Policosanol: Clinical Use. Dosage

Most clinical studies have been conducted in Cuba with policosanol derived from sugar cane.

HYPERLIPIDAEMIA

Numerous randomised, double-blind clinical trials conducted prior to 2005 demonstrated significant cholesterol-lowering effects of oral policosanol; however, one recent study has produced negative results. Several previous studies conducted with postmenopausal women have confirmed efficacy in this population. Overall, these results show that a daily dose of 5 mg policosanol may:

• reduce LDL-cholesterol by 11 -18%

• reduce total cholesterol by 8-1 5%

• increase HDL by 8-1 5%

Whereas a higher dose of 20 mg policosanol daily can:

• reduce LDL-cholesterol by 31%

• reduce total cholesterol by 23%

• increase HDL by 27%.

Recent controversy

It is important to note that previous research had been conducted almost entirely by the same research group in Cuba and involved Hispanic patients. In 2006, Berthold et al conducted a 12-week randomised study of 143 Caucasian subjects with hypercholesterolaemia or combined hyperlipidaemia. In contrast to previous studies, policosanol failed to significantly reduce LDL-cholesterol, total cholesterol, HDL-cholesterol, triglycerides and other lipid parameters at all test doses (10, 20, 40, 80 mg/day). It has been proposed that these results differed from previous studies because of possible differences between test subjects and/or bias, which could have influenced the conduct of previous studies, leading to erroneous positive findings.

Studies of type 2 diabetes

Policosanol has proven effects in dyslipidaemia secondary to type 2 diabetes mellitus according to two studies.

Comparative trials with HMG-CoA reductase inhibitor

Several randomised, double-blind studies comparing the effects of policosanol with standard hyperlipidaemic treatment (with statin drugs such as simvastatin and pravastatin) have produced favourable results. A dose of 10 mg policosanol daily reduced LDL-cholesterol by 24%, compared with 22% reduction with lovastatin and 1 5% reduction with simvastatin. Additionally, policosanol treatment reduced HDL significantly, whereas the other treatments had no effect. Another study demonstrated better cholesterol- and LDL-lowering effects for 10 mg policosanol compared with 20 mg lovastatin. Additionally, policosanol significantly raised HDL-cholesterol levels, was better tolerated and had a superior safety profile. A trial comparing pravastatin 10 mg/day with policosanol 10 mg/day found that the policosanol treatment produced greater reductions in total cholesterol and LDL levels and was the only treatment to increase HDL. Additionally, policosanol was more effective than pravastatin in inhibiting platelet aggregation.

More recently, policosanol (10 mg/day) taken for 8 weeks was found to be less effective than atorvastatin (10 g/day) in reducing serum LDL-cholesterol and total cholesterol levels in older patients with type II hypercholesterolaemia. Policosanol, but not atorvastatin, however, significantly increased serum HDL-cholesterol levels, whereas both drugs similarly reduced atherogenic ratios and serum triglycerides.

Concurrent use with omega-3 essential fatty acids

Due to the favourable effects of omega-3 fatty acids (FAs) in cardiovascular disease, in practice clinicians have recommended policosanol together with fish-oil supplements. According to an 8-week, double-blind, randomised study, the combination effectively reduced total cholesterol, LDL-cholesterol and triglycerides and increased HDL-cholesterol. The study of 90 patients with type II hypercholesterolaemia found that when omega-3 FAs (2 g/day) were combined with policosanol (10 mg/day), there was a significant decrease in total cholesterol (1 5.3%) and triglycerides (14.7%), and a significant increase in HDL-cholesterol (1 5.5%).

Concurrent use with beta-blockers

A 3-year randomised study of 205 older hypercholesterolaemic patients taking beta-blockers to showed that after 1 year of therapy, policosanol significantly reduced LDL-cholesterol (20.9%), total cholesterol (19.3%) and triglycerides (25.7%) and increased HDL-cholesterol levels (4.1 %), effects that lasted for the duration of the study. The frequency of mild, moderate or severe adverse events was lower in the policosanol group than in the placebo group; however, an additional reduction in SBP and DBP was observed in the policosanol patients compared with those in the placebo group. Wheat-germ-derived policosanol No beneficial effects on blood lipid profiles were observed in a double-blind, randomised study of 58 subjects with normal to mildly elevated plasma cholesterol who were given 20 mg wheat-germ policosanol in the short 4-week study.

INTERMITTENT CLAUDICATION

Policosanol treatment for intermittent claudication has produced encouraging results in several randomised studies. Policosanol 10 mg/day taken for 6 months significantly increased initial claudication distance by approximately 70 metres and absolute claudication by approximately 140 metres in one double-blind study, whereas placebo produced no changes. A single-blind study using 20 mg policosanol daily showed significant improvements after 6 months’ treatment, which further increased after 12 months. In both studies patients in the policosanol group reported improvements in lower limb symptoms that were greater than those in the placebo group.

More recently, policosanol (10 mg twice daily) was shown to be as effective as ticlopidine (250 mg twice daily) for improving walking distances of claudicant patients. In the 20-week double-blind, randomised study of 28 subjects, policosanol significantly increased mean values of initial and absolute claudication distances from 162.1 to 273.2 metres and from 255.8 to 401.0 metres, respectively, which was not significantly different to ticlopidine. Both treatments were well tolerated.

Policosanol: Other Uses

PRE-EXISTING CORONARY HEART DISEASE (CHD)

A randomised double-blind study of 45 subjects with documented CHD found that a dose of 10 mg policosanol daily increased maximum oxygen uptake and exercise ECG responses. The effects were further enhanced by co-administration of 125 mg aspirin.

CEREBROVASCULAR DISEASE

In two different experimental models policosanol had anti-ischaemic activity when administered after induction of cerebral ischaemia, suggesting a possible therapeutic effect in CVD.

Policosanol: Dosage Range

• The doses tested in clinical trials range from 5-20 mg/day.

More specific doses are:

• hypercholesterolaemia: 5-20 mg/day

• intermittent claudication: 10-20 mg/day; 3 months’ continual use may be required before effects are observed

• platelet inhibition: 10 mg/day

• policosanol is usually taken after the evening meal.