Academic literature on the topic '111199 Nutrition and Dietetics not elsewhere classified'

AbstractMalnutrition predicts preterm death, but whether this is valid irrespective of the cause of death is unknown. The aim of the present study was to determine whether malnutrition is associated with cause-specific mortality in older adults. This cohort study was conducted in Sweden and included 1767 individuals aged ≥65 years admitted to hospital in 2008–2009. On the basis of the Mini Nutritional Assessment instrument, nutritional risk was assessed as well nourished (score 24–30), at risk of malnutrition (score 17–23·5) or malnourished (score <17). Cause of death was classified according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, into twenty different causes of death. Data were analysed using Cox proportional hazards regression models. At baseline, 55·1 % were at risk of malnutrition, and 9·4 % of the participants were malnourished. During a median follow-up of 5·1 years, 839 participants (47·5 %) died. The multiple Cox regression model identified significant associations (hazard ratio (HR)) between malnutrition and risk of malnutrition, respectively, and death due to neoplasms (HR 2·43 and 1·32); mental or behavioural disorders (HR 5·73 and 5·44); diseases of the nervous (HR 4·39 and 2·08), circulatory (HR 1·95 and 1·57) or respiratory system (HR 2·19 and 1·49); and symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (HR 2·23 and 1·43). Malnutrition and risk of malnutrition are associated with increased mortality regardless of the cause of death, which emphasises the need for nutritional screening to identify older adults who may require nutritional support in order to avoid preterm death.

AbstractObjectiveOver 300 million people rely on desalinated seawater and the numbers are growing. Desalination removes iodine from water and could increase the risk of iodine-deficiency disorders (IDD). The present study assessed the relationship between iodine intake and thyroid function in an area reliant on desalination.DesignA case–control study was performed between March 2012 and March 2014. Thyroid function was rigorously assessed by clinical examination, ultrasound and blood tests, including serum thyroglobulin (Tg) and autoimmune antibodies. Iodine intake and the contribution made by unfiltered tap water were estimated by FFQ. The contribution of drinking-water to iodine intake was modelled using three iodine concentrations: likely, worst-case and best-case scenario.SettingThe setting for the study was a hospital located on the southern Israeli Mediterranean coast.SubjectsAdult volunteers (n102), 21–80 years old, prospectively recruited.ResultsAfter screening, seventy-four participants met the inclusion criteria. Thirty-seven were euthyroid controls. Among those with thyroid dysfunction, twenty-nine were classified with non-autoimmune thyroid disease (NATD) after excluding eight cases with autoimmunity. Seventy per cent of all participants had iodine intake below the Estimated Average Requirement (EAR) of 95 µg/d. Participants with NATD were significantly more likely to have probable IDD with intake below the EAR (OR=5·2; 95 % CI 1·8, 15·2) and abnormal serum Tg>40 ng/ml (OR=5·8; 95 % CI 1·6, 20·8).ConclusionsEvidence of prevalent probable IDD in a population reliant on desalinated seawater supports the urgent need to probe the impact of desalinated water on thyroid health in Israel and elsewhere.

AbstractObjectivesTo estimate the dietary intakes of heterocyclic amines (HCAs), to examine the intakes in relation to socio-economics, lifestyle and other dietary factors and to compare the classification of subjects by intake of HCA versus intake of meat and fish.DesignCross-sectional analysis within the Malmö Diet and Cancer (MDC) cohort. Data were obtained from a modified diet history, a structured questionnaire on socio-economics and lifestyle, anthropometric measurements and chemical analysis of HCAs. HCA intake was cross-classified against meat and fish intake. The likelihood of being a high consumer of HCAs was estimated by logistic regression analysis. Dietary intakes were examined across quintiles of HCA intake using analysis of variance.SettingBaseline examinations conducted in 1991–1994 in Malmö, Sweden.SubjectsA sub-sample of 8599 women and 6575 men of the MDC cohort.ResultsThe mean daily HCA intake was 583 ng for women and 821 ng for men. Subjects were ranked differently with respect to HCA intake compared with intake of fried and baked meat and fish (κ = 0.13). High HCA intake was significantly associated with lower age, overweight, sedentary lifestyle and smoking. Intakes of dietary fibre, fruits and fermented milk products were negatively associated with HCA intake, while intakes of selenium, vegetables, potatoes, alcohol (among men) and non-milk-based margarines (among women) were positively associated with HCA intake.ConclusionsThe estimated daily HCA intake of 690 ng is similar to values obtained elsewhere. The present study suggests that lifestyle factors (e.g. smoking, physical activity, fruit and vegetable intakes, and types of milk products and margarines) may confound associations between HCA intake and disease. The poor correlation between HCA intake and intakes of fried meat and fish facilitates an isolation of the health effects of HCAs.

Abstract Objective: To examine the adherence to the Mediterranean diet in the adult general population of Cyprus and assess its relationship with multi-morbidity. Design: A representative sample of the adult population of Cyprus was selected in 2018–2019 using stratified sampling. Demographics, Mediterranean diet, smoking and physical activity, as well as the presence of chronic, clinical and mental conditions, were collected using a validated questionnaire. Diseases were classified according to the International Classification of Diseases, 10th Revision. Setting: The five government-controlled municipalities of the Republic of Cyprus. Participants: A total of 1140 Cypriot men and women over 18 years. Results: The average Mediterranean diet score was 15·5 ± 4·0 with males and residents of rural regions being more adherent to the Mediterranean diet compared with females and residents of urban regions (P < 0·05). Being in the higher tertile of adherence to the Mediterranean diet was associated with lower odds of multi-morbidity compared with the lower tertile, and this result was statistically significant even after adjusting for age, gender, smoking habits and physical activity (OR = 0·68, 95 % CI 0·46, 0·99). Conclusions: The study provides evidence of the adherence to the Mediterranean diet in Cypriot population and its association with multi-morbidity. Adherence to the Mediterranean diet was associated with lower risk of multi-morbidity. Future research would attempt to replicate such results that could add solid pieces of evidence towards meeting some criteria of causality and severity tests; hence, prevention programmes and practice guidelines in Cyprus and elsewhere should take into account those beneficial effects.

Cows’ milk generally contains two types of β-casein, A1 and A2 types. A2 beta-casein is recognized as the original beta-casein variant because it was present before a proline to histidine point mutation occurrence in the polypeptide chain at 67th position. A1 and A2 are processed differently by digestive enzymes, and once milk or milk products are consumed, a seven-amino acid bioactive opioid peptide, beta-casomorphin-7, is released as a result of incomplete digestion of A1-beta-casein. This is a single-dose, randomized and double-blinded study. Participants received four different treatments (Regular milk, A2 milk, Jersey cow milk, and lactose free milk) in a randomized order. The lactose free milk acted as a negative control. This study aimed to evaluate tolerance to milks containing different levels of A2 β-casein (Jersey and A2 milks) as compared to commercial A1 (regularmilk containing both A1 and A2 β-casein) and lactose-free milk controls in lactose digesters and maldigesters. Seven subjects completed this double-blinded, randomized, crossover trial. Lactose malabsorption (LM) was determined by breath hydrogen test and milk intolerance were assessed by validated questionnaires. Treatments were fed as a single dose with a 6-day washout period to minimize any residual effects. Each subject was fed milk containing 0.5 g lactose per kg body weight. The pilot data from the seven subjects does strongly suggest greater hydrogen production from commercial A1 milk as compared to lactose-free, A2 and Jersey milks. Regular milk containing high A1 β-casein produced significantly higher hydrogen compared to lactose-free milk from 2 hours until 5hours. This suggests biologically relevant differences in lactose digestion among these milks. In addition, Jersey milk produced significantly higher hydrogen compared to lactose-free milk similar to regular milk between 2 and 6 hours while A2 milk was acting similar to lactose-free milk and did not result in increased hydrogen throughout the same time intervals. Taken together, these results suggest that the amount of A2 β-casein in Jersey milk was not adequate to attenuate the increased hydrogen concentration while pure A2 milk was effective. In this pilot clinical trial, abdominal pain, bloating, flatulence, diarrhea, fecal urgency and total GI symptoms were reported as measures of digestive discomfort. Although the mean values of total GI symptom scores were numerically lower on the lactose free, pure A2 and Jersey group compared to regular milk group, none were statistically different. With seven subjects reported in this pilot data, and a calculated sample size requirement of 26, we can interpret trends that ultimately could result in significant differences as additional subjects complete this protocol.

Fruit and vegetable derived polyphenols have been linked with many health benefits. In light of this, many consumers are seeking to increase their intake of polyphenols, with many turning to dietary supplements that contain concentrated doses of purified polyphenols. However, the safety of this consumption modality is not known, nor are the dose-dependent metabolic changes that may be present, especially when considering colonically generated phenolic metabolites. Using blueberry polyphenols as a model, we explored these phenomena in a rat model. Animals were dosed with blueberry polyphenols at levels up to 20 times what would be consumed in 1-2 servings of whole blueberries in an adult human. In the first study, animals were acutely dosed with blueberry polyphenols and urine and plasma pharmacokinetics measured. In the second study, animals were repeatedly dosed for 90d, with urinary metabolites monitored throughout the study and a complete necropsy performed following standard guidelines. In both studies, metabolite excretion patterns were similar: cinnamic acids accounted for a majority of the observed metabolites, followed by hippuric acids and then phenylpropionic acids (PPA). A dose-dependent shift in metabolite production was observed; as the dose increased, the relative amounts of PPA increased while hippuric acids decreased. No adverse or toxic effects were found, and, though there were several statistically significant differences in toxicological endpoints, all measured parameters remained in the normal range for these animals and thus were not deemed biologically significant. These results indicate that high doses of blueberry polyphenols, as may be present in dietary supplements, are safe for consumption. These results also demonstrate dose-dependent shifts in metabolism that may impact gut function and affect the health benefits derived from blueberry polyphenols.

Breast cancer is the predominant cancer diagnosed among women, and the second most deadly cancer. The vast majority of cancer-related deaths is caused by the metastatic spread of cancer from the primary tumor to a distant site in the body. Therefore, new strategies which minimize breast cancer metastasis are imperative to improve patient survival. Cancer cells which acquire anchorage independence, or the ability to survive without extracellular matrix attachment, and metabolic flexibility have increased potential to metastasize. In the present studies, the ability to survive detachment and subsequent metabolic changes were determined in human Harvey-ras transformed MCF10A-ras breast cancer cells. Detachment resulted in reduced viability in a time-dependent manner with the lowest cell viability observed at forty hours. In addition, decreased cell viability was observed in both glutamine and glucose depleted detached conditions, suggesting a dependence on both nutrients for detached survival. Compared to attached cells, detached cells had reduced total pool sizes of pyruvate, lactate, α-ketoglutarate, fumarate, malate, alanine, serine, and glutamate, suggesting the metabolic stress which occurs under detached conditions. However, intracellular citrate and aspartate pools were unchanged, demonstrating a preference to maintain these pools in detached conditions. Compared to attached cells, detached cells had suppressed glutamine metabolism, as determined by decreased glutamine flux into the TCA cycle and reduced mRNA abundance of glutamine metabolizing enzymes. Further, detached glucose anaplerosis through pyruvate dehydrogenase activity was decreased, while pyruvate carboxylase (PC) expression and activity were increased. A switch in metabolism was observed away from glutamine anaplerosis to a preferential utilization of PC activity to replenish the TCA cycle, determined by reduced PC mRNA abundance in detached cells treated with a cell-permeable analog of α-ketoglutarate, the downstream metabolite of glutamine which enters the TCA cycle. These results suggest that detached cells elevate PC to increase flux of carbons into the TCA cycle when glutamine metabolism is reduced.

Vitamin D is recognized for its role in preventing breast cancer progression, and recent studies suggest that regulation of energy metabolism may contribute to its anticancer effects. Vitamin D primarily acts on target tissue through its most active metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)₂D). The present work investigated 1,25(OH)₂D’s effects on viability of detached cells through regulation of energy metabolism. Treatment of MCF10A-ras cells with 1,25(OH)₂D resulted in decreased viability of detached cells. While 1,25(OH)₂D treatment did not affect many of the glucose metabolism outcomes measured, including intracellular pyruvate and lactate pool sizes, glucose flux to pyruvate and lactate, and mRNA abundance of enzymes involved in glucose metabolism, 1,25(OH)₂D treatment reduced detached PC expression and glucose flux through PC. A reduction in glutamine metabolism was observed with 1,25(OH)₂D treatment, although no 1,25(OH)₂D target genes were identified. Further, PC depletion by shRNA decreased cell viability in detached conditions with no additional effect with 1,25(OH)₂D treatment. Moreover, PC overexpression resulted in increased detached cell viability and inhibited 1,25(OH)₂D’s negative effects on viability. These results suggest that 1,25(OH)₂D reduces detached cell viability through regulation of PC. Collectively this work identifies a key metabolic adaptation where detached cells increase PC expression and activity to compensate for reduced glutamine metabolism and that 1,25(OH)₂D may be utilized to reverse this effect and decrease detached cell viability. These results contribute to an increased understanding of metastatic processes and the regulation of these processes by vitamin D, which may be effective in preventing metastasis and improve breast cancer patient survival.

Osteoporosis and fractures are debilitating skeletal problems. Accumulating the highest peak bone mass in both cortical and trabecular bone (Tb) as well as developing strong Tb microarchitecture play an integral role in preventing bone loss and osteoporotic fractures later in life. Because Tb is modulated by genetics (G) and environment (e.g. diet, D), my dissertation research focuses on the influence of dietary calcium (Ca) intake, genetics as well as GxD interaction controlling Tb phenotypes in two clinically relevant skeletal sites, i.e. the femur and the L5 vertebra. Male mice from 11 in bred lines and 51 BXD recombinant inbred (RI) lines were fed either adequate (Basal, 0.5%) or low (0.25%) Ca diets from 4-12 weeks of age. We used micro-computed tomography to measure Tb mass and microarchitecture phenotypes. We systematically proved that there are site-specific effects of diet, genetic, and GxD interactions influencing Tb phenotypes. This indicates that there are unique genetic effects modulating Tb at each bone site. Therefore, we conducted a genetic mapping experiment using the 51 BXD RI lines separately for each bone site. We coupled genetic mapping analysis with bioinformatics analysis to identify novel genetic variation and candidate genes accounting for the variation in each phenotypes. The findings from this work serve as a foundation for future research to identify novel pathways and genes underlying the development of Tb as well as an adaptation to Ca insufficiency.

T-cells are present in the immune system to fight against invaders. Once their job is done, suppressing their activity is an important step in maintaining a proper immune response. Myeloid derived suppressor cells (MDSCs) are immune cells that suppress T-cell activity. Currently, MDSCs are defined as a heterogeneous population of immature cells that are derived in the bone marrow and travel to the site of inflammation or cancer. Two major subtypes of MDSCs have been identified in mice and humans, monocyte-like MDSCs (M-MDSC) and granulocyte MDSCs (G-MDSC). G-MDSCs typically make up the majority of the total population of MDSCs but are less T-cell suppressive than M-MDSCs. One of the major problems in the study of MDSCs is that the current marker system for subtypes does not differentiate between precursor MDSCs (lacking suppressive ability) and functional MDSCs (those with suppressive ability). Therefore, using cancer models in mice, we investigated the development and potential to classify precursor MDSCs from functional MDSCs. While MDSCs have been highlighted as a target cell to inhibit in cancer, in other conditions, such as pregnancy, MDSCs have been shown to be beneficial in maintaining a normal pregnancy. Therefore, targeting the increase of MDSCs in abnormal pregnancy conditions like pre-eclampsia may act as a prevention or therapeutic strategy. Finally, it is known that many dietary components can act as modulators of immune cells. Specifically, the polyphenol like phytochemical, curcumin has been shown to act as an anti-inflammatory agent with the potential to modulate multiple immune cells. Therefore, we propose two different studies to investigate the potential of curcumin as either an inhibitor and/or promotor of MDSCs in a disease-specific context. Together the role of phytochemicals as immunomodulators of MDSCs is still very young, in part due to the complexity of phytochemicals themselves, but the studies cited here provide evidence that the field is ripe for additional questions to be asked.

Inadequate nutrition in childhood can inhibit optimal growth and development, and is also associated with increased risk of chronic diseases later in life. Children living in households with limited financial resources may face a number of challenges to meet nutrient needs through unhealthy eating patterns, which may lead to health inequalities throughout the life-course. Therefore, improving low-income children’s diet would be an effective strategy for their health promotion and disease prevention, and potentially for narrowing health inequalities. The essential step for an efficient intervention would be to identify the unique nutrition risk that low-income children have. Therefore, the overarching aim of research in this dissertation was to identify nutrition risk of U.S. infants and children with low income or food insecurity, or participating in federal nutrition assistance programs using data from nationally representative surveys. An additional aim was to assess whether the inclusion of micronutrient intake from dietary supplements impacts micronutrient inadequacy in children.

For low-income infants and young children up to the age of 5 years, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides tailored food packages to improve dietary intake that may be inadequate due to economic constraints. Therefore, it is expected that nutrient intake of WIC participants would be more like those of higher-income nonparticipants and higher than those of lower-income nonparticipants who are likely to be eligible for WIC. The results from the Feeding Infants and Toddlers Study 2016 data analysis supported the hypothesis for several nutrients of concern, although WIC participants were more likely to exceed the recommended limits for sodium and added sugars compared to higher-income nonparticipants. However, higher-income nonparticipants were more likely to use dietary supplements than both WIC participants and lower-income nonparticipants, which can impact total nutrient intake (i.e., nutrient intake from all sources).

Systematic differences in dietary supplement use by income and WIC participation were also observed in a nationally representative sample of children aged 18 years and younger from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Dietary supplement use was lower among children in low-income families compared to those in higher-income families. Among children in low-income families, those participating in WIC were less likely to use dietary supplements compared to nonparticipants. In addition, food insecurity and the Supplemental Nutrition Assistance Program (SNAP) participation were associated with lower use of dietary supplements. Overall, one-third of children used any dietary supplements, mostly multivitamin-minerals, with primary motivations for use as “improve” or “maintain” health.

The following analysis of the 2011-2014 NHANES data showed that the inclusion of dietary supplements in nutrient intake assessments may lead to wider disparities in dietary intake by food security. This study also demonstrated the dose-response relationship between food security status and mean adequacy ratio, a summary measure of micronutrient adequacy. The mean adequacy ratio, inclusive of dietary supplements, was the highest in high food-security group (mean of 0.77), lower in marginal and low food security group (mean of 0.74), and the lowest in very low food security group (mean of 0.66), based on classification by food security among household children. However, the mean adequacy ratio does not reflect the usual intake (i.e., a long-term, habitual intake).

Therefore, another analysis of the 2011-2016 NHANES data estimated total usual nutrient intake of U.S. children 18 years and younger by food security status, using the National Cancer Institute method that adjusts for random error by statistical modeling. The results suggested that food insecurity was associated with higher risks of inadequate intakes for some nutrients, such as vitamins D and E and magnesium among boys and girls and vitamin A and calcium among girls only. Poor overall dietary quality and excessive sodium intake were of concern, regardless of food security status.

Collectively, the results from the studies in this dissertation add value to the evidence base about the adverse association of low income level and food insecurity status with dietary intake and extend the finding to include nutrient intakes from dietary supplements, which widens the disparity in nutrition risk. These findings highlight a need for interventions to reduce nutrient inadequacies and improve dietary quality among children across all socioeconomic levels, but especially among those with low income or food insecurity.

Vitamin A deficiency is the leading cause of childhood blindness affecting over 190 million preschool children around the world where the highest rates are found in Sub-Saharan Africa (1). The coexistence of this deficiency with shortfalls in iron and zinc has resulted in a shift in intervention strategies from single targeted approach to broader diet diversification. As a result, food-based strategies leveraging local nutrient-dense plants as natural fortificants have gained significant interest for their potential to simultaneously address multiple micronutrient, and in some instances macronutrient, deficiencies. However, the efficacy of such approach depends upon several factors including knowledge on the nutritional composition of native plant materials as well as strategies for their incorporation into staple consumer products. Additionally, there is lack of information on impact of concurrent introduction of mineral and provitamin A rich plants on the stability and bioavailability of each individual nutrients including changes in these factors over extended periods of exposure. This is a key point considering that many of these materials are reported to have potential inhibitors of carotenoid absorption (minerals, fiber and phenolics).

To address these research gaps, this dissertation focuses on three areas including 1) micronutrient, phytochemical and polysaccharide characterization of three commercially available native micronutrient dense African plant materials [Adansonia digitata (baobab), Moringa Oleifera (moringa) and Hibiscus Sabdariffa (hibiscus)] that have been targeted for use as natural iron fortificants; 2) determination of the impact of these materials on the bioaccessibility and intestinal uptake of provitamin A carotenoids from model composite cereal products and 3) assess the effect of longer term exposure to baobab and moringa on provitamin A carotenoid absorption and cellular differentiation biomarkers of human intestinal Caco-2 cells to better understand the potential impacts of extended exposure periods on long term micronutrient uptake.

Characterization of the plant fortificants focused on understanding both nutritive components and potential limiters of carotenoid bioavailability. Baobab, moringa and hibiscus all were found to contain key phytochemical and polysaccharide components that could be leveraged as nutritional and function ingredients. The relatively higher levels of lutein (57  4.6 g/g), zeaxanthin (11  0.1g/g) and -carotene (20  2 g/g) in moringa leaf powder support the notion that this plant material can be used as a source of provitamin A and non-provitamin A carotenoids. Phenolic analysis revealed the presence of substantial amounts of flavan-3-ols (1234  16 mg/100g) in baobab, anthocyanins (2001  56 mg/100g) in hibiscus, and flavonols (5352  139 mg/100g) in moringa leaf powder. Polysaccharide analysis demonstrated that the primary monosaccharide in baobab was found to be xyloglucan (47 %) which is in agreement with the tentative identification Xyloglucans (hemicellulosic polysaccharide) based on linkage analysis. Hibiscus was found to contain similar amounts of xylose (20%) and galactose (27%) supporting the presence of similar proportions of xyloglucans and pectic polysaccharides (type I, type II AG, RG I). The main monosaccharide in moringa was found to be galactose (36%) followed by glucose (23%) and linkage analysis revealed the presence of high proportions of pectic polysaccharides (type I, type II AG, RG I). These results provide insight into presence of potential enhancer or inhibitors of target micronutrient (provitamin A carotenoids or iron/zinc) bioavailability when used as functional and nutritional food ingredients.

Subsequently, the impact of mineral-rich baobab formulated at levels relevant for iron fortification on the bioaccessibility of provitamin A carotenoids (proVAC) from composite millet porridges containing dried carrot and mango was assessed using in vitro digestion. Proportions of millet flour and plant materials were dry blended to deliver ~25% of the RDA for vitamin A(VA) and iron(Fe) as follows: decorticated extruded millet (Senegalese Souna var.) (40-60%), dried proVA rich carrot and mango blend (30%), and dried Fe and ascorbic acid rich Adansonia digitata (baobab) (0-25%). While there were no significant differences in proVAC bioaccessibility from porridge formulations with 5 and 15% baobab (18.8+/-2.0 and 18.8±2.0% respectively) as compared to control containing no mineral-rich plant (23.8 +/- 1.2%), 25% baobab resulted in a significant decrease (p<0.05) in bioaccessibility of proVAC (13.3+/-1.6%). However, baobab inclusion did not impact intestinal uptake efficiency of provitamin A carotenoids by Caco-2 human intestinal cells

(3.3-3.6% -carotene and 3.7-4.5% for -carotene) across all formulation. These results suggest that any potential negative effects of baobab inclusion may be limited to food matrix interactions and digestion. This was confirmed in separate experiments that with experiments on baobab and carotenoid blends showing that digested baobab did not affect carotenoid absorption by Caco-2 cells. Overall these data support the notion that that modest inhibition of carotenoid bioaccessibility by baobab may not significantly limit carotenoid delivery from composite porridges. Furthermore, bioaccessible provitamin A content of a serving (200 g) of composite porridges can provide 27 - 48% of the RDA of vitamin A for children 1-3 years of age.

Finally, we evaluated the impact of long-term exposure to baobab and moringa digesta on Caco-2 cell differentiation biomarkers and provitamin A uptake to gain insight into how inclusion of these materials in to a daily diet may alter absorption and transport of nutrients or otherwise have potential negative effects on the intestine. Based on NMR analysis of intracellular metabolites in differentiating Caco-2 monolayers, significant alterations in specific osmotic pressure regulators, particularly glycerophosphocholine, taurine and myo-inositol were observed with repeated exposure to all treatment groups including the control (digested 0.9% saline solution). Changes in these metabolites levels have been linked with specific cellular function including protection against hyperosmotic stress and regulation of paracellular permeability of Caco-2 cells. Evaluation of carotenoid uptake comparing acute and acute on repeated exposure to treatment groups demonstrated that there was an overall significant reduction in carotenoid uptake with repeated exposure across all treatment groups including the control. Despite the reduction in carotenoid uptake, mRNA and protein levels of carotenoid transporters (CD-36, SR-B1 and FABP1) were not significantly altered with exposure through differentiation (except for SR-B1 protein levels). Decrease in SR-B1 levels may be due to bile acid accumulation from the digesta matrix which is known to regulate its own biosynthesis by a mechanism that involves the down-regulation SR-B1 expression to protect cells from cytotoxicity. Our results provide some insight into the impact of simulated gastrointestinal fluids alone on provitamin A uptake in this model system which are usually not taken into consideration in most Caco-2 cell studies. However, overall, these findings indicate that the introduction of baobab and moringa at levels relevant for delivery of meaningful levels of iron (15-23% RDA) should not have negative impacts on human intestinal function or carotenoid uptake over chronic use.

Taken together, our findings indicate that the three native Africa plant materials selected for investigation in these studies can be important sources of key micronutrients (iron, zinc and provitamin A carotenoids) and have potential as natural fortificants with application in staple foods such as cereal porridges. Incorporation of these plant materials, do not appear to negatively affect carotenoid bioavailability although there is a potential for their interaction during micellarization of carotenoids during normal digestion. While in vivo studies evaluating the bioavailability of provitamin A carotenoids from such composite formulations are required, these data support the further exploration of such natural fortification strategies in addressing micronutrient deficiencies in local African communities.

As obesity has become one of the most prevalent metabolic diseases, and diabetes mellitus has become the seventh leading causes of death in the United States, alternative food/nutrition-based approaches to tackle obesity that are both efficacious and cost effective are in high demand. Since starch and its derived products are the principal dietary supply of glucose, strategies of using slowly digestible starch to achieve moderated glycemic response and prolonged glucose delivery, as well as to locationally digest starch into the ileum, have shown successful results such as moderation of insulinemia and reducing food intake in obese animals. An important regulator of appetite suppression is the neuroendocrine system of the gut-brain axis. Glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are the main anorexigenic peptide products of the intestinal enterendocrine L-cells that regulate postprandial insulin levels as well as satiety signals. The stimulation of the enteroendocrine L-cells throughout the gastrointestinal tract through glucose, fatty acids and proteins has been extensively studied and confirmed. However, the stimulatory effect of complex dietary carbohydrates on L-cells is not described. In this dissertation, we investigated the in vitro intestinal cell chemosensation of L-cells to α-amylase starch digestion products, named maltooligosaccharides (MOS), and in the possible application of using slowly digestible starch delivery of MOS in vivo.

In Chapter II of this dissertation, we reported a significantly higher stimulatory effect of MOS on GLP-1 and OXM secretion compared to glucose in mouse and human L-cells, respectively. Additionally, maltotriose enhanced the relative expression of the gastrointestinal peptide, cholecystokinin. Moreover, MOS exhibited protective effects on barrier function and monolayer integrity of intestinal epithelial cells.

In Chapters III and IV, we performed a multiomics approach where transcriptomic analysis and global protein profiling of mouse L-cells treated with different types of MOS showed that the carbohydrates exhibit their effects through the induction of exocytosis of GLP-1- or OXM-containing vesicles and not through a positive regulation of the proglucagon gene expression. It is suggested that MOS induce higher secretion, but not higher synthesis, of the proglucagon gene products. In addition, maltotriose treatment downregulated the relative expression of the glucotoxicity marker, thioredoxin-interacting protein, and upregulated the relative expression of tight junction proteins supporting a role of MOS in barrier function integrity.

Translating the in vitro findings into an in vivo application that is beneficial for human health required the use of controllable tool for the delivery of MOS throughout the small intestine for sensing by a higher number of L-cells. Slowly digestible starch (SDS), compared to rapidly digestible starch, provided such a tool. For this purpose, we used alginate-entrapped SDS microspheres that digest distally into the ileum to examine the role of SDS in the intervention and prevention of obesity in C57BL/6J diet-induced obese (DIO) and lean mice models.

Results showed that 20% SDS in low-fat diets significantly improved weight loss and food intake reduction in DIO mice converted to low-fat diet for 12 weeks. Similarly, 15% SDS in high-fat diets showed significant reduction in body fat percent and significant increase in lean body mass as well as considerable reduction in weight gain rate and food intake in lean mice fed on 45% of calories high-fat diet. Immunohistochemistry of small intestine of mice in both the intervention and prevention studies revealed an even and thorough distribution of GLP-1 positive L-cells.

Overall, this dissertation proposes several insights into L-cell sensation of dietary starch-degraded MOS delivered by the consumption of slowly digestible starch. MOS exhibit unique influences on L-cell sensitivity and gut hormone productivity. Future research investigating the mechanisms of intestinal sensing of MOS, as well as the development of bioactive carbohydrate structures that could preserve body weight and modulate glucose tolerance in vivo is needed to translate these findings into nutritional recommendations and food products beneficial for human health. The intricate role of dietary carbohydrates on gut physiological response, related to satiety and food intake could be a new approach for design of foods for health applications.

Colorectal cancer is one of the leading causes of cancer deaths in the United States and multiple modifiable factors contribute to colorectal carcinogenesis. Gut microbiota are believed to play key roles in colon cancer development. Dietary factors may modulate gut microbiota composition, which may potentially have impact on carcinogenesis. Thus, it is reasonable to develop dietary interventions to effectively prevent colorectal cancer development through alteration of gut microbiota. In this thesis, the first objective is to evaluate the effect of vitamin E forms and metabolites, i.e., δ-tocotrienol (δTE), γ-tocotrienol (γTE) and δTE-13’-COOH (δTE-13’), respectively, on gut microbiota in mice. Healthy male balb/c mice were supplemented with a δTE/γTE mixture or δTE-13’ by gavage for two weeks, while control mice received soybean oil. We isolated DNAs from fecal samples and used 16S rRNA gene sequencing to evaluate the impact of these compounds on gut microbiota compositions. Further, we also examined the effect on short chain fatty acids (SCFAs). We observed that supplementation of δTE-13’ increased microbial richness using the Faith index. On the other hand, supplementation did not separate the microbial communities from the control group. But, these compounds managed to alter the relative abundances of several taxa that might present chemopreventive activities against colon cancer. Specifically, Desulfovibrio, a sulfur-reducing bacterium, was decreased after δTE/γTE supplementation. Eubacterium coprostanoligenes group, a group of microbes that can reduce circulating cholesterol, was increased after δTE/γTE supplementation. In addition, several members from the Lachnospiraceae family were elevated under δTE/γTE and δTE-13’ supplementation, and these microbes are known to produce SCFAs and maintain colonic health. However, the measurement of SCFAs showed that supplementation of δTE/γTE and δTE-13’ did not change SCFAs compared with controls. In the second project, I investigated anti-proliferative effects of combining δTE or δTE-13’ with sodium butyrate (NaBu) on human colorectal carcinoma HCT116 cells. Our data showed promising additive effects against cell growth. Collectively, these results indicate that δTE/γTE and δTE-13’ can modulate gut microbiota under healthy conditions, which provides insights into potential chemopreventive activities of these vitamin E forms. Our cell-based studies also showed additive anticancer effects of combining δTE or δTE-13’ with NaBu, which provides rationale to further develop combination of butyrate producers with vitamin E forms for cancer prevention.

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.