Low-carbohydrate vegan diets in diabetes for weight loss and sustainability: a randomized controlled trial.

BACKGROUND: Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option. OBJECTIVES: We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes. METHODS: One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants. RESULTS: Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (-5.9 kg; 95% CI: -6.5, -5.28 kg; and -5.23 kg; 95% CI: -5.84, -4.62 kg), glycated hemoglobin (-0.99%; 95% CI: -1.07, -0.9%; and -0.88%; 95% CI: -0.97, -0.8%), systolic blood pressure (-4 mmHg; 95% CI: -7, -2 mmHg; and -6 mmHg; 95% CI: -8, -3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of -0.63 kgCO2/d (95% CI: -0.99, -0.27 kgCO2/d) favoring the low-carbohydrate vegan diet. CONCLUSIONS: Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions. TRIAL REGISTRATION NUMBER: clinicaltrials.gov identifier NCT02245399.

The Manitoba Personalized Lifestyle Research (TMPLR) study protocol: a multicentre bidirectional observational cohort study with administrative health record linkage investigating the interactions between lifestyle and health in Manitoba, Canada.

INTRODUCTION: Lifestyle factors, such as diet, physical activity and sleep, are associated with the development of many chronic diseases. The objective of The Manitoba Personalized Lifestyle Research study is to understand how these lifestyle factors interact with each other and with other factors, such as an individual's genetics and gut microbiome, to influence health. METHODS: An observational study of adults, with extensive phenotyping by objective health and lifestyle assessments, and retrospective assessment of early life experiences, with retrospective and prospective utilisation of secondary data from administrative health records. STUDY POPULATION: A planned non-random convenience sample of 840 Manitobans aged 30-46 recruited from the general population, stratified by sex (equal men and women), body mass index (BMI; 60% of participants with a BMI>25 kg/m2) and geography (25% from rural areas). These stratifications were selected based on Manitoba demographics. MEASUREMENTS: Lifestyle factors assessed will include dietary pattern, physical activity, cardiovascular fitness, and sleep. Factors such as medical history, socioeconomic status, alcohol and tobacco consumption, cognition, stress, anxiety, and early life experiences will also be documented. A maternal survey will be performed. Body composition and bone density will be measured by dual energy X-ray absorptiometry. Blood pressure, pulse wave velocity, and augmentation index will be measured on two consecutive days. Chronic disease risk biomarkers will be measured in blood and urine samples. DNA will be extracted for genetic analysis. A faecal sample will be collected for microbiome analysis. Participants may provide their Manitoba personal health information number to link their study data with administrative health records. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of Manitoba Health Research Ethics Board (protocol # HS18951; 05/01/2016). Data analysis, release of results and publication of manuscripts are scheduled to start in early 2019. Additional information at www.TMPLR.ca. TRIAL REGISTRATION NUMBER: NCT03674957; Pre-results.

Modulating Sterol Concentrations in Infant Formula Influences Cholesterol Absorption and Synthesis in the Neonatal Piglet.

Formula-fed infants present higher cholesterol synthesis rates and lower circulating cholesterol during the postnatal feeding period compared to breast-fed infants, though the mechanisms underlying this phenotype are not fully understood. Typical infant formulas contain vegetable-based fats, inherently including phytosterols (PS), which are structurally similar to cholesterol and may interfere with their absorption. A seven-day old piglets model was used to test the inhibitory effects of PS on cholesterol absorption during postnatal feeding. Following feeding for 21 days with milk-based formulas containing PS and cholesterol levels resembling those in formulas or human-milk, apparent cholesterol digestibility was analyzed in ileal digesta, and cholesterol, PS, and cholesterol synthesis markers were analyzed in plasma and liver samples. Ileal cholesterol digestibility content was increased in the piglets fed low PS formulas and the rate of the hepatic cholesterol synthesis, as determined by the lathosterol-to-cholesterol ratios (L:C), was decreased in the piglets fed LP-formulas and corresponded to reduced nuclear expression of SREBP2 relative to those fed HP-formulas. These results are consistent with the hypothesis that PS in formula can inhibit cholesterol absorption and enhance cholesterol synthesis. Whether or not this leads to entrainment of cholesterol synthesis later in life via early programming awaits further research.

Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: a randomized controlled trial.

Background: Controversies persist concerning the association between intake of dietary saturated fatty acids (SFAs) and cardiovascular disease risk.Objective: We compared the impact of consuming equal amounts of SFAs from cheese and butter on cardiometabolic risk factors.Design: In a multicenter, crossover, randomized controlled trial, 92 men and women with abdominal obesity and relatively low HDL-cholesterol concentrations were assigned to sequences of 5 predetermined isoenergetic diets of 4 wk each separated by 4-wk washouts: 2 diets rich in SFAs (12.4-12.6% of calories) from either cheese or butter; a monounsaturated fatty acid (MUFA)-rich diet (SFAs: 5.8%, MUFAs: 19.6%); a polyunsaturated fatty acid (PUFA)-rich diet (SFAs: 5.8%, PUFAs: 11.5%); and a low-fat, high-carbohydrate diet (fat: 25%, SFAs: 5.8%).Results: Serum HDL-cholesterol concentrations were similar after the cheese and butter diets but were significantly higher than after the carbohydrate diet (+3.8% and +4.7%, respectively; P < 0.05 for both). LDL-cholesterol concentrations after the cheese diet were lower than after the butter diet (-3.3%, P < 0.05) but were higher than after the carbohydrate (+2.6%), MUFA (+5.3%), and PUFA (+12.3%) diets (P < 0.05 for all). LDL-cholesterol concentrations after the butter diet also increased significantly (from +6.1% to +16.2%, P < 0.05) compared with the carbohydrate, MUFA, and PUFA diets. The LDL-cholesterol response to treatment was significantly modified by baseline values (P-interaction = 0.02), with the increase in LDL cholesterol being significantly greater with butter than with cheese only among individuals with high baseline LDL-cholesterol concentrations. There was no significant difference between all diets on inflammation markers, blood pressure, and insulin-glucose homeostasis.Conclusions: The results of our study suggest that the consumption of SFAs from cheese and butter has similar effects on HDL cholesterol but differentially modifies LDL-cholesterol concentrations compared with the effects of carbohydrates, MUFAs, and PUFAs, particularly in individuals with high LDL cholesterol. In contrast, SFAs from either cheese or butter have no significant effects on several other nonlipid cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT02106208.

Common Variants in Cholesterol Synthesis- and Transport-Related Genes Associate with Circulating Cholesterol Responses to Intakes of Conventional Dairy Products in Healthy Individuals.

BACKGROUND: Dairy intake has been associated with varying impacts on circulating cholesterol concentrations across nutritional epidemiology and intervention studies, with findings attributed mainly to differences in the nature of dairy products consumed or study designs. The contribution of the genomic architecture to such observations has yet to be revealed. OBJECTIVE: We assessed the impact of multiple common genetic variations in cholesterol-related genes on responses of serum cholesterol to the recommended amount of dairy product intake in Canada. METHODS: In a multicenter, randomized crossover design, 101 normolipidemic adults (n = 29 men and 72 women), with a mean ± SD age of 41.7 ± 16.7 y and a body mass index (BMI, in kg/m(2)) of 25.9 ± 4.3 consumed 3 servings/d of dairy [375 mL 1% milk-fat (MF) milk, 175 g 1.5% MF yogurt, and 30 g of 34% MF cheese] or energy-matched control products (juice, cashews, and cookies) provided within a prudent background diet for 4 wk each, separated by a 4- to 8-wk washout period. Serum lipid variables were determined by standard enzymatic methods by using an autoanalyzer. Candidate single nucleotide polymorphisms were assessed by TaqMan genotyping assay. RESULTS: The responsiveness of serum total cholesterol (TC) and LDL cholesterol to the dairy compared with the control diet was associated with individuals' genotypes. The cholesterol transport gene ATP-binding cassette subfamily G, member 5 (ABCG5) rs6720173-GG homozygotes had higher concentrations of TC (+0.18 mmol/L; P = 0.0118) and LDL cholesterol (+0.17 mmol/L; P = 0.0056) relative to C-allele carriers (-0.07 and -0.06 mmol/L, respectively). The bile acid synthesis gene cholesterol 7α-hydroxylase (CYP7A1) rs3808607-G-allele carriers had higher TC (+0.20 to +0.28 mmol/L; P = 0.0026) and LDL cholesterol (+0.19 mmol/L for GT genotype; P = 0.0260) relative to TT homozygotes (-0.11 and -0.03 mmol/L, respectively). In addition, the cholesterol synthesis gene 7-dehydrocholesterol reductase (DHCR7) rs760241-A-allele carriers had higher LDL cholesterol (+0.26 mmol/L; P = 0.0399) relative to GG homozygotes (+0.06 mmol/L). CONCLUSION: Genetic variations in ABCG5, CYP7A1, and DHCR7 may contribute to differing responses of serum cholesterol to dairy intake among healthy adults. This trial was registered at clinicaltrials.gov as NCT01444326.

High-Molecular-Weight ß-Glucan Decreases Serum Cholesterol Differentially Based on the CYP7A1 rs3808607 Polymorphism in Mildly Hypercholesterolemic Adults.

BACKGROUND: ß-Glucan, a soluble fiber with viscous property, has a documented cholesterol-lowering effect. The molecular weight (MW) of ß-glucan, which contributes to viscosity, and an individual's genotype might influence the cholesterol-lowering efficacy of ß-glucan. OBJECTIVES: This study was designed to determine whether the cholesterol-lowering efficacy of barley ß-glucan varied as a function of MW and the daily dose consumed. Our second aim was to determine whether any gene-diet interactions are associated with the cholesterol-lowering efficacy of ß-glucan. METHODS: In a randomized controlled crossover trial, 30 mildly hypercholesterolemic adults [12 men and 18 women, aged 27-78 y; body mass index (in kg/m(2)): 20-40; total cholesterol (TC): 5.0-8.0 mmol/L; LDL cholesterol: 2.7-5.0 mmol/L] were randomly assigned to receive a breakfast that contained either barley ß-glucan at 3 g high MW (HMW)/d, 5 g low MW (LMW)/d, or 3 g LMW/d or a control diet, each for 5 wk. The washout period between the phases was 4 wk. Fasting blood samples were collected at the start and end of each phase for blood lipid analysis and genotyping. RESULTS: Consumption of 3 g HMW ß-glucan/d lowered TC by -0.12 mmol/L (95% CI: -0.24, -0.006 mmol/L) compared with the control diet (P= 0.0046), but the LMW ß-glucan, at either 3 g/d or 5 g/d, did not change serum cholesterol concentrations. This effect of HMW ß-glucan was associated with gene-diet interaction, whereby individuals with the single nucleotide polymorphism (SNP) rs3808607-G allele (GG or GT) of the cytochrome P450 family 7 subfamily A member 1 gene (CYP7A1) had greater responses to 3 g HMW ß-glucan/d in lowering TC than TT carriers (P= 0.0006). CONCLUSIONS: The HMW ß-glucan rather than LMW ß-glucan reduced circulating TC effectively in mildly hypercholesterolemic adults. The cholesterol-lowering effect of ß-glucan may also be determined by the genetic characteristics of an individual. These data show that individuals carrying theCYP7A1SNP rs3808607-G allele are more responsive to the cholesterol-lowering effect of ß-glucan with HMW than TT carriers. This trial was registered atclinicaltrials.govasNCT01408719.

CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial.

BACKGROUND: The benefits of plant sterols (PSs) for cholesterol lowering are hampered by large heterogeneity across individuals, potentially because of genetic polymorphisms. OBJECTIVE: We investigated the impact of candidate genetic variations on cholesterol response to PSs in a trial that recruited individuals with high or low endogenous cholesterol synthesis, estimated by lathosterol to cholesterol (L:C) ratio. DESIGN: Mildly hypercholesterolemic adults preselected as possessing either high endogenous cholesterol synthesis (n = 24; mean ± SEM: L:C ratio = 2.03 ± 0.39 µmol/mmol) or low endogenous cholesterol synthesis (n = 39; mean ± SEM: L:C ratio = 0.99 ± 0.28 µmol/mmol) consumed 2 g PS/d or a placebo for 28 d by using a dual-center, single-blind, randomized crossover design. Cholesterol synthesis and change in cholesterol absorption were measured with stable isotopic tracers. Candidate single-nucleotide polymorphisms and apolipoprotein E (APOE) isoform were assessed by TaqMan genotyping assay. RESULTS: The cholesterol fractional synthesis rate was higher (P < 0.001) in participants with high endogenous cholesterol synthesis (mean ± SEM: placebo: 9.16% ± 0.47%; PSs: 9.74% ± 0.47%) than in participants with low endogenous cholesterol synthesis (mean ± SEM placebo: 5.72% ± 0.43%; PS: 7.10% ± 0.43%). Low-density lipoprotein (LDL) cholesterol lowering in response to PSs was associated with individuals' genotypes. Cholesterol 7 alpha-hydroxylase (CYP7A1-rs3808607) T/T homozygotes showed no LDL cholesterol lowering (mean ± SEM: -0.05 ± 0.07 mmol/L, P = 0.9999, n = 20), whereas the presence of the G-allele associated with LDL cholesterol response in a dose-dependent fashion (mean ± SEM G/T: -0.22 ± 0.06 mmol/L, P = 0.0006, n = 35; G/G: -0.46 ± 0.12 mmol/L, P = 0.0009, n = 8). Similarly, APOE ɛ3 carriers (mean ± SEM: -0.13 ± 0.05 mmol/L, P = 0.0370, n = 40) responded less than APOE ɛ4 carriers (mean ± SEM: -0.31 ± 0.07 mmol/L, P < 0.0001, n = 23). Moreover, genoset CYP7A1-rs3808607 T/T/APOE ɛ3 was associated with nonresponsiveness (mean ± SEM: +0.09 ± 0.08 mmol/L, P = 0.9999, n = 14). rs5882 in cholesteryl ester transfer protein (CETP) and rs4148217 in ATP-binding cassette subfamily G member 8 (ABCG8) did not associate with LDL cholesterol lowering. Cholesterol absorption decreased as a result of PS consumption, but this decrease was not related to circulating LDL cholesterol concentrations, cholesterol synthesis phenotype, or genotypes. CONCLUSION: CYP7A1-rs3808607 and APOE isoform are associated with the extent of reduction in circulating LDL cholesterol in response to PS consumption and could serve as potential predictive genetic markers to identify individuals who would derive maximum LDL cholesterol lowering with PS consumption. The trial was registered at clinicaltrials.gov as NCT01131832.

Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans.

BACKGROUND: Diets enriched with sphingolipids may improve blood lipid profiles. Studies in animals have shown reductions in cholesterol absorption and alterations in blood lipids after treatment with sphingomyelin (SM). However, minimal information exists on effect of SM on cholesterol absorption and metabolism in humans. The objective was to assess the effect of SM consumption on serum lipid concentrations and cholesterol metabolism in healthy humans. METHODS: Ten healthy adult males and females completed a randomized crossover study. Subjects consumed controlled diets with or without 1 g/day SM for 14 days separated by at least 4 week washout period. Serum lipid profile and markers of cholesterol metabolism including cholesterol absorption and synthesis were analyzed. RESULTS: Serum triglycerides, total, LDL- and VLDL- cholesterol were not affected while HDL cholesterol concentrations were increased (p = 0.043) by SM diet consumption. No change in cholesterol absorption and cholesterol fractional synthesis rate was observed with supplementation of SM compared to control. Intraluminal cholesterol solubilization was also not affected by consumption of SM enriched diet. CONCLUSIONS: In humans, 1 g/day of dietary SM does not alter the blood lipid profile except for an increased HDL-cholesterol concentration and has no effect on cholesterol absorption, synthesis and intraluminal solubilization compared to control. TRIAL REGISTRATION: Clinicaltrials.gov # NCT00328211.

Cholesterol-lowering effects of oat ß-glucan.

Elevated total and low-density lipoprotein (LDL) cholesterol levels are considered major risk factors for cardiovascular disease. Oat ß-glucan, a soluble dietary fiber that is found in the endosperm cell walls of oats, has generated considerable interest due to its cholesterol-lowering properties. The United States Food and Drug Administration (FDA) approved a health claim for ß-glucan soluble fiber from oats for reducing plasma cholesterol levels and risk of heart disease in 1997. Similarly, in 2004 the United Kingdom Joint Health Claims Initiative (JHCI) allowed a cholesterol-lowering health claim for oat ß-glucan. The present review aims to investigate if results from more recent studies are consistent with the original conclusions reached by the FDA and JHCI. Results of this analysis show that studies conducted during the past 13 years support the suggestion that intake of oat ß-glucan at daily doses of at least 3 g may reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 5-10% in normocholesterolemic or hypercholesterolemic subjects. Studies described herein have shown that, on average, oat consumption is associated with 5% and 7% reductions in total and LDL cholesterol levels, respectively. Significant scientific agreement continues to support a relationship between oat ß-glucan and blood cholesterol levels, with newer data being consistent with earlier conclusions made by the FDA and JHCI.

Plant sterols, marine-derived omega-3 fatty acids and other functional ingredients: a new frontier for treating hyperlipidemia.

As hyperlipidemia, including hypercholesterolemia (HC) and hypertriglyceridemia (HTN), continue to challenge North America's healthcare systems, patients continue to seek efficacious and safe natural therapies that complement pharmaceutical interventions. However, despite the ever-growing body of research supporting the use of functional foods and nutraceuticals (FFN) for the prevention and treatment of hyperlipidemia, reception amongst the medical community regarding the implementation of FFN into clinical guidelines continues to lag. Research demonstrates that specific FFN target and modulate molecular processes that perpetuate hyperlipidemia. In addition, studies consistently demonstrate that combining certain FFN such as marine-derived omega-3 fatty acids or plant sterols/stanols with statins enhances triglyceride and cholesterol-lowering efficacy, respectively. Thus, the purpose of this commentary is to contend that efficacious FFN not only reduce HC and HTG but also boost the lipid-lowering effects of pharmaceutical hypolipidemic medications. Finally, this editorial aims to challenge current medical guidelines to emphasize efficacious FFN during all stages of treatment of hyperlipidemias as adjuncts to pharmacotherapy.

High basal fractional cholesterol synthesis is associated with nonresponse of plasma LDL cholesterol to plant sterol therapy.

BACKGROUND: The cholesterol-lowering effectiveness of plant sterol (PS) therapy is hindered by wide-ranging variability in LDL-cholesterol responsiveness across individuals. To capitalize on the LDL-cholesterol-lowering potential of PS in the clinical setting, it is paramount to characterize the metabolic factors that underlie this heterogeneity of responsiveness. OBJECTIVE: The objective was to investigate the relation between cholesterol synthesis and plasma LDL-cholesterol reductions in response to PS consumption. DESIGN: We evaluated previously conducted clinical PS interventions incorporating stable-isotope measures of cholesterol synthesis and conducted feeding studies in animal models of response (Syrian Golden hamsters) and nonresponse (C57BL/6J mice) to PS consumption. RESULTS: From our clinical study population (n = 113), we identified 47 nonresponders (3.73 +/- 1.10% change in LDL cholesterol) and 66 responders (-15.16 +/- 1.04% change in LDL cholesterol) to PS therapy. The basal cholesterol fractional synthesis rate (FSR) as measured by direct deuterium incorporation was 23% higher (P = 0.003) in the nonresponder subgroup than in responders to PS therapy. The basal cholesterol FSR correlated (r = 0.22, P = 0.02) with the percentage change in LDL cholesterol after PS intervention. In support of our clinical observations, nonresponding mice showed a 77% higher (P = 0.001) basal cholesterol FSR than that of responding hamsters. Compared with control mice, PS-fed mice showed an increase in hepatic nuclear sterol regulatory element binding protein 2 abundance (1.3-fold of control, P = 0.04) and beta-hydroxy-beta-methylglutaryl coenzyme A reductase-mRNA expression (2.4-fold of control, P = 0.00). CONCLUSION: The results suggest that subjects with high basal cholesterol synthesis are less responsive to PS treatment than are subjects with low basal cholesterol synthesis.

Low and moderate-fat plant sterol fortified soymilk in modulation of plasma lipids and cholesterol kinetics in subjects with normal to high cholesterol concentrations: report on two randomized crossover studies.

BACKGROUND: Although consumption of various plant sterol (PS)-enriched beverages is effective in lowering plasma cholesterol, the lipid-lowering potential of PS in a soymilk format has not been investigated thoroughly. Therefore, to evaluate the efficacy of PS-enriched soy beverages on plasma lipids and cholesterol kinetics, we conducted two separate 28 d dietary controlled cross-over studies. In study 1, the cholesterol-lowering efficacy of a low-fat (2 g/serving) PS enriched soy beverage was examined in 33 normal cholesterolemic subjects in comparison with 1% dairy milk. In study 2, we investigated the efficacy of a moderate-fat (3.5 g/serving) PS-enriched soy beverage on plasma cholesterol concentrations and cholesterol kinetic responses in 23 hypercholesterolemic subjects compared with 1% dairy milk. Both the low and moderate-fat PS-enriched soymilk varieties provided 1.95 g PS/d. Endpoint plasma variables were analyzed by repeated-measures ANOVA using baseline values as covariates for plasma lipid measurements. RESULTS: In comparison with the 1% dairy milk control, the low-fat soy beverage reduced (P < 0.05) total and LDL-cholesterol by 10 and 13%, respectively. Consumption of the moderate-fat PS-enriched soy beverage reduced (P < 0.05) plasma total and LDL-cholesterol by 12 and 15% respectively. Fasting triglycerides were reduced by 9.4% following consumption of the moderate-fat soy beverage in comparison with the 1% dairy milk. Both low and moderate-fat PS-enriched soy varieties reduced (P < 0.05) LDL:HDL and TC:HDL ratios compared with the 1% dairy milk control. Consumption of the moderate-fat PS-enriched soymilk reduced (P < 0.05) cholesterol absorption by 27%, but did not alter cholesterol synthesis in comparison with 1% dairy milk. CONCLUSION: We conclude that, compared to 1% dairy milk, consumption of low and moderate-fat PS-enriched soy beverages represents an effective dietary strategy to reduce circulating lipid concentrations in normal to hypercholesterolemic individuals by reducing intestinal cholesterol absorption. TRIAL REGISTRATION (CLINICALTRIALS.GOV): NCT00923403 (Study 1), NCT00924391 (Study 2).

Conjugated linoleic acids: why the discrepancy between animal and human studies?

Conjugated linoleic acids (CLA) are positional and geometric isomers of linoleic acid. In animals, CLA consumption reduces body fat but results in humans are less conclusive. This review of the literature on CLA and loss of body fat or body weight in humans was conducted to explore the reasons for the discrepancy between animal and clinical trials. It indicates that the incongruity between human and animal data is largely related to methodological differences in the experimental design, including age and gender and, to a lesser extent, to CLA dose and isomers. The relatively unknown metabolic fate of CLA in humans may also be a contributing factor that helps explain the lack of consistency for CLA efficacy across studies.

Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: current understandings and future research priorities.

The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in 'high-dimensional' biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of 'omic' technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based "cocktails" that target specific metabolic pathways to gain maximal cholesterol reductions.