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Policosanol

Common Name(s): Policosanol, Polycosanol

Clinical Overview

Use

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.

Dosing

Policosanol is typically initiated at 5 mg/day and titrated up to 20 mg/day for hypercholesterolemia. Adjunctive use of 40 mg/day for 30 days has been used with antiplatelet regimens after percutaneous stent implantation.

Contraindications

Contraindications have not been identified.

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/day.

Interactions

See Drug Interactions section.

Adverse Reactions

Animal and human studies have demonstrated few adverse reactions from policosanol.

Toxicology

Limited animal and human studies have found policosanol to be safe.

Source

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

History

Policosanol has been used most often for cholesterol-lowering effects.

Chemistry

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

Cholesterol 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.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

Animal data

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

Clinical 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.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

Intermittent claudication

Platelet aggregation is believed to be reduced with policosanol through a reduction in the synthesis of thromboxane B2.8

Animal data

In rabbits with arterial wall damage, policosanol was found to reduce platelet adhesion.33

Clinical 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.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

Other uses

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

Dosing

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

Interactions

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

Adverse Reactions

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

Toxicology

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

References

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2. Liu F, Sun D. Active constituents lowering blood-lipid in beeswax [in Chinese]. Zhongguo Zhong Yao Za Zhi. 1996;21(9):553-554, 576.9772646
3. Saint-John M, McNaughton L. Octacosanol ingestion and its effects on metabolic responses to submaximal cycle ergometry, reaction time and chest and grip strength. Int Clin Nutr Rev. 1986;6:81-87.
4. Francini-Pesenti F, Beltramolli D, Dall'acqua S, Brocadello F. Effect of sugar cane policosanol on lipid profile in primary hypercholesterolemia. Phytother Res. 2008;22(3):318-322.18167048
5. Marinangeli CP, Jones PH, Kassis AN, Eskin MN. Policosanols as nutraceuticals: fact or fiction. Crit Rev Food Sci Nutr. 2010;50(3):259-267.20301014
6. Gonzalez VL, Magraner J, Otero T, Garcia E. Validation and interlaboratory study of a new GC analytical method for the determination of policosanol in raw material [in Spanish]. Rev CENIC Cienc Quim. 1999;30:148-152.
7. Gonzalez CV, Magraner HJ. Validation of a gas chromatographic method for determining fatty alcohols that compose policosanol in five-milligram film-coated tablets. J AOAC Int. 1999;82(4):834-839.
8. Policosanol. Altern Med Rev. 2004;9(3):312-317.15387722
9. Liu TN, Wu CT, He F, et al. Relationship between the G75A polymorphism in the apolipoprotein A1 (ApoA1) gene and the lipid regulatory effects of pravastatin in patients with hyperlipidemia. Genet Mol Res. 2016;15(2).27323196
10. Banerjee S, Ghoshal S, Porter TD. Activation of AMP-kinase by policosanol requires peroxisomal metabolism. Lipids. 2011;46(4):311-321.21359855
11. Kim JY, Kim SM, Kim SJ, Lee EY, Kim JR, Cho KH. Consumption of policosanol enhances HDL functionality via CETP inhibition and reduces blood pressure and visceral fat in young and middle-aged subjects. Int J Mol Med. 2017;39(4):889-899.28259941
12. Murphy KJ, Saint DA, Howe PR. Lack of effect of sugar cane and sunflower seed policosanols on plasma cholesterol in rabbits. J Am Coll Nutr. 2008;27(4):476-484.18978167
13. Dullens SP, Mensink RP, Bragt MC, Kies AK, Plat J. Effects of emulsified policosanols with different chain lengths on cholesterol metabolism in heterozygous LDL receptor-deficient mice. J Lipid Res. 2008;49(4):790-796.18162663
14. Kassis AN, Marinangeli CP, Jain D, Ebine N, Jones PJ. Lack of effect of sugar cane policosanol on plasma cholesterol in golden Syrian hamsters. Atherosclerosis. 2007;194(1):153-158.17123537
15. Policosanol: a sweet nothing for high cholesterol. Harv Heart Lett. 2006;17(1):7.
16. Lin Y, Rudrum M, van der Wielen RP, et al. Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations. Metabolism. 2004;53(10):1309-1314.15375787
17. Chen JT, Wesley R, Shamburek RD, Pucino F, Csako G. Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy. 2005;25(2):171-183.15767233
18. Francini-Pesenti F, Brocadello F, Beltramolli D, Nardi M, Caregaro L. Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study. Complement Ther Med. 2008;16(2):61-65.18514906
19. Kassis AN, Jones PJ. Changes in cholesterol kinetics following sugar cane policosanol supplementation: a randomized control trial. Lipids Health Dis. 2008;7:17.18447941
20. Castaño G, Fernández L, Mas R, Illnait J, Mesa M, Fernández JC. Comparison of the effects of policosanol and atorvastatin on lipid profile and platelet aggregation in patients with dyslipidemia and type 2 diabetes mellitus. Clin Drug Invest. 2003;23(10):639-650.17535079
21. Castano G, Mas R, Fernandez L, et al. A comparison of the effects of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia: a randomized, double-blinded study. Drugs Exp Clin Res. 2005;(31 suppl);31-44.16444910
22. Swanson B, Keithley JK, Sha BE, et al. Policosanol for managing human immunodeficiency virus-related dyslipidemia in a medically underserved population: a randomized, controlled clinical trial. Altern Ther Health Med. 2011;17(2):30-35.21717822
23. Backes JM, Gibson CA, Ruisinger JF, Moriarty PM. Modified-policosanol does not reduce plasma lipoproteins in hyperlipidemic patients when used alone or in combination with statin therapy. Lipids. 46(10):923-929.
24. Musto D, Martorelli L, Russo M, et al. Non-alcoholic hepatic steatosis: the role of policosanols in associated hyperlipidemia. Minerva Gastroenterol Dietrol. 2010;56(4):389-395.21139538
25. Gupta H, Pawar D, Riva A, Bombardelli E, Morazzoni P. A randomized, double-blind, placebo-controlled trial to evaluate efficacy and tolerability of an optimized botanical combination in the management of patients with primary hypercholesterolemia and mixed dyslipidemia. Phytother Res. 2011 Jun 14. [Epub ahead of print].21674629
26. Martino F, Puddu PE, Pannarale G, et al. Low dose chromium-polynicotinate or policosanol is effective in hypercholesterolemic children only in combination with glucomannan. Atherosclerosis. 2013;228(1):198-202.23453352
27. Cubeddu LX, Cubeddu RJ, Heimowitz T, Restrepo B, Lamas GA, Wienberg GB. Comparative lipid-lowering effects of policosanol and atorvastatin: a randomized, parallel, double-blind, placebo-controlled trial. Am Heart J. 2006;152(5):982. e1.5.17070175
28. Dulin MF, Hatcher LF, Sasser HC, Barringer TA. Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial. Am J Clin Nutr. 2006;84(6):1543-1548.17158441
29. Kassis AN, Jones PJ. Lack of cholesterol-lowering efficacy of Cuban sugar cane policosanols in hypercholesterolemic persons. Am J Clin Nutr. 2006;84(5):1003-1008.17093150
30. Greyling A, De Witt C, Oosthuizen W, Jerling JC. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolaemic and heterozygous familial hypercholesterolaemic subjects. Br J Nutr. 2006;95(5):968-975.16611388
31. Berthold HK, Unverdorben S, Degenhardt R, Bulitta M, Gounti-Berthold I. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial. JAMA. 2006;295(19):2262-2269.16705107
32. Kassis AN, Kubow S, Jones PJ. Sugar cane policosanols do not reduce LDL oxidation in hypercholesterolemic individuals. Lipids. 2009;44(5):391-396.19337769
33. Noa M, Rás M, Lariot C. Protective effect of policosanol on endothelium and intimal thickness induced by forceps in rabbits. J Med Food. 2007;10(3):452-459.17887938
34. Arruzazabala ML, Valdés S, Más R, Carbajal D, Fernández L. Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Pharmacol Res. 1997;36(4):293-297.9425618
35. Arruzazabala ML, Valdés S, Más R, Fernández L, Carbajal D. Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers. Pharmacol Res. 1996;34(5-6):181-185.9076841
36. Arruzazabala ML, Más R, Molina V, et al. Effect of policosanol on platelet aggregation in type II hypercholesterolemic patients. Int J Tissue React. 1998;20(4):119-124.10093795
37. Carbajal D, Arruzazabala ML, Valdés S, Más R. Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers. Prostaglandins Leukot Essent Fatty Acids. 1998;58(1):61-64.9482167
38. Valdés S, Arruzazabala ML, Fernández L, et al. Effect of policosanol on platelet aggregation in healthy volunteers. Int J Pharmacol Res. 1996;16(2-3):67-72.9063758
39. Castaño G, Más R, Roca J, et al. A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication. Angiology. 1999;50(2):123-130.10063942
40. Castaño G, Más Ferreiro R, Fernández L, Gámez R, Illnait J, Fernández C. A long-term study of policosanol in the treatment of intermittent claudication. Angiology. 2001;52(2):115-125.11228084
41. Illnait J, Castano G, Alvarez E, et al. Effects of policosanol (10 mg/d) versus aspirin (100 mg/d) in patients with intermittent claudication: a 10-week, randomized, comparative study. Angiology. 2008;59(3):269-277.18388038
42. Castaño G, Más R, Gámez R, Fernández L, Illnait J. Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. Angiology. 2004;55(4):361-371.15258682
43. Xu K, Liu X, Li Y, et al. Safety and efficacy of policosanol in patients with high on-treatment platelet reactivity after drug-eluting stent implantation: two-year follow-up results. Cardiovasc Ther. 2016;34(5):337-342.27328023
44. Reiner Z, Tedeschi-Reiner E. Rice policosanol does not have any effects on blood coagulation factors in hypercholesterolemic patients. Coll Antropol. 2007;31(4):1061-1064.18217459
45. Fontani G, Lodi L, Migliorini S, Corradeschi F. Effect of omega-3 and policosanol supplementation on attention and reactivity in athletes. J Am Coll Nutr. 2009;(28 suppl):473S-481S.20234035
46. Abdul MI, Jiang X, Williams KM, et al. Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. BJCP. 2010;69(5):508-515.20573086
47. Molina Cuevas V, Arruzazabala ML, Carbajal Quintana D, Más Ferrerio R, Valdés García S. Effect of policosanol on arterial blood pressure in rats. Study of the pharmacological interaction with nifedipine and propranolol. Arch Med Res. 1998;29(1):21-24.9556918
48. Arruzazabala ML, Carbajal D, Más R, Valdés S, Molina V. Pharmacological interaction between policosanol and nitroprusside in rats. J Med Food. 2001;4(2):67-70.12639414
49. Fernández S, Más R, Gámez R, et al. A pharmacological surveillance study of the tolerability of policosanol in the elderly population. Am J Geriatr Pharmacother. 2004;2(4):219-229.15903280
50. Rodríguez MD, García H. Evaluation of peri- and post-natal toxicity of Policosanol in rats. Teratog Carcinog Mutagen. 1998;18(1):1-7.9586765
51. Rodríguez MD, García H. Teratogenic and reproductive studies of policosanol in the rat and rabbit. Teratog Carcinog Mutagen. 1994;14(3):107-113.7940402
52. Alemán CL, Puig MN, Elías EC, et al. Carcinogenicity of policosanol in mice: an 18-month study. Food Chem Toxicol. 1995;33(7):573-578.7628793
53. Alemán CL, Más Ferreiro R, Noa Puig M, Rodeiro Guerra I, Hernández Ortega C, Capote A. Carcinogenicity of policosanol in Sprague Dawley rats: a 24-month study. Teratog Carcinog Mutagen. 1994;14(5):239-249.7855743

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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