What is Policosanol?

Derived from Rice Bran Policosanol is a mixture of naturally occurring, long-chain alcohols isolated and purified from Rice Bran. Policosanol consists of 60% octacosanol. Researchers have reported that 5-20mg daily of policosanol to be effective at improving serum lipid profiles equal or better than simvastatin, pravastatin, lovastatin, probucol, or acipimox. Policosanol is believed to decrease total cholesterol (TC), low-density lipoprotein (LDL), and increase high-density lipoprotein (HDL) by inhibiting cholesterol synthesis and increasing LDL processing. This could be especially useful as common medications to address elevated cholesterol can produce some unpleasant side effects and stall endogenous co-enzyme Q10 production.

What is Policosanol used for?

CHOLESTEROL REDUCTION

Elevated or oxidised cholesterol is considered a major risk marker for cardiovascular outcomes. It is suggested that oxidised LDL-C is highly damaging and that it is involved in the aggressive formation of arterial plaque, known as atherosclerosis. Cholesterol production can be either from acetate which involves acetyl-coA or via the mevalonate pathway which activates the HMG- CoA enzyme in the liver. However, Policosanol decreases cholesterol synthesis from acetate but not via the mevalonate pathway. This means that unlike statin drugs, Policosanol does not inhibit HMG-CoA reductase enzyme but modulates its activity through the activation of AMP-kinase.

Cholesterol modification was investigated in a 14-week RCT, whereby adult patients with elevated total cholesterol showed a reduced LDL-C value in response to a 6-week lifestyle intervention followed by 8 weeks of 5mg Policosanol. Eighty-four percent of the Policosanol group resulted in a ≥15% decrease in serum LDL-C compared to 4% of the placebo group. The Policosanol group reported a significantly decreased total cholesterol and triglyceride levels alongside a significant increase in HDL-C. Policosanol did not impair any safety indicator and was well tolerated. Similarly, decreased triglycerides and increased HDL-C were observed in response to 10mg Policosanol daily for 12 weeks in non-insulin dependent diabetic patients with elevated cholesterol. While the same dose improved both LDL-C:HDL-C and Total Cholesterol:HDL-C ratios in older patients with elevated cholesterol and high coronary risk. These methodologies were replicated in older patients with hypertension and elevated cholesterol. Whereby, Policosanol significantly lowered LDL-C, TC, triglycerides, LDL-C:HDL-C and TC:HDL-C ratios and significantly increased HDL-C. Of further benefit the Policosanol group reported a significantly decreased systolic blood pressure. Furthermore, the frequency of vascular and all-cause serious adverse events was reduced in the Policosanol group.

When compared to the statin, Fluvastatin, 10mg of Policosanol in elderly patients with elevated cholesterol showed a significantly reduced LDL-C, TC, triglycerides and the ratios of LDL-C and TC to HDL-C, and significantly increased HDL-C. While Fluvastatin also showed improvements in the same measures it was not as effective as Policosanol. Additionally, Policosanol, but not Fluvastatin, delayed LDL-C peroxidation and significantly reduced the rate of oxidation.

When compared in a Meta-analysis of 23 studies to plant stanols and plant sterols, Policosanol produced a superior reduction of LDL-C, TC, Triglycerides and LDL-C:HDL-C ratio, besides an increased HDL-C.

In addition to cholesterol modification, Policosanol shows benefits in antiplatelet activity which may contribute to risk reduction for cardiovascular outcomes. A group of researchers set out to investigate the tolerability of Policosanol alongside platelet modifying medications. After 5 weeks on a diet only run in, 205 older hypercholesterolemic patients prescribed beta-blockers were randomised to 5mg Policosanol or placebo daily for 3 years. At 12 months, Policosanol significantly reduced LDL-C, TC and triglycerides besides increased HDL-C. These treatment effects continued to the 3 year follow up and study completion. No impairment of safety indicators was reported. Furthermore, reductions in systolic and diastolic blood pressure were observed. This shows that Policosanol alongside antiplatelet medications handled by cytochrome P450 detoxification are well tolerated and beneficial for the normalisation of lipid profiles and blood pressure. 8

The ‘6% statin rule’ is the effect that has been recorded in relation to statin therapy. Each time the statin dose is doubled, a further 6% reduction in LDL-C occurs. In addition to the downregulation of the enzyme HMG-CoA, which reduces cholesterol synthesis, statins also increase the number of LDL receptors, whereby reducing the amount of circulating LDL-C. In normal cholesterol metabolism the degradation of the LDL-C receptor is facilitated by a protein called

Proprotein convertase subtilisin/kexin type 9 (PCSK9). This protein also increases circulating LDL-C. In statin therapy, it is suggested that serum PCSK9 may be increased, whereby an increased PCSK9 level largely negates further statin-induced increases of LDL-C receptor sites. Thus, statin efficacy is limited and may explain the 6% rule.

There have been suggestions in unpublished data that Policosanol might not increase PCSK9 to the same degree as statin therapy. Therefore, a group of researchers investigated the effects of 8 weeks of statin therapy (20mg Atorvastatin) compared to statin therapy plus 20mg Policosanol upon PCSK7 expression in 36 atherosclerotic patients. Concurrently, the effects of 20mg Policosanol compared to placebo was investigated in 16 healthy participants for 12 weeks. In both interventions’ serum lipids and PCSK9 levels were monitored. In the statin group a significant increase in PCSK9 level by 39.4% was observed, which was far greater than the statin therapy plus Policosanol group which showed an increase in serum PCSK9 levels of 17.4%. In the second intervention using Policosanol and healthy participants there was a trend towards a decreased serum PCSK9 levels in the Policosanol group.

These findings show that Policosanol may modestly reduce circulating PCSK9 levels and contribute to a cholesterol lowering effect via the preservation of the LDL-C receptor and decreased circulating LDL-C.

Policosanol and CARDIOVASCULAR PROTECTION

Besides improving serum lipid profile, Policosanol may reduce several other cardiovascular disease risk factors, including LDL oxidation, platelet aggregation, endothelial cell damage, smooth muscle proliferation, angina, and maximum oxygen uptake. Policosanol may decrease platelet aggregating thromboxane B2 without affecting platelet anti-aggregating prostacyclin (PGI2).

To investigate the effects of Policosanol on blood pressure in prehypertensive patients a group of researchers conducted 2 studies. The first investigated either 10mg Policosanol, 20mg Policosanol or placebo for 24 weeks and the second investigated the same intervention for 12 weeks.

At week 24, both Policosanol groups had a significantly decreased systolic blood pressure besides a significantly decreased systolic and diastolic aortic blood pressure.

The authors hypothesised that oxidised cholesterols may contribute to glycation of such cholesterols and arterial stiffness, of which, increases blood pressure. Subsequently, the alleviation of oxidized cholesterols could be the source of the reduction in blood pressure. While in the second study, reductions were observed in both diastolic and systolic blood pressure in response to 10mg and 20mg of Policosanol, however the observations were statistically significant for 20mg of Policosanol upon systolic blood pressure at 12 weeks and for diastolic blood pressure at both 8 and 12 weeks. In addition, both Policosanol groups had a significant reduction in aortic systolic and diastolic blood pressure, total cholesterol, and LDL-C alongside elevations of HDL-C.

These results show that cardiovascular biomarkers can be modified in short time frames of 12 weeks with 20mg of Policosanol taken daily. These findings were further supported by a meta- analysis which concluded that Policosanol could modulate systolic and diastolic blood pressure except in those with mixed dyslipidaemia and for solely diastolic blood pressure in those who were overweight.

Long term Policosanol use was investigated in 23 patients with hyperlipidaemia and coronary heart disease. The intervention of 1mg of Policosanol was given to 12 patients and placebo to the remainder for 14 months. The Policosanol group showed a significant reduction in total cholesterol and in LDL-C. Overall, 5 of the 12 Policosanol-treated patients displayed a clinical tendency towards an improvement in coronary heart disease. 15 These findings show that lower doses of Policosanol can be effective it taken for a long duration.

Several biomarkers of cardiovascular disease were reduced in response to Policosanol and a low- calorie diet. Significant reductions were observed in Overall, the most rapid results for blood pressure were using 20mg of Policosanol, however other evidence shows that lower quantities of Policosanol can be beneficial if taken for a long duration.

Policosanol for POSTMENOPAUSAL HEALTH

The reduction in oestrogen in response to the menopause reduces the protective effects of the reproductive hormones. Once women are postmenopausal, they can be at an increased risk for cardiovascular disease. Subsequently, it is considered beneficial to take steps to regulate serum cholesterol levels. To investigate an effective dietary intervention, a study of 244 postmenopausal women with type 2 hypercholesterolemia were given 5mg Policosanol for 12 weeks followed by 10mg Policosanol daily, for a further 12 weeks or placebo. At 24 weeks the Policosanol group showed a reduction in total cholesterol of 16.8%, LDL-C of 25.4%, the LDL-C:HDL-C ratio of 29.6%, and total cholesterol:HDL-C of TC/HDL, while HDL-C was increased 29.3%.

These results show that Policosanol can modify cholesterol in a beneficial manner in postmenopausal and hypercholesterolaemic participants. Meanwhile a similar study that used 5mg for 8 weeks then 8 mg for a further 8 weeks showed solely an increase in HDL-C. These results show that postmenopausal hypercholesterolemic women may require a larger and longer intervention.

Overall, these findings show that at least 10-20mg of Policosanol is necessary to achieve modification of lipid profiles that would constitute to a decreased risk for cardiovascular outcomes.

Dosage

20mg capsule taken 1-3 times daily at mealtimes. May be used long term within normal dosage range.

Potential applications of Policosanol for health.

Elevated serum lipids (cholesterol / triglycerides), hypertension, angina, intermittent claudication, reduces LDL oxidation, atherosclerosis, reduced ischaemia (decreased blood supply), general cardiovascular protection, elevated liver enzymes (10mg policosanol shown to reduce gamma- glutamyl transferase (GGT) and Alanine transaminase (ALT).

Known contraindications

None known

Interactions

Results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure
Those undergoing treatment for cardiovascular disease should discuss any adjunct treatment with their health professional.

No other interactions known.

Side Effects of Policosanol

Studies have shown Policosanol to be very safe and well tolerated.

Directions: As a food supplement, take one to three capsules daily with food, or as directed by your healthcare practitioner.

One vegan capsule provides:

Ingredient	Weight	%EC NRV
Policosanol (60% octacosanol)	20mg
in a base of alfalfa, spirulina and bilberry
Policosanol is derived from rice bran.