Reduced Cholesterol Concentrations Research Articles

The change of composition as well as the concentration of serum Lp(a) can be a sign for end-stage renal failure

Plasma sphingomyelin (SM) has been suggested as a risk factor for coronary heart disease independent of cholesterol levels. A decrease of SM in lipoproteins is known to improve the activities of lecithin:cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL) in vitro. Inhibition of SM biosynthesis may reduce lipoprotein SM content and thus improve cholesterol distribution in lipoproteins by enhancing reverse cholesterol transport and clearance of triglyceride-rich lipoproteins. To examine this hypothesis, ApoE KO mice were fed a western diet and treated for 4 weeks with various concentrations of myriocin, a specific inhibitor of serine palmitoyltransferase. Myriocin treatment lowered plasma cholesterol and TG levels in a dose-dependent manner. In addition, myriocin treatment reduced cholesterol contents in VLDL and LDL and elevated HDL-cholesterol. Observed lipid-lowering effects of myriocin were associated with suppression of HMG CoA reductase and fatty acid synthase via reduced levels of SREBP-1 RNA and protein. Induction of apoAI and lecithin:cholesterol acytransferase (LCAT) in the liver by myriocin was associated with an increased HDL. Lesion area and macrophage area were also diminished in the cuffed femoral artery of ApoE KO mice. In conclusion, inhibition of sphingolipid biosynthesis can be a novel therapeutic target for dyslipidemia and atherosclerosis.

Dietary supplementation with bean extract improves lipid profile in overweight and obese subjects

Objectives The aim of this study was to evaluate the long-term effects of a dietary supplementation of bean extract on serum lipids, nutritional parameters, and fat excretion in feces. Methods Sixty-two overweight and obese (body mass index > 25 kg/m 2) volunteers were randomized to receive the dietary supplement ( n = 31, supplement group) or the placebo ( n = 31, placebo group). There were 41 women and 21 men, ages 22 to 66 years. Two capsules of a dietary supplement or a placebo were administered three times daily for 3 mo. The supplement group was then invited to participate in an open-label study for 9 mo. Twenty-four subjects (7 men and 17 women) were randomized to receive two or four capsules of the supplement three times daily. Lipids and nutritional blood parameters were measured at baseline, after 3 mo, and at 12 mo. Excretion of fat in feces was measured. Results At 3 mo, reduction in serum concentration of cholesterol was found in the supplement group but not in the placebo group. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triacylglycerols in serum did not change in either group. In the 9-mo open-label study, no further reduction in serum cholesterol was observed. Low-density lipoprotein and the ratio of low- to high-density lipoprotein decreased, whereas triacylglycerols remained unchanged. Serum vitamin B12 and folic acid decreased but remained within the normal range. Ferritin and albumin in serum remained unchanged. No differences were observed in serum lipids and nutritional parameters between groups. The bean extract significantly increased fat excretion in feces. Conclusions In conclusion, this dietary supplementation improved lipoprotein profile and enhanced fat excretion in feces in overweight and obese subjects.

Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans

Although supplementing the diet with large quantities of phytosterols reduces cholesterol absorption and LDL-cholesterol concentrations, very little is known about the smaller amounts of phytosterols present naturally in food. Vegetable oils are the richest dietary source of phytosterols; corn oil contains 0.77% phytosterols by weight. We tested the hypothesis that removing phytosterols from corn oil would increase cholesterol absorption when measured in single-meal tests containing corn oil as a source of fat. Free and esterified phytosterols were removed from corn oil on a kilogram scale by a new technique of competitive saturation adsorption to silica. Healthy subjects with a mean (+/-SEM) serum cholesterol concentration of 5.10 +/- 0.18 mmol/L received an otherwise sterol-free test breakfast on 2 occasions 2 wk apart that contained 35 mg hexadeuterated cholesterol and 30-35 g of a corn oil preparation. The plasma enrichment of tracer was measured by negative ion mass spectrometry. Cholesterol absorption was 38.0 +/- 10.2% higher after consumption of the sterol-free corn oil than after consumption of commercial corn oil with an identical fatty acid content (P = 0.005; n = 10). When corn oil phytosterols were added back to sterol-free corn oil at a concentration of 150 mg/test meal, cholesterol absorption was reduced by 12.1 +/- 3.7% (P = 0.03; n = 5) and by 27.9 +/- 9.1% (P = 0.01; n = 10) after inclusion of 300 mg phytosterols. Phytosterols comprising < 1% of commercial corn oil substantially reduced cholesterol absorption and may account for part of the cholesterol-lowering activity of corn oil previously attributed solely to unsaturated fatty acids.

Disparity between angiographic regression and clinical event rates with hydrophobic statins

Statins are effective at lowering blood cholesterol concentration, and are given to patients with hypercholesterolaemia or hyperlipidaemia. Reduction of cholesterol concentration in serum can delay, or even regress, atherosclerotic lesions, leading to diminution of risk of cardiovascular disease. Results of studies have shown that the beneficial effects of statins depend not only on lowering cholesterol but also on many other factors. Production of mevalonic acid, a precursor of various essential substances for cell function (figure), is inhibited by hydrophobic statins.

Plant sterols alter bile acid metabolism and reduce cholesterol absorption in hamsters fed a beef-based diet

This study examined the cholesterol-lowering properties of dietary plants sterols (PS) when consumed in a beef-based diet. Male Syrian hamsters were fed freeze-dried ground beef supplemented with maltodextrin, vegetable oil, vitamins, minerals, and soybean sterol esters at 0.0, 0.3, 1.0, or 3.0% sterol by weight of the diet. After 4 weeks, plasma and liver total cholesterol concentrations were significantly and incrementally reduced at all levels of dietary PS tested compared to no dietary PS. Cholesterol absorption was also significantly reduced by dietary PS, resulting in greater fecal excretion of neutral steroids. Total bile acid excretion was also significantly increased with PS feeding. A novel finding in the present study was that PS feeding caused an alteration in the gallbladder bile acid profile, resulting in a significantly lower hydrophobicity index. The present study demonstrates that the consumption of ground beef containing PS can significantly lower plasma cholesterol concentration at relatively low doses, indicating that ground beef can be used as a functional food to lower cholesterol while providing superior nutritional benefits over the high fat PS-containing margarines and salad dressings currently available.

Phytosterols in human nutrition.

Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. They are absorbed only in trace amounts but inhibit the absorption of intestinal cholesterol including recirculating endogenous biliary cholesterol, a key step in cholesterol elimination. Natural dietary intake varies from about 167-437 mg/day. Attempts to measure biological effects in feeding studies have been impeded by limited solubility in both water and fat. Esterification of phytosterols with long-chain fatty acids increases fat solubility by 10-fold and allows delivery of several grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester reduces low density lipoprotein cholesterol by 10%, and little difference is observed between Delta(5)-sterols and 5alpha-reduced sterols (stanols). Phytosterols can also be dispersed in water after emulsification with lecithin and reduce cholesterol absorption when added to nonfat foods. In contrast to these supplementation studies, much less is known about the effect of low phytosterol levels in the natural diet. However, reduction of cholesterol absorption can be measured at a dose of only 150 mg during otherwise sterol-free test meals, suggesting that natural food phytosterols may be clinically important. Current literature suggests that phytosterols are safe when added to the diet, and measured absorption and plasma levels are very small. Increasing the aggregate amount of phytosterols consumed in a variety of foods may be an important way of reducing population cholesterol levels and preventing coronary heart disease.

Effects of different fibre sources and fat addition on cholesterol and cholesterol‐related lipids in blood serum, bile and body tissues of growing pigs

Knowledge is limited on the efficacy of hindgut-fermentable dietary fibre to reduce blood, bile and body tissue cholesterol levels. In three experiments with growing pigs the effects of different kinds and levels of bacterially fermentable fibre (BFS) on cholesterol metabolism were examined. Various diets calculated to have similar contents of metabolizable energy were supplied for complete fattening periods. In the first experiment, a stepwise increase from 12 to 20% BFS was performed by supplementing diets with fermentable fibre from sugar beet pulp (modelling hemicelluloses and pectin). Beet pulp, rye bran (modelling cellulose) and citrus pulp (pectin) were offered either independently or in a mixture in the second experiment. These diets were opposed to rations characterized in carbohydrate type by starch either mostly non-resistant (cassava) or partly resistant (maize) to small intestinal digestion. The third experiment was planned to explore the interactions of BFS from citrus pulp with fat either through additional coconut oil/palm kernel oil blend or full-fat soybeans. In all experiments the increase of the BFS content was associated with a constant (cellulose) or decreasing (hemicelluloses, pectin) dietary proportion of non-digestible fibre. In experiment 1 an inverse dose-response relationship between BFS content and cholesterol in blood serum and adipose tissue as well as bile acid concentration in bile was noted while muscle cholesterol did not respond. In experiment 2 the ingredients characterized by cellulose and hemicelluloses/pectin reduced cholesterol-related traits relative to the low-BFS-high-starch controls whereas, except in adipose tissue cholesterol content, the pectinous ingredient had the opposite effect. However, the changes in serum cholesterol mainly affected HDL and not LDL cholesterol. Adipose tissue cholesterol also was slightly lower with partly resistant starch compared to non-resistant starch in the diet. Experiment 3 showed that the use of citrus pulp increased serum cholesterol concentrations when levels were low in the corresponding low-BFS diets (low-fat and soy bean diets), but caused no further increase in the coconut-oil/palm kernel oil blend diet. From the present results it seems that fermentable hemicelluloses have a more favourable effect of decreasing metabolic cholesterol and related traits than hardly digestible fibre, fermentable cellulose or, particularly, pectin. Furthermore, some types of fibre expressed a certain potential to reduce cholesterol content of fat pork and pork products by up to 10% (experiment 1) and 25% (experiment 2).

Cholesterol absorption

Cholesterol absorption is a key regulatory point in human lipid metabolism because it determines the amount of endogenous biliary as well as dietary cholesterol that is retained, thereby influencing whole body cholesterol balance. Plant sterols (phytosterols) and the drug ezetimibe reduce cholesterol absorption and low-density lipoprotein cholesterol in clinical trials, complementing the statin drugs, which inhibit cholesterol biosynthesis. The mechanism of cholesterol absorption is not completely known but involves the genes ABC1, ABCG5, and ABCG8, which are members of the ATP-binding cassette protein family and appear to remove unwanted cholesterol and phytosterols from the enterocyte. ABC1 is upregulated by the liver X (LXR) and retinoid X (RXR) nuclear receptors. Acylcholesterol acytransferase-2 is an intestinal enzyme that esterifies absorbed cholesterol and increases cholesterol absorption when dietary intake is high. New clinical treatments based on better understanding of absorption physiology are likely to substantially improve clinical cholesterol management in the future.

Baseline intestinal absorption and synthesis of cholesterol regulate its response to hypolipidaemic treatments in coronary patients

Baseline cholesterol metabolism was hypothesized to regulate responses of cholesterol synthesis and absorption, and serum cholesterol lowering to hypolipidaemic treatment. Thus, serum cholesterol and non-cholesterol sterols were measured before and during long-term simvastatin treatment (inhibition of cholesterol synthesis) and subsequent combination of statin with plant stanol ester margarine (inhibition of cholesterol absorption) consumption in subjects with low ( n=15) and high ( n=15) absorption of cholesterol, defined by respective low and high baseline ratios of serum cholestanol to cholesterol. Cholesterol synthesis (defined by precursors of cholesterol) was markedly reduced by the long-term statin treatment in both groups, but more extensively in the low than high absorption group ( P<0.05), yet the respective serum cholesterol reductions were similar. From among the absorption markers, sitosterol and cholestanol ratios were correspondingly increased more in the low than in the high absorption group. Plant stanol ester margarine consumption, combined with chronic statin treatment, further lowered the serum cholesterol level ( P<0.001) only in the high absorption group. The sum of cholesterol absorption markers was reduced more ( P<0.05) in the high than in the low absorption group, while the non-significant serum cholesterol reduction of the low absorption group was associated with relatively high increase of cholesterol synthesis. Thus, stanol ester margarine combined with chronic simvastatin treatment reduces cholesterol absorption and serum cholesterol more consistently in subjects with high than low baseline absorption of cholesterol. The profile of baseline cholesterol metabolism determines the changes in synthesis and absorption of cholesterol to hypolipidaemic treatments, but affects less differently serum cholesterol level.

Evidence that leptin contributes to intestinal cholesterol absorption in obese (ob/ob) mice and wild-type mice.

In the present study, the effect of leptin on intestinal cholesterol absorption was investigated in C57 BL/6 OlaHsd Lep(ob)/Lep(ob) obese (ob/ob) mice and lean C57 BL/6 (wild-type) mice. Animals were treated either with or without recombinant leptin for 2 wk. Cholesterol absorption was measured by the constant isotope feeding method and indirectly by the ratio of campesterol to cholesterol in serum. In ob/ob mice, cholesterol absorption was significantly higher compared to wild-type mice [83.4 +/- 2.3% (SD) vs. 77.6 +/- 1.5%, P < 0.01]. Treatment with leptin significantly reduced cholesterol absorption in both ob/ob and wild-type mice by 8.5 (P < 0.001) and 5.2% (P < 0.05), respectively. Serum concentrations of campesterol and the ratio of campesterol to cholesterol in ob/ob mice were significantly higher compared to wild-type mice (2.2 +/- 0.3 mg/dL vs. 1.2 +/- 0.3 mg/dL, P< 0.001; and 36.8 +/- 2.8 microg/mg vs. 28.0 +/- 3.3 microg/mg, P < 0.001). After treatment of ob/ob mice with leptin, concentrations of campesterol and its ratio to cholesterol were significantly lower (2.2 +/- 0.3 mg/dL vs. 1.0 +/- 0.2 microg/mg, P < 0.001; and 36.8 +/- 2.8 microg/mg vs. 13.2 +/- 2.2 microg/mg, P < 0.001, respectively). In wild-type mice, the ratio of campesterol to cholesterol in serum was also significantly lower after treatment with leptin (28.0 +/- 3.3 microg/mg vs. 22.6 +/- 5.0 microg/mg, P < 0.05). A significant positive correlation (r = 0.701, P < 0.01) between cholesterol absorption and the ratio of campesterol to cholesterol in serum was found. It is concluded that leptin contributes to intestinal cholesterol absorption in ob/ob mice and lean wild-type mice.

A Review : Dietary Fiber Biochemical Inductions and Its Hypocholesterolemic Effects

Most people already know that dietary_ fiber can have detrimental or beneficial effects on health, primarily with regard to nutritional status. In this writing one of the beneficial effects of the consumption ofdietary fiber especially its hypocholesterolemic effect will be discussed. Many research papers have already showed regarding the connection between the biochemical induction of soluble fiber and the hypocholesterolemic effect of soluble fiber. In these investigations treatments were given to various kinds of experimental animals and to humans as experimental subjects. Kinds of foods were used as sources of fiber. The researchers were able to discover a variety of biochemical inductions that led to a hypocholesterolomic effect and were able to lower the cholesterol concentration in various kinds of lipoprotein fractions. Biochemical inductions discovered were, among others: fiber making food difficult to be digested, thereby inhibiting lipid absorption, decreasing cholesterol synthesis, increase of cholesterol excretion through the bile, decreasing of Apo B synthesis in the liver, decrease of the mRNA Apo B concentration of the liver, decrease in mRNA Apo A-I and mRNA Apo A-IV concentration in intestinal cells, decrease in HMG-CoA reductase activity and decrease in insulin secretion. Every soluble .fiber from specific sources of dietary fiber produced a certain biochemical induction and also hypocholesterolemic effect to a certain lipoprotein fraction. The concentration of total cholesterol and cholesterol in lipoproteins containing Apo B, and the LDL-C: HDL-C ratio are all lowered. Thus the patient is able to choose as a source offiber, the food of his or her preference appropriate to his or her kind of hypercholesterolemic disorder, with the goal of reduction of cholesterol concentration.

The Diet1 Locus Confers Protection against Hypercholesterolemia through Enhanced Bile Acid Metabolism

The C57BL/6ByJ (B6By) mouse strain is resistant to diet-induced hypercholesterolemia and atherosclerosis, despite its near genetic identity with the atherosclerosis-susceptible C57BL/6J (B6J) strain. We previously identified a genetic locus, Diet1, which is responsible for the resistant phenotype in B6By mice. To investigate the function of Diet1, we compared mRNA expression profiles in the liver of B6By and B6J mice fed an atherogenic diet using a DNA microarray. These studies revealed elevated expression levels in B6By liver for key bile acid synthesis proteins, including cholesterol 7alpha-hydroxylase and sterol-27-hydroxylase, and the oxysterol nuclear receptor liver X receptor alpha. Expression levels for several other genes involved in bile acid metabolism were subsequently found to differ between B6By and B6J mice, including the bile acid receptor farnesoid X receptor, oxysterol 7alpha-hydroxylase, sterol-12alpha-hydroxylase, and hepatic bile acid transporters on both sinusoidal and canalicular membranes. The overall expression profile of the B6By strain suggests a higher rate of bile acid synthesis and transport in these mice. Consistent with this interpretation, fecal bile acid excretion is increased 2-fold in B6By mice, and bile acid levels in blood and urine are elevated 3- and 18-fold, respectively. Genetic analysis of serum bile acid levels revealed co-segregation with Diet1, indicating that this locus is likely responsible for both increased bile acid excretion and resistance to hypercholesterolemia in B6By mice.

Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet

Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia.

Evidence for Distinct Cholesterol Domains in Fiber Cell Membranes from Cataractous Human Lenses

Previous studies in our laboratory have provided direct evidence for the existence of distinct cholesterol domains within the plasma membranes of human ocular lens fiber cells. The fiber cell plasma membrane is unique in that it contains unusually high concentrations of cholesterol, with cholesterol to phospholipid (C/P) mole ratios ranging from 1 to 4. Since membrane cholesterol content is disturbed in the development of cataracts, it was hypothesized that perturbation of cholesterol domain structure occurs in cataracts. In this study, fiber cell plasma membranes were isolated from both normal (control) and cataractous lenses and assayed for cholesterol and phospholipid. Control and cataractous whole lens membranes had C/P mole ratios of 3.1 and 1.7, respectively. Small angle x-ray diffraction approaches were used to directly examine the structural organization of the cataractous lens plasma membrane versus control. Both normal and cataractous oriented membranes yielded meridional diffraction peaks corresponding to a unit cell periodicity of 34.0 A, consistent with the presence of immiscible cholesterol domains. However, comparison of diffraction patterns indicated that cataractous lens membranes contained more pronounced and better defined cholesterol domains than controls, over a broad range of temperature (5-40 degrees C) and relative humidity (52-92%) levels. In addition, diffraction analyses of the sterol-poor regions of cataractous membranes indicated increased membrane rigidity as compared with control membranes. Modification of the membrane lipid environment, such as by oxidative insult, is believed to be one potential mechanism for the formation of highly resolved cholesterol domains despite significantly reduced cholesterol content. The results of this x-ray diffraction study provide evidence for fundamental changes in the lens fiber cell plasma membrane structure in cataracts, including the presence of more prominent and highly ordered, immiscible cholesterol domains.

The cholesterol absorption inhibitor, ezetimibe, decreases diet-induced hypercholesterolemia in monkeys

Ezetimibe (1-(4-fluorophenyl)-(3 R)-[3-(4-fluorophenyl)-(3 S)-hydroxypropyl]-(4 S)-(4-hydroxyphenyl)-2-azetidinone) potently and selectively inhibits the intestinal absorption of cholesterol, thereby reducing plasma cholesterol in preclinical models of hypercholesterolemia. In rhesus monkeys fed a diet containing 375 mg/day of cholesterol, 0.1 mg/kg of ezetimibe completely prevented the doubling of plasma cholesterol normally induced under these dietary conditions (ED 50=0.0005 mg/kg). Low-density lipoprotein cholesterol (LDL) was dose-dependently reduced, while high-density lipoprotein cholesterol (HDL) and plasma triglyceride were unchanged. A single dose of an ezetimibe analog administered to cynomolgus monkeys fed a single cholesterol-containing meal caused a significant reduction (−69%) of cholesterol in chylomicrons during the postprandial phase without affecting triglyceride content. In rhesus monkeys, apolipoprotein (apo) B 48 concentrations in chylomicrons did not differ between control and the ezetimibe analog, but apo B 100 was significantly reduced in LDL (−41%). These data indicate that these cholesterol absorption inhibitors reduce cholesterol content in chylomicrons, which indirectly leads to a decrease in LDL cholesterol and particle number.

Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomised, double-blind trial

High LDL-cholesterol is a risk factor for atherosclerosis. We aimed to determine whether aggressive cholesterol lowering with statins was more effective than conventional statin treatment in this disease. We investigated the effect of high-dose atorvastatin on carotid atherosclerosis progression. We did a randomised, double-blind clinical trial in 325 patients with familial hypercholesterolaemia. Patients were given either atorvastatin 80 mg (n=160) or simvastatin 40 mg (n=165) daily, on an intent-to-treat basis. The primary endpoint was the change of carotid intima media thickness (IMT), as measured by quantitative B-mode ultrasound, over 2 years. The overall baseline IMT, combining the measurements of the common and internal carotid artery and the carotid bifurcation on both sides, was 0.93 mm (SD 0.22) and 0.92 mm (0.21) in the atorvastatin and simvastatin groups, respectively. After treatment with atorvastatin for 2 years, IMT decreased (-0.031 mm [95% CI -0.007 to -0.055]; p=0.0017), whereas in the simvastatin group it increased (0.036 [0.014-0.058]; p=0.0005). The change in thickness differed significantly between the two groups (p=0.0001). Atorvastatin showed greater reductions in cholesterol concentrations than did simvastatin. HDL-cholesterol concentrations increased in both groups. Both drugs were equally well tolerated. Our results show that aggressive LDL-cholesterol reduction by atorvastatin was accompanied by regression of carotid intima media thickness in patients with familial hypercholesterolaemia, whereas conventional LDL lowering was not.

Pharmacological Properties of R-755, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, in Cholesterol-Fed Rats, Hamsters and Rabbits

R-755 (N-(2,6-diethylphenyl)-#’-[3-(2-methylphenyl)-6,7-dihydro-5H-cyclopenta[f][l]benzo-thiophen-2-yl]urea), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, has been characterized in vitro, ex vivo and in vivo. R-755 potently inhibited ACAT activities, with IC50 values from 2.5 to 64 nM, in rabbit intestinal microsomes and several cell lines (CaCo-2, THP-1 and J774A.1 cells). R-755 reduced serum cholesterol and triglyceride levels and liver cholesterol contents in cholesterol-fed rats, hamsters and rabbits. Rabbits were fed a high cholesterol diet for 2 weeks and further fed the same diet containing R-755 for 2 weeks. R-755 dose-dependently reduced cholesterol content and ACAT activity in the aorta. When phorbol 12-myristate 13-acetate-treated THP-1 and J774A.1 cells were incubated in the medium containing 20% of serum from rats administered R-755, the ACAT activities of the cells were inhibited. Rabbits were fed a high cholesterol diet for 8 weeks to establish aortic atherosclerosis and then fed a normal diet with or without R-755 for 8 weeks. R-755 dose-dependently reduced the surface area with atherosclerotic involvement and cholesterol contents in the aorta, although plasma cholesterol level did not differ from that in the control group. These results suggest that R-755 is a potent hypolipidemic agent and has a direct antiathero-sclerotic activity at the arterial wall.

The association of low serum cholesterol with depression and suicidal behaviours: new hypotheses for the missing link.

Several observational studies indicate that reduction of serum cholesterol levels is related to an increase in violent deaths and suicide but the nature of this possible relationship remains unclear. Many confounding factors, e.g. poor health, depression and loss of appetite may play a role in the apparent relationship between serum cholesterol levels and suicide. Two separate phenomena should be considered: lowering total cholesterol and low total cholesterol. This review considers the evidence from epidemiological studies on serum cholesterol lowering and psychiatric disturbances. The available evidence does not seem to substantiate the view that large-scale intervention to reduce cholesterol concentrations could lead to more violent and aggressive behaviour, and generally greater unhappiness. In recent trials using statin treatment, there were slightly fewer deaths from accidents and suicide in the treated group compared with the placebo group. We believe that clinicians should not be deterred from prescribing cholesterol-lowering drugs, to reduce the risk of death from coronary heart disease, when they are indicated.

Are phytoestrogens a "natural alternative" to estrogen replacement therapy?

Phytoestrogens, compounds derived from plants and converted into weak estrogenic substances in the gastrointestinal tract, are heavily promoted as the “natural alternative” to estrogen replacement therapy for postmenopausal women or women who have undergone a hysterectomy. The use of soy products rich in these phytoestrogens is now widespread in the United States. Isoflavones are the best-known phytoestrogens, but only a few studies have been done of their effects. The results of these studies have not been promising. Their supposed benefits are based on the observation that the incidence of certain disorders or diseases affected by estrogen status—perimenopausal syndrome, cardiovascular disease, and osteoporosis—is lower in populations with diets high in phytoestrogens. There is no laboratory or clinical evidence to support claims of benefit or even to demonstrate hormonal effects of phytoestrogens. A recent commentary on phytoestrogens concluded: “Until such time as there are data from controlled studies on the dangers as well as the benefits of plant extracts, the drawing of firm conclusions about the long-term benefits of increased phyto-oestrogen consumption is unwise.”1(p164) For most of the world's population, the principal source of phytoestrogen is soy in the diet. Since October 1999, the Food and Drug Administration has allowed food companies to claim that soy protein reduces cholesterol concentrations and the risk of heart disease. Although consuming soy products seems to reduce cholesterol levels, there may be an increased cancer risk associated with their isoflavone components; this risk may be heightened when isoflavones alone are offered in the form of dietary supplements. The highest levels of naturally occurring isoflavones are found in soy beverages, cooked soybeans, and tempeh (textured fermented soy). One gram of soybeans contains about 1 mg of isoflavones. Some nutritional experts are willing to assume that a daily intake of 50 mg of isoflavones is safe. The typical daily consumption in Japan is 25 to 50 mg of isoflavones. Dietary supplements, however, can contain more than 85 mg of isoflavones in a single unit, and some manufacturers advise taking 2 a day. Soy protein concentrate powders have as much as 160 mg of isoflavones per serving. According to some evidence, large quantities of isoflavones may increase the risk of breast cancer.

Ten year audit of secondary prevention in coronary bypass patients

Treatment of risk factors in patients who have had coronary artery bypass surgery improves their prognosis. 1 2 A national survey performed in Britain in 1994 showed that risk factor...