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This study evaluated spouse health behavior outcomes from a randomized controlled trial of a spouse-assisted lifestyle intervention to reduce patient low-density lipoprotein cholesterol and improve patient health behaviors. Participants were 251 spouses of patients from the Durham Veterans Affairs Medical Center randomized to intervention or usual care. The intervention comprised 9 monthly telephone calls to patients and spouses. Outcomes were assessed at baseline, 6 and 11 months. At 11 months, there were no differences in spouse outcomes between intervention and usual care groups for moderate intensity physical activity (i.e., frequency, duration) or dietary intake (i.e., total calories, total fat, percentage of calories from total fat, saturated fat, percentage of calories from saturated fat, cholesterol, fiber). To improve spouse outcomes, couple interventions may need to include spouse behavior change goals and reciprocal support between patients and spouses and consider the need for improvement in spouse outcomes. Keywords Spouse * Couple * Dietary intake * Physical activity * Intervention * Social support, Introduction Couple interventions (i.e., both patient and partner are active participants) for chronic illness have significant small effects on some patient outcomes and in some cases are more efficacious than [...]

Background/Objectives: Viscous fibers typically reduce total cholesterol (TC) by 3-7% in humans. The cholesterol- lowering properties of the viscous fiber pectin may depend on its physico-chemical properties (viscosity, molecular weight (MW) and degree of esterification (DE)), but these are not typically described in publications, nor required by European Food Safety Authority (EFSA) with respect to its generic pectin cholesterol-lowering claim. Subjects/Methods: Here, different sources and types of well-characterized pectin were evaluated in humans. Cross-over studies were completed in mildly hyper-cholesterolemic persons receiving either 15g/day pectin or cellulose with food for 4 weeks. Results: Relative low-density lipoprotein (LDL) cholesterol (LDL-C) lowering was as follows: citrus pectin DE-70 = apple pectin DE-70 (7-10% reduction versus control) >apple pectin DE-35 = citrus pectin DE-35>OPF (orange pulp fiber) DE-70 and low-MW pectin DE-70> citrus DE-0. In a subsequent 3-week trial with 6g/day pectin, citrus DE-70 and high MW pectin DE- 70 reduced LDL-C 6-7% versus control (without changes in TC). In both studies, high DE and high MW were important for cholesterol lowering. Source may also be important as citrus and apple DE-70 pectin were more effective than OPF DE-70 pectin. Pectin did not affect inflammatory markers high-sensitivity C-reactive protein (hsCRP) nor plasma homocysteine. Conclusions: Pectin source and type (DE and MW) affect cholesterol lowering. The EFSA pectin cholesterol-lowering claim should require a minimum level of characterization, including DE and MW. European journal of Clinical Nutrition (2012) 66, 591-599; doi: 10.1038/ejcn.2011.208; published online 21 December 2011 Keywords: pectin; viscous fiber; cholesterol; lipoproteins; CRP; homocysteine, Introduction Pectin: what is it? Pectin is a complex polysaccharide present in plant cell walls, extracted commercially from pulp waste during fruit juice pressing (for example, from citrus peel and [...]

Abstract: P-glycoprotein (P-gp) is believed to be one of the most common causes of multidrug resistance (MDR) in chemotherapy. Studies have shown that the biosynthesis of cholesterol and cholesterol esters [...]

Very low-carbohydrate diets (VLCDs) are popular, but remain controversial. This review summarizes the latest studies that have examined the effects of VLCDs on lipoproteins and related risk factors for cardiovascular disease. Prospective studies indicate that VLCDs improve the lipoprotein profile independently of weight loss. Although not as effective at lowering LDL cholesterol (LDL-C), VLCDs consistently improve postabsorptive and postprandial triacylglycerols (TAGs), HDL cholesterol (HDL-C), and the distribution of LDL-C subfractions to a greater extent than low-fat diets. VLCDs also improve proinflammatory markers when associated with weight loss. Studies usually report mean lipid responses, but individual data indicate a large degree of variability in the magnitude and in some cases the direction (e.g., LDL-C) of lipoprotein responses to both low-fat and VLCDs. Such variability makes it hard to defend a single diet recommendation, especially considering the potential for low-fat/high-carbohydrate diets to exacerbate TAG, HDL-C, and other characteristics of the metabolic syndrome. Considering the effectiveness of VLCDs in promoting fat loss and improving the metabolic syndrome, discounting or condemning their use is unjustified. We encourage a more unbiased, balanced appraisal of VLCDs. KEY WORDS: * cholesterol * low-carbohydrate diet * ketogenic * triglycerides * lipoproteins

A study compared to the susceptibility of plasma low-density lipoprotein (LDL) to oxidation in healthy volunteers who had been on regular long-term diets. It was found the long-term dietary habits predict the fatty acid composition of serum and LDL and have an effect on the susceptibility of LDL to oxidation.

Research was conducted to examine the hypothesis that high-density lipoprotein (HDL) may inhibit the oxidative modification of low-density lipoprotein (LDL) by playing an anti-atherogenic role as an antioxidant. One HDL-associated protein, namely, lecithin:cholesterol acyltransferase, was purified to apparent homogeneity. The oxidation-dependent accumulation of both conjugate dienes and lipid hydroperoxides was found to be inhibited by the addition of pure human LCAT to LDL. LCAT, therefore, can act as an antioxidant to prevent the accumulation of oxidized lipid in plasma lipoproteins.

The human Niemann-Pick type C (NPC) protein is studied to identify its structural features which are critical to intracellular cholesterol trafficking. The results show that in human fibroblasts, NPC1 protein is localized in a subset of vesicles containing LAMP2, a marker for late endosomes and lysosomes. Transient interactions with cholesterol laden lysosomes have been observed in wild-type NPC1-containing vesicles. Under experimental conditions, NPC1 appears to move through prelysosomal vesicles before entering the lysosomal compartment.

Fermented milk product Gaio and its effects on the lipid profile in people with mild to moderate primary hypercholesterolemia were investigated. The study found that patients who were fed with Gaio had their total and low density lipoprotein-cholesterol levels decline by a small but statistically significant percentage. However, not all subjects appeared to respond to the milk product and cholesterol levels even seemed to increase in some of the subjects. Gaio was supplied by the Brazilian company Vigor Co.

Vitamin E was advocated as an effective treatment for heart disease by Dr. Even Shute of London, Ontario more than 50 years ago. His pioneering claims, which were unacceptable to the medical community at large, have been confirmed by recent findings from epidemiologic studies and clinical trials. This review integrates our current knowledge of atherogenesis with the biological functions of vitamin E. The response-to-injury hypothesis explains atherosclerosis as a chronic inflammatory response to injury of the endothelium, which leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components. Inflammatory and other stimuli trigger an overproduction of free radicals, which promote peroxidation of lipids in LDL trapped in the subendothelial space. Products of LDL oxidation are bioactive, and they induce endothelial expression and secretion of cytokines, growth factors and several cell surface adhesion molecules. The last-mentioned are capable of recruiting circulating monocytes and T lymphocytes into the intima where monocytes are differentiated into macrophages, the precursor of foam cells. In response to the growth factors and cytokines, smooth muscle cells proliferate in the intima, resulting in the narrowing of the lumen. Oxidized LDL can also inhibit endothelial production of prostacyclin and nitric oxide, two potent autacoids that are vasodilators and inhibitors of platelet aggregation. Evidence is presented that vitamin E is protective against the development of atherosclerosis. Vitamin E enrichment has been shown to retard LDL oxidation, inhibit the proliferation of smooth muscle cells, inhibit platelet adhesion and aggregation, inhibit the expression and function of adhesion molecules, attenuate the synthesis of leukotrienes and potentiate the release of prostacyclin through up-regulating the expression of cytosolic phospholipase [A.sub.2] and cyclooxygenase. Collectively, these biological functions of vitamin E may account for its protection against the development of atherosclerosis. KEY WORDS: * vitamin E * endothelium * smooth muscle cell * monocyte * eicosanoids * platelets * oxidized LDL

Fasting cholesterol and beta-carotene levels were measured in a cohort of moderately severe anorectics to examine the role of hypercholesterolemia and hypercarotenemia in anorexia nervosa. Findings revealed normal total cholesterol and low-density lipoprotein cholesterol values among the 23 patients. However, high levels of high-density lipoprotein cholesterol values were found among the subjects. Hypercarotenemia was not linked to anorexia nervosa.

Fatty streaks deposited during childhood and adolescence can become advanced lesions and fibrous plaques later in life, causing adult cardiovascular disease. Children and young adults can safely follow and benefit from adult fat-limited diets, since childhood/adolescence nutrition appears to be an important component in determining cholesterol and obesity later in life. There may also be a correlation between adult obesity or lipoprotein problems and preweaning nutrition.

A study was conducted to determine the mechanism and specificity of the influx of free cholesterol (FC) from plasma and plasma lipoproteins into cultured skin fibroblasts. The results indicate that a high-capacity, ATPase-dependent pathway is responsible for the transport of low-density lipoprotein (LDL) FC into a temporary storage domain in the cell. From there, LDL FC is either transported further into the cell for metabolism or storage, or lost by efflux as high-density lipoprotein is taken in by the cell.

Time-dependent inactivation of the enzyme lanosterol 14-alpha-methyl demethylase can be accomplished using selected 15-,32- and 15,32-substituted lanosterol analogs. These substrate- and mechanism-based inhibitors use NADPH and O2 to demonstrate time-dependance. This and other findings suggest that lanosterol demethylation involves stereoselective oxidation, and that the demethylation reaction includes abstraction of the 32-pro-S proton.

A set of 15- and 32- and 15,32-substituted lanost-8-en-3-beta-ols inhibit the activity of lanosterol 14-alpha-methyl demethylase, restrict HMG-CoA reduction activity, restraining cholesterol biosynthesis, and cause LDL receptor induction. This suggests that compounds can be created to suppress reductase and and cause DL receptor induction without demethylase inhibition, possibly resulting in the lowering of cholesterol levels.

Studies on the lipoprotein level of an identical group of middle-aged Danish men for 6 weeks after consuming a new milk product fermented with bacteria obtained from the intestinal flora of the people in Abkhasia show a 10% reduction in LDL-cholesterol with no changes in the placebo group. The new milk contained a strain of enterococcus faecium and 2 strains of streptococcus termophilus. The placebo product was chemically fermented.

The 5' cholesteryl (chol)-modified oligonucleotides were compared to the unmodified phosphodiester (PO) oligonucleotides to determine whether chol modification of PO oligonucleotides might improve their antisense efficacy. It was shown that chol PO oligonucleotides can be sequence-specific antisense agents and are more potent than unmodified oligonucleotides. Moreover, it was demonstrated that chol oligonucleotides are internalized by cells at least partially through the low density lipoprotein receptor.

The effects of prickly pear pectin on plasma LDL metabolism were investigated by feeding guinea pigs either a diet containing 15 g/100 g lard and 0.25 g/100 g cholesterol (LC diet) or the LC diet in which cellulose was partially replaced (2.5 g/100 g) by prickly pear pectin (LC-P diet). The LC-P diet lowered plasma LDL cholesterol concentrations by 33% (P < 0.001). Low density lipoprotein composition was modified by intake of prickly pear pectin; the relative percentages of free and esterified cholesterol were lower and triglycerides were higher in LDL from animals fed the LC-P diet (P < 0.05). Intake of prickly pear pectin did not affect hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity; however, hepatic free and esterified cholesterol concentrations were lowered by 46 and 64%, respectively. Hepatic apolipoprotein B/E receptor expression (B(sub max)) was 60% higher in animals fed the LC-P diet (P < 0.01). Similar to the in vitro data, receptor-mediated LDL fractional catabolic rates were 190% higher in animals fed the LC-P diet (P < 0.05), whereas apolipoprotein LDL flux rates were not affected. Apolipoprotein LDL pool size and fractional catabolic rates exhibited a significant correlation (r = -0.52, P < 0.01). These data indicate that an increase in apolipoprotein B/E receptor expression is a major metabolic response by which intake of prickly pear pectin decreases plasma LDL concentrations. J. Nutr. 122: 2330-2340, 1992.

The effects of major storage globulins from soybean on cholesterol homeostasis were investigated in in vitro and in vivo systems. The low density lipoprotein (LDL) uptake and degradation was studied both in human skin fibroblasts (HSF) and in a human hepatoma cell line (Hep G2). In Hep G2 cells a dose-dependent increase of both uptake and degradation of [sup.125]I-LDL was induced by the 7S globulin, whereas the 11S globulin exerted a lesser effect that was not dose-related. In HSF cells the 11S globulin increased the uptake of (125)I-LDL to a greater extent than did 7S globulin; in this cell line, LDL degradation was not stimulated by either of the globulins. Rats fed a casein-cholesterol diet were treated daily with 11S or 7S globulins for 2 wk. The administration of soybean globulins significantly reduced cholesterolemia (-35 and -34% with 7S and 11S globulins, respectively, vs. controls). Liver membrane preparations from the casein-cholesterol-fed rats showed a nonsignificant increase in the maximal binding of labeled cholesterol-rich lipoprotein fraction ([Beta]-VLDL) to high affinity receptors. J. Nutr. 122: 1971-1978, 1992., The soybean 7S globulin induced LDL uptake and degradation in a human hepatoma cell line (Hep G2) in a dose-related manner while soybean 11S globulin had the same effect but to a lesser degree. LDL uptake in human skin fibroblasts (HSF) was stimulated more with the 11S globulin than the 7S globulin whereas degradation was not stimulated by either globulin fraction. Soybean globulins decreased hypercholesterolemia in rats fed high cholesterol diets but beta-very low density lipoprotein (VLDL) receptor activity in liver membranes had a nonsignificant increase.

The possible role of growth hormone (GH) in the hormonal regulation of hepatic low density lipoprotein (LDL) receptor expression was investigated. Rats were hypophysectomized and treated with estrogen, the known inducer of LDL receptors. The results showed that GH was required to induce the expression of hepatic LDLs in these rats. The induction of LDL receptors was accompanied by a decrease in serum cholesterol levels. These results indicate that GH plays an important role in regulating the expression of LDL receptors.

The LDL receptor (LDLR) in patients with the disease familial hypercholesterolemia (FH) was investigated. The molecular basis of FH was studied by determining the structure of one of seven ligand-binding repeats of the LDLR, called LR5, through X-ray crystallography. Many point mutations that cause FH can be traced to LR5. X-ray crystallography shows that the LR5 structure is organized around one calcium ion. Acidic residues directly coordinate and form the scaffolding of the LR5 calcium ion. The FH point mutations found in patients with the disease alter the residues that directly coordinate the LR5 calcium ion.

Eriocitrin, the main flavonoid in lemon fruit was investigated for its lowering effect on serum and hepatic lipids in high fat and high-cholesterol fed rats. It was found that eriocitrin has a lowering effect for total cholesterol, VLDL+LDL, triglyceride in high-fat and high-cholesterol fed rats and lowering effect of eriocitrin is caused by a decrease in VLDL+LDL.

LOW density lipoprotein (LDL), the major cholesterol-carrying lipoprotein in human plasma, is the offending agent in coronary heart disease, which causes one-third of all deaths in the United States. Originally, [...]

An activation of LDL receptors was recently described in a human hepatoma cell line (Hep G2) exposed to purified ([Alpha] + [Alpha]') subunits from 7S soy globulin; [Beta] chains were ineffective (Lovati et al. 1998). By using a mutant soy cultivar devoid of the [Alpha]' subunits (Keburi), further experiments in HepG2 cells demonstrated a marked LDL-receptor activation by the [Alpha]' vs. [Alpha] subunit. A commercial isoflavone-free, heat-hydrolyzed soy concentrate (Croksoy), found effective in type II hypercholesterolemic patients, showed an LDL-receptor activation similar to that of the 7S globulin when incubated under the same conditions (Manzoni et al. 1998). To assess the final identity of the putative peptide (or peptides) responsible for the biochemical effect, experiments were performed in Hep G2 cells exposed to either synthetic peptides corresponding to specific sequences differing among the [Alpha] + [Alpha]' and [Beta] subunits or peptides coming from the in vitro digestion (trypsin + pepsin) of Croksoy. Moreover, the ability of the whole 7S globulin, its [Alpha] + [Alpha]' and [Beta] subunits, and whole Croksoy to interfere in the apoB secretion in the medium as well as in sterol biosynthesis was evaluated in the same model. Hep G2 cells were preincubated for 24 h at 37 [degrees] C in minimal essential medium with 5% lipoprotein-deficient serum in the presence or absence of synthetic and in vitro-produced peptides at different concentrations ([10.sup.-4] or [10.sup.-6] mol/L for synthetic peptides, 0.5 mg/mL for digested Croksoy). After addition of [I-LDL.sup.125], cells were incubated at 37 [degrees] C for a further 4 h to determine the uptake and degradation of LDL. Increased [I-LDL.sup.125] uptake (+41%) and degradation (+10%) vs. controls were shown after Hep G2 incubation with a synthetic peptide ([10.sup.-4] mol/L, MW 2271) corresponding to the 127-150 positions of the consensus sequence present in the [Alpha]' and not in the [Beta] subunit of the 7S globulin. Cells exposed to Croksoy enzyme digestion products showed a marked up-regulation of LDL receptors vs. that in controls as well as vs. HepG2 cells incubated with undigested Croksoy ([I-LDL.sup.125] uptake: +58% and +17%, respectively; [I-LDL.sup.125] degradation: +113% and +26%, respectively). Among soy-derived products, only the 7S soy globulin showed an inhibitory activity on apolipoprotein B secretion (-80% secretion) and 14C-acetate incorporation (-70, -60 and -48% into free and esterified cholesterol and triacylglycerol, respectively) when tested in Hep G2 cells at a concentration of 1.0 mg/mL. These findings support the hypothesis (Sirtori et al. 1998) that one or more peptides escaping detection in vivo may reach the liver after intestinal digestion, thus eliciting a cholesterol-lowering effect. Moreover, these data indicate that the protein moiety, devoid of isoflavone components, is responsible for the biochemical effect.