The objective was to assess the effect of a high-monounsaturated fat (MUFA) dietary portfolio of cholesterol-lowering foods on oxidative stress and cardiovascular risk. Twenty-four hyperlipidemic subjects followed a very low-saturated-fat therapeutic control diet for 4 weeks after which they were randomized to receive the dietary portfolio, consisting of soy protein (20g/1000kcal), viscous fibre (10.3g/1000kcal), plant sterols (2-3g) and almonds (21.5g/1000kcal), in combination with high- or low-MUFA (25.9% and 12.9% MUFA, respectively) for the next 4 weeks, where MUFA replaced 13.0% of dietary carbohydrate. On high-MUFA, there were significantly greater increases in HDL-C and apoA1 and significantly greater reductions in total:high-density lipoprotein cholesterol (total:HDL-C) ratio and high-sensitivity C-reactive protein (hs-CRP) compared to the low-MUFA dietary portfolio. In all diets there were significant increases in protein thiols and reductions in conjugated dienes and thiobarbituric acid reactive substances (TBARS) measured in the LDL-fraction, however no difference between the high- and low-MUFA diets.

The effects of high maternal folate status on the offspring are unknown; however, early life exposure to environmental stimuli, including dietary factors, is thought to influence the risk of developing chronic disease. An animal study was performed to determine the effect of maternal folic acid supplementation during pregnancy and lactation on DNA methylation and global gene expression patterns in the offspring. Supplementation of the maternal diet with folic acid (5, 8, and 25 mg/kg diet) induced global DNA hypomethylation in the liver of juvenile and adult offspring, and altered the expression of the imprinted H19 gene and genes involved in lipid metabolism, coagulation, and iron transport and homeostasis. Our data suggest that intrauterine and early postnatal periods are susceptible to changes in DNA methylation and gene expression in response to high levels of folic acid, which may be associated with health status and disease later in life.

H. pylori has been classified by World Health Organization as type I carcinogen for its association with gastric cancer. Among its suggested pathological pathways is oxidative stress, which may reduce the bioavailability of dietary antioxidants. The main objectives of this thesis were to estimate the prevalence of H. pylori infection in Ontario and to assess its effect on the bioavailability of two main dietary antioxidants, vitamins E and C. To estimate the prevalence of H. pylori infection, a volume of 10 ul of plasma was aliquoted from stored blood of 1306 adults from Ontario. The blood samples belonged to controls of a population-based study of colorectal cancer. The overall weighted seroprevalence of H. pylori was 23.1% (95% CI: 17.7-29.5) with males having higher infection rates than females. Seroprevalence of the infection increased with age and number of siblings. Being non-white, born outside Canada and immigrating at an age greater than 20 years increased risk for H. pylori infection. An inverse association with seroprevalence was found for education and alcohol consumption. In order to investigate whether H. pylori positive compared to H. pylori negative subjects have lower changes in plasma concentrations of ascorbic acid and alpha tocopherol when supplemented with these vitamins, H. pylori negative (n=32) and H. pylori positive (n=27) volunteers received vitamin C (500 mg) and alpha tocopherol (400 IU) supplementation daily for 28 days. H. pylori infection status was determined by 13C urea breath test. Post supplementation plasma ascorbic acid and alpha tocopherol were significantly higher than pre supplementation concentrations in both groups. The changes in plasma ascorbic acid and alpha tocopherol were not significantly different between H. pylori negative and positive groups (ascorbic acid: 13.97±16.86 vs. 20.87±27.66, p=0.76; alpha tocopherol: 15.52±9.4 vs. 14.47±15.77; p=0.39 for H. pylori negative and positive groups respectively). The weighted seroprevalence of H. pylori infection was 23.1%. Age, sex, ethnicity, place of birth, age at immigration, education and alcohol consumption were factors associated with the infection prevalence in the population studied. In addition, we found no effect of H. pylori infection on the bioavailability of vitamins E and C.

Potatoes are often thought of as high GI. It is known that cooking and cooling affect GI and that these effects may be mediated through the physicochemical properties of their starch. As part of a Canadian initiative to develop low GI potatoes, novel potato varieties which differed in starch composition were tested in 2 separate studies. In study 1, we determined the GI of 8 varieties and found that cooling produced a wide range of effects (0-50% reduction in GI). In study 2, four previously tested varieties were re-examined. A significant variety-x-treatment interaction (p<0.01) was observed with cooling reducing GI in some potatoes. Examination of the starch properties and their role in determining GI showed that RDS was positively associated with GI (r2= 0.85, p= 0.001) and SDS (r2=-0.60, p= 0.02) and amylose (r2=-0.99, p=0.007) negatively associated with GI. No relationship between RS and phosphorous content and GI was observed.

Potatoes are often thought of as high GI. It is known that cooking and cooling affect GI and that these effects may be mediated through the physicochemical properties of their starch. As part of a Canadian initiative to develop low GI potatoes, novel potato varieties which differed in starch composition were tested in 2 separate studies. In study 1, we determined the GI of 8 varieties and found that cooling produced a wide range of effects (0-50% reduction in GI). In study 2, four previously tested varieties were re-examined. A significant variety-x-treatment interaction (p<0.01) was observed with cooling reducing GI in some potatoes. Examination of the starch properties and their role in determining GI showed that RDS was positively associated with GI (r2= 0.85, p= 0.001) and SDS (r2=-0.60, p= 0.02) and amylose (r2=-0.99, p=0.007) negatively associated with GI. No relationship between RS and phosphorous content and GI was observed.

Background: The amount of parenteral protein to produce nitrogen balance in infants diagnosed with severe heart defects undergoing cardiopulmonary bypass surgery was investigated. Methods: Infants born at ≥36 weeks and ≤ 12 months of age were randomized to one of three parenteral protein intakes, the control group received 1.5 g/kg/d and intervention groups received either, 2.2 or 3.0 g/kg/d of protein, respectively. Timed 24 hour urine collections were obtained for three consecutive days following surgery. Total urinary nitrogen was measured through Kjeldahl analysis. Results: A significant difference was demonstrated between the lowest protein intake level of 1.5 g/kg/d and both 2.2 g/kg/d (p ≤ 0.03) and 3.0 g/kg/d (p ≤ 0.001), on study day 1. Nitrogen balance results were 4.0 ± 52.9 (1.5 g/kg/d), 97.0 ± 96.2 (2.2 g/kg/d) and 149.7 ± 90.9 (3.0 g/kg/d). Conclusion: Protein delivery of 1.5 g/kg/d was insufficient to produce nitrogen balance on post-operative day 1.

Background: The amount of parenteral protein to produce nitrogen balance in infants diagnosed with severe heart defects undergoing cardiopulmonary bypass surgery was investigated. Methods: Infants born at ≥36 weeks and ≤ 12 months of age were randomized to one of three parenteral protein intakes, the control group received 1.5 g/kg/d and intervention groups received either, 2.2 or 3.0 g/kg/d of protein, respectively. Timed 24 hour urine collections were obtained for three consecutive days following surgery. Total urinary nitrogen was measured through Kjeldahl analysis. Results: A significant difference was demonstrated between the lowest protein intake level of 1.5 g/kg/d and both 2.2 g/kg/d (p ≤ 0.03) and 3.0 g/kg/d (p ≤ 0.001), on study day 1. Nitrogen balance results were 4.0 ± 52.9 (1.5 g/kg/d), 97.0 ± 96.2 (2.2 g/kg/d) and 149.7 ± 90.9 (3.0 g/kg/d). Conclusion: Protein delivery of 1.5 g/kg/d was insufficient to produce nitrogen balance on post-operative day 1.

Epidemiologic, laboratory and clinical data suggest that vitamin D plays a favourable role in the prevention and prognosis of prostate cancer (PCa) and other malignancies. However, the metabolism and function of vitamin D in tissues beyond those involved in bone metabolism are poorly understood. The objective of this thesis was to investigate whether higher levels of vitamin D consumed orally or achieved in the circulation result in increased concentrations of vitamin D metabolites in human tissue, and how this affects cellular biology. The hallmark of this work is a randomized clinical trial of oral vitamin D3 (400-, 10,000-, or 40,000 IU/d) in PCa patients to evaluate the effects of supplementation on prostatic vitamin D metabolism and on PCa pathology. Various methods to measure vitamin D metabolites in serum were evaluated and modified to allow for measurement of these metabolites in tissue. Ultimately, I developed a robust tissue extraction method coupled to enzyme immunoassay and liquid chromatography-tandem mass spectrometry for measurement of calcitriol hormone, as well as 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D), respectively. Human colon tissue was analyzed first and found to contain calcitriol at physiologically relevant concentrations partly determined by serum calcitriol, with some evidence of local colonic synthesis. In the clinical trial, prostate tissue and serum levels of calcitriol, 25(OH)D and 24,25(OH)2D increased dose-dependently (p<0.02) without adverse side effects. The level of calcitriol attained in prostate tissue was inversely associated with the expression of Ki67 protein, a proliferation marker (p<0.05). Serum parathyroid hormone (PTH) and prostate specific antigen (PSA) declined from baseline in the combined higher-dose groups (10,000-40,000 IU/d) (p<0.02). We provide clinical trial evidence that prostatic vitamin D metabolism can be modulated in vivo by oral consumption of vitamin D3. Higher prostate calcitriol and vitamin D doses also showed suggestion of clinical benefit, including lowered Ki67 expression and modest reductions in serum PSA and PTH. Further studies are needed to validate the potential utility of dietary vitamin D3 supplementation in cancer prevention and therapy.

Epidemiologic, laboratory and clinical data suggest that vitamin D plays a favourable role in the prevention and prognosis of prostate cancer (PCa) and other malignancies. However, the metabolism and function of vitamin D in tissues beyond those involved in bone metabolism are poorly understood. The objective of this thesis was to investigate whether higher levels of vitamin D consumed orally or achieved in the circulation result in increased concentrations of vitamin D metabolites in human tissue, and how this affects cellular biology. The hallmark of this work is a randomized clinical trial of oral vitamin D3 (400-, 10,000-, or 40,000 IU/d) in PCa patients to evaluate the effects of supplementation on prostatic vitamin D metabolism and on PCa pathology. Various methods to measure vitamin D metabolites in serum were evaluated and modified to allow for measurement of these metabolites in tissue. Ultimately, I developed a robust tissue extraction method coupled to enzyme immunoassay and liquid chromatography-tandem mass spectrometry for measurement of calcitriol hormone, as well as 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D), respectively. Human colon tissue was analyzed first and found to contain calcitriol at physiologically relevant concentrations partly determined by serum calcitriol, with some evidence of local colonic synthesis. In the clinical trial, prostate tissue and serum levels of calcitriol, 25(OH)D and 24,25(OH)2D increased dose-dependently (p<0.02) without adverse side effects. The level of calcitriol attained in prostate tissue was inversely associated with the expression of Ki67 protein, a proliferation marker (p<0.05). Serum parathyroid hormone (PTH) and prostate specific antigen (PSA) declined from baseline in the combined higher-dose groups (10,000-40,000 IU/d) (p<0.02). We provide clinical trial evidence that prostatic vitamin D metabolism can be modulated in vivo by oral consumption of vitamin D3. Higher prostate calcitriol and vitamin D doses also showed suggestion of clinical benefit, including lowered Ki67 expression and modest reductions in serum PSA and PTH. Further studies are needed to validate the potential utility of dietary vitamin D3 supplementation in cancer prevention and therapy.

The objective was to assess the effect of a high-monounsaturated fat (MUFA) dietary portfolio of cholesterol-lowering foods on oxidative stress and cardiovascular risk. Twenty-four hyperlipidemic subjects followed a very low-saturated-fat therapeutic control diet for 4 weeks after which they were randomized to receive the dietary portfolio, consisting of soy protein (20g/1000kcal), viscous fibre (10.3g/1000kcal), plant sterols (2-3g) and almonds (21.5g/1000kcal), in combination with high- or low-MUFA (25.9% and 12.9% MUFA, respectively) for the next 4 weeks, where MUFA replaced 13.0% of dietary carbohydrate. On high-MUFA, there were significantly greater increases in HDL-C and apoA1 and significantly greater reductions in total:high-density lipoprotein cholesterol (total:HDL-C) ratio and high-sensitivity C-reactive protein (hs-CRP) compared to the low-MUFA dietary portfolio. In all diets there were significant increases in protein thiols and reductions in conjugated dienes and thiobarbituric acid reactive substances (TBARS) measured in the LDL-fraction, however no difference between the high- and low-MUFA diets.