Common Name(s): Policosanol, Polycosanol
Policosanol is a generic term referring to a mixture of high molecular weight, aliphatic primary 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 most commonly isolated from sugar cane wax, but can also be extracted from beeswax, rice bran, or wheat germ. However, these sources may have different relative proportions of policosanol components. Octacosanol and related substances also are found in wheat germ oil, vegetable oils, alfalfa, and animal products.1, 2, 3, 4
Policosanol has been used most often for cholesterol-lowering effects.
Policosanol is derived through hydrolysis of wax esters and isolation of the alcohol constituent.5 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-tetratriacontanol5, 6, 7 each having 24 to 34 carbons.5 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.5
Uses and Pharmacology
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.8 It has also recently been demonstrated that the effect of policosanol, as well as statins, on lipid regulation differs according to patient genotypes.9 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.10 Policosanol has affected low-density lipoprotein (LDL) metabolism through increasing LDL binding, uptake, and degradation.8 Age and smoking status have been shown to impact the effect of policosanol on lipid levels as well as functionality including oxidation resistance, anti-gylcation, and high-density lipoprotein (HDL) particle size.11
In a study of normocholesterolemic rabbits, total, non–HDL, and HDL cholesterol increased following supplementation with sugar cane policosanol.12 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.13 Similarly, plasma lipid levels were not reduced in golden Syrian hamsters supplemented with policosanol.14
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.5, 15, 16, 17, 18, 19, 20, 21 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.22 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.23 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.24 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.25 One recent study was published that included chromium policosanol. This randomized, placebo-controlled, 8-week pediatric study (n = 120, age 9 ±4 years) evaluated two 1.2 mg chromium products, chromium polynicotinate (CPNC) and chromium policosanol (CPC), and glucomanna (GM) 500 mg in hypercholesterolemia. Patients were randomized to 1 of 5 groups: placebo, CPNC, CPC, GM, CPNC with GM, or CPC with GM. No significant lipid-lowering benefit was seen with any of the 3 monotherapy groups (CPNC, CPC, GM). The CPNC-GM group, but not the CPC-GM group, had significant reductions in total cholesterol and LDL-C.26
Later trials published from 2006 to 2009 in the United States, Italy, 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.4, 16, 27, 28, 29, 30, 31, 32
More recently, genetic studies are demonstrating the importance of single nucleotide polymorphisms (SNPs) on treatment response and lipid regulation in patients with hyperlipidemia. A 12-week controlled trial conducted in North China (n=179) revealed differing responses to pravastatin as well as policosanol on total cholesterol, LDL, and apolipoprotein B (apoB) depending on the patient’s gene variant of the apolipoprotein A1 G75A gene. Patients treated with pravastatin 10 mg/day expressing the AA or GA alleles, but not GG, experienced statistically significant reductions in total cholesterol (P=0.002) and apoB (P=0.014). In contrast, patients treated with policosanol 10 mg/day and with the GG genotype, but not AA or GA, showed statistically significant reductions in total (P=0.003) and LDL cholesterol (P=0.000). Additionally, apoB was reduced significantly in patients with AA or GA, but not GG, with both pravastatin and policosanol.9
Platelet aggregation is believed to be reduced with policosanol through a reduction in the synthesis of thromboxane B2.8
In rabbits with arterial wall damage, policosanol was found to reduce platelet adhesion.33
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.34, 35, 36, 37, 38, 39, 40 In a 10-week, randomized, comparative study, policosanol 10 mg/day increased the initial and absolute claudication distances in patients with intermittent claudication. This effect was not noted with aspirin 100 mg/day.41 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.42
In patients undergoing percutaneous stent implantation, the addition of policosanol 40 mg/day for 30 days to routine antiplatelet therapy demonstrated reduced platelet reactivity similar to a high-dose regimen but with significantly less bleeding (P=0.04) in a Chinese 2-year multicenter randomized trial (n=350). Eligible patients were diagnosed with acute coronary syndrome and exhibited high on-treatment platelet reactivity.43 In a double-blind, randomized, controlled crossover trial (n=66), the effect of rice policosanol on blood coagulation factors was investigated in hypercholesterolemic patients. Prior to the intervention, patients were maintained on a cholesterol-lowering diet and taken off their lipid-lowering medications. After the 16-week study period in which patients received 10 mg/day rice policosanol or placebo for 8 weeks and then crossed over, no significant differences were found between treatments in plasma fibrinogen or coagulation factors VII, VIII, XII, or XIII. Policosanol was well tolerated with no significant differences from baseline on safety parameters seen for either the intervention or placebo.44
Policosanol has been used to reduce smooth muscle proliferation and improve symptoms associated with cardiovascular disease.8 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.45
Policosanol is typically initiated at 5 mg/day and titrated up to 20 mg/day for hypercholesterolemia.5
Pregnancy / Lactation
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.8
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).8 However, a study in 11 healthy men receiving warfarin 25 mg before and after treatment with policosanol 10 mg twice daily for 2 weeks found no effect of policosanol on the pharmacokinetics of (S)- or (R)-warfarin.46 Policosanol also did not alter the response to warfarin on platelet aggregation. Animal studies suggest policosanol may increase the hypotensive effects of beta-blockers47 and nitroprusside.48
Policosanol was generally well tolerated in human trials, with adverse reactions including rash, fatigue, headache, weight loss, excess urination, and insomnia.27, 28, 30, 34, 35, 36, 37, 38, 39, 40 A surveillance study of 2,252 elderly patients taking policosanol supplementation found long-term tolerability with the supplements.49
Limited animal and human studies have found policosanol to be safe. In rats, administration of policosanol did not adversely affect reproductive performance and fetal development.50 Policosanol was also nonteratogenic in rats and rabbits.51 No evidence of carcinogenicity was observed in mice52 or rats53 even at doses equivalent to 1,500 times the human dose of 20 mg/day.8
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