The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in rats


  • D. Haim Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile - Faculty of Medicine, University of the Andes
  • A. Valenzuela Laboratory of Lipids and Antioxidants, Institute of Nutrition and Food Technology, University of Chile - Faculty of Medicine, University of the Andes
  • M. C. Brañes Naturalis S.A.
  • M. Fuenzalida Naturalis S.A.
  • L. A. Videla Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile



Bioavailability, Cholesterol lowering effect, Octacosanol, Policosanol, Policosanol absorption, Rats, Triacontanol


Policosanol comprises a mixture of long-chain aliphatic alcohols from sugarcane wax. More than 50 studies indicate that policosanol decreases serum cholesterol, while others failed to reproduce this effect. The objective of this investigation was to assess the bioavailability of esterified policosanol and non-esterified policosanol (NEP), in relation to their hypocholesterolemic effects. Sprague Dawley rats were given a daily oral dose of 100 mg/kg of NEP, 117 mg kg–1 of butyric acid esterified policosanol (BAEP), or 164 mg kg–1 of oleic acid esterified policosanol (OAEP). Policosanol absorption was evaluated in plasma between 0 and 3 hours after ingestion. To assess changes in total cholesterol, LDL-cholesterol, HDLcholesterol and triacylglycerols in plasma and liver 3-hydroxy- 3-methylglutaryl coenzyme A reductase (HMG- CoA red) phosphorylation, the rats were supplemented with nonesterified or esterified policosanol for 5 weeks. The results indicate that policosanol absorption was significantly greater in OAEP-treated rats than in those subjected to NEP or BAEP administration. OAEP significantly reduced plasma total and LDL-cholesterol in rats, in addition to a 5.6-fold increase (P < 0.05) in the hepatic content of phosphorylated HMG-CoA red over the control values. In conclusion, esterification of policosanol with oleic acid enhances policosanol bioavailability, and significantly improves the serum lipid profile in normocholesterolemic rats in association with the inactivation of HMG-CoA red controlling cholesterogenesis.


Download data is not yet available.


Arruzazabala ML, Noa M, Menéndez R, Mas R, Carbajal D, Valdes S, Molina V. 2000. Protective effect of policosanol on atherosclerotic lesions in rabbits with exogenous hypercholesterolemia. Braz. J. Med. Biol. Res. 33, 835-840. PMid:10881060

Batista J, Stusser R, Saez F, Pérez B. 1996. Effect of policosanol on hyperlipidemia and coronary heart disease in middle-aged patients. A 14-month pilot study. Int. J. Clin. Pharmacol. Ther. 34, 134-137. PMid:8705091

Berthold H, Unverdoeben S, Degenhardt R, Bulitta M, Gouni-Berthold I. 2006. Effect of lipids policosanol on lipid levels among with hypercholesterolemia or combined hyperlipidemia. JAMA. 295, 2262-2269. PMid:16705107

Brockerhoff H. 1970. Substrate specificity of pancreatic lipase: Influence of the structure of fatty acids on the reactivity of esters. Biochim. Biophys. Acta. 212, 92-101.

Buhman KK, Accad M, Novak S, Choi RS, Wong JS, Hamilton RL, Turley S, Farese RV Jr. 2000. Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat. Med. 6, 1341-1347. PMid:11100118

Castaño G, Mas R, Arruzazabala ML, Noa M, Illnait J,Fernandez JC, Molina V, Menendez A. 1999. Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients. Int. J. Clin. Pharm. Res. 19, 105-116. PMid:10939028

Castaño G, Mas R, Fernández L, Fernández JC, Illnait J, López LE, Alvarez E. 2000. Effects of policosanol on postmenopausal women with type II hypercholesterolemia. Gynecol. Endocrinol. 14, 187-195. PMid:10923280

Castaño G, Mas R, Fernández L, Illnait J, Gámez R, Alvarez E. 2001. Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study. Int. J. Clin. Pharmacol. Res. 21, 43-57. PMid:11708574

Castaño G, Mas R, Fernández L, Illnait J, López E, Gamez R, Mendoza S, Fernández J, Mesa M. 2003. Effects of D-003 on the lipid profile of patients with type II hypercholesterolemia: a phase II clinical study. Clin. Drug Investig. 23, 789-802. PMid:17536893

Choudhury N, Tan L, Truswell AS. 1995. Comparison of palmolein and olive oil: effects on plasma lipids and vitamin E in young adults. Am. J. Clin. Nutr. 61, 1043-1051. PMid:7733026

Clifton P. 2009. Lowering cholesterol - a review on the role of plant sterols. Aust. Fam. Physician 38, 218-221. PMid:19350071

Crespo N, Illnait J, Mas R, Fernández L, Fernández JC, Castaño G. 1999. Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. Int. J. Clin. Pharmacol. Res. 29, 117-127.

Dulin M, Hatcher L, Sasse H, Barringer T. 2006. Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled. Am. J. Clin. Nutr. 84, 1543–1548. PMid:17158441

Francini-Pesenti F, Brocadello F, Beltramolli D, Nardi M, Caregaro L. 2008a. Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study. Complement Ther. Med. 16, 61-65. PMid:18514906

Francini-Pesenti F, Beltramolli D, Dall'acqua S, Brocadello F. 2008b. Effect of sugar cane policosanol on lipid profile in primary hypercholesterolemia. Phytother. Res. 22, 318-322. PMid:18167048

González-Bravo L, Magraner-Hernández J, Acosta-Gonzalez PC, Pérez-Souto N. 1996. Analytical procedure for the determination of 1-octacosanol in plasma by solvent extraction and capillary gas chromatography. J. Chromatogr. B Biomed. Appl. 682, 359-363.

Gouni-Berthold I, Berthold HK. 2002. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am. Heart J. 143, 356-365. PMid:11835043

Greyling A, DeWitt C, Oosthuizen W, Jerling J. 2006. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolemic and heterozygous familial hypercholesterolemic subjects. Br. J. Nutr. 95, 968–975. PMid:16611388

Haim D, Berrios M, Valenzuela A, Videla L. 2009. Trace quantification of 1-octacosanol and 1-triacontanol and their main metabolites in plasma by liquid-liquid extraction coupled with gas chromatography mass spectrometry. J. Chromatogr. B. Biomed. Appl. 887, 4154-4158.

Haim D, Videla L. 2008. Policosanols, protective natural compounds in cardiovascular disease. Agro Food Industry Hi-Tech. 19, 60-63.

Hargrove JL, Greenspan P, Hartle DK. 2004. Nutritional significance and metabolism of very long chain fatty alcohols and acids from dietary waxes. Exp. Biol. Med. 229, 215-226.

Hayes KC, Khosla P. 1992. Dietary fatty acid thresholds and cholesterolemia. FASEB J6, 2600-2607. PMid:1592210

Hernandez F, Illnait J, Mas R. 1992. Effect of policosanol on serum lipid and lipoproteins in healthy volunteers. Curr. Ther. Res. Clin. Exp. 51, 568-575.

Janikula M. 2002. Policosanol: a new treatment for cardiovascular disease? Altern. Med. Rev. 7, 203-217. PMid:12126462

Kabir Y, Kimura S. 1993. Biodistribution and metabolism of orally administered octacosanol in rats. Ann. Nutr. Metab. 37, 33-38. PMid:8470870

Kassis AN, Jones PJ. 2006. Lack of cholesterol-lowering efficacy of Cuban sugar cane policosanols in hypercholesterolemic persons. Am. J. Clin. Nutr. 84, 1003-1008. PMid:17093150

Kassis AN, Marinangeli CP, Jain D, Ebine N, Jones PJ. 2007. Lack of effect of sugar cane policosanol on plasma cholesterol in Golden Syrian hamsters. Atherosclerosis 194, 153-158. PMid:17123537

Keller S, Gimmler F. 2008. Octacosanol administration to humans decreases neutral sterol and bile acid concentration in feces. Lipids. 43, 109-115. PMid:18004604

Laemmli UK. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227, 680-685. PMid:5432063

Marrero D, González-Bravo L. 2001. Trace determination of 1-octacosanol in rat plasma by solid-phase extraction with Tenax GC and capillary gas chromatography. J. Chromatogr B. Biomed. Appl. 762, 43-49.

Mas R, Castaño G, Illnait J, Fernandez L, Fernandez J, Aleman C, Pontigas V, Lescay M. 1999. Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors. Clin. Pharmacol. Ther. 65, 439-447.

Mendoza S, Gamez R, Noa M, Mas R, Castaño G, Mesa R, Mesa MS, Armas M. 2001. Comparison of the effects of D-003 and policosanol on lipid profile and endothelial cells in normocholesterolemic rabbits. Curr. Ther. Res. 62, 209-220.

Menendez R, Amor AM, Gonzalez RM, Fraga V, Mas R. 1996. Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats. Biol. Res. 29, 253-257. PMid:9278716

Menéndez R, Amor AM, Rodeiro I, González RM, Gonzalez PC, Alfonso JL, Mas R. 2001. Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts. Arch. Med. Res. 31, 8-12.

Menéndez R, Marrero D, Más R, Fernández I, González L, González RM. 2005. In vitro and in vivo study of octacosanol metabolism. Arch. Med. Res. 36, 113–119. PMid:15847942

Murphy KJ, Saint DA, Howe PR. 2008. Lack of effect of sugar cane and sunflower seed policosanols on plasma cholesterol in rabbits. J. Am. Coll. Nutr. 27, 476-484. PMid:18978167

Ng TK, Hayes KC, DeWitt GF, Jegathesan M, Satgunasingam N, Ong AS, Tan D. 1992. Dietary palmitic acid and oleic acid exert similar effects on serum cholesterol and lipoprotein profiles in normocholesterolemic men and women. J. Am. Coll. Nutr. 11, 383-390. PMid:1506599

Ng Chi H, Leung Ka Y, Huan Y, Cehn Zhen Y. 2005. Policosanol has no antioxidant activity in human lowdensity lipoprotein but increases excretion of bile acids in hamsters. J. Agric. Food Chem. 53, 6289-6293. PMid:16076108

Nissinen MJ, Gylling H, Miettinen TA. 2006. Effects of plant stanol esters supplied in a fat free milieu by pastilles on cholesterol metabolism in colectomized human subjects. Nutr. Metab. Cardiovasc. Dis. 16, 426-435. PMid:16935701

Oliaro-Bosso S, Calcio Gaudino E, Mantegna S, Giraudo E, Meda C, Viola F, Cravotto G. 2009. Regulation of HMG-CoA reductase activity by policosanol and octacosadienol, a new synthetic analogue of octacosanol. Lipids. 44, 907-916. PMid:19763655

Place AR. 1992. Comparative aspects of lipid digestion and absorption: physiological correlates of wax ester digestion. Am. J. Physiol. 263, R464–R471. PMid:1415629

Pons P, Mas R, Illnait J, Fernandez L, Rodriguez M, Robaina C, Fernández JC. 1992. Efficacy and safety of policosanol in patients with primary hypercholesterolemia. Curr. Ther. Res. Clin. Exp. 52, 507-513.

Prat H, Roman O, Pino E. 1999. Comparative effects of policosanol and two HMG-CoA reductase inhibitors on type II hypercholesterolemia. Rev. Med. Chile 127, 286-294. PMid:10436712

Sánchez-Muniz FJ, Cruz-Merinero M, Rodríguez-Gil S, Ordovás JM, Ródenas S, Cuesta C. 2002. Dietary fat saturation affects apolipoprotein AII levels and HDL composition in postmenopausal women. J. Nutr. 132, 50-54. PMid:11773507

Singh BK, Mehta JL. 2002. Management of dyslipidemia in the primary prevention of coronary heart disease. Curr. Opin. Cardiol. 17, 503-511. PMid:12357127

Singh D, Li L, Porter T. 2006. Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP kinase. J. Pharm. Exp. Therap. 318, 1020-1026. PMid:16714400

Torres O, Agramonte AJ, Más R, Fernández L, Fernández JC. 1995. Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care. 18, 393–397. PMid:7555484

Towbin H, Staehelin T, Gordon J. 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA. 76, 4350-4354. PMid:388439 PMCid:411572

Wong AK, Howie J, Petrie JR, Lang CC. 2009. AMPactivated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. Clin. Sci. 16, 607-620. PMid:19275766 PMCid:2762688

Wu T, Fu J, Yang Y, Zhang L, Han J. 2009. The effects of phytosterols/stanols on blood lipid profiles: a systematic review with meta-analysis. Asia Pac. J. Clin. Nutr. 18, 179-186. PMid:19713176




How to Cite

Haim D, Valenzuela A, Brañes MC, Fuenzalida M, Videla LA. The oleic acid esterification of policosanol increases its bioavailability and hypocholesterolemic action in rats. Grasas aceites [Internet]. 2012Dec.30 [cited 2024Jul.24];63(4):345-54. Available from:




Most read articles by the same author(s)