Policosanol News

Alternative Medicine Review, Sept, 2004

Introduction
Policosanol, an extract from sugar cane (Saccharum officinarum L.), has been heavily researched in Cuba in several human populations for its cholesterol-lowering properties. In addition to improving serum lipids, policosanol reduces LDL oxidation, decreases platelet aggregation, decreases smooth muscle proliferation, and improves symptoms of cardiovascular disease. Side effects are virtually non-existent.

Biochemistry
Cuban-manufactured policosanol is a mixture of alcohols isolated and purified from sugar cane. It consists of 66-percent octacosanol (C[H.sub.3]-C[H.sub.2](26)-C[H.sub.2]-OH), 12-percent triacontanol, and 7-percent hexacosanol. Other alcohols (15%), namely tetracosanol, heptacosanol, nonacosanol, dotriacontanol, and tetratriacontanol, are minor components. (1)

Mechanisms of Action
Policosanol appears to cause decreased synthesis and increased degradation of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA), the rate-limiting step in cholesterol synthesis. (2,3) This is different than the mechanism of action of statin drugs, which work by competitively inhibiting HMG-CoA. Policosanol has also demonstrated improvement in LDL metabolism by increasing LDL binding, uptake, and degradation in human fibroblasts. (4)

LDL oxidation is thought to be a necessary step in the development of atherosclerosis. Studies on humans and rats show policosanol decreases in vitro LDL oxidation using multiple oxidation models. (5,6) Another step in the formation of atherosclerotic plaques is an increase in smooth muscle proliferation. In rabbits, policosanol decreased neointimal formation, indicating decreased smooth muscle cell proliferation. (7) In a comparative study, policosanol demonstrated a greater effect than lovastatin on neointimal formation. (8)

Policosanol decreases platelet aggregation by decreasing the synthesis of platelet-aggregating thromboxane B2 (TXB2), with no effect on prostacyclin (PGI2). (2) Studies demonstrate policosanol reduces platelet aggregation induced by a number of experimental substances, (9-14) with dose-dependent increases from 10-50 mg/day. Policosanol alone at 20 mg/day was more effective than 100 mg aspirin at reducing platelet aggregation induced by ADR and equally effective when induced by epinephrine and collagen. (13) Despite decreased platelet aggregation, there was no increase in coagulation time when policosanol was taken alone; however, when combined with 100 mg/day aspirin, coagulation time increased.

Clinical Indications
Hypercholesterolemia The majority of policosanol research is on patients with type II hypercholesterolemia. Fifteen randomized, placebo-controlled, double-blind studies have shown positive results. (15-29) Significant decreases in total cholesterol (TC) (8-23%), LDL (11.3-27.5%), LDL/HDL (15.3-38.3%), and TC/HDL (9.1-30.5%) were observed in all trials. Of the 13 trials measuring HDL, seven showed significant increases and in six HDL was unchanged. Doses ranged from 2-40 mg/day, with decreases in TC, LDL, LDL/HDL, and TC/HDL and increases in HDL being dose-dependent up to 20 mg/day, with no further benefit at 40 mg/day. However, 40 mg/day significantly decreased triglycerides (TG), which was not seen with lower doses. (28)

Policosanol was effective in three studies on patients with type 2 diabetes mellitus and hypercholesterolemia. (30-32) All three trials used 5 mg twice daily for 12 weeks. Total cholesterol was reduced by 14-29 percent, LDL was reduced by 20-44 percent, LDL/ HDL ratio was reduced by 24-52 percent, and HDL was increased by 8-24 percent. No adverse effect on glycemic control was noted in any of the studies. In trials comparing policosanol with lovastatin (20 mg/ day), policosanol performed significantly better at raising HDL and lowering the LDL/HDL ratio. (32,33)

Two studies with a total of 300 patients indicate policosanol is effective in postmenopausal women with hyperlipidemia. (34,35) Both studies started with 5 mg daily, which was later increased (at week 8 in one study. (34) and week 12 in the other (33)) to 10 mg daily for a period of eight or 12 more weeks. At the end of the 5-mg portion, TC, LDL, LDL/HDL, and TC/HDL decreased by 13-20 percent, 17-18 percent, 17.0-17.2 percent, and 16.3-16.7 percent, respectively, whereas HDL was unchanged in one trial and increased by 16.5 percent in the other. At the end of the 10-mg/day period policosanol supplementation resulted in decreased TC, LDL, LDL/HDL, and TC/ HDL by 17-20 percent, 25-28 percent, 27-30 percent, and 21-27 percent, respectively, and increased HDL 7-29 percent. Significantly more side effects were seen in the placebo group in each trial.

In comparative trials policosanol generated lipid profiles similar to simvastatin, (36,37) pravastatin, (10,38) lovastatin, (32,35,39) probucol, (40) acipimox, (41) and atorvastatin. (42) First, two trials on patients with type II hypercholesterolemia, comparing low dose simvastatin (5 or 10 mg/day) and moderate dose policosanol (5 or 10 mg/day), demonstrated that both substances greatly improved lipid profiles with no significant differences in results or side effects between the groups. (36,37) Second, policosanol (10 mg/day) compared favorably to low-dose pravastatin (10 mg/day) in patients with type II hypercholesterolemia in two studies. (10,38) In one trial. policosanol-treated patients had significantly greater decreases in LDL, LDL/HDL, TC/HDL, and increases in HDL, (38) while in another trial policosanol-treated patients had significantly greater increases in HDL. (10) The pravastatin group had more side effects in both studies. A study comparing policosanol to lovastatin in patients with type 2 diabetes and hypercholesterolemia (type II) found policosanol (10 mg/ day) is more effective at lowering LDL/HDL and increasing HDL than 10 mg/day lovastatin, with significantly fewer side effects. (32) In addition, in patients with type II hypercholesterolemia and concomitant coronary risk factors, policosanol (10 mg/day) decreased LDL/HDL and increased HDL more effectively than 20 mg/day lovastatin, with fewer side effects. (39) Policosanol (5 mg twice daily) also compared favorably to probucol (500 mg twice daily) at reducing TC, LDL, and TG in patients with type II hypercholesterolemia. (40) Again, policosanol (10 mg/day) compared favorably to acipimox (750 mg/day), a niacin derivative, in regard to TC, LDL, LDL/HDL, TC/HDL, and HDL, with fewer side effects. (41) Lastly, policosanol was significantly less effective than atorvastatin (Lipitor) in reducing both LDL and TC, although it was similar in reducing both atherogenic ratios and TG. Atorvastatin, however, significantly increased (p < 0.05) creatine phosphokinase (CPK) and creatinine, whereas policosanol significantly reduced alanine aminotransferase (AST), glucose (p < 0.01), and CPK (p < 0.05) levels. (42) These studies suggest a therapeutic benefit to policosanol in type II hypercholesterolemia, while presenting no adverse effects on the liver.

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