much needed. Recent advances in neuroscience suggest that omega-3 fatty acids may play an important role in the psychological well-being of those in the military. The purpose of this research was to explore the relationship between omega-3 status and psychological outcome variables among soldiers deploying to combat. Data collection was preceded by the development and reliability testing of a novel food frequency questionnaire (FFQ) designed to capture intake from contemporary sources of omega-3 fatty acids including functional foods and supplements. Based on the instrument assessment study (Chapter 2) conducted among university students (n = 165), this FFQ appears to be a comprehensive and reliable (n = 54, ρ = 0.86, p < 0.001) instrument for measuring docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) intakes in young adults. As described in Chapter 3, intake of EPA + DHA as estimated by the FFQ was positively correlated (r = 0.39, p < 0.001) with biomarker measurements of omega-3 status. Primary data were obtained from a volunteer sample of soldiers (n = 272) scheduled for deployment to Iraq. Preliminarily analyses revealed relationships between attention deficit hyperactivity disorder (ADHD) screening scores and psychological outcome variables (Chapter 4). Primary analyses (Chapter 5) indicated intake of EPA + DHA was not significantly correlated with mood, nor were omega-3 exposure variables correlated with cognitive performance based on the required p value (< 0.001) calculated using the Bonferroni correction for multiple tests. Among participants with EPA + DHA intakes at or below the median, omega-3 HUFA was related (p < 0.002) to happiness (β = -0.46), depression (β = 0.44), and fatigue (β = 0.43). Although exploratory in nature, the results of this study suggest a relationship between omega-3 fatty acids and mood. Given the current concerns regarding the psychological health of those in the military, additional research is warranted.