Policosanol: Cuban lipid crisis revisited

Policosanol was borne out of the first state-sponsored research centre after the Cuban revolution, the Cuban Institute for Research on Sugar Cane Derivatives.1 As the name implies, policosanol is a mixture of many (poly) cosanols, cosanols being long-chain aliphatic alcohols (LCAs; 22-38 carbons in length), and is derived from the waxy fraction of sugar cane.

The unique Cuban policosanol mixture (CPC) houses the vast majority of the clinical evidence base. But because the Cuban entity that markets the material (Dalmer Laboratories, Havana) failed to register a trademark for the name 'policosanol,' it has taken on a generic persona and ushered in a generic ingredient supply chain. Other policosanol biomass sources under exploration include wheat, rice bran, beeswax, sorghum and even flax waste stream.2,3,4,5

The initial excitement with policosanol was linked to research on the Cuban variety. Most research resides in lower-impact journals, was conducted by the inventors of CPC and their Cuban colleagues, and employed sample cohorts comprising almost exclusively Latino subjects from Central and South America. A 2002 review of the CPC data published in a top-tier cardiology journal greatly enhanced CPC/policosanol.6 More than 20 peer-reviewed randomised controlled trials (RCTs) were profiled in this review, which described CPC as very well tolerated and safe, natural, and "a fascinating new agent for the prevention and treatment of atherosclerotic disease."

A 2005 review, which compared the efficacy of CPC to phytosterols and stanols, found CPC to be superior in its hypolipidaemic activity.7 However, this review failed to discern the difference between generic policosanol and CPC.

The efficacy and effectiveness of generic, non-CPC policosanol (gPC) until recently has been unknown. In the first gPC RCT, German researchers randomised 60 normo- to mildly hyperlipidaemic subjects to receive 20mg/day of a wheat germ-derived gPC for four weeks.8 No changes in blood lipids were noted in this very short study, which used a gPC with a chemoprofile quite similar to that of CPC.

Another RCT included an eight-week run-in phase with an American Heart Association Step I diet, followed by randomisation to 10mg of rice-derived gPC (with a chemoprofile quite different from CPC) once nightly, or placebo, for eight weeks.9 Total cholesterol fell by only five per cent in the gPC group, a statistically significant but clinically insignificant outcome, with no changes in LDL or HDL cholesterol, C-reactive protein, or total homocysteine.

A 2006 South African RCT using a Chinese-produced sugar-cane wax gPC, boasting a similar chemoprofile to CPC, assigned 19 hyperlipidaemic men and women to placebo or 20mg gPC for 12 weeks, followed by a four-week washout, and then a crossover.10 The gPC proved no different than placebo.

Two recent clinical trials done outside of Latin America have raised the spectre of 'ethnopharmacogenomic' specificity and/or publication bias with CPC. In the first study, Canadian researchers randomised 21 Canadian hyperlipidaemic men and women to placebo or 10mg CPC for 28 days, with a washout and crossover.11 None of the blood-lipid parameters changed significantly. In a widely publicised study in the Journal of the American Medical Association, the same researchers that were exuberant about the promise of CPC6 collaborated on a German multi-centre, dose-escalation RCT randomising 143 hyperlipidaemic men and women after a run-in diet phase.12 Subjects were assigned to receive 10, 20, 40 or 80mg/day CPC (supplied by Dalmer Laboratories), or placebo. None of the lipid parameters changed significantly in any group.

The evidence base supporting CPC has eroded dramatically since its global 'birth' at the turn of the 21st century. The ostensible promise and the eventual disappointment underscore the need for independent RCTs, and for multi-ethnic interventions.

1. Carr K. Cuban biotechnology treads a lonely path. Nature 1999;398:A22-3.
2. Irmak S, et al. Policosanol contents of beeswax, sugar cane and wheat extracts. Food Chem 2006;95:312-8.
3. Ha TY, et al. Changes in nutraceutical lipid components of rice at different degrees of milling. Eur J Lipid Sci Technol 2006;108:175—81.
4. Awika JM and Rooney LW. Sorghum phytochemicals and their potential impact on human health. Phytochemistry 2004;65:1199—1221.
5. Morrison WH III, et al. Cuticular wax from flax processing waste with hexane and super critical carbon dioxide extractions. Ind Crops Prod 2006;in press.
6. Gouni-Berthold I and Berthold HK. Policosanol: Clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002;143:356-65.
7. Chen JT, et al. Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy 2005;25:171-83.
8. Lin Y, et al. Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations. Metabolism 2004;53:1309-14.
9. Reiner Z, et al. Effects of rice policosanol on serum lipoproteins, homocysteine,.fibrinogen and C-reactive protein in hypercholesterolaemic patients. Clin Drug Invest 2005;25:701-7.
10. Greyling A, et al. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolaemic and heterozygous familial hyper-cholesterolaemic subjects. Br J Nutr 2006 (in press).
11. Kassis AN and Jones PH. Evaluation of policosanols as functional foods for cholesterol-lowering. FASEB J 2006;20:A1026.
12. Berthold HK, et al. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia. JAMA 2006;295:2262-9.

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