Policosanol was a name originally given to a unique extract of Cuban sugarcane (Saccharum officinarum) derived from the plant's waxy fraction. The origins of policosanol read more like a sociopolitical treatise than a science experiment. In 1964, Che Guevara, Cuba's minister of industry, created the first post-revolution state-sponsored research center, the Cuban Institute for Research on Sugar Cane Derivatives.1 The Institute's intent was to identify high-value bioactive sugarcane derivatives that would ultimately surpass the value of refined white sugar. The first product with such potential was policosanol. It is sold as a patented agent for lowering cholesterol in more than 40 countries. One notable exception is the United States.
Policosanol's Chemical Composition
As the name implies, policosanol is a mixture of many (poly) cosanols, cosanols being long-chain alcohols, with no biological similarity to ethanol. The length of these LCAs ranges from 22 to 38 carbons (for reference, the long-chain fatty acids EPA and DHA have 20 and 22 carbons, respectively). Cuban policosanol contains eight LCAs in specific amounts. This LCA blend is the subject of several patents pending and issued worldwide, including two U.S. patents issued.2,3
Erroneously, the term octacosanol is sometimes used to refer to policosanol, even in the biomedical literature. This once-lauded ergogenic aid that still lacks convincing evidence of efficacy in humans contains roughly two-thirds the LCAs of Cuban policosanol. Studies conducted by Cuban researchers show octacosanol has only mild, if any, blood-lipid-modifying effects compared with the native sugarcane wax LCA blend.2 Given the claims of issued patents, producing, marketing, selling or importing a mixture that falls into the recipe described therein would constitute patent infringement. However, simply removing one of the LCAs described in the Cuban policosanol composition would enable "patent circumvention." At least one U.S. company has tried this maneuver, but the science that lauds policosanol refers to the Cuban material only.
Barrier To Entry
Only the Havana-based Dalmer Laboratories' Cuban policosanol product is backed with substantive science, but it is not available in the United States. (Recall the United States' total trade embargo with Cuba.) A few years ago, commercial interests were attracted by the evidence supporting Cuban sugarcane-derived policosanol, but the economic embargo forced them to search for an alternative. Some companies have introduced imitations and falsely claimed the scientific efficacy of the Cuban original. Unfortunately, Dalmer Laboratories never registered the trademark "policosanol," so any company or entity can associate this name with products or ingredients containing LCAs.
The sources for imitation policosanol products include sugarcane wax extracts produced outside of Cuba, rice bran wax and beeswax. For the latter, a U.S. patent4 has been issued and two more have been filed in alliance with Hauser Laboratories in Boulder, Colo. The patent describes two different apisol (api- for bee-derived) compositions with eight or nine LCAs derived from beeswax via organic solvent extraction. The research is solid for the Cuban policosanol derived from sugarcane wax. But there have been no systematic and placebo-controlled studies to date documenting the long-term safety and efficacy of non-Cuban sugarcane "policosanol" products or of products derived from other LCA sources. Although such "policosanol" products may lower cholesterol, it is wise to consider them ineffective until proven otherwise.
Basic and clinical pharmacology
In numerous studies, researchers have tried to determine how Cuban policosanol modifies blood-lipid and lipoprotein metabolism. Some compare Cuban policosanol to statin drugs, theorizing it inhibits the enzyme HMG-CoA reductase (the rate-limiting step in cholesterol synthesis), but there is no convincing evidence to support this assertion.5 Recently, researchers suggested Cuban policosanol alters the enzyme activity via mechanisms that operate independent of direct inhibition.6 This could include an alteration of enzyme turnover, that is, either decreased gene expression, protein synthesis of the enzyme itself, accelerated enzyme breakdown or some combination thereof. No studies have directly measured any of these parameters, however. It does appear that, at least as described in in vitro studies, Cuban policosanol could achieve the same results as a statin drug, albeit through a slightly different mechanism.
From an in vivo perspective, it is more difficult to ascertain Cuban policosanol's mechanism of action. It appears that a fractional dose of the LCAs is absorbed. No available data describe the pharmacokinetics of the various LCAs that comprise Cuban policosanol. Of the evidence that is available, there are only studies with radioactively labeled octacosanol and they do not discern if this 28-carbon LCA enters the circulation intact. Moreover, octacosanol alone does not have potent blood-lipid-modulating activity. Thus, octacosanol's pharmacokinetic data cannot be extrapolated to Cuban policosanol in vivo.
Results of clinical trials indicate doses ranging from 5 to 40 mg per day modify lipid metabolism. Further, Cuban policosanol has clinical efficacy and tolerability documented in more than 3,000 patients from more than 60 clinical trials.9 However, almost all of the studies have been conducted in Hispanic populations, primarily in Central and South America. This raises the question: Do certain ethnic groups respond differently to individual drugs?10 The following literature review centers on research studies originally published in English.
- Short-term blood-lipid modification
- Long-term blood-lipid modification
- Standing up to statins
Results of several short-term (six- to eight-week) randomized placebo-controlled trials involving individuals with elevated low-density lipoprotein cholesterol taking 5-mg doses of policosanol once or twice daily have been positive. Subjects reduced their LDL cholesterol levels by 11 percent and 22 percent from baseline.11,12Two randomized controlled trials have shown a dose-dependent (5, 10 or 20 mg per day) reduction in LDL levels, with a 10-mg twice-daily dose eliciting LDL reductions similar to statin drugs (30 percent from baseline).13,14 In these two studies, researchers employed successive dose escalation schedules: Subjects took one dose for six or eight weeks then transferred to a higher dose with no washout interval. Statistically significant or favorable changes in high-density lipoprotein cholesterol or triglycerides did not occur in either study.
Most of the subjects in the aforementioned randomized controlled trials were asked to follow a lipid-lowering diet prior to and during the supplementation period. Among individuals with blood lipids in the normal range who did not modify their diets, four weeks of dose-dependent (10 or 20 mg per day) Cuban policosanol supplementation lowered blood LDL cholesterol levels.15 The patients who received 20 mg per day displayed a statistically significant reduction in LDL (22 percent below baseline), and a statistically significant increase in HDL (23.9 percent above baseline). Researchers conducting a more recent one-month randomized controlled trial with 45 normolipidemic subjects did not report any statistically significant changes in LDL or HDL cholesterol levels with 20 mg (10 mg twice daily) or 40 mg (20 mg twice daily).16 However, among another 45 subjects (in the same study) with elevated LDL cholesterol levels, both doses of Cuban policosanol caused equal reductions in LDL (16 percent and 17 percent, respectively), with a modest (5 percent) but significant increase in HDL. This is one of the very few randomized controlled trials involving "high" doses of Cuban policosanol.
Researchers have evaluated the responses of numerous specific patient groups to Cuban policosanol in more than a dozen studies. Two 12-week randomized controlled trials involved 48 patients who had elevated LDL cholesterol levels and type 2 diabetes.17,18 These patients were given 5 mg Cuban policosanol twice daily, which resulted in statistically significant reductions of LDL levels (22 percent to 44 percent). In one of these studies, researchers also reported a significant increase in HDL cholesterol levels (25 percent).17 One large randomized controlled trial involving 244 postmenopausal women with elevated LDL cholesterol levels (on a lipid-lowering diet) showed that a single daily 5-mg dose taken for 12 weeks reduced LDL levels by 18 percent and increased HDL levels by 17 percent. For a successive 12-week period, subjects given 10 mg per day further changed these lipids by 7 percent and 12 percent, respectively.19 In an even larger study involving 437 subjects with elevated LDL levels and more than two heart disease risk factors, such as hypertension, smoking or family history, and who were following a lipid-lowering diet, researchers noted favorable changes of 18 percent and 16 percent in LDL and HDL (from baseline), respectively. These patients received 5 mg per day for 12 weeks.20 As part of the same study, researchers increased the dose to 5 mg twice daily for an additional 12 weeks, which lowered LDL levels by 26 percent and increased HDL levels by 28 percent.
To understand policosanol's long-term effects on lipid profiles, researchers have conducted several randomized controlled trials. Two different one-year studies, one involving 59 subjects taking 5 mg daily, the other with 97 subjects taking 5 mg twice daily, revealed statistically significant favorable and sustained changes in LDL and HDL levels.21,22 In the first randomized controlled trial involving 280 patients (average age 65) with elevated LDL levels and preexisting coronary heart disease, researchers gave the subjects 5 mg once or twice daily (the dose was increased at six months if lipid response was deemed inadequate). This protocol produced statistically significant lipid changes in LDL and HDL levels and a lower number of adverse vascular events.23 Adverse events included transient ischemic strokes, thrombosis or edema of the limbs. Only one patient taking Cuban policosanol had an adverse cardiac event (unstable angina), compared with 10 taking placebo (four had heart attacks and six experienced unstable angina). In the second one-year randomized controlled trial involving 589 patients with elevated LDL levels (more than half had a family history of coronary heart disease) and a similar dosing regimen, researchers reported a 21 percent drop in patients' LDL levels, a 12 percent drop in triglycerides and a 13 percent increase in HDL levels.24 The policosanol group also experienced fewer adverse vascular events, a statistically significant finding. This study is notable because most Cuban policosanol studies have not reported triglyceride reductions. Results of the longest randomized controlled trial published to date involved only 69 patients with elevated LDL levels. Researchers followed them for more than two years, after which time subjects' LDL levels were 25 percent lower than at the start and HDL levels were 11 percent higher, both statistically significant findings.25
The true test of any natural product's efficacy, arguably, is how it performs in a head-to-head comparison trial against a drug of choice. In the land of lipids, the reigning king is statin. This class of drugs inhibits the "gatekeeper" of cholesterol synthesis in the body, HMG-CoA reductase.
In one eight-week study with 68 older patients who had both elevated LDL levels and various coronary heart disease risk factors, researchers found 10 mg of Cuban policosanol taken once daily reduced (from baseline) LDL levels by 19 percent and triglycerides by 14 percent, and increased HDL levels by 18 percent, all statistically significant changes.26 The statin group (10 mg per day of pravastatin, the lowest dose recommended) triggered a 16 percent reduction in LDL levels, no change in triglycerides, and a 6 percent increase in HDL levels.
Another eight-week trial compared 10 mg Cuban policosanol with 20 mg fluvastatin taken once daily in 70 older female subjects with elevated LDL levels.27 By the end of the trial, the LDL and HDL changes were statistically superior to those seen in the statin group, with no effect on triglycerides in either group.
What remains to be demonstrated is whether the long-term use of policosanol reduces coronary heart disease rates as well as statins do. Such studies are unlikely because of the near-prohibitive costs and time needed to complete such research.
The dozens of randomized controlled trials on Cuban policosanol have provided researchers abundant safety data and adverse events reports. The beneficial side effects associated with Cuban policosanol supplementation include modestly reduced body weight, lowered blood pressure, decreased oxidative stress markers and improved blood platelet function. Typical undesirable side effects include increased urination, headaches, dizziness and increased hunger.28 Compared with statin drugs, side effects typically were less frequent in the policosanol groups.9,26,27
Long-term animal toxicology studies show no increased incidence of cancer development for two years,29 reproductive harm or fetal toxicity,30 although use of Cuban policosanol is not recommended for pregnant or lactating women.9 This may be a prudent recommendation for any "policosanol" product.
Researchers recently demonstrated the safety and tolerability of Cuban policosanol at doses of 5 or 10 mg per day in hyperlipidemic adolescent boys and girls (11 to 19 years) in a 12-week randomized controlled trial.31 The only noted effect was a reduction in liver enzymes (suggesting nontoxicity) in the Cuban policosanol group, and the beneficial changes in LDL and HDL levels seen in virtually all the adult studies.
Cuban policosanol is by far the fastest runner, but is disallowed from winning the race in blood-lipid management and cardiovascular disease risk reduction. The Cuban embargo fosters a denial of data, and a surfeit of imposter products with no data or a paucity of data, and possibly some black-market imports. Until companies marketing "policosanol" from other sources make the research investment that has been made in the Cuban product, there is no substitute.
Disclosure: No conflicts related to Cuban policosanol or any "policosanol" manufacturer or marketer.
Anthony L. Almada, BSc, MSc, is the president and chief scientific officer of IMAGINutrition Inc. (www.imaginutrition.com) and has been a co-investigator on more than 60 randomized controlled trials.
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3. Granja AL, et al. Mixture of higher primary aliphatic alcohols, its obtention from sugar cane wax and its pharmaceutical uses. United States Patent No. 5856316, 1999.
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17. Torres O, et al. Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care 1995;18:393-7.
18. Crespo N, et al. Effects of policosanol on patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia: A pilot study. Curr Ther Res 1997;58:44-51.
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26. Castano G, et al. Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients. Int J Clin Pharmacol Res 1999;19:105-16.
27. Fernandez JC, et al. Comparison of the efficacy, safety and tolerability of policosanol versus fluvastatin in elderly hypercholesterolemic women. Clin Drug Invest 2001;21:103-13.
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29. Aleman CL, et al. Carcinogenicity of policosanol in Sprague Dawley rats: a 24 month study. Teratog Carcinog Mutagen 1994;14:239-49.
30. Rodriguez MD, Garcia H. Evaluation of peri- and post-natal toxicity of policosanol in rats. Teratogenesis Carcinog Mutagen 1998;18:1-7.
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Natural Foods Merchandiser volume XXIV/number 1/p. 50, 52, 56
Natural Foods Merchandiser volume XXIV/number 1/p. 50
Natural Foods Merchandiser volume XXIV/number 1/p. 52