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Thesis (PhD) -- University of Stellenbosch, 2001. / ENGLISH ABSTRACT: The advent of the new millennium saw the complete sequencing of the entire human genome. Only approximately 30 000 genes, much less than was initially predicted, have been identified to be responsible for the genetic diversity in humans. This discovery has prompted a shift in the approach to disease research, since one gene can be involved in numerous diseases. This phenomenon seems to be especially true for the low-density lipoprotein receptor (LDLR) gene. Various substances beside sterols can induce transcription of the LDLR gene. Non-communicable diseases (e.g. hypertension) are common in the developing world and contribute significantly to mortality rates. The fmding that a promoter variant (-175 g~t) in the LDLR gene is associated with elevated diastolic blood pressure may explain the phenomenon of high LDL-cholesterollevels in hypertensive individuals. Studies have demonstrated that the lowering of cholesterol, especially LDL-cholesterol, can reduce the incidence of hypertension. The -175 g~t variant is located in a newly described cis-acting regulatory element which contains a putative binding site for Yin Yang (YY)-l and also demonstrates great homology to the cAMP response element (CRE) which bind the Ca2+- dependent transcription factor, CRE binding protein (CREB). The fact that Ca2+ can induce transcription of the LDLR gene may, at least in part, explain the association between the - 175g~t variant and elevated diastolic blood pressure. Cholesterol is important for various processes, such as apoptosis, maintenance of cellular membranes and immune function. The -59 c-ot mutation in repeat 2 of the LDLR gene abolishes binding of the sterol regulatory element binding protein(SREBP) to the SRE-l site. SREBP is proteolytically activated during apoptosis by two caspases (CPP32 and Mch3) to induce cholesterol levels. Our results imply that the -59C/T mutation, in repeat 2 of the LDLR gene promoter, may inhibit apoptosis under normal immunological conditions. Atherosclerosis can be considered an immunological disease, since various humoral and cellular immune processes can be detected throughout the course of the disease. The fmding that certain lipoproteins can protect against infection by binding and lysing of pathogens, or competing with pathogens for cellular receptors, prompted the investigation into the potential role of variation in the LDLR gene promoter in immune function. A significant difference in allelic distribution was detected between asymptomatic HIY -infected subjects and fast progressors for the -124 c-ot variant (P=O.006), shown to increase (~160%) transcriptional activity of the LDLR gene. Of relevance to this particular study is the fact that human herpesvirus (HHV) 6 can transactivate CD4 promoters through a partial CRE site. It has been shown that the CREB and YYl can regulate viral and cellular promoters, and these transcription factors can potentially bind to the LDLR promoter at the FP2 site. The mutation enrichment in the LDLR gene promoter seen in the South African Black and Coloured population groups can possibly provide insight into the pathogenesis of various diseases. This could also potentially, provide novel targets for treatment, since manipulation of cholesterol levels may affect the pathogenesis of various diseases. / AFRIKAANSE OPSOMMING: Die volledige DNA volgorde bepaling van die mensgenoom is voltooi vroeg in die nuwe millennium. Slegs ongeveer 30 000 gene is geidentifiseer, heelwat minder as wat in die verlede voorspel is, wat verantwoordelik is vir die genetiese diversiteit in die mens. Hierdie ontdekking het gelei tot 'n verandering in die benadering van navorsing ten opsigte van siektes, aangesien een geen 'n rol by verskeie siektes kan speel. Hierdie gewaarwording blyk veral waar te wees vir die lae digtheids lipoproteien reseptor (LDLR) geen. Verskeie stimuli, buiten sterole, kan transkripie van die LDLR geen inisieer. Verskeie siektes soos hipertensie is algemeen in die ontwikkelende wereld, en dra by tot die hoe mortaliteit syfers. Die bevinding dat 'n promoter variant in die LDLR geen (-175g-H) geassosieer is met verhoogde diastoliese bloeddruk, kan moontlik verhoogde lipiedvlakke in hipertensiewe individue verklaar. Studies het aangetoon dat die verlaging van cholesterol, veral LDL-cholesterol, die voorkorns van hipertensie kan verlaag. Die -175 g~t variant is gelee in 'n cis-regulerende element wat na bewering 'n bindingsetel vir die Yin Yang (YY)-l transkripsie faktor bevat asook sterk homologie met die cAMP respons element (CRE) toon, wat bind aan die Ca2 +_ afhanklike transkripie faktor, CRE bindings proteiene (CREB). Die feit dat Ca2+ transkripsie van die LDLR geen kan inisieer, kan dalk tot 'n mate, 'n verklaring bied vir die assosiasie tussen die -175 (g~t) variant en verhoogde diastoliese bloeddruk. Cholesterol is noodsaaklik vir verskeie prosesse soos apoptose, die instandhouding van selmembrane sowel as immuun funksies. Die -59 c-ot mutasie in die sterol regulerende element 1 (SRE-l) van die LDLR geen vernietig binding van die sterol regulerende element bindingsprotei'en (SREBP) aan SRE-l. SREBP word proteolities geaktiveer tydens apoptose deur twee kaspases (CPP32 en Mch3) om cholesterolvlakke te induseer. Ons resultate impliseer dat die -59C/T mutasie, in herhaling-2 van die LDLR-geen promoter, apoptose kan inhibeer onder normale immunologiese toestande. Aterosklerose kan beskou word as 'n immunologiese siekte, aangesien verskeie humorale en sellulere immuun prosesse deur die verloop van die siekte waargeneem kan word. Die feit dat Iipoproteiene beskermend kan wees teen infeksies, deur binding en lisering van virusse of kompeteer met patogene vir sellulere reseptore, het aanleiding gegee tot 'n ondersoek na die potensiele rol van variasies in die promoter area van die LDLR geen in immuun funksie. Betekenisvolle verskille in alleel verspreiding vir die -124c~t variant (P=0.006) is waargeneem tussen asimptomatiese MIV -geinfekteerde pasiente en individue met vinnige siekte progressie. In vitro studies het voorheen getoon dat die -124c~t 'n verhoging in LDLR geen transkripsie (160%) tot gevolg het. Dit is noemenswaardig dat 'n vroee studie getoon het dat die mens like herpesvirus-6 (MHV6) transaktivering van die CD4 promoters deur 'n gedeeltelike CRE bindingsetel kan bewerkstellig. Beide CREB en YYl kan virus en sellulere promotors reguleer, en hierdie transkripsie faktore toon bindingshomologie met die FP2 element van die LDLR promotor Die mutasie verryking van die LDLR geen promoter soos waargeneem in Suid Afrikaanse Swart en Kleurling populasies, kan moontlik lig werp op die patogenese van verskeie siektetoestande. Hierdie bevindinge kan potensieel nuwe teikens vir behandeling identifiseer, aangesien manipulasie van cholesterolvlakke 'n effek mag he op die patogenese van verskeie siektes.

Two studies were conducted to determine how HDL cholesteryl ester and apoprotein catabolism might contribute to the observed hypercholesterolemia of copper-deficient rats. Weanling male Sprague-Dawley rats were divided into two dietary treatments; copper-adequate (control, 5-7 mg Cu/kg diet) and copper-deficient (0.6-0.8 mg Cu/kg diet). Deionized water and diet were provided ad libitum. Dietary copper deficiency resulted in enlarged intravascular pools of HDL cholesteryl esters and total protein. HDL were isolated from rats of both treatment groups, radiolabeled, and injected into animals of the respective groups. In Study I, HDL apoproteins were labeled by iodination, whereas HDL in Study II were doubly labeled by additionally incorporating into the particle core [³H]cholesteryl linoleyl ether, which served as a nondegradable analog of HDL cholesteryl ester. At specific time intervals up to 12 hours after injection, blood and tissue samples were removed and analyzed for radioactivity. Plasma disappearance curves indicated that HDL cholesteryl esters were preferentially catabolized 1.6-fold faster than HDL protein in controls and 2.5-fold faster in copper-deficient animals. Clearance of individual apoproteins did not occur at significantly different rates in either treatment group. Absolute mass removal of HDL cholesteryl ester and total protein from the plasma was significantly increased in copper-deficient rats. Virtually all of the increased removal of HDL cholesteryl ester was attributed to the liver, whereas most of the increased uptake of HDL protein was attributed to the bulk tissues and not the liver. Since previous studies indicate that copper deficiency may not result in increased cholesterol excretion, these data suggest that cholesteryl esters delivered to the liver of copper-deficient rats are possibly reassembled into new HDL particles at an increased rate. The observed hypercholesterolemia in this animal model, then, appears to be the result of an imbalance in the net flux of cholesterol between the tissues and the plasma.

Lee Chung-hung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 113-133). / Abstracts in English and Chinese. / Chapter Chapter 1 --- General Introduction / Chapter 1.1 --- History of soybean --- p.1 / Chapter 1.2 --- Health benefits of soybean --- p.2 / Chapter 1.3 --- Introduction to flavonoids --- p.3 / Chapter 1.4 --- Bioavailability of flavonoids --- p.5 / Chapter 1.5 --- Chemistry of isoflavones --- p.6 / Chapter 1.6 --- Estrogenic property of isoflavones --- p.8 / Chapter 1.7 --- Nutritional significance of isoflavones and their glycosides --- p.8 / Chapter 1.7.1 --- Anticarcinogenic activity --- p.9 / Chapter 1.7.2 --- Antioxidative activity --- p.10 / Chapter 1.7.3 --- Cardioprotective activity --- p.13 / Chapter 1.7.4 --- Osteoprotective activity --- p.14 / Chapter 1.7.5 --- Neuroprotective activity --- p.15 / Chapter 1.7.6 --- Antiangiogenic activity --- p.16 / Chapter Chapter 2 --- Composition of Soybean Isoflavones / Chapter 2.1 --- Introduction --- p.17 / Chapter 2.2 --- Objective --- p.19 / Chapter 2.3 --- Materials and Methods --- p.20 / Chapter 2.3.1 --- Extraction and isolation --- p.20 / Chapter 2.3.1.1 --- Preparation of soybean butanol extract --- p.20 / Chapter 2.3.1.2 --- Preparation of isoflavones and their glycosides from soybean butanol extract --- p.20 / Chapter 2.3.2 --- HPLC analysis --- p.21 / Chapter 2.3.2.1 --- Sample preparation for the HPLC analysis --- p.21 / Chapter 2.3.2.2 --- HPLC analysis --- p.22 / Chapter 2.3.2.3 --- Quantification of the flavonoids and their glycosides --- p.24 / Chapter 2.4 --- Results --- p.25 / Chapter 2.4.1 --- Structural identification --- p.25 / Chapter 2.4.1.1 --- Compound 1 --- p.25 / Chapter 2.4.1.2 --- Compound 2 --- p.26 / Chapter 2.4.1.3 --- Compound 3 --- p.26 / Chapter 2.4.1.4 --- Compound 4 --- p.27 / Chapter 2.4.1.5 --- Compound 5 --- p.27 / Chapter 2.4.1.6 --- Compound 6 --- p.28 / Chapter 2.4.1.7 --- Compound 7 --- p.28 / Chapter 2.4.1.8 --- Compound 8 --- p.29 / Chapter 2.4.2 --- Quantification of isoflavones in traditional Chinese foods --- p.29 / Chapter 2.5 --- Discussion --- p.32 / Chapter Chapter 3 --- Hypocholesterolemic Effects of Soymilkin Hamsters / Chapter 3.1 --- Introduction --- p.35 / Chapter 3.1.1 --- Lipoproteins and their functions --- p.35 / Chapter 3.1.2 --- Risk factors of cardiovascular disease --- p.36 / Chapter 3.1.3 --- Hamster as an animal model of cholesterol metabolism --- p.38 / Chapter 3.2 --- Objective --- p.39 / Chapter 3.3 --- Materials and Methods --- p.40 / Chapter 3.3.1 --- Preparation of soymilk --- p.40 / Chapter 3.3.2 --- Animals --- p.40 / Chapter 3.3.2.1 --- Experiment one - Hypocholesterolemic effect of soymilk in hamsters --- p.40 / Chapter 3.3.2.1 --- Experiment two 一 The effect of fluid cross-over between soymilk and cow´ة s milk on serum cholesterol in hamsters --- p.41 / Chapter 3.3.3 --- Serum lipid and lipoprotein determinations --- p.42 / Chapter 3.3.4 --- Determination of cholesterol in organs --- p.42 / Chapter 3.3.5 --- Statistics --- p.43 / Chapter 3.4 --- Results --- p.46 / Chapter 3.4.1 --- Experiment one-Hypocholesterolemic effect of soymilk in hamsters --- p.46 / Chapter 3.4.1.1 --- Growth and food intake --- p.46 / Chapter 3.4.1.2 --- "Effect of SM and CM on TG, TC and HDL-C" --- p.46 / Chapter 3.4.1.3 --- Effect of SM and CM on non-HDL-C and ratio of non-HDL-C to HDL-C --- p.46 / Chapter 3.4.1.4 --- Effect of SM and CM on concentration of hepatic cholesterol --- p.47 / Chapter 3.4.1.5 --- "Effect of SM and CM on brain, heart and kidney cholesterol" --- p.47 / Chapter 3.4.2 --- Experiment two - The effect of fluid cross-over between soymilk and cow´ةs milk on serum cholesterol in hamsters --- p.52 / Chapter 3.4.2.1 --- Growth and food intake --- p.52 / Chapter 3.4.2.2 --- Effect of fluid cross-over on serum TC --- p.52 / Chapter 3.5 --- Discussion --- p.55 / Chapter Chapter 4 --- Antioxidant Activities of Soybean Isoflavones and Their Glycosides / Chapter 4.1 --- Introduction --- p.58 / Chapter 4.1.1 --- Role of low density lipoprotein oxidation in the development of atherosclerosis --- p.59 / Chapter 4.1.2 --- LDL oxidation --- p.61 / Chapter 4.1.3 --- Thiobarbituric acid reactive substances (TBARS) as an index of LDL oxidation --- p.62 / Chapter 4.1.4 --- "The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power""" --- p.65 / Chapter 4.1.5 --- "1,1-diphenyl-2-picrylhydrazyl (DPPH) as a measure of free radical scavenging capacity" --- p.65 / Chapter 4.1.6 --- Antioxidant and LDL oxidation --- p.65 / Chapter 4.2 --- Objective --- p.67 / Chapter 4.3 --- Materials and Methods --- p.68 / Chapter 4.3.1 --- Preparation of samples --- p.68 / Chapter 4.3.2 --- Isolation of LDL from human serum --- p.68 / Chapter 4.3.3 --- LDL oxidation --- p.69 / Chapter 4.3.4 --- TBARS assay --- p.69 / Chapter 4.3.5 --- FRAP assay --- p.70 / Chapter 4.3.6 --- DPPH assay --- p.71 / Chapter 4.3.7 --- Statistics --- p.72 / Chapter 4.4 --- Results --- p.73 / Chapter 4.4.1 --- Effects of seven individual soybean isoflavones and their glycosides on LDL oxidation --- p.73 / Chapter 4.4.2 --- The antioxidant power of individual soybean isoflavones and their glycosides in the FRAP assay --- p.73 / Chapter 4.4.3 --- Activity of individual soybean isoflavones and their glycosides as radical scavenging antioxidants --- p.74 / Chapter 4.5 --- Discussion --- p.78 / Chapter Chapter 5 --- Hypocholesterolemic Effects of Soybean Isoflavones in Ovariectomized Golden Syrian Hamsters / Chapter 5.1 --- Introduction --- p.83 / Chapter 5.1.1 --- Coronary heart disease in women --- p.83 / Chapter 5.1.2 --- Menopause as a risk factor in CHD --- p.84 / Chapter 5.1.3 --- Dietary soy in treating postmenopausal hypercholesterolemia --- p.85 / Chapter 5.2 --- Objective --- p.87 / Chapter 5.3 --- Materials and Methods --- p.88 / Chapter 5.3.1 --- Preparation of soymilk --- p.88 / Chapter 5.3.2 --- Preparation of soybean extract --- p.88 / Chapter 5.3.3 --- Animals --- p.89 / Chapter 5.3.4 --- Serum lipid determinations --- p.90 / Chapter 5.3.5 --- Determination of tissue cholesterol content --- p.90 / Chapter 5.3.6 --- Extraction of neutral and acidic sterols from fecal samples --- p.90 / Chapter 5.3.6.1 --- Determination of neutral sterols --- p.91 / Chapter 5.3.6.2 --- Determination of acidic sterols --- p.92 / Chapter 5.3.6.3 --- GLC analysis of neutral and acidic sterols --- p.92 / Chapter 5.3.7 --- Statistics --- p.93 / Chapter 5.4 --- Results --- p.96 / Chapter 5.4.1 --- Growth and food intake --- p.96 / Chapter 5.4.2 --- Effect of ovariectomy on serum TC --- p.96 / Chapter 5.4.3 --- "Effect of soymilk and soybean extract on serum TC,TG and HDL-C" --- p.96 / Chapter 5.4.4 --- Effect of soymilk and soybean extract on non-HDL-C and ratio of non- HDL-C to HDL-C --- p.97 / Chapter 5.4.5 --- Effect of soymilk and soybean extract on concentration of hepatic cholesterol --- p.97 / Chapter 5.4.6 --- Effect of soymilk and soybean extract on heart and kidney cholesterol --- p.97 / Chapter 5.4.7 --- Effect of soymilk and soybean extract on fecal neutral and acidic sterols --- p.103 / Chapter 5.5 --- Discussion --- p.106 / Chapter Chapter 6 --- Conclusion --- p.110 / References --- p.113

Guan, Lei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 123-145). / Abstracts in English and Chinese. / ACKNOWLEDGEMENT --- p.I / ABSTRACT --- p.II / LIST OF ABBREVIATIONS --- p.VII / TABLE OF CONTENT --- p.IIX / Chapter Chapter 1 --- General Introduction --- p.1 / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Distribution and Origins --- p.1 / Chapter 1.3 --- History of Use --- p.2 / Chapter 1.4 --- Chemical Structure --- p.3 / Chapter 1.5 --- Physiologic Properties --- p.5 / Chapter 1.6 --- Absorption and Metabolism --- p.7 / Chapter 1.6.1 --- Concentration of Isoflavones in Plasma --- p.10 / Chapter 1.6.2 --- Urinary Excretion --- p.10 / Chapter 1.7 --- Healthy Effects --- p.11 / Chapter 1.7.1 --- Menopausal Symptom --- p.11 / Chapter 1.7.2 --- Cardiovascular Disease --- p.12 / Chapter 1.7.3 --- Osteoporosis --- p.13 / Chapter 1.7.4 --- Tumors --- p.14 / Chapter 1.7.4.1 --- Breast Cancer --- p.14 / Chapter 1.7.4.2 --- Prostate Cancer --- p.15 / Chapter 1.7.5 --- Alcohol Addiction --- p.16 / Chapter 1.7.6 --- Potential Adverse Effects --- p.16 / Chapter 1.8 --- Summary --- p.17 / Chapter Chapter 2 --- Determination of Isoflavones in Soybean and Gegen --- p.19 / Chapter 2.1 --- Introduction --- p.19 / Chapter 2.1.1 --- Classification and Structure of Phytoestrogens --- p.19 / Chapter 2.1.2 --- Isoflavones in Soybeans and Gegen --- p.21 / Chapter 2.1.3 --- Methods of Determination --- p.26 / Chapter 2.1.3.1 --- Isolation and Purification of Isoflavones --- p.26 / Chapter 2.1.3.2 --- Analytical Methods for Isoflavones in Soybeans and Gegen --- p.26 / Chapter 2.2 --- Objective --- p.28 / Chapter 2.3 --- Materials and Methods --- p.29 / Chapter 2.3.1 --- Extraction and Isolation of Soybean and Gegen Isoflavone Extracts --- p.29 / Chapter 2.3.2 --- HPLC Analysis --- p.29 / Chapter 2.3.2.1 --- Sample Preparation for the HPLC Analysis --- p.29 / Chapter 2.3.2.2 --- HPLC Analysis --- p.30 / Chapter 2.3.3.3 --- Qualitative Analysis of the Isoflavones and Their Glycosides in Soybean and Gegen --- p.30 / Chapter 2.4 --- Results --- p.31 / Chapter 2.4.1 --- Isoflavone Identification of Soybean Extract --- p.31 / Chapter 2.4.2 --- Isoflavone Identification of Gegen Extract --- p.33 / Chapter 2.5 --- Discussion --- p.35 / Chapter Chapter 3 --- Hypocholesterolemic Effects of Soybean and Gegen Isoflavone Extracts in Ovariectomized，Intact Male and Castrated Golden Syrian Hamsters --- p.38 / Chapter 3.1 --- Introduction --- p.38 / Chapter 3.2 --- Objective --- p.41 / Chapter 3.3 --- Materials and Methods --- p.42 / Chapter 3.3.1 --- Preparation of Soybean and Gegen Isoflavone Extracts --- p.42 / Chapter 3.3.2 --- Animals and Diets --- p.42 / Chapter 3.3.3 --- Serum Lipid and Lipoprotein Determinations --- p.45 / Chapter 3.3.4 --- Determination of Cholesterol Concentration in the Organs --- p.45 / Chapter 3.3.5 --- Statistics --- p.46 / Chapter 3.4 --- Results --- p.48 / Chapter 3.4.1 --- Food Intake and Body and Relative Organ Weights --- p.48 / Chapter 3.4.2 --- Effects of Soybean and Gegen Isoflavone Extracts on Serum and Organ Cholesterol in Ovariectomized and Intact Male and Castrated Hamsters --- p.56 / Chapter 3.5 --- Discussion --- p.61 / Chapter Chapter 4 --- Possible Developmental and Reproductive Toxicity of Soybean Isoflavones on SD Rats --- p.67 / Chapter 4.1 --- Introduction --- p.67 / Chapter 4.2 --- Objective --- p.70 / Chapter 4.3 --- Materials and Methods --- p.71 / Chapter 4.3.1 --- Diet --- p.71 / Chapter 4.3.2 --- Animals --- p.73 / Chapter 4.3.3 --- Study Design --- p.73 / Chapter 4.3.4 --- Measurement of Reproductive Hormones --- p.74 / Chapter 4.3.5 --- Measurement of Sperm Number --- p.74 / Chapter 4.3.6 --- Statistics --- p.75 / Chapter 4.4 --- Results --- p.77 / Chapter 4.4.1. --- Food Intake and Food Efficiency Ratio --- p.77 / Chapter 4.4.2 --- Growth Trend --- p.79 / Chapter 4.4.3 --- Organ Weight --- p.82 / Chapter 4.4.3.1 --- Absolute Organ Weight --- p.82 / Chapter 4.4.3.2 --- Relative Organ Weight --- p.84 / Chapter 4.4.4 --- Reproductive Hormone Levels --- p.86 / Chapter 4.4.5 --- Epididymis Parameters of Male Rats --- p.88 / Chapter 4.5 --- Discussion --- p.90 / Chapter Chapter 5 --- Possible Developmental and Reproductive Toxicity of Gegen Isoflavones on SD Rats --- p.97 / Chapter 5.1 --- Introduction --- p.97 / Chapter 5.2 --- Objective --- p.99 / Chapter 5.3 --- Materials and Methods --- p.100 / Chapter 5.3.1 --- Animals and Diets --- p.100 / Chapter 5.3.2 --- Study Design --- p.100 / Chapter 5.3.3 --- Statistics --- p.101 / Chapter 5.4 --- Results --- p.103 / Chapter 5.4.1 --- Food Consumption and Food Efficiency Ratio --- p.103 / Chapter 5.4.2 --- Growth Trend --- p.105 / Chapter 5.4.3 --- Organ Weights --- p.108 / Chapter 5.4.3.1 --- Absolute Organ Weights --- p.108 / Chapter 5.4.3.2 --- Relative Organ Weight --- p.110 / Chapter 5.4.4 --- Reproductive Hormone Levels --- p.112 / Chapter 5.4.5 --- Epididymis Parameters of Male Rats --- p.114 / Chapter 5.5 --- Discussion --- p.116 / Chapter Chapter 6 --- Conclusions --- p.121 / References --- p.123

published_or_final_version / Pathology / Master / Master of Philosophy

Plant sterols (PS) are effective in reducing plasma lipid concentrations, however, few studies have examined their cholesterol lowering effects in type 2 diabetics. The objective was to assess whether PS consumption alters blood lipid profile in hypercholesterolemic subjects with and without type 2 diabetes. Fifteen control subjects (age = 55.1 +/- 8.5 yr and BMI = 26.9 +/- 3.0kg/m2) and fourteen diabetic subjects (age = 54.5 +/- 6.7 yr and BMI = 30.2 +/- 3.0kg/m2) participated in a double-blinded, randomized, crossover, placebo-controlled feeding trial. The Western diet included either 1.8g/d of PS or cornstarch placebo each provided over 21 d separated by a 28 d washout period. Subjects consumed only foods prepared in Mary Emily Clinical Nutrition Research Unit of McGill University. Total cholesterol (TC) decreased (p < 0.05) from baseline with PS for control and diabetic subjects by 9.7% and 13.6%, respectively. TC decreased (P < 0.05) from baseline with placebo for control and diabetic subjects by 10.9% and 11.6%, respectively. Non high density lipoprotein cholesterol (non-HDL-C) decreased (p < 0.05) from baseline with PS for diabetic subjects by 18.5%. Low density lipoprotein cholesterol (LDL-C) levels were reduced (p < 0.05) from baseline with PS for control and diabetic subjects by 14.9% and 29.8%, respectively. The reduction of LDL-C due to PS alone is greater with type 2 diabetics. There were no significant changes in HDL-C and TG across diets or treatments. It is thus concluded that PS consumption with diet enhances non-HDL-C and LDL-C reduction compared with diet alone in hypercholesterolemic individuals with and without type 2 diabetes. Demonstration for the first time that PS alone are more efficacious in lowering LDL-C and non-HDL-C in diabetic individuals compared to non-diabetics confirm the beneficial effects of PS to help prevent cardiovascular disease (CVD) for this high risk population.

The objective of this research was to examine the effects of plant sterols and glucomannan on lipid profiles, plasma plant sterol levels and glycemic control in mildly hypercholesterolemic subjects. Thirteen type 2 diabetic and sixteen non-diabetic individuals participated in a randomized crossover trial consisting of 4 phases, of 21 days each. During the study period, subjects were supplemented with plant sterols and/or glucomannan. Overall reductions of total cholesterol and low-density lipoprotein (LDL) cholesterol concentrations were greater after consumption of plant sterols and glucomannan compared to plant sterol or glucomannan supplementation alone. Plasma lathosterol levels, indicators of cholesterol biosynthesis, were decreased after combination treatment. The results suggest that a combination of glucomannan and plant sterols substantially improve plasma lipids by reducing cholesterol absorption and synthesis simultaneously. Supplementation of plant sterols and glucomannan can thus be used as an effective treatment for management of circulating cholesterol levels and prevention of cardiovascular disease.

Localised accumulation of body fat significantly influences the development of obesity related co-morbidities and cardiovascular disease (CVD) risk. Medium chain triglycerides (MCT) have been suggested to modulate body fat distribution. Phytosterols (PS) have demonstrated unequivocal cholesterol-lowering effects. A healthy dietary solution combining MCT and PS could thus become first-line obesity and CVD prevention. The aim of this study was therefore to investigate the effects of a functional oil (FctO) rich in MCT and PS on blood lipid levels and body adiposity, compared to olive oil. Twenty-three hypercholesterolemic, overweight men, were randomly assigned, in a single-blind crossover study, to consume a FctO, or olive oil, incorporated into a 40% fat diet for 6 wks. Blood lipid levels were measured and body composition was assessed. Total and LDL cholesterol were significantly reduced in subjects consuming the FctO versus the control oil. No significant differences for weight or adiposity loss of subjects were observed between the two oils. Results support the cardio-protective role of this FctO.