Common Name(s): Policosanol , polycosanol
Uses of Policosanol
Cholesterol-lowering effects previously attributed to policosanol have not been validated by more recent trials. Policosanol has been studied in platelet aggregation and intermittent claudication, but data are insufficient to support this use.
Policosanol is typically initiated at 5 mg/day and titrated up to 20 mg/day for hypercholesterolemia.
Contraindications have not been identified.
Information regarding safety and efficacy in pregnancy and lactation is lacking. Studies in rats and mice demonstrated no adverse effects on fertility, reproduction, teratogenesis, or development at doses equivalent to 1,500 times the normal human dose of 20 mg/kg/day.
Because of policosanol's possible effects on platelet aggregation, caution is warranted if policosanol is used concurrently with anticoagulants (eg, warfarin) or antiplatelet agents (eg, aspirin, clopidogrel, prasugrel). In a study in healthy men, policosanol did not affect the pharmacokinetics of warfarin.
Policosanol Adverse Reactions
Animal and human studies have demonstrated few adverse reactions from policosanol.
Limited animal and human studies have found policosanol to be safe.
Policosanol, as reviewed in this monograph, is a mixture of high molecular weight, primary aliphatic alcohols (waxy substances), of which octacosanol (1-octacosanol) is the main component (approximately 60%). For information regarding the octacosanol component, refer to the Octacosanol monograph. Policosanol is isolated from sugar cane wax or beeswax, but these sources may have different proportions of policosanol components. Octacosanol and related substances also are found in wheat germ oil, vegetable oils, alfalfa, and animal products. 1 , 2 , 3
Policosanol has been used most often for cholesterol-lowering effects.
Policosanol is derived through hydrolysis of wax esters and isolation of the alcohol constituent. 4 Reports to determine constituents in policosanol from raw materials have been published. Eight aliphatic fatty alcohols in 1 study were 1-tetracosanol, 1-hexacosanol, 1-heptacosanol, 1-octacosanol, 1-nonacosanol, 1-triacontanol, 1-dotriacontanol, and 1-tetratriacontanol, 4 , 5 , 6 each having 24 to 34 carbons. 4 Three compounds isolated from Chinese beeswax were identified as dotriacontanol, triacontanol, and octacosanol in another report. 2 The saturated carbon structure results in policosanol being hydrophobic. 4
Policosanol Uses and PharmacologyCholesterol reduction
Policosanol's impact on cholesterol is mediated through a reduction in the synthesis and degradation of the rate-limiting step of cholesterol biosynthesis, the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. In comparison, statins competitively inhibit this enzyme. 7 In hepatoma cells and mouse liver, policosanol promoted the phosphorylation of adenosine monophosphate kinase, the principle enzyme for catalyzing the phosphorylation of HMG CoA reductase, thereby reducing its activity. 8 Policosanol has affected low-density lipoprotein (LDL) metabolism through increasing LDL binding, uptake, and degradation. 7Animal data
In a study of normocholesterolemic rabbits, total, non–high-density lipoprotein (HDL), and HDL cholesterol increased following supplementation with sugar cane policosanol. 9 However, in a study of LDL receptor knock-out mice, individual policosanol components, as well as the natural mixture, did not lower serum cholesterol concentrations. 10 Similarly, plasma lipid levels were not reduced in golden Syrian hamsters supplemented with policosanol. 11Clinical data
Despite the proliferation of studies primarily conducted by researchers in Cuba in the late 1990s and early 2000 proclaiming the efficacy of policosanol in lowering cholesterol, more recent studies have failed to validate early expectations. 4 , 12 , 13 , 14 , 15 , 16 , 17 , 18 In a study of patients with HIV-related dyslipidemia, policosanol 20 mg/day for a period of 12 weeks did not significantly affect patient lipid profiles or lipoprotein size or concentration. 19 In a study in which investigators modified the policosanol formulation in an effort to make it more effective, the product was not associated with a reduction in cholesterol parameters. 20 However, a small study in Italy found a reduction in total cholesterol, LDL, and Human Omeostatic Assessment Index in 52 patients with nonalcoholic fatty liver disease who were taking Frilipid , a policosanol supplement. 21 A more recent study found that policosanol in combination with tomato extract, grape procyanidins, and Oenothera biennis oil marketed as Cholactiv , given for 6 weeks, reduced LDL and total cholesterol levels. Reductions in C-reactive protein, malondialdehyde, and superoxide dismutase levels also occurred but were not statistically significant. 22
Trials published in 2006 in the United States, Germany, Netherlands, Canada, and South Africa found no effect on blood lipid profiles at dosages of 10 to 80 mg daily over 4 to 12 weeks. Additionally, no synergy with atorvastatin was demonstrated in one of these trials. 13 , 23 , 24 , 25 , 26 , 27Intermittent claudication
Platelet aggregation is believed to be reduced with policosanol through a reduction in the synthesis of thromboxane B2. 7Animal data
In rabbits with arterial wall damage, policosanol was found to reduce platelet adhesion. 28Clinical data
Multiple trials, all published by the same authors, suggest a role for policosanol in intermittent claudication and platelet aggregation inhibition. Independent validation of these trials is needed. 29 , 30 , 31 , 32 , 33 , 34 , 35 In a 10-week, randomized, comparative study, policosanol 10 mg/day was increased the initial and absolute claudication distances in patients with intermittent claudication. This effect was not noted with aspirin 100 mg/day. 36 In another 20-week, randomized, double-blind comparative study, policosanol 10 mg twice daily was associated with improvements in initial and absolute claudication distances. Ticlopidine 250 mg twice daily was the comparator drug that exhibited similar improvements with no differences between treatment groups. 37Other uses
Policosanol has been used to reduce smooth muscle proliferation and improve symptoms associated with cardiovascular disease. 7 In combination with omega-3 fatty acid supplementation, the use of policosanol was associated with an improvement in mood state and a reduction in reaction time in athletes given supplements for 21 days. 38
Policosanol is typically initiated at 5 mg/day and titrated up to 20 mg/day for hypercholesterolemia. 4
Information regarding safety and efficacy in pregnancy and lactation is lacking. Studies in rats and mice demonstrated no adverse effects on fertility, reproduction, teratogenesis, or development at doses equivalent to 1,500 times the normal human dose of 20 mg/kg/day. 7
Because of policosanol's potential effects on platelet aggregation, caution is warranted if it is used concurrently with anticoagulants (eg, warfarin) or antiplatelet agents (eg, aspirin, clopidogrel, prasugrel). 7 However, a study in 11 healthy men receiving warfarin 25 mg before and after 2 weeks of administration of policosanol 10 mg twice daily found no effect of policosanol on the pharmacokinetics of (S)- or (R)-warfarin. 39 Policosanol also did not alter the response to warfarin on platelet aggregation. Animal studies suggest policosanol may increase the hypotensive effects of beta-blockers 40 and nitroprusside. 41
Policosanol was generally well tolerated in human trials, with adverse reactions including rash, fatigue, headache, weight loss, excess urination, and insomnia. 23 , 24 , 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 A surveillance study of 2,252 elderly patients taking policosanol supplementation found long-term tolerability with the supplements. 42
Limited animal and human studies have found policosanol to be safe. In rats, administration of the drug did not adversely effect reproductive performance and fetal development. 43 Policosanol was also nonteratogenic in rats and rabbits. 44 No evidence of carcinogenicity was observed in mice 45 or rats, 46 even at doses equivalent to 1,500 times the human dose of 20 mg/kg/day. 7
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