Antihypercholesterolemic Effects Research Articles

Antihypercholesterolemic effects of atorvastatin in patients previously receiving other 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors: an open-label study

Background: Atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was introduced in Japan in May 2000 with purportedly potent cholesterol-lowering effects. However, only a handful of studies have assessed its efficacy and tolerability in Japanese patients. Objective: This study was conducted to assess the efficacy and tolerability of atorvastatin in Japanese patients with hypercholesterolemia. Methods: Outpatients at the Hiramitsu Clinic who were receiving HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia were enrolled in this open-label study. Previous HMG-CoA reductase inhibitor therapy was discontinued, and patients were uniformly switched to atorvastatin 10 mg/d with no intervening washout period. Clinical laboratory values and serumlipid levels were used as safety indices, and achievement rates of target total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were used to assess efficacy. Target TC/HDL-C levels in patients with Japan Atherosclerosis Society category B hypercholesterolemia (patients with risk factors) and category C hypercholesterolemia (patients with coronary heart disease) were <200/<120 mg/dL and <180/<100 mg/dL, respectively. Results: Seventy-nine patients (23 men, 56 women; mean [±SD] age, 63.9 ± 11.2 years) completed the study. The mean duration of atorvastatin therapy was 62.7 ± 9.0 days. The switch to atorvastatin produced significant reductions in mean levels of TC (from 212.8 ± 29.0 mg/dL to 165.7 ± 24.8 mg/dL; P < 0.001) and LDL-C (from 135.2 ± 24.3 mg/dL to 92.2 ± 20.7 mg/dL; P < 0.001). Achievement rates of target TC and LDL-C levels dramatically improved in patients with Japan Atherosclerosis Society category B or C hypercholesterolemia. In patients with category B hypercholesterolemia, the achievement rate improved from 30.8% (20/65) at baseline to 87.7% (57/65) with regard to target TC levels and from 26.2% (17/65) to 92.3% (60/65) with regard to target LDL-C levels. In category C, the corresponding results were 30.0% (3/10) to 80.0% (8/10) and 10.0% (1/10) to 70.0% (7/10). No side effects sufficiently serious to warrant discontinuation of atorvastatin therapy were observed. Conclusion: In this study, atorvastatin was effective and well tolerated for the treatment of hypercholesterolemia in Japanese patients.

Dipyridamole prevents the coconut oil-induced hypercholesterolemia: A study on lipid plasma and lipoprotein composition

For a better understanding of the hypolipidemic function of dipyridamole, we have studied the comparative effects of diet supplementation with 10% coconut oil with and without dipyridamole on the lipid plasma and lipoprotein composition in chicks. This study was performed under postprandial and food-deprivation (12 h) conditions. Coconut oil induced a clear hypercholesterolemia under both feeding conditions. Simultaneous administration of dipyridamole maintained total and esterified cholesterol at levels similar to those observed in control animals sacrificed under postprandial conditions. Under these conditions, our results also show that dipyridamole significantly reduced cholesterol levels in all the chick plasma lipoproteins that were increased by coconut oil administration. Nevertheless, it should be emphasised that the levels of total cholesterol found in intermediate- and very-low-density lipoproteins were lower than in control. All chemical components of these fractions were significantly decreased by dipyridamole. The effects were not significant in chicks deprived of food. In conclusion, our results show that the hypercholesterolemia induced by coconut oil was prevented by dipyridamole. To our knowledge, this is one of the first reports on the antihypercholesterolemic effects of dipyridamole.

Evaluation of the Antihyperlipidemic Properties of Dietary Supplements

We reviewed the published literature regarding the antihyperlipidemic effects of dietary supplements. A search of MEDLINE database, EMBASE Drugs and Pharmacology database, and the Internet was performed, and pertinent studies were identified and evaluated. References from published articles and tertiary references were used to gather additional data. Published trials indicate that red yeast rice, tocotrienols, gugulipid, garlic, and soy protein all have antihypercholesterolemic effects. These supplements, as well as omega-3 fatty acids, also have antihypertriglyceridemic effects. In clinical trials none of the agents led to a reduction in low-density lipoproteins greater than 25%, suggesting modest efficacy. When recommending these supplements, clinicians should keep in mind that their long-term safety is not established and patients should be monitored closely.

EFFECT OF SILYMARIN AND SILIBININ-PHOSPHATIDYLCHOLINE COMPLEX ON PLASMA AND LIPOPROTEIN CHOLESTEROL, AND OXIDATION OF LDL IN RATS FED ON HIGH CHOLESTEROL DIET SUPPLEMENTED WITH CURRANT OIL

This work was aimed to investigate the currant oil-induced modulation of antihypercholesterolemic and LDLantioxidant effects of silymarin (SM), the extract from Silybum marianum L. containing silibinin as the mainflavonolignan, and of better bioavailable silibinin-phosphatidylcholine complex (SPC) in rats fed on high-cholesterol(HC) high-fat diet. Feeding of rats on HC-diet supplemented with 10 % of currant oil (from Ribes nigrum L.)containing polyunsaturated fatty acids (PUFA, 61.1% of n&#8211;6 and 15.4 % of n&#8211;3) and lower amounts of saturated(SFA, 7.7%) and monounsaturated (MUFA, 14.3%) fatty acids caused a significant decrease in plasma cholesterolassociated with a mild decrease in VLDL-C and an increase in HDL-C, when compared to rats fed on HC-diet with10 % of lard fat containing low amounts of PUFA (7.7% of n&#8211;6 and 0.7 % of n&#8211;3) and higher amounts of SFA(42.7%) and MUFA (47.5%). However, currant oil feeding led to the increased oxidizability of LDL. Silymarin, butnot SPC, was effective in prevention of development of dietary induced hypercholesterolemia in the both dietaryfats with slightly better result in diet containing the currant oil. On the other hand, SPC supressed more effectivelythan silymarin LDL oxidizability. The results suggest that antihypercholesterolemic effect of SM in rats fed on HCdietis improved by dietary currant oil, but the currant oil induces an increased oxidizability of LDL. This can besupressed by improvement of bioavailability of silibinin, as shown here for silibinin-phosphatidylcholine complex.

Role of dietary lysine, methionine, and arginine in the regulation of hypercholesterolemia in rabbits

These experiments were conducted to see whether the hypercholesterolemia produced by a diet enriched in lysine (Lys) and methionine (Met) can be reproduced by feeding these amino acids separately, and whether dietary arginine (Arg) counteracts their hypercholesterolemic effects. Another aim was to investigate the mechanisms involved in modulations of serum cholesterol levels by these amino acids. The results of this study, which were in agreement with the results of earlier experiments in our laboratory, showed that feeding a low-fat, cholesterol-free, semipurified amino acid diet enriched with Lys + Met to rabbits caused a marked increase in serum total and low density lipoprotein cholesterol and apolipoprotein B levels, whereas a similar diet enriched in essential ketogenic amino acids (EketoAA) resulted in a more moderate increase in these parameters. Supplementing the diet with either Lys or Met alone was also less effective in inducing hypercholesterolemia than increasing levels of both amino acids. Dietary Arg partially counteracted the hypercholesterolemic effect of Lys + Met but not that of the EketoAA or of Lys and Met fed separately. The growth performance of rabbits fed the Lys + Met diet was inferior to that of those fed the other diets. Liver total phospholipid levels and the ratio of phosphatidylcholine to phosphatidylethanolamine were higher in rabbits fed the Lys + Met-enriched diet than in those animals fed a diet in which Arg was supplemented. In conclusion, our results indicate that high levels of both Lys and Met are needed to cause a maximum elevation of serum cholesterol and that the moderately antihypercholesterolemic effect of Arg is seen only when both amino acids are supplemented. They also suggest that these essential amino acids may affect cholesterol metabolism partly through alteration of liver phospholipids.

Dietary Grape Seed Tannins Affect Lipoproteins, Lipoprotein Lipases and Tissue Lipids in Rats Fed Hypercholesterolemic Diets , ,

The effects of monomeric and polymeric grape seed tannins on rat plasma lipoproteins, lipoprotein lipase, hepatic lipase and aortic and hepatic lipid concentration were studied. Male Sprague-Dawley rats received either a normal diet (with no added cholesterol and no tannins), a control diet (hyper-cholesterolemic diet) or hypercholesterolemic diets supplemented with 2% tannin monomers or 2% polymers 3 or 9 wk. Plasma total cholesterol, triacylglycerol, LDL cholesterol and VLDL concentrations were significantly higher and the HDL cholesterol concentration lower in controls and in rats fed the diet supplemented with monomers compared with rats fed polymeric tannins at both time points. Lipoprotein lipase and hepatic lipase activities were significantly higher in control and in monomer-fed groups than in the polymer-fed group. Hepatic and aortic cholesterol and triacylglycerol concentrations were significantly higher in control rats and those fed monomers than in the polymer-fed group. Moreover, plasma HDL cholesterol and hepatic lipase activity were closely associated with low aortic cholesterol and triacylglycerol in rats fed polymeric tannins. These rats also exhibited greater fecal excretion of cholesterol and especially bile acids than the control or monomer-fed groups. Thus dietary grape seed tannins have a pronounced anti-hypercholesterolemic effect by enhancing reverse cholesterol transport and also by reducing intestinal cholesterol absorption and increasing bile acid excretion.

Antihypercholesterolemic effect of dipyridamole in chickens

The administration of a 4 mg/kg dose of dipyridamole daily in chickens fed a diet supplemented with 2% cholesterol reversed the hypercholesterolemic effects of the diet. In particular, it reduced the plasma cholesterol concentration in approximately 18%; the levels of very-low-density lipoproteins and intermediate-density lipoproteins and the liver cholesterol content. Although the mechanism was not fully elucidated, the increased excretion of cholesterol seemed to be responsible for the lipid lowering effect. When dipyridamole was administered in chickens fed the same diet without cholesterol no significant changes were observed. Inasmuch as the chicken lipoprotein metabolism differs in several aspects to human, the extrapolation of the hypocholesterolemic effect of dipyridamole to man must be made with care.

Pravastatin

Pravastatin is an HMG-CoA reductase inhibitor which reduces plasma cholesterol levels by inhibiting de novo cholesterol synthesis and increasing the receptor-mediated catabolism of low density lipoprotein (LDL). Several large multicentre placebo-controlled trials have shown that pravastatin reduces total and LDL-cholesterol levels in a dose-proportional manner in patients with familial or nonfamilial hypercholesterolaemia. Reductions in LDL-cholesterol levels reported in the largest study were 18% (10 mg/day), 23% (20 mg/day) and 31% (40 mg/day) after 12 weeks. Once-daily administration appears to be as effective as two daily doses. Pravastatin consistently increases HDL-cholesterol levels and decreases levels of total triglycerides but these changes are not dose dependent. At the study dosages used, the antihypercholesterolaemic effects of pravastatin were superior to those of bezafibrate and clinofibrate, and were similar to those of simvastatin, lovastatin, gemfibrozil and cholestyramine although in some studies a trend towards a superior effect with pravastatin was seen. Pravastatin did not reduce HDL-cholesterol like probucol, or increase triglyceride levels like cholestyramine. Combined treatment with pravastatin and cholestyramine or colestipol enhances the cholesterol-lowering effects of either drug administered alone and offsets the increase in total triglyceride levels seen with cholestyramine or colestipol therapy. Pravastatin is well tolerated during treatment of up to 24 months but longer term tolerability has not yet been established. The effect of provastatin on cardiovascular events related to elevated plasma cholesterol levels is under investation in several large scale regression and primary and secondary prevention trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Elimination of toxicity from diets containing alfalfa seeds

Cynomolgus macaques were fed autoclaved alfalfa seeds for up to 1 yr. There were no humoral signs of a syndrome resembling systemic lupus erythematosus. The data are in contrast to those previously reported in monkeys fed raw alfalfa seeds, in which a systemic lupus erythematosus-like syndrome was induced in a shorter interval. The autoclaved seeds retained antihypercholesterolaemic effects.

Dietary protein-dependent modification of serum cholesterol level in rats. Significance of the arginine/lysine ratio.

Male rats were fed for 4 weeks cholesterol-free diets containing proteins from different sources, milk, fish, egg yolk, soybean, rice and peanut. The antihypercholesterolemic effect of vegetable proteins compared to animal proteins was certified. There was a negative correlation (gamma = -0.74) between the serum cholesterol level and the arginine/lysine ratio of dietary protein, suggesting a role of this ratio in determining the serum cholesterol level. In general, the fasting level of circulating insulin was lower whereas that of glucagon was higher on feeding vegetable proteins, thus resulting in a fall of the insulin/glucagon ratio. Changes in the hormonal status may be relevant to the protein effect.

COMPACTIN: antihypercholesterolaemic effects in combination with cholestyramine

COMPACTIN: antihypercholesterolaemic effects in combination with cholestyramine

Studies on the Mechanism of Antihypercholesterolemic Action of Soy Protein and Soy Protein-Type Amino Acid Mixtures in Relation to the Casein Counterparts in Rats

Given evidence of a hypocholesterolemic effect in rats, soy protein compared with casein showed the following effects on cholesterol dynamics: a) lower cholesterol absorption and greater fecal steroid excretion, b) more rapid turnover of serum cholesterol, c) a marked size reduction of the rapidly exchangeable cholesterol pool (pool A) through a significant increase in the removal rate in that compartment without influencing the production rate, and d) greater hepatic sterogenesis both in vitro and in vivo. In contrast, the amino acid mixture equivalent to soy protein compared with casein-type mixture showed: a) no effects on cholesterol absorption and fecal steroid excretion, b) no effects on the turnover of serum cholesterol, c) the reduction of pool A size as a result of decreased production, and d) the reduction of hepatic steroidogenesis in vitro, but not in vivo. These results indicate that decreased intestinal absorption of cholesterol and increased fecal steroid excretion are primarily responsible for the antihypercholesterolemic effect of soy protein compared with casein. The fecal loss of steroids far outweighs the activation of hepatic steroidogenesis. In the case of the soy protein-type amino acid mixture, the depression of hepatic cholesterol synthesis seems accountable for reducing serum cholesterol levels.soybean protein casein cholesterol absorption steroid excretion cholesterol turnover steriodogenesis

Effects of dietary soybean globulins on plasma and liver lipids and on fecal excretion of neutral sterols in rats.

Effects of low-fat (1% corn oil) diets containing an isonitrogenous level (3.2%) of either casein, soybean protein isolate or three soybean globulin fractions (total, 11S and 7S globulins) on plasma and liver lipids and on the excretion of fecal neutral sterols were examined in rats. When diets free of cholesterol were fed, the concentration of plasma cholesterol was significantly lower in all groups of rats given different soybean proteins than in the animals given casein. 11S globulin tended to produce a lower level of plasma cholesterol as compared with the 7S counterpart. Although the net decrease due to feeding plant proteins in high density lipoprotein cholesterol was to some extent greater than that of very low and low density lipoprotein cholesterol, the percentage of the former to total cholesterol remained in the normal range. The concentration of liver cholesterol appeared to be lower in rats given soybean proteins. Rats fed soybean globulins, as compared with the animals fed casein, tended to excrete larger amounts of neutral sterol into the feces. These soybean-effects disappeared when cholesterol and cholic acid were added to diets. The results indicated that the antihypercholesterolemic effect of soybean protein was attributable to protein per se, and not to the carbohydrate components which were associated with the protein preparation.

Antihypercholesterolemic Studies with Sterols: β-Sitosterol and Stigmasterol

Stigmasterol, which differs from β-sitosterol by unsaturation at C22, was tested for antihypercholesterolemic activity under an experimental protocol that gave the results expected with β-sitosterol and cholestyramine. In terms of serum cholesterol, stigmasterol had a barely significant antihypercholesterolemic effect while exhibiting no obvious effect on the heart or liver. It was concluded that saturation of the side chain, at least at C22, is important in conferring antihypercholesterolemic activity on a sterol.

Anti-hypercholesterolemic effect of a sulfur containing amino acid, S-methyl-L-cysteine sulfoxide, isolated from cabbage.

Die Antihypercholesterinwirkung der aus dem Kohl isolierten S-Methylcysteinsulfoxide (SMCS) wurde untersucht. Bei Ratten mit experimentell induzierter Hypercholesterinamie kam es zu einem Abfall der Cholesterinwerte im Blut und in der Leber.

Evidence for a Nonabsorptive Antihypercholesterolemic Action of Phytosterols in the Chicken

Soy sterols were administered orally (1% of diet) and subcutaneously (20 mg/day) to chicks with hypercholesterolemia induced by feeding a low protein, cholesterol-containing diet (8% protein, 5% medium-chain triglycerides (MCT), and 0.5% cholesterol). Sterol levels and patterns in plasma, tissues, and excreta were determined by spectrophotometric and gas-liquid chromatographic analysis. Strong evidence for a nonabsorptive antihypercholesterolemic action of soy sterols included: similar liver cholesterol reductions for both oral and subcutaneous soy sterol administration, and reduction by subcutaneous soy sterol injection of endogenous hypercholesterolemia due to ova resorption induced by feeding 0.04% Nicarbazin to laying hens. Estimation of absorptive effects from intestinal wall concentrations of cholesterol, and subtraction of these effects from total antihypercholesterolemic effects, indicated approximately equal absorptive and nonabsorptive activity from oral soy sterols and a predominantly nonabsorptive effect of subcutaneously administered soy sterols. A comparison of the oral administration of 1% soy sterols and 1% wheat germ sterols to chicks given a hypercholesterolemic diet (25% whole egg powder) resulted in a greater antihyper-cholesterolemic response from soy sterols which contain more campesterol (36%) than from wheat germ sterols (25% campesterol). Campesterol appears to be the major active component of soy and wheat sterols in relation to their antihypercholesterolemic activity.

Anti-hypercholesterolemic effect of dehydroepiandrosterone in rats.

SummaryDehydroepiandrosterone (DHA) and 3α-methoxy − 17α−methyl− 5α −androstane−17α−01 (SC-12790) were studied for their anti-hypercholesterolemic and thyromimetic activities. The following findings were established: 1. DHA (5 mg/kg/d per os for 10 days) was found to be an anti-hypercholesterolemic agent which prevented increase in the serum cholesterol level (SCL) of rats made hypercholesterolemic by propylthiouracil (PTU) treatment. It was also found that the same dose of DHA given over a period of 21 days prevented an increase in SCL in rats made hypercholesterolemic by combined PTU and cholesterol feeding. DHA, however, did not reduce the SCL of normal rats. 2. SC-12790, when given under the same experimental conditions as DHA, did not reduce the SCL of hypercholesterolemic rats. 3. DHA did not produce any change in thyroid weight as did exogenous TSH and T-3. It seems that the anti-hypercholesterolemic effect of DHA cannot be explained by a thyromimetic activity. These findings are of clinical import...

Effect of hyaluronidase on experimental hypercholesterolemia in rabbits and rats and atheromatosis in rabbits.

Summary1. Subcutaneous or intravenous injection of hyaluronidase depressed hypercholesterolemia in rabbits and rats. 2. Intraperitoneal injection of hyaluronic acid prevented hypercholesterolemia in nephrotic rats. 3. Hyaluronidase facilitated general lipidoses and aggravated atheromatosis in rabbits. 4. The advisability of indiscriminately lowering the blood cholesterol level in hypercholes-terolemics is questioned. 5. The antihyper-cholesterolemic effect of hyaluronidase was abolished when specific antibodies to the enzyme developed. 6. Endogenous experimental hypercholesterolemia in rabbits does not depend on the presence of the adrenals.