Hyperlipidemias: Rudkowska I

Rudkowska I, Jones PJ. · School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada. · Nutr Rev. · Pubmed #18522623 No free full text.

Abstract: ATP-binding cassette (ABC) transporters function in the homeostasis of lipids. Dysfunction of ABC transporters is frequently associated with disease. This review examines links between polymorphisms of ABC G5 (ABCG5) and G8 (ABCG8) transporter genes to hypercholesterolemia and to gallstone disease risk. Various polymorphisms (A632V, T400K, D19H, M429V, and C54Y) in the ABCG8 and ABCG5 (Q604E) gene have been found to be associated with several facets of cholesterol metabolism, including baseline cholesterol level, cholesterol kinetics, individual responsiveness of plasma cholesterol to dietary and pharmaceutical interventions for hypercholesterolemia, and increased risk of gallstones. Clearly, the ABCG5 and ABCG8 genes play an important role in cholesterol homeostasis. However, more research is needed to establish how specific polymorphisms of these genes confer to higher risk of these diseases.

Rudkowska I, AbuMweis SS, Nicolle C, Jones PJ. · School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada. · J Am Coll Nutr. · Pubmed #18845709 No free full text.

Abstract: OBJECTIVE: Plant sterols (PS) consumed as a snack may not have the same cholesterol-lowering potential as when consumed with a meal due to poor solubilization. It was hypothesized that the consumption of a single dose, low-fat yogurt rich in PS (1.6 g/d) with a meal over an afternoon snack will lead to favourable changes in plasma lipids, plasma PS concentrations, and cholesterol synthesis without negatively affecting alpha-tocopherol or carotenoids levels. METHODS: Twenty-six hyperlipidemic males and females completed the randomized trial of three phases (control, single PS dose consumed with a meal, or single PS dose as an afternoon snack) while consuming controlled, low-fat diets. Plasma lipids, cholesterol synthesis rates, plasma PS and serum fat-soluble antioxidants were measured at baseline and after 4 weeks. RESULTS: Endpoint total cholesterol (TC) levels after the PS snack phase were decreased (p = 0.04) (5.30 +/- 0.2 mmol/L) compared to the control phase (5.53 +/- 0.2 mmol/L). However, endpoints for TC (5.37 +/- 0.2 mmol/L) for PS dose with a meal were comparable to control phase. Low-density lipoprotein-cholesterol tended to be different (p = 0.06) at the end of the intervention phases (3.51 +/- 0.1, 3.43 +/- 0.1, and 3.33 +/- 0.1 mmol/L; control, meal and snack, respectively). Cholesterol fractional synthesis rates were higher (p = 0.007) by 25.8% and 19.5% at the end of the snack and meal phases, respectively, compared with the control phase. Plasma campesterol and beta-sitosterol concentrations, adjusted for TC, were higher (p < 0.01) in the snack phase (2.30 +/- 0.3 and 0.54 +/- 0.1 micromol/mmol, respectively) and in the meal phase (2.00 +/- 0.3 and 0.51 +/- 0.1 micromol/mmol, respectively) when compared to the control phase (1.81 +/- 0.3 and 0.40 +/- 0.1 micromol/mmol, respectively). No changes in alpha-tocopherol or carotenoids levels were detected after adjusting for TC, for all phases. CONCLUSION: These results indicate that a single dose of PS in low-fat yogurt, provided as a snack, lowers cholesterol levels but does not alter fat-soluble vitamin or carotenoid concentrations in hyperlipidemic participants.

Rudkowska I, AbuMweis SS, Nicolle C, Jones PJ. · School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, QC, Canada. · Appl Physiol Nutr Metab. · Pubmed #18641716 No free full text.

Abstract: Plant sterol (PS) consumption decreases low-density lipoprotein cholesterol (LDL-C) levels; however, high variability of responsiveness of lipid levels to PS intervention has been observed. We hypothesized that common single-nucleotide polymorphisms (SNPs) in the genes for the ATP binding cassette proteins G5 (ABCG5) and G8 (ABCG8), Niemann-Pick C1-like 1 (NPC1L1), or other proteins of the cholesterol pathway, would underline inter-individual variations in response to PS. Twenty-six hyperlipidemic subjects completed a randomized trial of 3 PS phases and a control phase. Three non-responders were identified who failed on 3 consecutive occasions to decrease either total cholesterol or LDL-C level vs. control. It was observed that after 3 PS phases compared with a control phase, cholesterol absorption changed to a lesser degree (-7.7% +/- 10.8%) in the non-responders than in the top 3 responders (-22.1% +/- 8.8%); however, cholesterol synthesis rates did not differ between sub-groups. No common polymorphisms in ABCG8, ABCG5, or NPC1L1 were demonstrated between the 3 top responders and the non-responders. Yet, 1 non-responsive subject did demonstrate a rare SNP in NPC1L1. Results indicate PS intake did not decrease cholesterol absorption rates to the same degree in certain subjects, possibly clarifying the inter-individual variability in the cholesterol-lowering effect; hence, this work should be expanded.

Rudkowska I, Roynette CE, Nakhasi DK, Jones PJ. · School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Québec, Canada H9X 3V9. · Metabolism. · Pubmed #16483884 No free full text.

Abstract: Phytosterols (PSs) have been recently added to various mediums. Nevertheless, matrices with functional properties, such as medium-chain triglycerides (MCTs), should be precisely examined for supplementary advantages. The objective of this study was to identify the existence of combined biological actions of a functional oil enriched in PSs within MCTs and high-oleic canola (HOC), relative to a control (olive oil), in overweight, hyperlipidemic men using a rigorously controlled dietary intervention. Twenty-three overweight, hyperlipidemic men consumed both types of oil in a randomized, crossover trial for 6 weeks each. Fasted plasma samples were collected on the first and last 2 days of each study period. Body weight decreased -1.22 +/- 0.35 kg (P = .0019) and -1.68 +/- 0.47 kg (P = .0016) after the 6-week study period in the olive oil and functional oil groups, respectively. The end points for total cholesterol and low-density lipoprotein cholesterol (LDL-C) in the functional oil group (P = .0006) were lower than in the olive oil group (P = .0002). Total cholesterol values decreased from comparable baseline to end point of 4.71 +/- 0.16 mmol/L (P < .0001) in the functional oil phase and 5.14 +/- 0.19 mmol/L (P = .0001) in the olive oil phase (P = .0592). In addition, LDL-C demonstrated a similar drop, to an end point of 3.12 +/- 0.16 mmol/L (P < .0001) and 3.54 +/- 0.18 mmol/L (P = .0002), for the functional oil and olive oil groups, respectively, with significant changes (P = .0221). High-density lipoprotein cholesterol levels did not change in either treatment. Triacylglycerol end points decreased in functional oil and olive oil groups (P = .0195 and .0105, respectively) to the same extent from baseline. Results indicate that PSs mixed within an MCT- and HOC-rich matrix lower plasma LDL-C, without significantly changing the high-density lipoprotein cholesterol concentrations, in hyperlipidemic, overweight men, and may therefore decrease the risk of cardiovascular events.