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Reducing intestinal cholesterol absorption with plant sterol consumption is a well-characterized strategy to lower LDL-C and potentially reduce cardiovascular disease risk. However, over 50 years of clinical research demonstrate that there is significant heterogeneity in the individual LDL-C lowering response to plant sterol therapy. A clear understanding of why plant sterols work effectively in some individuals but not in others will ensure optimal integration of plant sterols in future personalized nutritional lipid-lowering strategies. This review will examine the current knowledge base surrounding the metabolic and genetic determinants of LDL-C lowering in response to plant sterol consumption. [ABSTRACT FROM AUTHOR]

The mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2) and low density lipoprotein receptor (LDLr) were examined in pigs fed an atherogenic control diet or the control diet supplemented with 10% guar gum (GG). Compared to the control group, GG consumption reduced (P<0.05) plasma total cholesterol (27%), LDL cholesterol (37%), and hepatic free cholesterol concentrations. GG consumption increased hepatic LDLr mRNA (1.8 fold, P=0.09) and protein (2 fold, P<0.05) expression in comparison to the control group. Hepatic SREBP2 mRNA expression was not altered (P>0.05) in response to GG consumption. While expression of the cytoplasmic mature form of SREBP2 was similar (P>0.05) between the two groups, GG consumption increased (P<0.05) the expression of the cytoplasmic precursor (3 fold) and nuclear active forms (1.5 fold) of the SREBP2. We conclude that a reduction in hepatic free cholesterol concentration in response to GG consumption enhances nuclear SREBP2 expression by post-transcriptional events that are independent of the proteolytic release of the mature protein from the golgi apparatus. Furthermore, accumulation of nuclear SREBP2 increases the expression of hepatic LDLr and mediates the hypocholesterolemic effects associated with GG consumption. [ABSTRACT FROM AUTHOR]

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking. [ABSTRACT FROM AUTHOR]

We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (−21%), non-HDL-C (−25%), LDL-C (−16%), and total LDL particle number (−46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (−70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (−46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1β protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Information is scarce regarding the effect of dietary protein type, with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular risk factors and vascular reactivity in humans. Objective: Determine the effect of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults. Design: Randomized cross-over design of two 35-day diet phases; thirty adults (21 females and 9 males, ≥50 years, LDL cholesterol ≥120mg/dL). Diets had 20% energy (E) protein, 30%E fat, 50%E carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio. Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and flow mediated dilation (FMD) and peripheral artery tonometry (PAT). Results: No differences were observed in fasting and/or postprandial total, LDL, HDL and sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low, relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL cholesterol (−24%, P =0.001) and triglycerides (−23%, P =0.001), and small but significant differences in fasting (−3%, P =0.003) and postprandial (−3%, P =0.018) apo AI, and fasting adiponectin concentrations (+7%, P =0.035). Fasting and postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet (P =0.020 for both). Conclusions: Diets differing in Lys:Arg ratios had no or small effects on cardiovascular risk factors and vascular reactivity. [Copyright &y& Elsevier]