Background and Relevant Pharmacokinetics
Policosanol is isolated from the waxes of plants such as sugar cane. The main component, octacosanol, has variable absorption from the small intestine and is chiefly metabolised by the liver and excreted in the faeces.
Policosanol is a mixture of long-chain primary aliphatic alcohols.
Policosanol: Main Actions
LOWERS TOTAL CHOLESTEROL LEVELS, INCREASES HDL-CHOLESTEROL AND REDUCES LDL-CHOLESTEROL LEVELS
The exact mechanism of action responsible for this activity has not been fully elucidated; however, several theories exist. One observation that appears to be agreed on by researchers is that policosanol does not inhibit the activity of HMG-CoA reductase, although it produces similar clinical results to HMG-CoA reductase inhibitors.
Some data indicate that policosanol inhibits cholesterol synthesis at an earlier point in the cholesterol biosynthetic pathway and increases LDL-cholesterol processing. Other evidence indicates that policosanol downregulates the cellular expression of HMG-CoA reductase by up to 50%, thereby suppressing biosynthesis of the enzyme. It has also been suggested that policosanol may stimulate the degradation of HMG-CoA reductase. Furthermore, animal studies suggest that LDL catabolism may be enhanced.
REDUCES OXIDATION OF LDL-CHOLESTEROL
This has been demonstrated in vitro at an equivalent dose of 5 and 10 mg/day.
REDUCES PLATELET AGGREGATION
This has been confirmed in animal models and randomised double-blind studies, with effects starting at 10 mg/day. One clinical study found that a dose of 20 mg/day policosanol produces the same inhibitory effects on platelet aggregation as 100 mg aspirin daily. A higher dose of 40 mg policosanol does not appear to produce any further antiplatelet effects according to another double-blind study. Thromboxane, but not prostacyclin, generation induced by collagen is also inhibited by policosanol in clinical studies.
Policosanol: Other Actions
Oral administration of policosanol to spontaneously hypertensive rats resulted in a significant reduction in circulating endothelial cells compared with controls. Moreover, comparison between groups revealed a lower frequency of aortic lesions in policosanol-treated animals than in untreated animals.
ANTIHYPERTENSIVE EFFECTS AT VERY HIGH DOSES
Tests in animal models have identified enhancement of propranolol-induced hypotensive effects with pretreatment at 200 mg/kg policosanol, which is an extremely high dose and clinically irrelevant in humans.
REDUCES ATHEROSCLEROTIC LESION DEVELOPMENT
According to one animal study, most policosanol-treated animals did not develop atherosclerotic lesions compared with an untreated group, and the thickness of fatty streaks that did develop with treatment had fewer foam cell layers than in controls.