Policosanol has been studied extensively in animals and humans, including double-blind, placebo controlled clinical studies. Here are abstracts of some of the studies:

Comparison of the Efficacy, Safety and Tolerability of Policosanol versus Fluvastatin in Elderly Hypercholesterolaemic Women

J.C. Fernández, R. Más, National Center for Scientific Research, Havana City, Cuba; G. Castaño, Medical Surgical Research Center, Havana City, Cuba; R. Menéndez, A.M. Amor, R.M. González, E. Alvarez, National Center for Scientific Research, Havana City, Cuba

Clin Drug Invest 21(2):103-113, 2001. ©2001 Adis International Limited

Objective: To compare the efficacy and tolerability of policosanol with that of fluvastatin in older hypercholesterolaemic women.

Design and Setting: Randomised, single-blind, parallel-group study performed at a single centre in Cuba.

Patients and Participants: 70 women aged 60 to 80 years with type II hypercholesterolaemia.

Methods: Patients were randomised after 4 weeks' dietary stabilisation on a step-one cholesterol-lowering diet to treatment with policosanol (10mg) or fluvastatin (20mg) tablets once daily for 8 weeks.

Results: Policosanol significantly lowered low density lipoprotein cholesterol (LDL-C) [29.2%, p < 0.001], total cholesterol (TC) [19.3%, p <0.001], triglycerides (7%, p < 0.05) and the ratios of LDL-C (39.8%, p < 0.001) and TC (31.6%, p < 0.001) to high density lipoprotein cholesterol (HDL-C), and significantly increased HDL-C (19.8%, p < 0.001). Fluvastatin significantly lowered LDL-C (22.9%, p < 0.001), TC (16.7%, p < 0.001), triglycerides (8.2%, p < 0.05), LDL-C/HDL-C (28.4%, p < 0.001) and TC/HDL-C (22.8%, p < 0.001), and significantly increased HDL-C (9.2%, p < 0.001). Policosanol was more effective than fluvastatin in reducing LDL-C (p < 0.01), TC/HDL-C (p < 0.01) and LDLC/HDL-C (p < 0.001) as well as in increasing HDL-C (p < 0.01).

Policosanol, but not fluvastatin, significantly increased lag time for LDL lipid peroxidation (36.5%, p < 0.001) and significantly decreased the diene peroxidation rate (15.5%, p < 0.05). Both treatments were well tolerated. Five fluvastatin, but no policosanol, recipients discontinued the study, three because of adverse events (chest pain and gastric discomfort, skin rash, and dizziness). Overall, three policosanol and five fluvastatin recipients reported adverse events during the study.

Conclusions: The cholesterol-lowering effects of policosanol 10 mg/day administered for 8 weeks to older women with type II hypercholesterolaemia were slightly better than those of fluvastatin 20 mg/day with respect to the extent of the changes in LDL-C, atherogenic indices and HDL-C levels. In addition, policosanol, but not fluvastatin, significantly inhibited the susceptibility of LDL to undergo lipid peroxidation in this particular study population. Nevertheless, further studies in larger populations and with higher dosages must be conducted to corroborate the present results.

Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent.

Gouni-Berthold I, Berthold HK. Medical Policlinic, University of Bonn, Bonn, Germany. berthold@uni-bonn.de

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.

PMID: 11835043 [PubMed - indexed for MEDLINE]

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.

Drugs R D 2002;3(3):159-72

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.

PMID: 12099160 [PubMed - in process]

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.

Int J Clin Pharmacol Res 2001;21(1):43-57.

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.

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.

Int J Clin Pharmacol Res 2001;21(1):31-41.

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.

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.

Angiology 2001 Feb;52(2):115-25.

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.

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

Pharmacol Res 2001 Jan;43(1):31-7.

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.

Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro.

Menendez R, Mas R, Amor AM, Gonzalez RM, Fernandez JC, Rodeiro I, Zayas M, Jimenez S. Center of Natural Products, National Center for Scientific Research, PO Box 6880, Havana, Cuba.

Br J Clin Pharmacol 2000 Sep;50(3):255-62.

Aims: The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers.

Methods: The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation.

Results: At baseline all groups were well matched regarding all variables. After 8 weeks of therapy policosanol administered at 5 and 10 mg, significantly and in a dose-dependent manner increased the lag phase of conjugated diene generation (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from 8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found.

Conclusions: The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.

Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus.

Crespo N, Illnait J, Mas R, Fernandez L, Fernandez J, Castano G. Enrique Cabrera Hospital, Havana, Cuba.

Int J Clin Pharmacol Res 1999;19(4):117-27.

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6 weeks on a lipid lowering diet, 53 patients were randomized to receive either policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p < 0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did not significantly change after therapy. Policosanol, but not lovastatin, significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison between groups showed that changes in HDL-cholesterol induced by policosanol were significantly greater (p < 0.01) than those induced by lovastatin. Both treatments were safe and well tolerated. Lovastatin moderately but significantly (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin group (p < 0.01) than in the policosanol group. In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day.