- Title
- Enhancing the lipid-lowering potential of phytosterols in hypercholesterolaemic individuals
- Creator
- Ferguson, Jessica Jayne Anne
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Cardiovascular disease (CVD) remains the leading cause of death worldwide, accounting for over one third of all deaths. Since CVD is chronic, complex and multifaceted in pathological pathways, effective risk reduction and prevention strategies ought to be multi-targeted and easily compliable. CVD encompasses a vast complexion of non-modifiable and modifiable risk factors, the latter of which can be somewhat modulated by diet, physical activity and lifestyle changes. Abnormal blood lipids (dyslipidaemia) remain a key modifiable risk factor underpinning the pathological mechanism of atherosclerosis, a key manifestation of CVD. Changes to diet and lifestyle remain the first line of treatment for managing dyslipidaemia, however, pharmacological intervention is often indicated due to poor long-term adherence and inadequate results of solo diet and lifestyle management. Pharmacological intervention is also riddled with complications that impede long-term adherence and sustainability such as side effects, intolerance to statins, poor adherence and cost. Nutraceuticals, also referred to as bioactives, are potential alternatives and/or adjunct therapies to diet, lifestyle and/or pharmacological treatments; given their ability to effectively down-regulate multiple pathological mechanisms (elevated blood lipids, chronic low-grade inflammation, glycaemic parameters, hypertension) involved in CVD development. Phytosterols and phytostanols (PS) are a family of well-established cholesterol-lowering bioactive compounds commonly used in functional foods for the management of elevated bad cholesterol, namely low-density lipoprotein cholesterol (LDL-C). Foods enriched with 2 g PS when consumed daily can effectively lower LDL-C by 8-10%, with no effects on other blood lipids or CVD risk factors. The primary aim of my PhD project was to enhance lipid-modulating potential of phytosterols with the secondary aims of improving compliance and concurrently targeting other CVD risk factors for improved heart health. Given the widespread use and acceptance of PS enriched foods as a therapy, the first aim of my PhD project, presented in chapter 3, was to investigate whether the type of carrier fat used in common PS enriched products (i.e. vegetable fat spreads and dairy products) was a determinant of the cholesterol-lowering potential of PS. A systematic review and meta-analysis was conducted and we observed that most PS enriched products are based on either rapeseed/canola oil, sunflower/soybean oil or dairy fat. Since the dietary fat type is known to modulate blood cholesterol levels, it was logical to hypothesize that the carrier fat used in PS enriched functional foods may contribute to the overall reduction in LDL-C. The meta-analysis revealed that PS enriched products based on rapeseed/canola oil fat type had a significantly greater reduction (0.1 mmol/L or 26%) in LDL-C when compared to the sunflower/soybean oil. This is clinically significant since an average reduction in LDL-C following 2 g/day PS via rapeseed/canola oil enriched products was -0.38 mmol/L in this study. Therefore, fat type in PS enriched products is a determinant of the cholesterol-lowering potential of PS, and PS enriched foods that are predominately based on rapeseed/canola fat are more effective at lowering circulating cholesterol concentrations. The second aim, presented in chapter 4, was to investigate the novel combination of PS and curcumin on circulating blood lipids in free-living hypercholesterolaemic adults (PAC-CVD Trial). Curcumin was selected as the bioactive to combine with PS due to its lipid-modulating effects and potent anti-inflammatory effects, reported in several preclinical and some human studies. A randomised, 2x2 factorial, double-blinded, placebo-controlled trial in four parallel groups was conducted to investigate the effects of PS with or without curcumin on circulating blood lipids in hypercholesterolaemic otherwise healthy individuals. PS and curcumin were consumed as a daily dose of vegetable fat spread and tablets (respectively) as part of participant’s habitual diet and lifestyle for 4 weeks. Post-intervention, PS and the combined group had significantly lower fasting plasma total cholesterol (TC) and LDL-C, with more than additive reductions observed in the combined group. TC and LDL-C were 11% and 14% (respectively) lower in the combined group, resulting in a complementary and possibly synergistic action between the two bioactives, yielding a more effective hypocholesterolaemic bioactive therapy than either bioactive alone with potential for additional heart health benefits. The above findings prompted further investigation via the development of a staple functional food containing the novel bioactive combination of PS and curcumin, presented in chapter 5 (PAC-FOOD Trial). The third aim of my PhD project was to examine the effects of a bread enriched with PS and curcumin on blood lipid profile and whether this would increase compliance and yield more effective results than our previous research on separate dietary supplementation. Therefore, a randomised controlled trial (RCT) utilising the same study design and bioactive doses as the preceding study in chapter 4, was conducted and we observed increased compliance (~95% versus 99%) with consumption of only 2 slices of enriched bread daily compared to the previous study. In contrast to the PAC-CVD Trial, the curcumin enriched breads did not demonstrate any lipid-lowering effects, nor did they provide additional cholesterol-lowering to the PS + curcumin combined bread. LDL-particle (LDL-P) number concentration significantly reduced in the PS enriched groups and LDL-P size reduced in all groups. Bioavailability of curcumin remains a key concern and barrier to its therapeutic use, however, effective formulations of curcumin in which bioavailability has been enhanced has enabled its widespread use as a supplement for various health conditions. The same curcumin formulation was used for both studies involving curcumin; both in tablet (PAC-CVD Trial) and powder (PAC-FOOD Trial) form. The thermal stability of the patented technology used in these formulations is unknown, and therefore likely that the structure of the curcumin formulation degraded during food processing, therefore resulting in lack of clinical findings. The research presented here provides evidence warranting further investigation into the use of curcumin formulations in the food industry, as well as optimal food matrices in which to deliver future functional foods containing curcumin. The final aim of this PhD project, presented in chapter 6, was to investigate the lipid-modulating effects of a snack food enriched with PS and high molecular weight (MW) oat β-glucan (OBG) on circulating blood lipids in free-living hypercholesterolaemic individuals. The study design was the same as the PAC-CVD and PAC-FOOD trials, however, participants were instructed to consume 8 small lightly-sweetened biscuits enriched with PS with or without OBG, OBG alone or placebo as part of their daily habitual diet and lifestyle for 6 weeks. All bioactive treatment arms significantly lowered fasting plasma TC and LDL-C and, a complementary cholesterol-lowering effect was reported in the combined group of -11.5% for TC and -13.9% for LDL-C. A non-significant 8.4% reduction in triglycerides (TG) was also observed in the combined group. This study was the first to investigate PS combined with a high-MW form of OBG and demonstrated an effective strategy for optimising the lipid-lowering effects of one another, with the potential to provide additional health benefits pertaining to the OBG, such as improved gut health, satiety and hypoglycaemic effects. The research presented in this thesis provides novel supporting evidence for the effective use of bioactive combinations as alternatives and/or adjunct therapies for individuals with dyslipidaemia who are already at risk of CVD. Our findings from the clinical trials have direct translational capacity to the Australian adult population who have dyslipidaemia, presenting simple, efficacious and adherable strategies for lowering CVD risk. Findings from this thesis promote further investigation into the long-term effects of these combination therapies as well as supports the development of functional foods containing bioactives that can be incorporated into the average Australian diet for enhancing heart health. The work presented in this thesis provides significant gain to the Australian population, given the widespread prevalence of dyslipidaemia. Moreover, this research provides supporting evidence for safe, effective, potentially multidimensional approaches through diet intervention with bioactives to empower individuals to take better control of their blood lipid profile, with the potential to manage other CVD risk factors and/or prevent the development of CVD.
- Subject
- phytosterols; cholesterol; cardiovascular disease; curcumin; oat beta-glucan; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1406291
- Identifier
- uon:35613
- Rights
- Copyright 2019 Jessica Jayne Anne Ferguson
- Language
- eng
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