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ABSTRACT This randomized, controlled, double-blind crossover study examined the effects of a preprandial, 20g oral dose of apple cider vinegar (ACV) on colonic fermentation and glycemia in a normal population, with the ultimate intention of identifying the mechanisms by which vinegar has been shown to reduce postprandial glycemia and insulinemia.

ABSTRACT This randomized, controlled, double-blind crossover study examined the effects of a preprandial, 20g oral dose of apple cider vinegar (ACV) on colonic fermentation and glycemia in a normal population, with the ultimate intention of identifying the mechanisms by which vinegar has been shown to reduce postprandial glycemia and insulinemia. Fifteen male and female subjects were recruited, ages 20-60y, who had no prior history of gastrointestinal (GI) disease or resections impacting normal GI function, were non-smokers, were non-vegetarian/vegan, were not taking any medications known to alter (glucose) metabolism, and were free of chronic disease including diabetes. Subjects were instructed to avoid exercise, alcohol and smoking the day prior to their trials and to consume a standardized, high-carbohydrate dinner meal the eve prior. There was a one-week washout period per subject between appointments. Breath hydrogen, serum insulin and capillary glucose were assessed over 3 hours after a high-starch breakfast meal to evaluate the impact of preprandial supplementation with ACV or placebo (water). Findings confirmed the antiglycemic effects of ACV as documented in previous studies, with significantly lower mean blood glucose concentrations observed during ACV treatment compared to the placebo at 30 min (p=0.003) and 60 min (p=0.005), and significantly higher mean blood glucose concentrations at 180 min (p=0.045) postprandial. No significant differences in insulin concentrations between treatments. No significant differences were found between treatments (p>0.05) for breath hydrogen; however, a trend was observed between the treatments at 180 min postprandial where breath hydrogen concentration was visually perceived as being higher with ACV treatment compared to the placebo. Therefore, this study failed to support the hypothesis that preprandial ACV ingestion produces a higher rate of colonic fermentation within a 3 hour time period following a high-carbohydrate meal. Due to variations in experiment duration noted in other literature, an additional study of similar nature with an expanded specimen collections period, well beyond 3 hours, is warranted.
ContributorsMedved, Emily M (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2012
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Background: Sugars form advanced glycation end products (AGEs) throughnatural metabolism and interactions with proteins, lipids, and nucleic acids, which accumulate in tissues and have been implicated in the etiology of chronic diseases. Due to the increased consumption of fructose and its high ability to form AGEs, a further understanding of

Background: Sugars form advanced glycation end products (AGEs) throughnatural metabolism and interactions with proteins, lipids, and nucleic acids, which accumulate in tissues and have been implicated in the etiology of chronic diseases. Due to the increased consumption of fructose and its high ability to form AGEs, a further understanding of this association is important to clarify the role of sugars in disease. The objective was to explore the association between usual fructose intake and serum levels of AGEs, as measured by carboxymethyl-lysine (CML) and methylglyoxal derivative (MG-H1), in healthy adults. Methods: This is a secondary analysis of a 15-d controlled feeding study (n=100) with participants consuming their usual diet conducted in the Phoenix metropolitan area. To assess participants’ usual diet, they were asked to complete two 7-d food diaries, which were then used to create custom 15-d menu plans administered during the feeding period. Forty participants were selected based on their 15-d mean total fructose intake for this analysis [top and bottom 20% of the sample distribution (median, IQR); high fructose (HF) n= 20, 72.6 (66.1-90.4) g/day, low fructose (LF) n= 20, 28.8 (22.7-32.2) g/day. Fasting serum collected five weeks after the feeding period were analyzed for CML and MG-H1, two well-established AGEs, using ELISA kits. A database of 549 common foods with known CML amounts was used to calculate exogenous CML intake based on daily food intake data. A general linear model was fitted to investigate the difference in serum CML and MG-H1 between LF and HF groups while adjusting for age, gender, BMI, and exogenous CML intake. Results: Participants in the HF group had significantly higher serum CML and lower MG-H1 levels compared to participants in the LF group (p=0.013 and p=0.002, respectively). This difference remained statistically significant after adjusting for covariates. Conclusions: The findings suggest that endogenous CML formation may be an explanation for the significantly higher serum CML levels in the HF compared to the LF group. This is significant in further understanding mechanisms of fructose intake and disease etiology and could have implications for at-risk populations consuming a high fructose diet.
ContributorsWeigand, Bethany (Author) / Tasevska, Natasha (Thesis advisor) / Sweazea, Karen (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2021
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Diabetes is the 7th leading cause of death globally. In 2018, 34.2 million Americans had type 2 diabetes. Many symptoms of diabetes are similar to those of scurvy or vitamin C deficiency. Vitamin C marginality and inadequacy are more prevalent in Type 2 Diabetes/prediabetes than with normal glucose tolerance. Intracellular

Diabetes is the 7th leading cause of death globally. In 2018, 34.2 million Americans had type 2 diabetes. Many symptoms of diabetes are similar to those of scurvy or vitamin C deficiency. Vitamin C marginality and inadequacy are more prevalent in Type 2 Diabetes/prediabetes than with normal glucose tolerance. Intracellular vitamin C inadequacy is suspected due to competition between dehydroascorbic acid and glucose at GLUT 1 and 3 cellular receptors. Erythrocyte osmotic fragility is noted in Gulo -/- knockout mice unable to synthesize endogenous vitamin C. The ascorbate deficient red blood cells presented with low cytoskeletal B-spectrin, spherocyte appearance, and impaired deformability. This cross-sectional study investigated the relationships between diabetes status, erythrocyte osmotic fragility, and serum vitamin C status. Participants were aged 18-65, non-smoking, reported no unresolved health complications, and denied prior vitamin C supplementation. Those with T2D indicated diagnosis of >1 year. All participants provided written informed consent and the study was approved by the local Institutional Review Board in January 2021. Participants provided one fasted blood sample. Erythrocyte osmotic fragility was measured via UV/Vis spectrophotometry with various concentrations of sodium chloride (0.85% - 0.10%) to induce osmotic stress. In addition, plasma was extracted and mixed 1:1 with 10% (w/v) metaphosphoric acid in 2 mmol/L disodium EDTA and centrifuged. The supernatant was stored at -80°C until analysis with isocratic reverse-phase UV-HPLC separation. Participant characteristics did not differ significantly between groups apart from age (p< 0.01) and HbA1c (p=0.002). Data are presented for adults with T2D (n=14; 36% female; 55.5±8.2 y; 31.5±9.0 kg/m2; HbA1c: 7.4±1.9%; plasma vitamin C: 36.0±12.2 uM) and without T2D (n=16; 69% female; 38.7±13.5 y; 26.8±6.6 kg/m2; A1c: 5.4±0.3%; plasma vitamin C: 34.8±10.9uM). Erythrocyte osmotic fragility was significantly elevated (+4.4% hemolysis) in adults without T2D at 0.35% saline (p=0.039). Greater VC status (>30 uM) was associated with lower hemolysis at 0.35% NaCl (p=0.031). Erythrocyte osmotic stability was linked to greater vitamin C intake at 0.20% saline in those without T2D (p =0.019). In this pilot study, vitamin C status did not differ significantly by diabetes status. Vitamin C status was directly linked to erythrocyte osmotic stability in adults without T2D.
ContributorsLundy, Ciara Cheyanne (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Alexon, Christy (Committee member) / Arizona State University (Publisher)
Created2022
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Fish oil has been extensively researched for its protective effects on cognition. More recently, anthocyanins have also gained the attention of the medical community for their potential cognitive benefits. Maqui berries are one of the richest sources of anthocyanins known to science. While there are many randomized controlled trials (RCT)

Fish oil has been extensively researched for its protective effects on cognition. More recently, anthocyanins have also gained the attention of the medical community for their potential cognitive benefits. Maqui berries are one of the richest sources of anthocyanins known to science. While there are many randomized controlled trials (RCT) investigating the effects of fish oil and/or anthocyanins on cognition in various populations, there are no RCT that exclusively investigate the cognitive effects of these compounds in adults with Type 2 Diabetes (DM2). The purpose of this double-blinded, placebo-controlled RCT was to investigate the cognitive effects of maqui berry extract and fish oil supplements in adults with DM2 over the course of eight weeks. Adults with DM2 (n=29) were recruited by the researchers and randomized to either Group A or Group B. Because the study is ongoing, it is unknown which group received the intervention. The study used the Stroop Test and Trail Making Test (TMT) to measure cognition at baseline, 4 weeks, and 8 weeks. Anthropometrics, blood glucose, and hemoglobin A1C were also taken at these time points. Sixteen female participants were included in the final analysis. Neither group showed significant improvements in the cognitive tests. However, in Group A, the effect sizes were large for the change in Trail-Making Test A (0.167), Trail Making Test B (0.261), and Trail Making Test B minus A (0.296) scores. In Group A, the change in Trail Making Test B minus A scores between baseline and week 4, and between baseline and week 8 was significant (p=0.053) and produced a large effect size (0.258). The results suggest that fish oil and maqui berry extract may improve cognition in adults with DM2, but further studies with larger sample sizes are needed.
ContributorsDeimeke, Allyson (Author) / Johnston, Carol (Thesis advisor) / Grant, Shauna (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2023
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This feasibility study explored the use of an evolutionary mismatch narrative in nutritional education intervention aiming to reduce ultra-processed foods in the diets of veterans with type 2 diabetes and improve diabetic outcomes. Ultra-processed foods are foods that are primarily manufactured through industrial processes. These foods are high in calories

This feasibility study explored the use of an evolutionary mismatch narrative in nutritional education intervention aiming to reduce ultra-processed foods in the diets of veterans with type 2 diabetes and improve diabetic outcomes. Ultra-processed foods are foods that are primarily manufactured through industrial processes. These foods are high in calories but low in nutritional content. Diets high in these foods have been linked to increased health risks. One of the major health risks is type 2 diabetes. Type 2 diabetes is a chronic disease that is developed when cells become unable to properly utilize insulin. Over time this may lead to additional health conditions such as nerve damage, cardiovascular disease, and renal disease. Evolutionary mismatch narrative nutritional intervention offers a different approach to nutritional education to help reduce ultra-processed foods in diets. This study was a randomized controlled feasibility study at the Phoenix VA. Eleven participants were enrolled and randomly selected to be given either an evolutionary mismatch narrative education intervention or general nutritional education about ultra-processed foods. 24-hour diet recalls and blood chemistry were collected and analyzed. Blood chemistry provided diabetes related measurements which included glucose, HbA1c, insulin, HOMA-IR, and C-reactive protein. Statistically significant findings in this study included percentage of ultra-processed foods decreasing for both control and experimental groups from week 0 to week 4 (p=0.014), and C-reactive protein levels between the control and experimental groups (p=0.042). However, baseline C-reactive protein concentrations were lower in the experimental group such that normalizing for group differences at baseline revealed no significant difference in C-reactive protein change between interventions (p = 1.000). There were no other statistically significant values regarding diabetes related measurements. The results from this study suggest that nutritional education in general may help decrease ultra-processed food consumption.

ContributorsLiang, Nathan Adam (Author) / Sweazea, Karen (Thesis advisor) / Basile, Anthony J (Committee member) / Johnston, Carol (Committee member) / Arizona State University (Publisher)
Created2023
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Background: Despite research aimed at understanding the mechanisms of metabolic syndrome (MetS), this prevalence continues to rise. Recent literature indicates that dietary fiber may offer prevention and management of MetS in various studies involving human and animal subjects. Objective: This six-week study aimed to test the efficacy of a novel

Background: Despite research aimed at understanding the mechanisms of metabolic syndrome (MetS), this prevalence continues to rise. Recent literature indicates that dietary fiber may offer prevention and management of MetS in various studies involving human and animal subjects. Objective: This six-week study aimed to test the efficacy of a novel fiber-rich complex in young male Sprague-Dawley rats by examining the effects on high-fat diet-induced weight gain, adiposity, high blood sugar, lipid imbalance, and oxidative stress. Methods: 24 six-week-old male Sprague Dawley rats were randomly assigned into three diet groups (regular chow, high-fat, or high-fat + fiber) and fed for six weeks. Blood from the animals was collected at weeks 0, 3, and 6 for fasting blood glucose (FBG) analysis and at weeks 0 and 6 for lipid profile assessment. Body mass was weighed weekly. Organ mass, nasoanal, and tail length were measured at week 6. Findings were considered significant at p-value < 0.05. Data collected at week 6 were analyzed by one-way ANOVA, whereas data collected at multiple time points were analyzed by two-way ANOVA with diet and time as factors. Student-Newman-Keuls posthoc analyses were used to compare differences between and within groups. Results: No significant differences were found in the size of rats fed each diet as measured by tail length (p = 0.599) or nasoanal length (p = 0.875). Abdominal circumference was not significantly different (p = 0.477). There were no significant differences between groups in fasting whole blood HDL cholesterol (p = 0.297), fasting whole blood HDL triglycerides (p = 0.624), plasma total triglycerides (p = 0.137), or beta-hydroxybutyrate (p=0.185) after six weeks of each dietary treatment. Similarly, plasma true triglycerides and free glycerol were not significantly different between groups (p = 0.148 and 0.529, respectively). Thiobarbituric acid reactive substances (TBARS) were also not significantly different between groups (p = 0.412). Conclusion: The addition of the novel fiber-rich complex did not significantly affect high-fat diet-induced weight gain, adiposity, high blood sugar, lipid imbalance, or oxidative stress in this experimental design.
ContributorsLing, Jingyu (Author) / Sweazea, Karen (Thesis advisor) / Sears, Dorothy (Committee member) / Kim, Min-Hyun (Committee member) / Arizona State University (Publisher)
Created2024
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Cardiovascular disease (CVD) is characterized by impaired vasodilation and the development of atherosclerosis.78 A diet high in saturated fat, such as palmitate, contributes to this by promoting inflammation and oxidative stress in human vascular smooth muscle cells (VSMC). 11,12,84,88 The inflammation cascade that occurs increases pro-inflammatory cytokines, like tumor necrosis

Cardiovascular disease (CVD) is characterized by impaired vasodilation and the development of atherosclerosis.78 A diet high in saturated fat, such as palmitate, contributes to this by promoting inflammation and oxidative stress in human vascular smooth muscle cells (VSMC). 11,12,84,88 The inflammation cascade that occurs increases pro-inflammatory cytokines, like tumor necrosis factor alpha (TNF-alpha) and increases proinflammatory enzymes like cyclooxygenase 2 (COX-2) contributing to inflammation, oxidative stress, blood pressure shifts, and atherosclerosis.11,12,69,84 Palmitate has been found to upregulate TNF-alpha,85 and COX-2. 11,12, 84

In various studies, sumac, a Mediterranean spice and known antioxidant,39,7,66,67 has been shown to have antioxidant properties through its ability to inhibit reactive oxygen species (ROS) such as superoxide.39,7,66,67 Sumac has also been found to reduce TNF-alpha.100 Results from a study of hypertensive human subjects fed a sumac supplement showed a decrease in blood pressure.59

In the current study, COX-2 levels were determined to evaluate the level of inflammation in response to palmitate when primary aortic human vascular smooth muscle cells (HAoVSM) were treated with sumac. The treatments included: vehicle (bovine serum albumin), 100 µM palmitate, and 10, 20, 40, 60, and 80 µg/mL sumac. Sumac did not alter COX-2 protein levels between vehicle and sumac groups. Additional studies were designed to examine whether 80 µg/mL sumac could reverse impaired vasodilation caused by 10 weeks of high fat intake, consisting of 60% of total calories from fat, in Sprague-Dawley rats. Mesenteric arteries were isolated and exposed to sumac. High fat diet (HFD) arteries had impaired vasodilation compared to arteries from chow-fed fats. HFD arteries exposed to sumac had similar endothelium-dependent vasodilation responses as those not exposed to sumac, however, there were trends for improved vasodilation. I suggest that sumac likely exhibits antioxidant capabilities that prevent superoxide from decreasing the bioavailability of nitric oxide in the vasculature, thus promoting endothelium-dependent vasodilation and preventing the creation of more harmful reactive oxygen species. Isolated arteries from chow fed rats developed irreversible vasodilation when exposed to sumac and were therefore not responsive to pre-constriction with phenylephrine (PE) likely related to nitrates and gallic acid naturally present in sumac whereby inhibiting PE.
ContributorsBarberes, Julia (Author) / Sweazea, Karen (Thesis advisor) / Gonzales, Rayna (Committee member) / Alexon, Christy (Committee member) / Arizona State University (Publisher)
Created2018
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According to a 2016 census, eight million adults conform to a vegetarian diet within the United States, and about 50% of these adults follow a vegan diet. The census determined that plant-based diets are quickly growing in popularity particularly in young adults between the ages of 18 to 34 years.

According to a 2016 census, eight million adults conform to a vegetarian diet within the United States, and about 50% of these adults follow a vegan diet. The census determined that plant-based diets are quickly growing in popularity particularly in young adults between the ages of 18 to 34 years. Many Americans are aware of the health benefits of a plant-based diet, however, the dietary risks associated with these diets are not well emphasized. Health concerns such as vitamin deficiencies and altered metabolism are heightened in vegetarian populations.

One Particular nutrient that is commonly lacking in the vegetarian diet is vitamin B12. Vitamin B12 is found mainly in animal-derived food sources such as meat, poultry, fish, dairy, and eggs. Although some vegetarians, called lacto-ovo vegetarians, consume dairy and eggs, vegans do not consume any animal products at all. Vitamin B12 deficiency can have devastating consequences on the human body due to its role as a methylation cofactor. Metabolism, DNA replication, and cancer formation all involve methylation processes.

This cross-sectional, differential study aimed to further understand the relationship between vegetarianism, vitamin B12 status, and methylation capacity in healthy adults. A group of 34 healthy adults (18 vegetarians and 16 omnivores) was recruited to analyze serum B12, homocysteine, methylmalonic acid, serum total folate, and transcobalamin II status. It was hypothesized that (1) vegetarians would have a lower vitamin B12 status, and thus, a lower methylation capacity than omnivores and that (2) low vitamin B12 status would be correlated with low methylation capacity.

The data show that vegetarians did not have significantly lower vitamin B12 methylation capacity status than omnivores. Nor was vitamin B12 status correlated with methylation capacity. However, the data revealed that diet quality had a positive influence on folate status. There was also a statistical trend (p=0.08) for homocysteine reduction in participants consuming high-quality diets. The data herein suggest that methylation capacity may be impacted by the quality of diet rather than the type of diet.
ContributorsUgarte, Noel (Author) / Johnston, Carol S (Thesis advisor) / Whisner, Corrie (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2019
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Background. Despite extensive research in the literature aimed at understanding the role of hypertension as a major risk factor for numerous leading causes of death in the United

States, rates of this disease continue to rise. Recent findings suggest that antiseptic mouthwash use may increase blood pressure through elimination of oral

Background. Despite extensive research in the literature aimed at understanding the role of hypertension as a major risk factor for numerous leading causes of death in the United

States, rates of this disease continue to rise. Recent findings suggest that antiseptic mouthwash use may increase blood pressure through elimination of oral bacteria that facilitate the enterosalivary nitrate-nitrite-nitric oxide pathway.

Objective. The purpose of this randomized, controlled, crossover trial was to examine the effects of antiseptic mouthwash use and sodium intake on blood pressure and salivary nitrate levels in prehypertensive adults.

Methods. Healthy adults (n=10; 47.3±12.5) with mildly elevated blood pressure (average baseline blood pressure of 114.9/75.2 mmHg) were recruited and were randomly assigned to a control condition, antiseptic mouthwash use, or antiseptic mouthwash use + consumption of three pickles per day (~6000 mg/day of sodium) for a total of 7 days. Given the crossover design of this study, participants adhered to a 1-week washout period between each condition and all participants received all three treatments. Findings were considered significant at a p-value of <0.05 and a repeated measures ANOVA test was used to compare change data of each condition.

Results. Changes in systolic and diastolic blood pressure were not statistically significant (p=0.469 and p=0.859, respectively). Changes in salivary nitrite levels were not statistically significant (p=0.493). Although there appeared to be fluctuations in sodium intake between interventions, differences in sodium intake were not statistically significant when pickles were not accounted for (p=0.057).

Conclusion. Antiseptic mouthwash use did not appear to induce significant changes in systolic or diastolic blood pressure in this population.
ContributorsShaw, Karrol (Author) / Johnston, Carol (Thesis advisor) / Alexon, Christy (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2019
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The glycation of plasma proteins leading to the production of advanced glycation end products (AGEs) and subsequent damage is a driving factor in the pathophysiology of diabetic complications. The overall research objective was to elucidate the mechanisms by which birds prevent protein glycation in the presence of naturally high plasma

The glycation of plasma proteins leading to the production of advanced glycation end products (AGEs) and subsequent damage is a driving factor in the pathophysiology of diabetic complications. The overall research objective was to elucidate the mechanisms by which birds prevent protein glycation in the presence of naturally high plasma glucose concentrations. This was accomplished through the specific purpose of examining the impact of temperature and glucose concentration on the percent glycation of chicken serum albumin (CSA) in comparison to human serum albumin (HSA). Purified CSA and HSA solutions prepared at four different glucose concentrations (0 mM, 5.56 mM, 11.11 mM, and 22.22 mM) were incubated at three different temperatures (37.0°C, 39.8°C, and 41.4°C) on separate occasions for seven days with aliquots extracted on days 0, 3, and 7. Samples were analyzed by LC-ESI-MS for percent glycation of albumin. The statistically significant interaction between glucose concentration, temperature, albumin type, and time as determined by four-way repeated measures ANOVA (p = 0.032) indicated that all independent variables interacted to affect the mean percent glycation of albumin. As glucose concentration increased, the percent glycation of both HSA and CSA increased over time at all temperatures. In addition, HSA was glycated to a greater extent than CSA at the two higher glucose concentrations examined for all temperature conditions. Temperature differentially affected percent glycation of HSA and CSA wherein glycation increased with rising temperatures for HSA but not CSA. The results of this study suggest an inherent difference between the human and chicken albumin that contributes to the observed differences in glycation. Further research is needed to characterize this inherent difference in an effort to elucidate the mechanism by which birds protect plasma proteins from glycation. Future related work has the potential to lead to the development of novel therapies to prevent or reverse protein glycation prior to the formation of AGEs in humans, thus preventing the development and devastating effects of numerous diabetic complications.
ContributorsZuck, Jessica (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2016