Int J Clin Pharmacol Res 2001;21(1):43-57. Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study. Castano G, Mas R, Fernandez L, Illnait J, Gamez R, Alvarez E. Medical Surgical Research Center, National Center for Scientific Research, Havana City, Cuba.
Policosanol is a well defined mixture of higher aliphatic primary alcohols isolated from sugar cane wax with cholesterol-lowering effects proven for a dose range from 5-20 mg/day in patients with type II hypercholesterolemia and dyslipidemia associated with noninsulin dependent diabetes mellitus. This randomized, double-blind study investigated the cholesterol-lowering efficacy and tolerability of policosanol 20 mg/day compared with 40 mg/day. Changes in low-density lipoprotein (LDL)-cholesterol levels were predefined as the primary efficacy endpoint. Patients with type II hypercholesterolemia were enrolled in the study and instructed to continue a step I cholesterol-lowering diet for 6 weeks and those eligible to be included (89) were randomly allocated to receive under double-blind conditions placebo (n = 30), policosanol 20 mg/day (n = 29) or 40 mg/day (n = 30). After 24 weeks, policosanol at 20 and 40 mg/day significantly (p < 0.00001) lowered LDL-cholesterol by 27.4% and 28.1%, total cholesterol (p < 0.00001) by 15.6% and 17.3%, and the LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 37.2% and 36.5%, respectively The ratio of total cholesterol/HDL-cholesterol was lowered by 27.1% and 27.5%, while HDL-cholesterol levels increased (p < 0.001) by 17.6% and 17.0%, respectively. Compared with baseline, policosanol 20 mg/day lowered triglycerides (p < 0.05) by 12.7%, while they were lowered (p < 0.01) by 15.6% at a dose of policosanol 40 mg/day All the above-mentioned significant differences were also different from placebo and no significant changes occurred in any lipid profile parameters in the placebo group. Based on the mean values of LDL-cholesterol levels at study completion, the mean percent reductions from baseline were 27.4% and 28.1% for the 20 and 40 mg/day groups, respectively. Thus, the effects of both policosanol doses on the main efficacy variable were practically identical. Consistent with the data obtained for LDL-cholesterol, both doses were similarly effective in changing all the other lipid profile parameters. No unexpected adverse effects were observed and there were no significant between-group differences regarding safety indicator values or reported adverse effects. In conclusion, although the tolerability profile remains excellent, according to the present results policosanol at a dose of 40 mg/day does not offer significant additional cholesterol-lowering efficacy over the 20 mg/day dose.
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Int J Clin Pharmacol Res 2001;21(1):31-41. Efficacy and tolerability of policosanol in hypercholesterolemic postmenopausal women. Mirkin A, Mas R, Martinto M, Boccanera R, Robertis A, Poudes R, Fuster A, Lastreto E, Yanez M, Irico G, McCook B, Farre A. Eva Peron Hospital, Rosario, Argentina.
This randomized, double-blind, multicenter placebo-controlled study was conducted to investigate the efficacy and tolerability of policosanol, a cholesterol-lowering drug purified from sugar cane wax, in women who had experienced menopause and showed elevated serum total cholesterol and low density lipoprotein (LDL)-cholesterol levels despite a 6-week standard lipid-lowering diet. Thus, 56 eligible patients were randomized to receive placebo or policosanol 5 mg/day for 8 weeks and the dose was doubled to 10 mg/day during the next 8 weeks. Policosanol (5 and 10 mg/day) significantly decreased LDL-cholesterol (17.3% and 26.7%, respectively), total cholesterol (12.9% and 19.5%) as well as the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (17.2% and 26.5%) and total cholesterol to HDL-cholesterol (16.3% and 21.0%) compared with baseline and placebo. HDL-cholesterol levels were significantly raised by 7.4% at study completion. No significant changes occurred in the lipid profile of the placebo group. The drug was safe and well tolerated. No drug-related adverse effects were observed. None of the patients administered policosanol but three of those administered placebo withdrew from the trial because of adverse effects: one due to a serious hypertensive status, one because of an allergic reaction (pruritus plus skin rash) and one due to gastrointestinal disturbances (nauseas plus vomiting). Eleven placebo patients reported 24 adverse effects compared with six policosanol patients who reported seven adverse effects (p < 0.05). In addition, five placebo (17.9%) and 13 policosanol patients (46.4%) (p < 0.05) reported improvements in habitual symptoms and health perception during the study. In conclusion, policosanol was effective and well tolerated in hypercholesterolemic postmenopausal women, showing additional benefits in the health perception of the study patients.
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J Chromatogr B Biomed Sci Appl 2001 Oct 5;762(1):43-9. Trace determination of 1-octacosanol in rat plasma by solid-phase extraction with Tenax GC and capillary gas chromatography. Marrero Delange D, Gonzalez Bravo L. Center of Natural Products, CNIC, Havana, Cuba. david_delange@yahoo.com
1-Octacosanol is the major component of policosanol, a new natural lowering-cholesterol agent. A sensitive solid-phase extraction with a Tenax GC capillary gas chromatography method for determining the proportion of this fatty alcohol in plasma after its denaturation with trichloroacetic acid was developed. The trimethylsilyl ether derivative of the target analyte obtained from the organic extract showed excellent chromatographic properties and was detectable in the low nanogram range (1 ng/ml). Adequate separation from plasma's extract was achieved with a fused-silica capillary column (30m x 0.25 mm I.D.) with SPB-5 (0.5 microm film thickness) and operated with temperature programming from 100 to 200 degrees C at 40 degrees C/min and from 200 degrees C increased at 10 degrees C/min to 320 degrees C, then held for 30 min, the carrier gas flow-rate (argon) was 1 ml/min. Quantification was performed by the internal standard method using 1-hexacosanol. The reliable relative retention parameters and the mass response factors values, and their confidence levels, ensure a proper GC sensitivity, necessary for the determination of the alcohol being analyzed. The method was evaluated to a concentration range from 6 to 47.6 ng/ml of plasma obtaining recoveries from 95 to 98%. The correlation between the theoretical concentration values and the corresponding experimental values was appropriate (gamma=0.9718 x -0.0915; r2=0.9998). The method showed a good within-day (RSD=4.3%) and between-day (RSD=6.0%) precision according to the acceptance criteria (<10%). This procedure was successfully applied to the study of 1-octacosanol in rat plasma samples after a single oral administration (40 mg/kg) of policosanol.
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Arch Med Res 2001 Jan-Feb;32(1):8-12. Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts. Menendez R, Amor AM, Rodeiro I, Gonzalez RM, Gonzalez PC, Alfonso JL, Mas R. Laboratorio de Bioquimica, Centro de Productos Naturales, Centro Nacional de Investigacion Cientifica, Havana, Cuba. dalmer@ip.etccsa.cu
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.
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J Gerontol A Biol Sci Med Sci 2001 Mar;56(3):M186-92. Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk. Castano G, Mas R, Fernandez JC, Illnait J, Fernandez L, Alvarez E. Medical Surgical Research Center, National Center for Scientific Research, Havana City, Cuba.
BACKGROUND: The present study was undertaken to investigate the effects of policosanol in older patients with type II hypercholesterolemia and more than one concomitant atherosclerotic risk factor. METHODS: After 6 weeks on a lipid-lowering diet, 179 patients randomly received a placebo or policosanol at doses of 5 followed by 10 mg per day for successive 12-week periods of each dose. Policosanol (5 and 10 mg/d) significantly (p < .001) reduced low-density lipoprotein cholesterol (LDL-C; 16.9% and 24.4%, respectively) and total cholesterol (TC; 12.8% and 16.2%, respectively), while significantly (p < .01) increasing (p < .001) high-density lipoprotein cholesterol (HDL-C) by 14.6% and 29.1%, respectively. RESULTS: Policosanol significantly decreased (p < .01) the ratios of LDL-C to HDL-C (29.1%) and TC to HDL-C (28%) at study completion, although triglycerides remained unchanged. Policosanol, but not the placebo, significantly improved (p .01) cardiovascular capacity, which was assessed using the Specific Activity Scale. No serious adverse experiences occurred in policosanol patients (p < .01), compared with seven adverse experiences (7.9%) reported by placebo patients. CONCLUSIONS: This study shows that policosanol is effective, safe, and well tolerated in older hypercholesterolemic patients.
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Angiology 2001 Feb;52(2):115-25. A long-term study of policosanol in the treatment of intermittent claudication. Castano G, Mas Ferreiro R, Fernandez L, Gamez R, Illnait J, Fernandez C. Medical Surgical Research Center, Havana City Cuba.
Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.
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Pharmacol Res 2001 Jan;43(1):31-7. A comparative study of policosanol vs lovastatin on intimal thickening in rabbit cuffed carotid artery. Noa M, Mas R, Mesa R. Department of Pharmacology, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. dalmer@ip.etecsa.cu
Policosanol is a cholesterol-lowering drug isolated from sugar cane wax, which acts by inhibiting cholesterol biosynthesis. Previous studies have demonstrated that policosanol inhibited smooth muscle cell (SMC) proliferation in the cuffed carotid artery of the rabbit and in arterial wall damage induced by forceps in the central artery of the ear of rabbits. The present study was undertaken to compare the effects of policosanol and lovastatin on SMC proliferation in the cuffed carotid artery of rabbits. Collars were placed around the left carotid for 7 and 15 days. The contralateral artery was sham operated. We studied eight experimental groups: two controls groups receiving vehicle for 7 and 15 days, respectively, a satellite sham operated control group, four groups treated with policosanol at 5 and 25 mg kg(-1)for 7 and 15 days and a reference group receiving lovastatin at 20 mg kg(-1)for 15 days. Samples of arteries were examined by light and electron microscopy. To evaluate intimal thickening the cross-sectional areas of intima and media were measured. Neointima was significantly reduced in treated animals compared with controls, but the reduction in lovastatin animals was significantly lower than in policosanol-treated groups. The SMC proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen and the reduction observed in policosanol-treated rabbits was significantly larger than in lovastatin-treated animals. It is concluded that the protective effect of policosanol against neointima formation in this experimental model was slightly better than that of lovastatin. Copyright 2001 Academic Press.
