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Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet

The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugarcane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50 mg/kg) the increases in plasma total cholesterol and LDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125I-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t1/2) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.

Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors.

This study was undertaken to evaluate the efficacy, safety, and tolerability of policosanol, a new cholesterol‐lowering drug, in patients with type II hypercholesterolemia and additional coronary risk factors.

Policosanol Modulates HMG-CoA Reductase Activity in Cultured Fibroblasts

BACKGROUND Cholesterol biosynthesis is strictly controlled by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. METHODS Transfer of cultured fibroblasts to a lipid-depleted medium (LDM) up-regulates the enzyme levels. This, in turn, is followed by an accelerated biosynthesis of cholesterol. RESULTS Exposure of Vero fibroblasts to LDM and policosanol (0.5-50 microg/mL), a new cholesterol-lowering drug purified from sugarcane (Saccharum officinarum L.) wax, decreased in a dose-dependent manner cholesterol biosynthesis from [14C]-acetate and 3H-water, but not from [14C]-mevalonate. CONCLUSIONS This suggests an effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis. When enzyme activity was measured in the presence of various concentrations of policosanol (0.5-50 microg/mL), reductase was not suppressed. Therefore, there was no evidence for a competitive or noncompetitive inhibition of enzyme activity. However, after treatment of intact cells with policosanol (50 microg/mL) in the presence of LDM, a suppressive effect on enzyme activity was observed, suggesting a modulatory effect of policosanol on reductase activity. The previous inhibition of enzyme up-regulation by policosanol suggests to date a depression of de novo synthesis of HMG-CoA reductase and/or stimulation of its degradation. However, the exact mechanism by which policosanol inhibits the activity of HMG-CoA reductase still remains unclear. Further studies are needed to clarify the precise mechanism of its inhibitory action on cholesterol biosynthesis.

Effects of Policosanol on platelet aggregation in rats.

Policosanol is the trivial name of a mixture of high molecular weight alcohols isolated from sugar cane, wherein octacosanol is the main component. The effects of Policosanol treatment on rat platelet aggregation were studied. Depending on the dose, Policosanol (5-20 mg/kg, perorally) inhibited the decrease in circulating platelet counts and collagen-induced malondialdehyde concentration in plasma. In rat clotted whole blood thromboxane B2 formation was inhibited by Policosanol (25 mg/kg). Policosanol (50-200 mg/kg, single doses) inhibited ADP-induced platelet aggregation in platelet-rich plasma, while lower doses (25 mg/kg) did not change responses to ADP significantly. However, rats treated with this dose (25 mg/kg) for 4 weeks showed a significant inhibition of platelet aggregation in PRP when a submaximal ADP concentrations was administered.

Effect of policosanol in lowering cholesterol levels in patients with type II hypercholesterolemia

Abstract A randomized double-blind, placebo-controlled study was conducted in 45 patients with type II hypercholesterolemia to investigate the efficacy and safety of policosanol administered at 10 mg daily (5 mg twice daily). After adhering to a cholesterol-lowering diet-only period, 45 outpatients in whom serum cholesterol and LDL-C values were not controlled sufficiently b diet alone were randomized to receive policosanol or placebo at the evening and the morning meal for 6 weeks. Policosanol significantly decreased total cholesterol by 162% and low-density lipoprotein cholesterol (LDL-C) by 21.5%. Ratios of total cholesterol to high-density lipoprotein cholesterol (HDL-C) and of LDL-C to HDL-C were also significantly reduced by 17.7% and 22.3%, respectively. HDL-C values increased by 14% in the policosanol-treated group, but this increase was not significant ( P = 0.07). No significant changes in triglycerides were observed compared with baseline or placebo. No clinically significant differences in clinical and biochemical safety indicators were observed in policosanol-treated patients compared with those receiving placebo. No patient withdrew from the study becasue of adverse experiences, and there were no clinically significant drug-related adverse effects. These data indicate that polico sanol (5 mg twice daily) is effective and well tolerated in patients with type II hypercholesterolemia.

Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers.

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and patients with type II hypercholesterolemia. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. This study reports the results of a 2-week, randomized, double-blind, placebo-controlled trial investigating the effects of policosanol on platelet aggregation and thromboxane B2 and prostacyclin (6 keto PGF1alpha) production after stimulation with collagen in healthy volunteers. The volunteers were on a placebo-baseline period for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10 mg/day) for 15 days. Platelet aggregation was determined at baseline and after 15 days of treatment. Significant reductions of arachidonic acid and collagen-induced platelet aggregation were observed. Thromboxane, but not prostacyclin, generation induced by collagen was also inhibited by policosanol.

A 12-month study of policosanol oral toxicity in Sprague Dawley rats.

Policosanol is a natural mixture of higher aliphatic primary alcohols. Oral toxicity of policosanol was evaluated in a 12-month study in which doses from 0.5 to 500 mg/kg were given orally to Sprague Dawley (SD) rats (20/sex/group) daily. There was no treatment-related toxicity. Thus, effects on body weight gain, food consumption, clinical observations, blood biochemistry, hematology, organ weight ratios and histopathological findings were similar in control and treated groups. This study supports the wide safety margin of policosanol when administered chronically.

Efficacy and safety of policosanol in patients with primary hypercholesterolemia

Abstract A double-blind, placebo-controlled study was conducted in patients with primary hypercholesterolemia to examine the effects of policosanol on plasma lipids and lipoproteins. After adhering to a cholesterol-lowering diet for 6 weeks, 56 patients were randomized to receive placebo or policosanol 5 mg once daily in the evening for 8 weeks. Total cholesterol and low-density lipoprotein cholesterol decreased significantly, by an average of 13.1% and 17.7%, respectively. No significant changes were observed for triglycerides, very-low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol. No significant differences in clinical and biochemical safety indicators were seen in the treated patients compared with those receiving placebo. There were no adverse effects attributable to treatment, and no patient was withdrawn from the trial. These data indicate that policosanol therapy is effective and very well tolerated.

Comparison of the Efficacy and Tolerability of Policosanol with Atorvastatin in Elderly Patients with Type II Hypercholesterolaemia

BackgroundHypercholesterolaemia is a risk factor for coronary heart disease (CHD). Clinical studies have shown that lowering elevated serum total cholesterol (TC) levels, and particularly low density lipoprotein-cholesterol (LDL-C) levels, reduces the frequency of coronary morbidity and deaths, whereas high serum levels of high density lipoprotein-cholesterol (HDL-C) protect against CHD. Policosanol is a cholesterol-lowering drug purified from sugar cane wax with a therapeutic dosage range from 5–20 mg/day. Atorvastatin is an HMG-CoA reductase inhibitor which across its dosage range (10–80 mg/day) has shown significantly greater lipid-lowering effects than all previously marketed statins.ObjectiveThis study was undertaken to compare the efficacy and tolerability of policosanol with atorvastatin in older patients with type II hypercholesterolaemia.Patients and methodsThis randomised, single-blind, parallel-group study was conducted in older patients (60–80 years) with type II hypercholesterolaemia. After 4 weeks on a cholesterol-lowering diet, 75 patients were randomised to policosanol or atorvastatin 10mg tablets taken once daily with the evening meal for 8 weeks. An interim and final check-up were performed at 4 and 8 weeks, respectively, after treatment was initiated.ResultsAt 4 (p < 0.0001) and 8 (p < 0.00001) weeks, policosanol 10 mg/day significantly lowered serum LDL-C levels by 17.5 and 23.1%, respectively compared with baseline; corresponding values for atorvastatin were 28.4 and 29.8%. At study completion, policosanol significantly (p < 0.0001) reduced serum TC (16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), as well as (p < 0.001) triglyceride levels (15.4%). Atorvastatin significantly (p < 0.0001) decreased serum TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%) ratios, as well as (p < 0.001) triglyceride levels (15.5%). Atorvastatin was significantly more effective than policosanol in reducing LDL-C and TC, but similar in reducing both atherogenic ratios and triglyceride levels. Policosanol, but not atorvastatin, significantly (p < 0.05) increased serum HDL-C levels by 5.3%. Both treatments were well tolerated. At study completion, atorvastatin mildly, but significantly (p < 0.05) increased creatine phosphokinase (CPK) and creati-nine, whereas policosanol significantly reduced AST and glucose (p < 0.01) and CPK (p < 0.05) levels. All individual values, however, remained within normal limits. Three atorvastatin but no policosanol patients withdrew from the study because of adverse events: muscle cramps (1 patient), gastritis (1 patient) and uncontrolled hypertension, abdominal pain and myalgia (1 patient). Overall, no policosanol and seven atorvastatin patients (18.9%) reported a total of nine mild or moderate adverse events during the study (p < 0.01).ConclusionsThis study shows that policosanol (10 mg/day) administered for 8 weeks was less effective than atorvastatin (10 mg/day) in reducing serum LDL-C and TC levels in older patients with type II hypercholesterolaemia. Policosanol, but not atorvastatin, however, significantly increased serum HDL-C levels, whereas both drugs similarly reduced atherogenic ratios and serum triglycerides. Policosanol was better tolerated than atorvastatin as revealed by patient withdrawal analysis and overall frequency of adverse events. Nevertheless, further studies must be conducted in larger sample sizes and using dose-titration methods to achieve target lipid levels in order to reach wider conclusions.

Effects of Policosanol and Lovastatin in Patients with Intermittent Claudication: A Double-Blind Comparative Pilot Study

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The present study was undertaken to compare the effects of policosanol and lovastatin on patients with moderately severe intermittent claudication. The study had a 4-week baseline step, followed by a 20-week double blinded, randomized treatment period. Twenty-eight patients who met study entry criteria were randomized to policosanol 10 mg or lovastatin 20 mg tablets once daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10°, temperature 25°C) were assessed before and after 20 weeks of treatment. Both groups were similar at random ization. Compared with baseline, policosanol increased significantly (p<0.01) the initial claudi cation distance (ICD) from 160.39 ±15.82 m to 211.31 ±21.48 m (+33.7%) and the absolute claudication distance (ACD) (p<0.001) from 236.39 ±25.44 m to 288.09 ±28.47 m (+24.3%); meanwhile both variables remained unchanged after lovastatin therapy. Changes in ICD and ACD were significantly larger in the policosanol than in the lovastatin group (p<0.01). Policosanol, but not lovastatin, significantly increased (p < 0.05) the ankle/arm index, although between-group differences were not significant. The frequency of patients reporting improve ment on quality of life domains was greater in the policosanol than in the lovastatin group. Policosanol significantly (p< 0.00 1 ) lowered total cholesterol (TC) and low-density lipoprotein- cholesterol (LDL-C) by 17.5% and 31.0%, respectively, and meanwhile increased (p<0.01) high- density lipoprotein-cholesterol (HDL-C) levels by 31.5%. Lovastatin reduced (p<0.01) TC (18.0%), LDL-C (22.6%), and (p<0.05) triglycerides (9.8%). In addition, policosanol, but not lovastatin, moderately, but significantly, reduced (p < 0.05) fibrinogen levels, so that final values and percent changes in both groups were different (p<0.01). Treatments were well tolerated. Only 1 lovastatin patient withdrew from the study because of a nonfatal myocardial infarction. Five lovastatin patients, but none from the policosanol group, experienced 6 adverse events (AE) (p<0.01). The present results indicate that policosanol, but not lovastatin, is a suitable alternative to manage patients with intermittent claudication because of pleiotropic properties beyond its cholesterol-lowering effects.