The role of variation in the TAS2R50 bitter taste receptor gene is unknown, but may influence taste perception and dietary habits. Individuals (n=1171) aged 20 to 29, from the Toronto Nutrigenomics and Health Study, completed a food preference checklist and a semi-quantitative food frequency questionnaire to assess their preference and intake of potentially bitter foods and beverages. DNA was isolated from blood and genotyped for 3 polymorphisms in the TAS2R50 gene (rs2900554 A>C; rs10772397 A>G; rs1376251 A>G). Taste intensity was examined using taste strips infused with 3µg of naringin. The rs2900554 SNP was associated with naringin taste intensity, grapefruit preference and grapefruit intake in females. Homozygotes for the C allele reported the highest frequency of experiencing a high naringin taste intensity, disliking grapefruit and not consuming grapefruit. The rs10772397 and rs1376251 SNPs were associated with disliking grapefruit. These results suggest that naringin may be a ligand for the T2R50 receptor.

Folate intake in North America has drastically increased over the past decade due to folic acid fortification and widespread supplemental use. The role of folate in breast cancer is highly controversial and the effects of folic acid supplementation on breast cancer patients are currently unknown. An animal study was performed to determine the effects of folic acid supplementation on the progression of the mammary tumors in the DMBA-carcinogen model. Folic acid supplementation was associated with more rapid sentinel tumor progression and with higher sentinel tumor weight, volume, and area, although no clear dose-responsive relationship was observed. Folic acid supplementation was associated with an increased expression of proapoptotic protein PARP and decreased expression of proliferation protein PCNA. These data suggest that folic acid supplementation may promote the progression of established mammary tumors. Whether or not folic acid supplementation may adversely affect the outcome of patients with breast cancer warrants further studies.

In response to evidence of inadequate fibre and magnesium intakes across the Canadian population, the most recent edition of Canada’s Food Guide included a recommendation for increased whole grain consumption. However, whole grain labelling on food packaging remains voluntary and unregulated. The aim of this research was to examine the nature of nutrition guidance provided by whole grain labelling in the Canadian marketplace through a survey of front-of-package nutrition-related marketing in three supermarkets and a detailed examination of nutrient content, ingredients, and price of breads. Whole grain promotion occurred on relatively few products, predominantly among processed foods, and it frequently appeared in conjunction with references to other nutritional characteristics. The whole grain labelling observed was not misleading with respect to highlighting products with whole grain ingredients and higher levels of fibre and magnesium content; however, products with whole grain labelling were less likely to be lower in price.

Folate blood levels in North America have dramatically increased over the past decade owing to folic acid (FA) fortification and widespread supplement use. Furthermore, over 50% of newly diagnosed colorectal cancer (CRC) patients use vitamin supplements containing FA while receiving chemotherapy whose mechanisms of action are based on interruption of folate metabolism. This study therefore investigated whether FA supplementation can affect chemosensitivity of human colon cancer cells to 5FU, the cornerstone of CRC treatment, using a xenograft model. FA supplementation was associated with a non-dose dependent decrease in chemosensitivity, where mice receiving 8 mg FA did not respond to 5FU and had greater tumor growth with treatment, compared to 2 (control) or 25 mg FA. Results of this study pose concern given the drastically increased intake of FA, particularly among recently diagnosed CRC patients, and from mandatory fortification. Further studies are warranted to confirm our findings and to elucidate underlying mechanisms.

In order to examine the effects of industry processed pulse powder (navy bean, lentil and chickpea) on postprandial glycaemic response (BG) and subjective appetite (App) before and after a subsequent meal, three randomized, within-subject experiments on healthy young men were conducted. In experiment 1, all navy bean treatments reduced BG at 30 min and navy bean powder suppressed pre-meal App compared to whole wheat flour. In experiment 2, all lentil treatments reduced pre-meal BG compared to whole wheat flour. However, no App differences were observed. In experiment 3, all chickpea treatments reduced pre-meal BG compared to whole wheat flour. However, no App differences were observed. Therefore, navy bean powder, lentil powder and chickpea powder maintain their low GI and satiating effects, regardless of processing. Pulse powder can be used as a value-added food ingredient to moderate glycaemic response and increase satiety.

All populations risk vitamin D inadequacy. We conducted a randomized double- blind trial of vitamin D3 fortified cheddar cheese to study bioavailability based on serum 25-hydroxyvitamin D [25(OH)D] concentrations, and its effects on mental health scores in older adults. Once a week, 28 subjects received 200 IU or 28000 IU of vitamin D3 per fortified cheese serving. The mean increases in 25(OH)D over 8 weeks were: 4.2±11.4 and 29.4±16.2 for the 200 IU/week and 28,000 IU/ week dose groups, respectively (groups differ, P<0.001). Subjects who consumed 28,000 IU/week cheese improved their Mental Component Summary (MCS) scores, based upon the SF-36v2 questionnaire conducted at baseline and at 8 weeks (P<0.05). There was also a positive correlation between the change in MCS score and the change in 25(OH)D (1 tail; P<0.05). These data demonstrate the suitability of fortified cheddar cheese, and provide evidence of neurocognitive benefits with higher 25(OH)D levels.

Folate is an essential cofactor in one-carbon transfer reactions including nucleotide biosynthesis, thereby playing an important role in DNA replication and repair. In cancer cells, folate depletion interrupts DNA synthesis, thereby causing cancer cell death. This has been the basis for chemotherapy using antifolates and 5-fluorouracil (5FU). We determined the effect of folate deficiency on the sensitivity of colon cancer cells to 5FU in a well established in vitro model of folate deficiency. Folate deficient cells had lower intracellular folate concentrations, had functional evidence of intracellular folate depletion, proliferated less, and had increased chemosensitivity to 5FU with and without Leucovorin. These data suggest that folate deficiency significantly enhances the sensitivity of colon cancer cells to 5FU based chemotherapy via changes in intracellular folate. Dietary or other strategies to deplete intracellular folate concentrations in colon cancer cells to enhance chemosensitivity to 5FU are worthy of further investigation.

Sodium restriction is the primary dietary therapy for individuals with heart failure (HF); however, there is little information available to support or refute the use of sodium restriction to manage HF. The overall goal of this work was to generate data related to dietary sodium in patients with chronic HF that would contribute to the development of evidence-based guidelines. The specific objectives were to investigate the optimal methods for measuring sodium intake in HF, to describe the habitual consumption of sodium and other nutrients in HF, and to evaluate the relationship between sodium intake and clinical outcomes in HF. We studied stable ambulatory HF patients who were optimally medicated and participating in multidisciplinary HF programs. We determined that: (1) a strong relationship exists between 24-hour urine collections and food records for sodium intake assessment in non-HF cardiac patients and HF patients not taking loop diuretics. However, the relationship between urinary sodium excretion and sodium intake in HF patients taking loop diuretics was disturbed, suggesting that food records may be a better method for estimating sodium intake in this group. (2) Mean sodium intake in HF and non-HF cardiac patients was similar, and approximately half of patients in each group had sodium intake levels that exceeded the Dietary Reference Intakes tolerable upper level of 2300 mg/d. We also found that both groups had inadequate intakes of several nutrients, including potassium, calcium, magnesium, folate, and vitamin D and E. (3) Finally, we showed that a high sodium diet (>2800 mg/day) in HF was associated with risk of acute decompensated HF, all-cause hospitalization, and all-cause mortality over a median 3 year follow-up period. This is the first published study that prospectively related sodium intake to clinical outcomes in HF. In summary, these data provide novel contributions related to the measurement of sodium intake that can be used in clinical or academic settings. We also describe inadequacies in intake of several vitamins and minerals, which could be addressed through dietary counselling. Finally, we importantly offer insight into a threshold of sodium intake (>2800 mg/day) that could contribute to adverse clinical outcomes in HF.

Flaxseed (FS) is a rich source of lignans and n-3 polyunsaturated fatty acids (PUFA), compounds that may help preserve normal bone cell function during aging. Understanding the effect of FS alone or combined with lower doses of estrogen therapy on bone and other estrogen-responsive tissues (e.g. uterus) is of particular interest to postmenopausal women who combine dietary bioactives (e.g. FS) with pharmacological agents (e.g. estrogen monotherapy) to attenuate postmenopausal bone loss. The overall objective of my research was to determine the effects and mechanisms of FS, alone or combined with lower doses of estrogen therapy, on bone and uterus health by measuring a comprehensive set of outcomes in the ovariectomized rat model of postmenopausal osteoporosis. The results demonstrated that FS enhances the protective effect of low-dose estrogen therapy (LD) on vertebral bone mineral density (BMD), three-dimensional microarchitecture and strength in ovariectomized rats. Moreover, FS exerts a stronger effect on bone outcomes when combined with LD than when combined with ultra-low-dose estrogen therapy (ULD). These studies also showed that FS feeding results in higher lignans and n-3 PUFAs in vertebrae, tibias and femurs. Histological analyses at the lumbar vertebra (LV) showed that there were no differences in TRAP-5β, CTX, or OPG/RANKL ratio between the FS+LD and LD groups. FS+LD did however result in lower protein expression of osteocalcin, a marker of bone formation and overall bone turnover, and higher expression of OPG compared to the negative control (NEG), while LD did not. While these findings suggest that FS+LD results in greater attenuation of deterioration of bone tissue compared to LD due to a reduction in bone turnover, significant differences between FS+LD and LD were not observed. Elucidating these specific mechanisms of action require further investigation. In the uterus, FS+LD did not induce greater cell proliferation or differences in qualitative indices of uterine morphology compared to LD. These findings suggest that there may be no increase in the risk of endometrial hyperplasia and carcinoma with FS+LD compared to LD. These findings may lead to the development of strategies that combine food bioactives and current pharmacological agents to more effectively normalize bone turnover during aging.

Household food insecurity, defined as "the inability to acquire or consume an adequate diet quality or sufficient quantity of food in socially acceptable ways, or the uncertainty that one will be able to do so”, affected almost one in ten Canadian households in 2004. Responses have been dominated by community-based food initiatives with little attention paid to potential policy directions to alleviate this problem. The lack of impetus for policy responses may stem from the paucity of evidence documenting the nutrition implications of household food insecurity. Further, the development of policy interventions is hindered by a lack of understanding of the factors that influence vulnerability to food insecurity. This thesis comprises three studies aimed at providing stimulus and directions for policy responses to household food insecurity in Canada. The first study, an analysis of data from the 2004 Canadian Community Health Survey, documents poorer dietary intakes and heightened risk of nutrient inadequacies among adults and adolescents in food-insecure households, providing evidence of the public health implications and public policy relevance of household food insecurity. The second and third studies are examinations of household-level factors associated with vulnerability to household food insecurity. Analysis of data from the 2001 Survey of Household Spending demonstrates the relevance of housing costs to household food access. Among lower-income households, as the proportion of income allocated to housing costs increased, the adequacy of household food spending declined significantly. Receipt of a housing subsidy was associated with an improvement in food spending but mean food spending adequacy fell below the cost of a basic nutritious diet even among subsidized households. The final study comprises a cross-sectional survey of 464 low-income Toronto families, two-thirds of whom were food insecure over the preceding 12 months. Analysis of predictors of severe food insecurity highlights the centrality of income and housing costs and raises serious questions about current definitions of housing affordability and the adequacy of current housing subsidy levels. This work provides a public health imperative for action and points to the urgent need for social policy reform to ameliorate problems of household food insecurity in Canada.