Policosanol Ineffective for Treating Hyperlipidemia

By Donald Brown, ND, Founder and Director, Natural Product Research Consultants, Inc.; Advisory Board, American Botanical Council; President's Advisory Board, Bastyr University, Seattle; Advisor to the Office of Dietary Supplements at the National Institutes of Health. Dr. Brown is a consultant for Nature's Way, Inc.

Source: Berthold HK, et al. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: A randomized controlled trial. JAMA 2006;295:2262-2269.

Abstract: In a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, the efficacy of policosanol was studied in adults with hyperlipidemia. The trial included 143 subjects (aged 18-80 years) with hypercholesterolemia or combined hyperlipidemia. Inclusion criteria included an LDL-C level of at least 150 mg/dL (≥ 3.88 mmol/L) and either no or one cardiovascular risk factor other than known coronary heart disease, or baseline LDL-C levels of between 150-189 mg/dL (3.88–4.89 mmol/L) and two or more risk factors. Following an open-label, six-week placebo and diet run-in phase, subjects were randomized to one of five groups: 10, 20, 40, or 80 mg/d of policosanol or placebo. The policosanol in the study was derived from sugar cane and was provided by Dalmer Laboratories (La Habana, Cuba). The tablets were manufactured by Madaus AG (Cologne, Germany). The treatment period was 12 weeks.

The main primary outcome measure was the percentage change of LDL-C, with changes in other lipoproteins (TC, VLDL-C, HDL-C, lipoprotein[a] and triglycerides) as secondary outcome measures. In addition to screening and baseline blood draws, patients were seen for blood draws at weeks 6 and 12. The per-protocol analysis was completed on 129 patients (placebo, n = 25; 10 mg policosanol, n = 26; 20 mg, n = 25; 40 mg, n = 24; 80 mg, n = 29). LDL-C levels did not decrease by more than 103% of baseline in any of the five treatment groups. No statistically significant difference was found between placebo and any of the four policosanol groups. A nonparametric test analyzing dose-dependency yielded nonsignificant results. There were no significant effects for policosanol on any of the secondary measures including ratio of TC or LDL-C to HDL-C. Policosanol was well tolerated without any serious adverse events.

Comments

Policosanol is a natural mixture of alipathic alcohols derived from beeswax and plant sources such as sugar cane, wheat germ, and rice bran. Originally developed by Dalmer Laboratories in Havana, Cuba, the most widely researched form is derived from sugar cane (Saccharum officinarum L.) by hydrolytic cleavage. The major components of the mixture are octocosanol (62.9%), triacontanol (12.6%), and hexacosanol (6.2%). Because of trade restrictions with Cuba, the Dalmer Laboratories policosanol product has not been available in the United States. This has not stopped alternative forms from appearing on the market. In fact, in May 2005 Bayer introduced a One-A-Day Cholesterol Plus product that contains 10 mg of policosanol said to be derived from sugar cane.

A 2002 meta-analysis of Cuban clinical trials completed with policosanol found that at doses of 10-20 mg/d, the sugar cane-derived extract lowered total cholesterol by 17-21% and LDL-C by 21-29% and raised HDL-C by 8-15%.1 The meta-analysis also reports that in doses up to 20 mg/d, policosanol is safe in studies lasting up to three years. The authors mention that the efficacy and tolerability of policosanol have been documented in more than 3,000 patients in more than 60 clinical trials. No evaluation of the quality of these clinical trials is provided, but the reviewers did stress the need for independent confirmation of these results. The two authors of the review got their chance as they are two of the five principal investigators in this new clinical trial.

The current German clinical trial is the best designed study to date with policosanol. Not only does it use the original Dalmer Laboratories Cuban sugar cane extract but it also provides the highest dose studied to date (80 mg/d). The authors of the study noted that previous studies supporting the efficacy of policosanol primarily were completed by a single research group in Cuba (one positive trial was completed in Russia). Although the number of trials and the number of patients studied has been impressive, a close look at the data found that the quality of statistical analysis to be poor—incredibly high P values based on comparison to baseline with no inter-group comparisons completed. Although the new study supports the safety and tolerance of policosanol, it strongly refutes these earlier findings and suggests that policosanol is devoid of any significant lipid-lowering properties.

A small clinical trial published this year also found no significant effect on serum lipid levels after 12 weeks of 20 mg/d of sugar cane-derived policosanol in 44 adult patients with hypercholesterolemia.2 As mentioned above, the Cuban policosanol currently is not available in the United States and translating these findings to the alternate sources sold in dietary supplements is difficult. So, the ball is now squarely in the court of manufacturers of policosanol to demonstrate that their products are clinically effective.

Conclusion

Although many critics of the Cuban clinical trials on policosanol have called for independent studies to confirm its effectiveness for hyperlipidemia, policosanol products have continued to flourish in the U.S. supplement market. This clinical trial is the first to be completed outside of Cuba and also the first to add higher doses of 40 mg/d and 80 mg/d. While demonstrating safety, the study finds no clinically relevant lipoprotein-lowering effects. Until another well-designed, independent study demonstrates efficacy for policosanol, it should be removed from the list of clinical considerations for patients with hyperlipidemia.

References

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

2. Greyling A, et al. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolemic and heterozygous familial hypercholesterolemic subjects. Br J Nutr 2006;95:968-975.