The experiments in this thesis tested <i>in vitro</i> and <i>in vivo</i> the proposal that zinc-deficient superoxide dismutase, resulting from mutations or oxidative damage to the enzyme, gains ascorbate oxidase activity that contributes to the pathology of amyotrophic lateral sclerosis (ALS). They also tested whether flavonoids can help protect against this activity.<p>The <i>in vitro</i> experiments showed that zinc-extracted Cu/Zn-SOD (Cu-SOD) as well as SOD treated with H2O2 or H2O2 plus ascorbate accelerated ascorbate oxidation 100 to 300 %, while native SOD had no effect. With Cu-SOD, the activity was unaffected by EDTA, EGTA, or catalase, showing that the catalytic copper was firmly bound and that the H2O2 product of SOD activity was not responsible. Catechin and uric acid slowed ascorbate oxidation by Cu-SOD by 72% and 67%, respectively.<p>The <i>in vivo</i> study investigated tissue levels of ascorbate and biomarkers of oxidative stress in a transgenic mice bearing a mutation in Cu/Zn-SOD as a model of familial ALS (FALS mice), and the effects of dietary ascorbate and quercetin. In FALS mice on control modified AIN93G diet for 10 weeks compared to the wild-type, liver thiobarbituric acid reactive substances (TBARS) were 47% higher and liver oxidized vitamin C was 2800% higher. These results support, in liver, that mutant SOD acquired ascorbate oxidase activity and increased oxidative stress. The only difference in other tissues was a 136% increase in GSH/GSSG ratio in thigh muscle of FALS mice.<p>In dietary treatments of FALS mice, spinal cord TBARS was 93 % higher with ascorbate-supplemented diet compared to control diet, suggesting that dietary ascorbate increased oxidative stress. Also in spinal cord, oxidized-vitamin C was 250% higher in ascorbate + quercetin-fed FALS mice, which suggests there is no protection by quercetin against ascorbate oxidation. In brain, protein thiols were 56% and 58% lower in quercetin-fed and ascorbate + quercetin-fed FALS mice, suggesting that quercetin worsened oxidative damage. In liver, quercetin feeding produced a 40% decrease in vitamin C, total vitamin C and oxidized-vitamin C, perhaps by down-regulating ascorbate biosynthesis. Overall the results support a gain of ascorbate oxidase activity of mutant SOD in ALS, but do not support protection by dietary treatment with ascorbate or quercetin.

It has long been known that vitamin D is important for calcium absorption and bone health. More recently, vitamin D has been found to modulate breast cancer cell growth and increasingly epidemiologic studies suggest vitamin D may be associated with reduced breast cancer risk. The primary objective of this thesis was to evaluate the associations between vitamin D from all sources (food, supplements and sunlight exposure) and breast cancer. Secondary objectives were focused on methodological issues including the development of a solar vitamin D score and adapting the measurement of vitamin D from foods for use among Canadians. The data source for this study was the “Ontario Women’s Diet and Health Study”, a population-based case-control study of women in Ontario. Cases (n = 3,101) diagnosed between 2002 and 2003 were identified through the Ontario Cancer Registry and controls (n = 3,471) were identified through random digit dialing of Ontario households. Study participants completed mailed risk factor and food frequency questionnaires. Vitamin D intake from supplements (>400 IU/day compared to none) was found to be associated with reduced breast cancer risk (OR = 0.76; 95% CI: 0.59, 0.98). However, total vitamin D intake (from food and supplements) and intake from food alone were not associated with breast cancer risk. Time spent outdoors during 4 periods of life (including adolescence) was associated with reduced breast cancer (e.g., highest versus lowest categories of exposure at age 40 to 59: OR = 0.74; 95% CI: 0.61, 0.88). The novel solar vitamin D score, derived from time spent outdoors, skin color, sun protection practices, and ultraviolet radiation of residence, was also associated with reduced breast cancer risk. In summary, there is some evidence to suggest that vitamin D intake from supplements and determinants of cutaneous vitamin D production are associated with reduced breast cancer risk.

Graduation date: 1992

Purpose: National prevalence of childhood overweight and obesity has plateaued in recent years, but rates remain high, with approximately 10% among children“high weight.” The relationship between adiposity and serum 25-hydroxyvitamin D [25(OH)D] status has been well-explored in older individuals, with inconsistent results. Furthermore, previous studies have suggested a relationship between adequate consumption of calcium and vitamin D and healthy weight status in older children and adults. However, in the infant population, there are few studies detailing the interaction between body composition and serum 25(OH)D or intake of calcium and vitamin D. Our study aims were to assess the association between serum 25(OH)D and body composition and to examine the association between adiposity and dietary intake of calcium and vitamin D in a sample of infants and toddlers. Methods: Our population included healthy male and female infants and toddlers from Pittsburgh, PA who participated in the “Practices Affecting Vitamin D Status in Pittsburgh Infants and Toddlers” study. Parents completed a Vitamin D and Sunlight Exposure Questionnaire, which assessed dietary intake of foods high in calcium and vitamin D as well as daily sunlight exposure (≥2 hours vs. >2 hours). Anthropometric measures and bloodwork for serum 25(OH)D were obtained during at the time of the study visit. Weight-for-length (WFL) percentile status was determined using WHO growth standards (low weight97.7 %ile) and WFL z-scores were calculated. ANOVA was used to compare mean serum 25(OH)D and calcium and vitamin D intake by WFL status. Chi square analysis was used to evaluate the relationship between serum 25(OH) D status (deficient =/mL, insufficient = 12-20 ng/mL, sufficient >20 ng/mL), calcium intake status (sufficient = >700 mg), vitamin D intake status (sufficient = >400 IU) and WFL percentile status. Pearson’s correlation coefficient was used to assess the strength and significance of associations between serum 25(OH)D, calcium and vitamin D intake and WFL z-score. The analysis was repeated after subdivision by race and sun exposure. Results: 125 infants and toddlers (9 to 24 months of age, 68% African American) participated in the study. Approximately 11% of the population had a high weight. Mean vitamin D intake (~600 IU/d) and median calcium intake (~1550 mg/d) exceeded recommendations. Prevalence of high weight was higher among children with adequate intake compared to those who consumed less than the recommendations (calcium: 41% vs. 36%, respectively; vitamin D: 45% vs. 29%, respectively). However, this difference was not statistically significant. Mean serum 25(OH)D level (37 ng/mL) was sufficient. When compared across WFL status, neither mean serum 25(OH)D nor mean intake of calcium and vitamin D varied significantly. No significant correlation was found between WFL and serum 25(OH)D for the cohort or any of the subgroups examined. Conclusions: Rates of infant overweight and obesity in our sample are similar in comparison with the national average. Our results do not support a relationship between calcium and vitamin D intake on weight status or an association between serum vitamin D and body composition in children of this age. Future studies are needed to re-examine these relationships in a larger group of children of more evenly distributed weight status.

The experiments in this thesis tested <i>in vitro</i> and <i>in vivo</i> the proposal that zinc-deficient superoxide dismutase, resulting from mutations or oxidative damage to the enzyme, gains ascorbate oxidase activity that contributes to the pathology of amyotrophic lateral sclerosis (ALS). They also tested whether flavonoids can help protect against this activity.<p>The <i>in vitro</i> experiments showed that zinc-extracted Cu/Zn-SOD (Cu-SOD) as well as SOD treated with H2O2 or H2O2 plus ascorbate accelerated ascorbate oxidation 100 to 300 %, while native SOD had no effect. With Cu-SOD, the activity was unaffected by EDTA, EGTA, or catalase, showing that the catalytic copper was firmly bound and that the H2O2 product of SOD activity was not responsible. Catechin and uric acid slowed ascorbate oxidation by Cu-SOD by 72% and 67%, respectively.<p>The <i>in vivo</i> study investigated tissue levels of ascorbate and biomarkers of oxidative stress in a transgenic mice bearing a mutation in Cu/Zn-SOD as a model of familial ALS (FALS mice), and the effects of dietary ascorbate and quercetin. In FALS mice on control modified AIN93G diet for 10 weeks compared to the wild-type, liver thiobarbituric acid reactive substances (TBARS) were 47% higher and liver oxidized vitamin C was 2800% higher. These results support, in liver, that mutant SOD acquired ascorbate oxidase activity and increased oxidative stress. The only difference in other tissues was a 136% increase in GSH/GSSG ratio in thigh muscle of FALS mice.<p>In dietary treatments of FALS mice, spinal cord TBARS was 93 % higher with ascorbate-supplemented diet compared to control diet, suggesting that dietary ascorbate increased oxidative stress. Also in spinal cord, oxidized-vitamin C was 250% higher in ascorbate + quercetin-fed FALS mice, which suggests there is no protection by quercetin against ascorbate oxidation. In brain, protein thiols were 56% and 58% lower in quercetin-fed and ascorbate + quercetin-fed FALS mice, suggesting that quercetin worsened oxidative damage. In liver, quercetin feeding produced a 40% decrease in vitamin C, total vitamin C and oxidized-vitamin C, perhaps by down-regulating ascorbate biosynthesis. Overall the results support a gain of ascorbate oxidase activity of mutant SOD in ALS, but do not support protection by dietary treatment with ascorbate or quercetin.

In the poultry industry, further processed meat products have the highest share in the market, and because there is a growing demand of food products with enriched amounts of unsaturated fatty acids, the objectives of this research were to assess lipid oxidation development and quality characteristics of chicken meat as affected by dietary fat and vitamin E levels. Broilers were fed during six weeks with diets containing animal/vegetable, lard, palm kernel, soybean, conjugated linoleic acid, flaxseed, or menhaden oil. Each lipid diet was supplemented with either a control (33 or 42 mg/kg) or a supranutritional level (200-400 or 200 mg/kg) of vitamin E. Breast and thigh meat, or skin, were processed, packaged, and refrigerated as raw meat, cooked patties, or cooked sous vide meat. The results showed that the chicken meat fatty acid composition reflected those from the dietary fats. In the meat or skin there was a higher lipid oxidation susceptibility as the proportion of unsaturated fatty acids increased, shown as malonaldehyde values, particularly in the treatments with low supplemented level of vitamin E (P<0.05). The relative lipid oxidative stability of the meat decreased in consecutive order from raw, cooked sous vide, and cooked meat patties. Sous vide cooked meat developed lipid oxidation at a slow rate and showed not to be affected by nonheme iron values. Dietary fat and vitamin E level affected breast meat lightness (L* color space) values (P<0.05), but not muscle pH, Allo-Kramer shear force, or water holding capacity. In conclusion, the increment in the proportion of unsaturated fatty acids increases the susceptibility to lipid oxidation in the meat. Supranutritional supplementation levels of vitamin E are more effective at inhibiting the lipid oxidation development in chicken meat than some current levels used by the poultry industry. Neither dietary fat nor vitamin E level seems to affect the development of pale, soft, and exudative meat condition in chicken meat.

Zugl.: Berlin, Freie Universiẗat, Diss., 2009.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 117-153).

Zugl.: Zürich, Univ., Diss., 2008

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Food Science." Includes bibliographical references (p. 78-97).