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Policosanol
Robert L. Pastore, Ph.D., CNC, CN
Nutritionist for the Hoffman Center
Policosanol is a mixture of alcohols isolated and purified from sugar cane (Saccharum officinarum L). We are currently utilizing policosanol at the Hoffman Center to address hyperlipidemia (elevated lipid levels – increased LDL, total cholesterol, triglycerides and low HDL). Prior to getting into how we employ policosanol, let’s take a closer look at cholesterol metabolism.
Sterols are compounds composed of carbon, hydrogen and oxygen atoms arranged in rings, like those of cholesterol, with any of a variety of side chains attached. Regular readers of my articles will recall that about 2 months ago I wrote about sterol compounds found in plant foods. Cholesterol behaves differently than plant sterols. Cholesterol is a sterol that is widely distributed in all cells of the body, but found predominantly in the brain and nervous system. It is the precursor for sex hormones, adrenal hormones (such as cortisol), bile acids, vitamin D and cardiac glycosides. Cholesterol can be synthesized in many tissues in the body and ultimately eliminated in the bile as bile salts or cholesterol. The biosynthesis of cholesterol may be separated into five steps involving numerous enzymes. Step 1, acetyl-CoA forms HMG-CoA and mevalonate. Step 2, mevalonate forms active isoprenoid Units. Step 3, six isoprenoid Units form squalene. Step 4, squalene is converted to lanosterol. Step 5, lanosterol is converted to cholesterol. Cholesterol is made up of various lipoprotein fractions, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL). It is understood that elevated LDL and VLDL, and low HDL levels increase the risk of cardiovascular disease. (1)
The importance of cholesterol is well established in human health, but as mentioned, excessive levels have been associated with cardiovascular disease (2). The most common medical approach for cholesterol reduction is the use of statin drugs. The method of action for these drugs is to inhibit HMG-CoA reductase (3-5). HMG-CoA reductase is the enzyme responsible for the conversion of HMG-CoA to mevalonate, an early step in cholesterol biosynthesis. Unfortunately for many patients, statin drugs have been documented to have potential side effects such as fatigue, muscle weakness and liver dysfunction (3, 6). The symptoms of muscle weakness and fatigue may be related to a depletion of Coenzyme Q 10, which has been linked to statin drug use (7-10). CoQ10 plays a vital role as an electron carrier in the mitochondrial synthesis of adenosine triphosphate (ATP) and energy production. ATP is the primary energy source for heart and skeletal muscle (1). Because of these potential drug side effects, people are seeking out alternative, natural approaches to cardiovascular health care (11, 12).
Policosanol is a mixture of essential alcohols isolated from sugar cane wax (13). The main constituents are octacosanol (66%), hexacosanol (7%), and triacontanol (12%). Eicosanol, tetracosanol, nonacosanol, dotriacontanol, tetratriacontanol and heptacosanol make up the remaining 15% of essential alcohols. There is a significant body of evidence demonstrating the benefits of policosanol with respect to cardiovascular disease. In the mid to late nineties, one research group proposed that policosanol was able to reduce endothelial damage by inhibiting the production of foam cells (14, 15). Foam cells are macrophages that can migrate into the endothelium of the blood vessels and contribute to atherosclerotic plaque formation (2). Other researchers believe policosanol has a modulating effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis, but the precise mechanism remains unclear (16-18). Still, other investigators believe policosanol may inhibit cholesterol synthesis in the liver at a step before mevalonate production, but total inhibition of the HMG-CoA reductase is doubtful (13). More recent work suggests policosanol inhibits LDL cholesterol oxidation (19, 20). This was revealed when markers of peroxidation, such as thiobarbituric acid reactive substances (TBARS), and malondialdehyde (MDA) were lower in the cultures treated with policosanol. Oxidation of LDL cholesterol has been linked to heart disease and was the recent cover story in Scientific American magazine (2). Bi-products of LDL oxidation are bioactive, and secrete inflammatory cytokines, growth factors and cell surface adhesion molecules. In response to these oxidative bi-products, smooth muscle cells proliferate in the wall of the artery, resulting in the narrowing of the lumen and eventual blockage. Oxidized LDL cholesterol can also inhibit the production of prostacyclin and nitric oxide, which act as vasodilators and inhibitors of platelet aggregation.
Policosanol and Cholesterol
In clinical research and in my experience as a clinical nutritionist, policosanol has shown the ability to reduce cholesterol levels. In 1994, a randomized, double blind, placebo-controlled study was conducted on 22 patients with hypercholesterolemia. After eight weeks the patients taking policosanol had a marked reduction in total cholesterol and LDL cholesterol (21). A similar double blind, placebo-controlled study was performed on 69 patients, with comparable results. The group of patients taking 10mg of policosanol daily for two years had an 18% reduction in total cholesterol and a 25% reduction in LDL cholesterol (22). Notably, after 12 months, the so-called good HDL cholesterol was elevated by 21%. A follow up study was performed on a larger patient group. Researchers chose 437 patients randomized to receive, under double-blind conditions, policosanol or placebo once a day. After twelve weeks, patients receiving policosanol had a 25% reduction in LDL cholesterol, a 17% reduction in total cholesterol, and a 28% increase in HDL cholesterol (23). The placebo group did not achieve any reduction in total cholesterol, or LDL. Policosanol seems to be effective at lowering cholesterol on both men and women, and all age groups. A study on 179 older aged people resulted in a reduction in total cholesterol and LDL cholesterol by 13% and 16% respectively (24). Also on a positive note there was a 14% increase in HDL cholesterol and a 28% reduction in the total cholesterol to HDL ratio.
Policosanol and Cholesterol Lowering Drugs
There have been numerous studies comparing the effects of policosanol to cholesterol lowering drugs. In one study a group of patients were randomized to receive under double-blind conditions, either policosanol or pravastatin. The results were impressive, with the policosanol group seeing a 19.3% reduction in LDL cholesterol and a 13.9% reduction in total cholesterol. The group taking pravastatin had a 15.6% reduction in LDL cholesterol and an 11.8% reduction in total cholesterol (25). The patients taking policosanol noticed an increase in HDL cholesterol, while the patients taking pravastatin did not. The policosanol group did not experience any side effects, whereas several people taking pravastatin had elevation of liver function enzymes. Several other studies have demonstrated similar results when comparing policosanol to statin drugs (26-28). Cardiovascular Disease and Policosanol
More than just elevated cholesterol levels can cause cardiovascular disease. Platelet aggregation and intermittent claudication are conditions associated with cardiovascular disease. Intermittent claudication is caused by inadequate blood supply attributable to atherosclerosis or hardening of the arteries (29). Usually the first symptoms are severe pains in the calf muscle. Intermittent claudication and atherosclerosis can be caused by platelet aggregation. Platelets are small discs in the blood responsible for blood coagulation and thrombus formation. This process is important to stop the loss of blood after surgery or an injury. However, excessive platelet aggregation caused by vascular injury or excessive stress can lead to atherosclerotic plaque formation. This, in turn can lead to cardiovascular disease. Researchers have discovered the benefits of Policosanol in patients experiencing intermittent claudication and platelet aggregation. Early animal studies demonstrated that policosanol reduced platelet aggregation by inhibiting the inflammatory mediator thromboxane B2 (30, 31). More recent human studies revealed the same positive effects. Randomized, double-blind, placebo-controlled trials investigating the effects of policosanol on platelet aggregation found that patients receiving policosanol had significantly less platelet aggregation than did the placebo group (32-34). The method of action for reducing platelet aggregation was the ability of policosanol to inhibit the production of inflammatory mediators arachidonic acid, thromboxane B2 and prostacyclin. By reducing platelet aggregation there was a noticeable decline in intermittent claudication. A six-week study demonstrated that patients with moderately severe intermittent claudication had a considerable improvement after supplementing with policosanol (35, 36). These patients reported less lower leg pain, and were able to increase their walking distance. It was noted that Policosanol did not affect the coagulation time when administered at single or repeated doses. That is to say, policosanol did not change the bleeding time similar to that of the blood thinning drug warfarin. Moreover, the addition of policosanol to warfarin therapy did not add to the bleeding time induced by warfarin alone (37). In addition to the results with heart disease patients, animal studies revealed that policosanol protected against cerebral ischemia, suggesting a possible therapeutic effect in cerebral vascular disorders (30, 38). In the animals treated with policosanol, swelling and necrosis of neurons were significantly reduced in all areas of the brain.
Postmenopausal Women and Heart Disease
Female hormones, estrogen and progesterone, appear to provide a protective effect against cardiovascular disease. As women go through menopause, when hormone levels drop, there is often an elevation of cholesterol and increased risk of cardiovascular disease (2, 39). A large randomized, double blind, placebo-controlled study, with 224 postmenopausal women with elevated cholesterol was conducted to investigate the efficacy of policosanol. After eighteen weeks, the group receiving policosanol experienced a 17% reduction in total cholesterol, a 25% reduction in LDL cholesterol, and a significant 29% rise in HDL cholesterol (40). Four serious cardiac events occurred in the placebo group compared to none in the policosanol group.
Diabetes and Cardiovascular Disease
Type II or non-insulin-dependent diabetes mellitus (NIDDM) predisposes patients to elevated cholesterol and cardiovascular disease (2, 41). Fifty-three diabetic patients with hypercholesterolemia were enrolled in a randomized, double blind study of policosanol. After 12 weeks, total cholesterol was lowered 14%, LDL cholesterol by 20% and HDL cholesterol increased by 7.5% in the group receiving policosanol (27). Several other studies had similar positive results with type II diabetic patients (41, 42). It was noted that blood sugar levels were not affected by policosanol supplementation. This is a critical point. When I decide to put a patient on policosanol, and explain to them that it is an extract of sugar cane, concern arises as to the effects on blood sugar. Note that there is no viable carbohydrate value to policosanol, and thus no elevation in blood sugar.
Safety and Efficacy
Most studies have shown a positive effect at doses ranging from 5mg to 20mg daily. When evaluating policosanol for toxicity, animals were given as much as 500mg per kg of body weight. This is over 600 times the recommended therapeutic dose. Even at these extremely high doses, there were no reports of toxicity or carcinogenicity (43-46). In human studies, patients receiving 20mg - 40mg of policosanol daily for two years had good tolerability and did not experience any adverse affects (22, 27, 47). My approach to dosing policosanol is to begin with 10mg per day and increase after the 8-week interval. Currently, I have not needed to go higher than 10mg to achieve the desired cholesterol lowering results. However, based on the body of clinical evidence referred to in this article, I will not hesitate to increase an individual dose to 20 or 40 mg per day.
Are all brands of policosanol the same? Many brands of policosanol are actually extracted from bees wax, and are rich in tetracosanol, and have no effect on cholesterol levels. It is imperative to have the “right” policosanol that is derived from sugar cane. Many products claiming to be derived from sugar cane are actually denatured and contain little of the essential alcohol mixture fundamental for cholesterol lowering effects. After an exhaustive search, Dr. Hoffman has found the one brand that he is confident will provide the essential mixture of extracted alcohols from sugar cane. Our Policosanol is only available from a physician’s office. Accept no imitations. Policosanol can be ordered from the Hoffman Center through the link to the web found in this article, or by calling 212 779-1744.
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