Nutrigenetic investigations into vitamin C and plant sterols

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Granger, Matthew
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This thesis focuses on the development and conduct of nutrigenetic studies: beginning with a literature review of ascorbic acid from a nutrigenetic perspective; to the protocol of an observational cohort study that could be utilized to find nutrigenetic associations; and finally to results of clinical trial investigating the responsiveness of LDL cholesterol to the consumption of plant sterols within a pre-defined genoset previously associated with plant sterol response. The convergence of large datasets pertaining to variations in genetics, nutrient status, and health status have resulted in an enormous number of putative associations between these variables. Findings from the literature review of the nutrigenetics of ascorbic acid in human health and disease found inconsistent effects of genetic associations related to ascorbic acid status. The likely source of this issue is that these hypotheses of these genetic associations are often developed and tested from post hoc analyses of observational cohort studies. A solution to these inconsistencies may be to progress nutrigenetics research into clinical intervention trials. As an example a randomized two-period cross-over clinical trial using a priori genetic recruitment of participants to determine if genotypes were predictive of a biological response to nutrients, a was conducted. In this trial participants consumed 2 g/day of plant sterols per day or placebo for 28 days and low density lipoprotein cholesterol response was measured. The hypothesis was that the combined APOE-(ε3/ε3) and CYP7A1-(T/T) genoset would predict non-response of LDL cholesterol to plant sterol consumption. 42 participants of 23 to 68 years of age completed the trial. Reductions in LDL cholesterol were consistent across all genoset groups indicating that the APOE-(ε3/ε3) and CYP7A1-(T/T) genoset is not predictive of non-response of LDL cholesterol to plant sterol consumption. Recruitment of participants that were genotyped a priori into a randomized clinical trial was unable to validate previous observations with respect to these genotypes, likely indicating that the initial associations were spurious.
Nutrigenetic, Vitamin C, Plant Sterols