The intake of sodium, potassium, and phosphorus has important implications for chronic disease risk. Excess sodium intake is shown to be associated with elevated blood pressure, which in turn is a risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). Potassium intake, on the other hand, is shown to be beneficial for lowering blood pressure and reducing the risk of CVD and CKD. Once an individual develops CKD, they experience alterations in mineral metabolism, especially phosphorus, and must closely monitor mineral intake and biochemical laboratory values in order to avoid complications. Thus, monitoring mineral intake is important in both healthy and CKD individuals in both research as well as clinical practice settings. It is therefore also important to have a method for estimating mineral intake that is both accurate as well as easy to administer. Two commonly used methods are self-report and 24-hour urinary mineral excretion. however, both methods have pros and cons. An alternative option that has been explored for all three minerals of interest is to collect a spot urine sample, then use one of several published equations to calculate an estimate of 24-hour urinary mineral excretion. While this method is relatively easy to administer, much remains unexplored regarding the accuracy of estimated 24-hour mineral excretion. My aim for my dissertation was to explore how estimated 24-hour sodium (e24hUNa), potassium (e24hUK) and phosphorus (e24hUP) compared to true mineral intake in healthy participants as well as those with CKD. We conducted secondary analyses from two controlled feeding studies, in which true mineral intake was known. Our results show that e24hUNa and e24hUK are not reliable indicators of true sodium and potassium intake, respectively, in healthy participants nor those with CKD, and e24hUP is not a reliable indicator of phosphorus intake in CKD participants. Though these findings should be confirmed by larger studies, these findings suggest that currently available equations may need to be revised and estimated 24-hour mineral excretion from spot urine samples should be interpreted with caution.

<p>Obesity has ascended to become the primary modifiable cause of death in the United States. New evidence has called into question the utility of BMI – the typical index of obesity – in predicting cardiometabolic disturbances. The distribution of body fatness may be just as important as the total quantity. Intermuscular adipose tissue (IMAT) has emerged as a distinct subset of adipose in skeletal muscle that may be particularly metabolically deleterious. Typically, sections of either the calf or thigh are used as proxy measurements for whole-body IMAT in investigations. However, IMAT dispersion may not be consistent across tissues, instead infiltrating specific muscle or muscle compartments, and these have may have different metabolic consequences. The study described in Chapter 2 was designed to address this possibility and investigate and compare associations among thigh and calf IMAT stores with indices of cardiometabolic health. The strength of the relationship between IMAT and glucose control-related indices of cardiometabolic health was dependent upon anatomic location. Specifically, thigh IMAT is a better predictor of cardiometabolic risk that calf IMAT. </p> <p>Skeletal muscle has gained increased recognition in recent years for its importance in promotion of health and wellness throughout the life course. While treatment models addressing issues of declining muscle mass and strength with age previously focused on older adults, the importance of utilizing a life course model to promote skeletal muscle health at all ages was more recently recognized. There is consistent evidence that higher-protein diets modestly improve body composition. However, women are at greater risk for not meeting protein requirements and seem to be less willing to adopt strategies to achieve greater protein intake, such as protein supplementation, for fear that it may cause ‘bulkiness’. Therefore, the study described in Chapter 3 was designed to critically evaluate the effect of whey protein supplementation on body composition changes in women via a systematic review & meta-analysis of published randomized controlled trials. It was hypothesized that whey protein supplementation would moderately improve body composition but would not cause excessive muscle hypertrophy. Consistent with our hypothesis, whey protein supplementation improved body composition by modestly (<1%) increasing lean mass, without influencing fat mass.</p> <p>Dietary protein and skeletal muscle are conceptually inseparable; protein is often only considered in terms of how it impacts skeletal muscle-related outcomes. However, it is of interest to determine if the proposed beneficial effects of increased dietary protein consumption extend beyond skeletal muscle. Consumption of higher protein diets result in lower resting blood pressure, but the potential for protein to attenuate acute exercise blood pressure responses is unclear. The study described in Chapter 4 was designed to investigate the effects of meals with different amounts of protein on blood pressure responses to exercise in a randomized, cross-over trial. We hypothesized that consuming the higher-protein meal would attenuate the blood pressure responses to exercise and result in a more robust post-exercise hypotensive response. Contrary to our hypothesis, a higher-protein meal does not attenuate exercise-induced blood pressure responses compared to a lower-protein meal. These findings build upon previous research suggesting that the beneficial effect of chronically elevated protein intake on blood pressure is typically not observed in an acute setting by extending these findings to encompass blood pressure responses to acute responses to exercise.</p> <p>The three studies packaged herein utilize different techniques and report on different outcomes, but conceptual threads unite these works which augment the collective findings. Future researchers investigating the effects of protein on skeletal muscle anabolism can: 1) learn of the importance of proper reflection on surrogate measures and potential for anatomic-specific effects from the IMAT findings (Chapter 2), 2) appreciate the relevance of energy and training states in modulating responses from the WP meta-analysis (Chapter 3), and 3) recognize the importance of holistic approaches and employing challenges to reveal heterogeneity from the protein and BP trial (Chapter 4). Taken together, the research presented in this dissertation forwards our understanding of the relations and effects of dietary protein with different components of body composition on cardiometabolic health. </p>

Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 118 pages. Includes vita. Includes bibliographical references.

Thesis (M.S.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Sept. 3, 2009). Includes bibliographical references (p. 27-31).

<p>Observational evidence links breakfast skipping, a behavior frequently observed among adolescents, with other poor health related behaviors that perpetuates a lifestyle associated with poor weight management and decreased cognitive performance. Furthermore, evidence suggests that both the consumption of breakfast and the quality of breakfast consumed may influence both weight and cognitive performance related outcomes. In an effort to improve the prevalence of breakfast consumption and the quality of breakfasts consumed among adolescents, recent initiatives have sought to increase participation in the federal School Breakfast Program (SBP). </p><p>The main objectives of this dissertation were to determine: 1) whether the habitual consumption of breakfast influences perceived appetite following the consumption of breakfast and whether habitual breakfast consumption influences post prandial appetitive sensations following the consumption of breakfasts varying in macronutrient distribution; 2) the feasibility of consuming an egg-based, ‘Breakfast in the Classroom’ (BIC) program in 8th grade students and whether the daily consumption of egg-based breakfasts improve School Breakfast Program participation, the quality of breakfasts consumed, and snacking behavior in 8th grade students; and 3) whether differences in cognitive performance exist between 6th-8th grade students who consume school breakfast, students who consume breakfast at home only, and students who skip breakfast following the initiation of a higher-protein Breakfast in the Classroom program. </p><p>This dissertation is organized into chapters that consist of published manuscripts or manuscripts formatted for submission to peer-reviewed journals. Chapter 2 consists of comprehensive review of the evidence linking breakfast consumption and composition to obesity and cognitive performance with an emphasis on the recent advances in school breakfast programs and future directions. Chapter 3 evaluates whether the habitual consumption of breakfast influences perceived appetite following the consumption of breakfast and whether habitual breakfast consumption influences postprandial appetitive sensations following the consumption of breakfasts varying in macronutrient distribution. Chapter 4 examines the feasibility of implementing an egg-based BIC program and subsequent effects on SBP participation, the quality of breakfasts consumed, and evening snacking in 8th grade students. Chapter 5 examines differences in cognitive performance between 6th-8th grade students who consume school breakfast, students who consume breakfast at home only, and students who skip breakfast following a higher-protein BIC. Chapter 6 summarizes the main findings and presents considerations for future research.</p><p>Collectively, the findings from this dissertation demonstrate:1) consuming 30 grams of protein at breakfast improves appetite and satiety compared to a breakfast containing 15 grams of protein, independent of habitual breakfast consumption in overweight adolescent females; 2) implementing a universally-free ‘Breakfast in the Classroom’ program that serves two additional eggs to a traditional school breakfast served via a traditional SBP is feasible and improves SBP participation, the quality of breakfast consumed, and reduces unhealthy evening snacking; and 3) students who consume breakfast at school, as part of a higher-protein BIC program, perform better on tasks assessing cognitive flexibility and executive function in middle school students when compared to students who skip breakfast, regardless of key behavioral and/or socioeconomic factors. Thus, this work suggests increasing protein content of school breakfasts using a universally-free distribution program is feasible and may provide benefits on overall diet quality and cognitive performance for 6th-8th grade students. <br></p>

<p>Vitamin E is a natural lipophilic antioxidant contains eight structurally related forms, i.e., α-, β-, γ-, δ-tocopherols (αT, βT, γT, and δT) and corresponding tocotrienols. Recent research indicates that vitamin E forms are differentially metabolized to various carboxychromanols. Some these vitamin E metabolites have been shown to exhibit strong anti-inflammatory and anticancer effects, yet little is known about their bioavailability. Without this knowledge, it is impossible to assess the role of vitamin E metabolism in biological functions of vitamin E forms and their protective effects on chronic diseases. While αT and γT appear to improved gut health, the underlying mechanisms are not well understood. Furthermore, specific forms of vitamin E such as γT have been reported to have cancer-preventing effects, but their anticancer efficacy is relatively modest. For these reasons, this dissertation focused on the characterization of the pharmacokinetic formation of vitamin E metabolites after supplementation, and the investigation of the underlying mechanisms of the protective effect of vitamin E forms, αT and γT, on gut health, as well as anticancer efficacy of the combination of aspirin and γT on carcinogen-induced colon tumorigenesis.</p><p><br></p><p>The first project focuses on characterizing the pharmacokinetic formation of vitamin E metabolites after single dose supplementation of γ-tocopherol-rich mixed tocopherol (γTmT) and δ-tocotrienol (δTE). With our recently developed LC/MS/MS assay for quantifying vitamin E metabolites, we can simultaneously quantify the level of short-chain, long-chain, and sulfated carboxychromanols in plasma, urine, and fecal samples of supplemented animals. In this study, we investigated the pharmacokinetics including excretion of vitamin E forms and the formation of their metabolites after a single dose intragastric administration of tocopherols and tocotrienols in rats. We also measured vitamin E metabolites in the serum obtained from healthy humans after gT supplementation. In the plasma of rat, the pharmacokinetic profiles of γT and δTE are described as the following: γT, Cmax = 25.6 ± 9.1 μM, Tmax = 4 h; δTE, Cmax = 16.0 ± 2.3 μM, Tmax = 2 h. Sulfated CEHCs and sulfated 11’-COOHs were the predominant metabolites in the plasma of rat with Cmax of 0.4-0.5 μM (Tmax ~ 5-7 h) or ~0.3 μM (Tmax at 4.7 h), respectively. In 24-h urine, 2.7% of γT and 0.7% of dTE were excreted as conjugated CEHCs, the major identified urinary metabolites. In the feces, 17-45% of supplemented vitamers were excreted as un-metabolized forms and 4.9-9.2% as metabolites. The majority of metabolites excreted in feces were unconjugated carboxychromanols, among which 13’-COOHs constituted ~50% of total metabolites. Interestingly, 13’-COOHs derived from δTE were 2-fold higher than 13’-COOH from γT. Unlike rats, γ-CEHC is the predominant metabolites found in human plasma, although 11’-COOHs and 13’-COOHs (sulfated and unconjugated) were elevated by >20 folds responding to γT supplement. In this study, we found that tocopherols and tocotrienols, when taken as supplements, are mainly excreted as un-metabolized forms and long-chain carboxychromanols in feces. High fecal availability of 13’-COOHs may contribute to modulating effects on gut health.</p><p><br></p><p>The second project of my dissertation investigated the effect of vitamin E forms, αT and γT, on intestinal barrier function in a cellular model and a mouse colitis model. Inflammatory bowel diseases (IBD) are chronic idiopathic inflammatory conditions characterized by disruption of intestinal barrier integrity. Previous studies by others and us had demonstrated that vitamin E forms, αT and γT, can protect against chemical-induced colitis in animal models. However, the role of these vitamin E forms on intestinal barrier function has not been studied. Herein, we investigated the potential protective effects of vitamin E forms, αT and γT, on intestinal barrier function in a Caco-2 colon epithelial cell model and a dextran sodium sulfate (DSS)-induced colitis mouse model. In Caco-2 cells, pretreatment with 25mM αT and γT attenuated Caco-2 monolayer barrier dysfunction induced by 10 ng/mL TNF-α/IFN-γ, suggesting that these vitamin E forms protect intestinal barrier integrity in this cellular model. In male BALB/c mice, the supplementation of αT (0.05%) or γTmT (0.05%) when given 3 weeks before DSS treatment or at the same time as DSS treatment alleviated DSS-induced fecal bleeding and diarrhea symptoms in mice, and attenuated colon inflammation and colitis-associated damages. Additionally, αT and γTmT supplementation attenuated DSS-induced intestinal barrier dysfunction, as indicated by improving the level of occludin, a tight junction protein, in the colon and reducing lipopolysaccharide-binding protein (LBP) in the plasma. Furthermore, gut microbiota analysis demonstrated that αT and γTmT supplementation could modulate intestinal microbiome composition in mice with DSS treatment. DSS treatment reduced the relative abundance of Lachnospiraceae compared to healthy mice, and supplementation of αT and γT partially reversed this effect. Interestingly, the family Lachnospiraceae has been reported to decrease in IBD patients. Our study demonstrated the protective effects of vitamin E forms on intestinal barrier integrity in a cell-based model and a colitis model in mice. Furthermore, we demonstrated that these vitamin E forms caused favorable changes in the intestinal microbial population under colitis condition.</p><p><br></p><p>The third project of my dissertation evaluated the anticancer efficacy of the combination of aspirin and γT using an azoxymethane (AOM)-induced and colitis-promoted colon tumorigenesis mouse model. Extensive inflammation in the colon promotes the development of colorectal cancer (CRC). Eicosanoid production by pro-inflammatory enzymes, cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) play a critical role in the initiation, progression, and invasion of CRC. Thus, nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, have been recommended for chemoprevention of CRC. However, long-term use of aspirin can cause many side effects, and the anticancer activity of aspirin is very modest. Previously, we have demonstrated that the combination of γT with aspirin prolonged the anti-inflammatory activity of aspirin and alleviated aspirin-associated adverse effects in a carrageenan-induced inflammation model in rats. Additionally, we found that the combination of γT and aspirin has stronger anticancer activity than aspirin or γT alone against HCT-116 human colorectal carcinoma cells. Therefore, we examined the anticancer effect of the combination of 0.025% aspirin and 0.05% γT against AOM-induced and DSS-promoted tumorigenesis in mice. In this study, we have found that the combination of aspirin and γT, but not aspirin or γT alone, suppressed colon tumorigenesis in mice, as indicated by 40% and 50% reduction in the multiplicity of total polyps (P < 0.05) and large adenomatous polyps (>2mm2, P < 0.05), respectively. More strikingly, the combination of aspirin and γT reduced the overall tumor area by 60% (P < 0.05). Noteworthy, the supplementation of γT also alleviated aspirin-induced stomach lesion and appeared to modulate intestinal microbial composition. Our study demonstrated that the combination of aspirin and γT has stronger anticancer activity than aspirin or γT alone while alleviates aspirin-associated adverse effect, suggesting that the combination of γT and aspirin is a more effective and safer chemopreventive agent for CRC than aspirin alone.</p>

Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1601. Adviser: Pamela M. Diamond. Includes bibliographical references.