According to the United States National Health and Nutrition Examination Survey (NHANES III), an estimated 5.5 million Americans with coronary heart disease (CHD) should be treated with lipid lowering medication under the National Cholesterol Education Program (NCEP) guidelines. While numbers may vary, it is the same story with every developing and developed country. However, there is a general reluctance among the population to be treated with chemically derived drugs, especially for primary prevention. There is, thus, a need for effective, safe, and ideally, naturally derived cholesterol-lowering drugs.

Policosanol is one such agent currently in use in more than 25 countries throughout the world to reduce elevated LDL-cholesterol in patients with hypercholesterolemia. Policosanol is a mixture of aliphatic primary alcohols isolated and purified from natural waxes. Although human diets have contained waxes for millennia, their metabolism in humans is not well understood.

Policosanol may be represented by the chemical formula CH 3-(CH 2)n-CH 2OH with chain lengths varying from 24 to 34 carbon atoms. Octacosanol (C-28), hexacosanol (C-26) and triacontanol (C-30) are the major constituents. The product was originally developed by the Dalmer Laboratories, Havana, Cuba.

Lipid-lowering effects of policosanol have been shown in a range of animal species. In cultured human fibroblasts, policosanol decreased 14C-labeled acetate into cholesterol whereas 14C-labeled mevalonate was not affected suggesting inhibition of cholesterol synthesis in vitro at a step before the mevalonate formation.

On the basis of published studies, the precise mechanism leading to LDL-C remains unclear, but inhibition of cholesterol synthesis, increased hepatic LDL uptake and increased serum LDL catabolic rates may play a role.

A substantial number of clinical studies have been carried out during short- and long term administration of policosanol in randomized placebo-controlled study designs. In nornocholesterolemic volunteers without dietary restrictions, 10 or 20 mg policosanol per day given for 4 weeks decreased total and LDL-C significantly and dose-dependently. Studies over 6-8 week period in patients with type II hypercholesterolemia indicated that 5 or 10 mg per day would lower total cholesterol by about 13-16% and LDL-C by about 18-22%, respectively. With 20 mg per day, LDL-C can be lowered by about 30%. HDL-C increased only slightly and triglyceride levels showed a variable response.

Long term studies over a 1-year period with 5 mg per day and over 2 years with 10 mg per day showed that the hypocholesterolemic action was maintained throughout and maximal effects were reached after 6-8 weeks of treatment. Increase in HDL-C seemed to develop more slowly. In this respect, policosanol seems to be superior to statins and fibrates. Policosanol does not induce a rebound effect after cessation of treatment.

In a study with type II hypercholesterolemia and concomitant hypertension, it was shown that policosanol significantly lowered systolic blood pressure by a mean 10 mmHg.

A study in patients with type II hypercholesterolemia and 2 or more additional risk factors confirmed the efficacy and safety profile of the drug.

A study over 1 year with 20 mg per day in patients with high risk (88% family history of premature CHD, 71% hypertension, 60% previous coronary events, 60% severe hypercholesterolemia) demonstrated an impressive decrease in LDL-C of 44% and an increase in HDL-C of 68.5%

In studies comparing the relative efficacies of policosanol with statins, results were comparable.

There is evidence from animal studies that policosanol prevents the onset of spontaneously and experimentally induced atherosclerosis. It also seems to have effects on smooth muscle cell proliferation, LDL oxidation and platelet aggregation.

In rabbits and rats it reduces the development of atherosclerotic lesions, including foam cell formation. Antiplatelet effects were also shown in healthy human volunteers, comparable to that of aspirin. This seems to be the most promising additional feature of this lipid lowering drug.

The recommended starting dose of policosanol is 5 mg once a day, taken with the evening meal, which can be increased to 10-20 mg/day. Higher doses, up to 80 mg per day, are currently being studied. The drug is contraindicated during pregnancy, although no teratogenic effects have been reported in animal models.

It is also not known whether the drug or its metabolites pass into human milk; therefore, therapy must be discontinued during lactation.

Treatment of children is not recommended for lack of data in this particular population. The drug seems to be safe in elderly subjects.