Altern Med Rev 2002 Jun;7(3):203-17. Policosanol: A new treatment for cardiovascular disease? Janikula M. ND Candidate 2003 - Southwest College of Naturopathic Health Sciences student representative to Thorne Research. Correspondence address: 1320 E Lemon St, Tempe, AZ 85281; email: mdjanikula@hotmail.com
Policosanol is a mixture of alcohols isolated and purified from sugar cane. Recently, Cuban researchers found 5-20 mg daily of policosanol to be effective at improving serum lipid profiles. Policosanol is believed to decrease total cholesterol (TC), low-density lipoprotein (LDL), and increase high-density lipoprotein (HDL) by inhibiting cholesterol synthesis and increasing LDL processing. Lipid profile improvements are seen in healthy volunteers, patients with type II hypercholesterolemia, type 2 diabetics with hypercholesterolemia, postmenopausal women with hypercholesterolemia, and patients with combined hypercholesterolemia and abnormal liver function tests. Additionally, policosanol has performed equal to or better than simvastatin, pravastatin, lovastatin, probucol, or acipimox with fewer side effects in patients with type II hypercholesterolemia. Policosanol also decreases several other risk factors of cardiovascular disease by decreasing LDL oxidation, platelet aggregation, endothelial damage, and smooth muscle cell proliferation. Furthermore, policosanol decreases progression and increases regression of cardiovascular disease assessed by thallium-labeled myocardial perfusion scintigraphy (TL-MPS) and Doppler-ultrasound, and decreases symptoms of cardiovascular disease assessed by the Specific Activity Scale. In post-marketing studies, only 0.31 percent of patients have had adverse events. Furthermore, in animal toxicity studies doses up to 1500 times normal human doses (on the basis of body weight) have shown no negative effects on carcinogenesis, reproduction, growth, and development. However, despite the positive research on policosanol on Cubans, policosanol produced in Cuba is not available in the United States, and only Cuban subjects have been studied. Further research is needed to determine if the same effects will be obtained in U.S. populations with non-Cuban produced policosanol.
Drugs R D 2002;3(3):159-72. Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia. Castano G, Mas R, Fernandez JC, Fernandez L, Illnait J, Lopez E. Surgical Medical Research Center, Havana City, Cuba.
OBJECTIVE: This study was conducted to investigate the effects of policosanol administered for 12 months on the lipid profile of older patients with hypertension and type II hypercholesterolaemia and no history of coronary heart disease (CHD) or cerebrovascular disease. PATIENTS AND PARTICIPANTS: 589 older male and female patients with hypertension and type II hypercholesterolaemia and no history of CHD or cerebrovascular disease were included. METHODS: This was a prospective, randomised, double-blind, placebo-controlled study in parallel groups treated with policosanol (5 to 10 mg/day) for 1 year. After 6 weeks on a standard step I cholesterol-lowering diet, 589 patients were randomised to policosanol (5 mg) or placebo tablets, to be taken once daily for 12 months. The dosage was doubled to 10 mg/day if total cholesterol values were > 6.1 mmol/L after 6 months of therapy. RESULTS: Policosanol significantly (p < 0.00001) lowered serum low-density lipoprotein-cholesterol (LDL-C) [20.5%], total cholesterol (TC) [15.4%], triglycerides (11.9%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) ratio [22.2%] and TC/HDL-C ratio (20.1%), and increased (p < 0.0001) HDL-C (12.7%). The frequency of vascular and all-cause serious adverse events (SAEs) was lower (p < 0.05) in the policosanol recipients (two vascular SAEs, 0.7%; five all-cause SAEs, 1.7%) than in the placebo recipients (six vascular SAEs, 2.0%; 12 all-cause SAEs, 4.1%). Similarly, total adverse events (AEs) were less frequent in the policosanol-treated group (29; 9.8%) compared with the placebo group (52; 17.7%) [p < 0.01]. Three placebo recipients and no policosanol recipents died during the study as a result of myocardial infarction (two patients) and sudden cardiac arrest (one). Policosanol was well tolerated, and no drug-related disturbances in safety indicators were found. Policosanol significantly decreased systolic blood pressure (BP) compared with baseline and placebo, which could be an additional advantage in this population at high coronary risk. CONCLUSIONS: Policosanol administered long term is effective in lowering LDL-C and TC as well as increasing HDL-C levels in older patients with hypertension and type II hypercholesterolaemia without a history of CHD or cerebrovascular disease. In addition, policosanol treatment also shows benefits in the occurrence of SAEs of vascular aetiology, on the general AE profile and the reduction of BP in treated patients compared with baseline.
J AOAC Int 2002 May-Jun;85(3):563-6. Validation of a gas chromatographic method for determination of fatty alcohols in 10 mg film-coated tablets of policosanol. Sierra R, Gonzalez VL, Magraner J. National Center for Scientific Research, Center for Natural Products, Cubanacan, Playa, Havana City, Cuba.
A gas chromatographic method using a packed column and 1-eicosanol as an internal standard was validated for the determination of the fatty alcohols that compose policosanol in 10 mg film-coated tablets. The alcohols were determined as trimethylsilyl derivatives, prepared with N-methyl-N-trimethylsilyltrifluoroacetamide. The method can detect degradation products with high retention times, without interfering with the peaks of the active principle. Good linearity (correlation coefficient = 0.9992) and accuracy (mean recovery -100.27 +/- 1.66%) were proven over a range of 25-200% of the nominal concentration. Within- and between-day precision at the nominal 100% value met the acceptance criteria (<2%). Ruggedness was examined through an intralaboratory experimental study in which 6 operational changes were made; the changes were found to have no effect on quantitation, repeatability, resolution, and relative retention time. The method is suitable for the quality control process and stability studies of these tablets.
Am Heart J 2002 Feb;143(2):356-65. Policosanol: Clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Gouni-Berthold I, Berthold HK. Medical Policlinic, University of Bonn, Bonn, Germany, and the Institute for Clinical Research/Department of Clinical Pharmacology, Center for Cardiovascular Diseases, Rotenburg der Fulda.
BACKGROUND: Policosanol is a mixture of higher primary aliphatic alcohols isolated from sugar cane wax, whose main component is octacosanol. The mixture has been shown to lower cholesterol in animal models, healthy volunteers, and patients with type II hypercholesterolemia. METHODS: We reviewed the literature on placebo-controlled lipid-lowering studies using policosanol published in peer-reviewed journals as well as studies investigating its mechanism of action and its clinical pharmacology. RESULTS: At doses of 10 to 20 mg per day, policosanol lowers total cholesterol by 17% to 21% and low-density lipoprotein (LDL) cholesterol by 21% to 29% and raises high-density lipoprotein cholesterol by 8% to 15%. Because higher doses have not been tested up to now, it cannot be excluded that effectiveness may be even greater. Daily doses of 10 mg of policosanol have been shown to be equally effective in lowering total or LDL cholesterol as the same dose of simvastatin or pravastatin. Triglyceride levels are not influenced by policosanol. At dosages of up to 20 mg per day, policosanol is safe and well tolerated, as studies of >3 years of therapy indicate. There is evidence from in vitro studies that policosanol may inhibit hepatic cholesterol synthesis at a step before mevalonate generation, but direct inhibition of the hydroxy-methylglutaryl-coenzyme A reductase is unlikely. Animal studies suggest that LDL catabolism may be enhanced, possibly through receptor-mediated mechanisms, but the precise mechanism of action is not understood yet. Policosanol has additional beneficial properties such as effects on smooth muscle cell proliferation, platelet aggregation, and LDL peroxidation. Data on efficacy determined by clinical end points such as rates of cardiac events or cardiac mortality are lacking. CONCLUSIONS: Policosanol seems to be a very promising phytochemical alternative to classic lipid-lowering agents such as the statins and deserves further evaluation.
Can J Physiol Pharmacol 2002 Jan;80(1):13-21. Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D003, a mixture of very long-chain saturated fatty acids. Menendez R, Mas R, Amor AM, Ledon N, Perez J, Gonzalez RM, Rodeiro I, Zayas M, Jimenez S. Laboratory of Biochemistry, Center of Natural Products, National Center for Scientific Research, Havana, Cuba. dalmer@ip.etecsa.cu
Previous results have demonstrated that policosanol, a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, whose main component is octacosanol, inhibited lipid peroxidation in experimental models and human beings. D003 is a defined mixture of very long-chain saturated fatty acids, also isolated and purified from sugar cane wax, whose main component is octacosanoic acid followed by traicontanoic, dotriacontanoic, and tetracontanoic acids. Since very long-chain fatty acids are structurally related to their corresponding alcohols, we investigated the effect of oral treatment with D003 (0.5, 5, 50, and 100 mg/kg) over 4 weeks in reducing the susceptibility of rat lipoprotein to oxidative modification. The combined rat lipoprotein fraction VLDL + LDL was subjected to several oxidation systems, including those containing metal ions (CuSO4), those having the capacity to generate free radicals 2,2-azobis-2-amidinopropane hydrochloride (AAPH), and a more physiological system (resident macrophages). D003 (5, 50, and 100 mg/kg) significantly inhibited copper-mediated conjugated-diene generation in a concentration-dependent manner. D003 increased lag phase by 53.1, 115.3, and 119.3%, respectively, and decreased the rate of conjugate-diene generation by 16.6, 21.5, and 19.6%, respectively. D003 also inhibited azo-compound initiated and macrophage-mediated lipid peroxidation as judged by the significant decrease in thiobarbituric acid reactive substance (TBARS) generation. In all the systems the maximum effect was attained at 50 mg/kg. There was also a parallel attenuation in the reduction of lysine amino groups and a significant reduction of carbonyl content after oxidation of lipoprotein samples. Taken together, the present results indicate that oral administration of D003 protects lipoprotein fractions against lipid peroxidation in the lipid as well in the protein moiety.
Drug Dev Ind Pharm 2002 Jan;28(1):89-93. Physico-mechanical characterization of policosanol, a novel hypocholesterolemic drug. Uribarri E, Laguna A, Sierra R, Ricardo Y. Laboratorios MedSol, Havana, Cuba.
As part of the formulation studies of policosanol, a new hypocholesterolemic drug, a physico-mechanical characterization was developed. Thermal analysis, using differential scanning calorimetry was used to evaluate the purity of policosanol from batch to batch and, also, the particle size distribution. The degree of wettability of policosanol was studied by measuring the contact angle and solubility in different solvents. The compressibility and cohesion of particles were evaluated using a profile of compression forces, ranging between 6.5 kN and 39.0 kN. Also, other properties such as flow properties, true density, and tapped and bulk density were measured. The industrial batches of policosanol that were studied show an adequate purity and a uniform distribution of the particle sizes. Policosanol shows good flow properties, compressibility, and cohesion as well as a low solubility in the majority of the solvents used in the pharmaceutical industry, and its solubility in water or in aqueous solutions was, mainly, null. The wettability of policosanol in the different solvents shows the following order: methylene chloride > ethanol > acetone >> water.
