Thiamin is a required coenzyme in the production of energy to fuel myocardial contraction. Therefore, thiamin deficiency (TD) may contribute to myocardial weakness by limiting the available energy for myocyte contraction. Previous studies report a wide range for the prevalence of TD in patients with heart failure (HF) (3% to 91%). These trials are limited by their small sample size, indirect measurement of thiamin status, exclusion criteria, and their focus on hospitalized patients. Therefore, this study determined the prevalence of TD in a large (n=100) group of ambulatory patients with HF, using high performance liquid chromotography. The prevalence of TD ([thiamin pyrophosphate (TPP)] ≤ 180 nM/l erythrocytes) was found to be 7%. TD was not related to furosemide use, dietary thiamin intake, severity of the HF, or age. More investigation into the factors that may influence development of TD in ambulatory patients with HF is warranted.

Thiamin is a required coenzyme in energy producing reactions that subsequently fuel myocardial contraction. Therefore, thiamin deficiency (TD) might contribute to the reduction in myocardial function observed in patients with heart failure (HF) by limiting the available energy and subsequently aggravating cardiac performance. While the prevalence of TD as well as the impact of supplementation has been examined in patients with HF, none of these studies to date has examined the impact of TD on clinical outcomes. Therefore, this study investigated the associations between erythrocyte [TPP] levels and outcomes in ambulatory patients with HF. Time-to-event probabilities were found to be not significant for acute decompensated heart failure, mortality, all-cause hospitalizations, arrhythmias, myocardial infarctions and other adverse events. Further investigations into the longer term impact of TD on outcomes and the effects of thiamin supplementation as an adjunct therapy in delaying the disease progression are needed.

B vitamins are of interest in preventative and protective strategies in cardiovascular disease. However, the safety and efficacy of B vitamins has been questioned. Previous research from this group has demonstrated that B6 supplementation alone or in combination with folic acid and B12 reduces angiogenic response. This study determined the effect of vitamin B6 deficiency on the angiogenic response after ischemia in vivo and in vitro using a rodent model. Results indicated that vitamin B6 deficiency enhanced the early angiogenic response by increasing blood flow in vivo after an ischemic event. In vitro measurements demonstrated that vitamin B6 deficiency influenced endothelial progenitor cell (EPC) function and angiogenic growth factor release early after ischemia. In conclusion, B6 deficiency appears to have a modest effect on increasing blood flow and angiogenic markers after ischemia. Additional research is needed to further characterize the impact of lowered vitamin B6 on angiogenesis and its mechanisms.

Arginine synthesis is a complex, age-dependant process involving multiple precursors and enzymes, and the interorgan transfer of substrates. The objectives of this thesis were to elucidate arginine synthesis from enteral precursors in newborn infants and in healthy adults using stable isotope methodology. In the first, of four studies, I validated the use of a non-invasive methodology using urinary amino acids for stable isotope studies of arginine synthesis and demonstrated a known, but under-recognised, problem with D-amino acid contamination of tracers. Implementing chiral chromatography, this issue was further investigated using samples from previous studies in our laboratory with several different isotopes. I demonstrated the novel finding that the impact of D-amino acids is dependent on the tracer used, and also on the age of the subject. In the second study, I used a multi-tracer design to assess arginine synthesis from enteral proline or glutamate in healthy preterm infants. Labeled arginine (M+2), proline (M+1) and glutamate (M+3) were given enterally to fifteen stable, growing preterm infants (gestational age at birth 30-35 weeks) at 1-3 weeks’ postnatal age. I found only arginine synthesis from proline, with no synthesis from glutamate. I conclude that enteral proline is the major contributor to arginine synthesis in vivo in human preterm infants. In the third study, I measured arginine synthesis from enteral proline in adults. I have demonstrated that enteral proline contributes significantly, ~25%, to newly synthesised arginine. In the fourth study, I used two glutamine tracers, 1-13C and 2-15N, to determine if glutamine is a carbon or nitrogen donor for arginine. I showed that enteral glutamine contributes ~50% of the carbon skeleton for arginine and that the 2-15N tracer significantly overestimates arginine synthesis, with the labeled N being transferred through transamination from pyrroline-5-carboxylate (to ornithine, rather than directly from glutamate to pyrroline-5-carboxylate. In conclusion, proline is the sole precursor for arginine in human neonates and combines with glutamaine as the dietary precusor in adults. As a precussor for arginine, though, glutamine’s main role is in provision of nitrogen independent of the carbon skeleton.

Thiamin is a required coenzyme in the production of energy to fuel myocardial contraction. Therefore, thiamin deficiency (TD) may contribute to myocardial weakness by limiting the available energy for myocyte contraction. Previous studies report a wide range for the prevalence of TD in patients with heart failure (HF) (3% to 91%). These trials are limited by their small sample size, indirect measurement of thiamin status, exclusion criteria, and their focus on hospitalized patients. Therefore, this study determined the prevalence of TD in a large (n=100) group of ambulatory patients with HF, using high performance liquid chromotography. The prevalence of TD ([thiamin pyrophosphate (TPP)] ≤ 180 nM/l erythrocytes) was found to be 7%. TD was not related to furosemide use, dietary thiamin intake, severity of the HF, or age. More investigation into the factors that may influence development of TD in ambulatory patients with HF is warranted.

Thiamin is a required coenzyme in energy producing reactions that subsequently fuel myocardial contraction. Therefore, thiamin deficiency (TD) might contribute to the reduction in myocardial function observed in patients with heart failure (HF) by limiting the available energy and subsequently aggravating cardiac performance. While the prevalence of TD as well as the impact of supplementation has been examined in patients with HF, none of these studies to date has examined the impact of TD on clinical outcomes. Therefore, this study investigated the associations between erythrocyte [TPP] levels and outcomes in ambulatory patients with HF. Time-to-event probabilities were found to be not significant for acute decompensated heart failure, mortality, all-cause hospitalizations, arrhythmias, myocardial infarctions and other adverse events. Further investigations into the longer term impact of TD on outcomes and the effects of thiamin supplementation as an adjunct therapy in delaying the disease progression are needed.

B vitamins are of interest in preventative and protective strategies in cardiovascular disease. However, the safety and efficacy of B vitamins has been questioned. Previous research from this group has demonstrated that B6 supplementation alone or in combination with folic acid and B12 reduces angiogenic response. This study determined the effect of vitamin B6 deficiency on the angiogenic response after ischemia in vivo and in vitro using a rodent model. Results indicated that vitamin B6 deficiency enhanced the early angiogenic response by increasing blood flow in vivo after an ischemic event. In vitro measurements demonstrated that vitamin B6 deficiency influenced endothelial progenitor cell (EPC) function and angiogenic growth factor release early after ischemia. In conclusion, B6 deficiency appears to have a modest effect on increasing blood flow and angiogenic markers after ischemia. Additional research is needed to further characterize the impact of lowered vitamin B6 on angiogenesis and its mechanisms.

Master of Science / Department of Hospitality Management and Dietetics / Betsy Barrett / The topic of athlete nutrition has been discussed amongst competitors, coaches, and nutrition professionals since the dawn of the Modern Olympic Movement in 1896 and has led to many strategies to help athletes compete at a higher level. Endurance athletes have been studied around the world. However, studies conducted with elite distance runners at altitude have focused mainly on male athletes in Kenya or Ethiopia. Despite the efforts of researchers over the years in the area of athlete nutrition there has been little research that specifically focuses on elite female distance runners and little evidence is available about the dietary habits and beliefs of these athletes. Therefore, the purpose of this study was to identify the macronutrient and fluid intakes of female distance runners and to determine if current fad diets and specific athletic events impact their eating habits. Seven female elite distance runners (six of European and one of Asian descent) training at altitude completed the study. Their specific events ranged from the 5-K to ultra-marathon. The athletes entered their food, fluid and physical activity for six weeks and submitted a report weekly to the researcher. The data was entered by the researcher into myfitnesspal.com which tabulated the data. The results recorded into Excel spreadsheets for each athlete. At the end of the six weeks, all data was compiled to get a total intake for each athlete and the group as a whole. Mean, minimums, maximums, and standard deviations were used for data analysis. At the end of the six weeks, a telephone interview was conducted with each athlete to determine their eating habits, attitudes towards food, how others impacted their eating and if they were following a fad diet and why. Results indicated that these athletes reported lower mean carbohydrate (51±19.4% of calories) and higher protein (19±6% of calories) intake than is recommended per the Joint Statement of the ADA, DC and ACSM (2009). Fat and fluid consumption were adequate, but overall calories taken in were a little lower than calories expended. The athletes avoided soy, high fructose corn syrup, artificial sweeteners, dairy, and fried foods and focused on eating more fruits and vegetables. Five of the seven athletes were following a gluten free diet because they felt it gave them a competitive edge, increased performance, and reduced GI distress. Based on the results of this study, coaches and athletes should focus on perceived exertion in workouts, macronutrient amounts and overall calories to ensure the athlete is able to compete at a high level.

Several studies have shown that dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) are beneficial in neurodegenerative diseases, although the mechanism of action is not agreed upon. Because most neurodegenerative diseases have an inflammatory component, it is possible that docosahexaenoic acid (DHA) is anti-inflammatory in the brain as it is known to be in several non-neural tissues. Specialized pro-resolving mediators (SPM) are metabolized from DHA and are leading candidates to explain the anti-inflammatory effects of DHA. The goal of this work was to investigate the role and potential mechanisms of action of DHA in neuroinflammation. In our first approach, fat-1 transgenic mice had higher phospholipid and unesterified DHA levels in their hippocampi, and attenuated lipopolysaccharide (LPS)-induced neuroinflammation, compared to wildtype littermates. Feeding wildtype littermates n-3 PUFA mimicked hippocampal DHA levels and LPS-induced neuroinflammatory responses of fat-1 mice, indicating DHA is anti-neuroinflammatory whether derived from the diet or the activity of the fat-1 protein. In an attempt to further augment hippocampal DHA levels, feeding n-3 PUFA adequate mice an n-3 PUFA diet increased phospholipid but not unesterified DHA levels, and did not attenuate LPS-induced neuroinflammation, highlighting the potential importance of unesterified DHA. Directly infusing unesterified DHA into a cerebral ventricle throughout LPS-induced neuroinflammation mimicked several aspects of the attenuated neuroinflammatory response seen with our chronic dietary and transgenic models, as did infusing its 17S-hydroperoxy-DHA (17S-HpDHA) derivative, a precursor to SPM. The metabolism of DHA to SPM in the brain was found to be distinct from non-neural tissues, characterized by the presence of protectin D1 and maresin 1, and the absence of resolvin D1 or D2. Further, infusing 17S-HpDHA increased protectin D1 concurrent to attenuating neuroinflammation, suggesting protectin D1 is responsible for some of the anti-neuroinflammatory effects of DHA. In conclusion, DHA is anti-neuroinflammatory in a mouse model of neuroinflammation, in part, via its metabolism to SPM.

Intrauterine exposures to environmental factors have been hypothesized to influence the risk of breast cancer in adulthood. The majority of epidemiological studies suggest that dietary folate intake is inversely related to breast cancer, however, the evidence have been inconsistent. An animal study was performed to determine the relationship between in utero and postnatal dietary folate intervention and the risk of breast cancer in the DMBA rodent model. Supplementation of maternal and offspring diet with folic acid (5 mg/kg diet) was observed to significantly increase the risk of mammary tumor development in the offspring compared to controls (2 mg/kg diet). Maternal diet and tumor status were also found to be significant predictors of global DNA methylation. Our data suggests that high intrauterine and postnatal exposures to folic acid increases the risk of breast cancer development. Epigenetic modifications may be an underlying mechanism by which folate mediates mammary tumorigenesis in the offspring.