Policosanol side effects and benefits
Research & Development, Composition & Extraction Methods
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Policosanol may benefit people suffered from high cholesterol by inhibiting cholesterol synthesis and increasing LDL
processing. Policosanol has been showed to   delay  the onset of spontaneously- and experimentally-induced
atherosclerotic lesions and cerebral ischemia in Mongolian gerbils.
POLICOSANOL SIDE, TOXIC EFFECTS AND SAFETY ISSUES

Policosanol appeared to be safe, without serious side effects in most of the clinical studies. In one study,
policosanol produced side effects in 0.31% of the population and the side effects included skin rash, headache,
gastrointestinal disturbances, weight loss, excessive urination and insomina. [13,14]  Studies concerning the
side effects or safety issues of policosanol are summarized as follows:

Animal Studies
In animal studies of mice, rats, dogs and monkeys, policosanol was well-tolerated and accepted with no toxic
symptoms nor side effects (including signs of cancer) The study period of most studies are 12-54 months. [1-6]

Human Studies - Policosanol benefits
HEALTHY HUMAN SUBJECT Researchers applied single doses (5-50 mg) to healthy volunteers. Policosanol
administered at 20 mg/day for 7 days significantly inhibited platelet aggregation without side effects. [7] Researchers
also found no serious toxic nor side effects in a long-term study of 2252 seniors at high vascular risk. [8]

PATIENT In a study of 4596 patients, researchers did not noticed serious adverse nor side effects related to
policosanol. [9] In a two-year study on the efficacy and tolerability (i.e.safety), researchers supplied 5 mg of
policosanol twice-a-day to 69 patients suffered from type II hyperlipoproteinaemia. They found reduction in LDL-C
and cholesterol, no drug-related clinical or biochemcial adverse effects but mild, transient adverse experiences. [10]
In another study, researchers supplemented patients with policosanol together with ezetimibe, and they observed
no adverse effects. [12]

Researchers compared efficacy and tolerance of polycosanol vs besafibrate in 113 patients with
hypercholesterolemia. 59 patients received polycosanol (10 mg/day), 54 patients were given besafibrate (400
mg/day) for 8 weeks. After 8-week course of treatment, daily 10 mg of policosanol is more effective on
cholesterol-lowering. And,  the adverse effects in the group taking policosanol were mild. [11]

Policosanol can affect platelet aggregation. [15-20] Consult with your doctor before taking policosanol supplements if
you are taking other medications which can also affecting platelet aggregation.


Research & Development about Policosanol

How did the scientists discover policosanol?
Researchers first noticed that sugar cane wax could lower lipid in rats and mice in 1984 [21] .Then, Shimura S. et al
isolated octacosanol (a polycosanol) isolated from sugar cane wax and this policosanol could reduced the content of
both triglycerides and cholesterol in the liversignificantly . [22]  In 1987, Hagiwara Y reported that high doses of
another policosanol -hexacosanolcould also achieve antilipaemic effects. [23]

How did the scientists develop policosanol?
In 1994, Cuban researchers reported that policosanol could inhibit the cholesterol synthesis at the early steps of the
cholesterol biosynthetic pathway from a study using human lung fibroblasts. They filed the first patent of  mixture
compositions for policosanol (polycosanol): 0.5-1% 1-tetracosanol, 5.5-8.5% 1-hexacosanol, 2-3.5% 1-heptacosanol,
60-70% 1-octacosanol, 0.4-1.2% 1-nonacosanol, 10-15% 1-triacontanol, 4-6% 1-dotriacontanol and 0.4-2%
1-tetratriacontanol. In 1996, this group filed their second patent on policosanol. However, the claims are very similiar
to the first one, but include the extraction methods. [24] In 1996, the Cuban researchers reported that oral
administration of policosanol could  inhibit hepatic cholesterol biosynthesis in rats and they observed that it was not
a direct inhibition. [25]  While, in 1998 and 1999, Sorkin Jr., and Harlan Lee (IL) filed a patent on composition
containing phytosterol and  polycosanol / policosanol to reduce serum cholesterol levels. [26]

In 2000, Nikitin IuP et al reported their study on efficacy and tolerance of polycosanol vs besafibrate in patients with
hypercholesterolemia (HCE). The study was a multicenter controlled double blind randomised trial entered 113
patients with HCE. After 5 weeks of diet the patients were randomised into two groups. 59 patients of group 1
received polycosanol (10 mg/day), 54 patients of group 2 were given besafibrate (400 mg/day) for 8 weeks. After
8-week course of treatment, they found  total cholesterol diminished by an average of 15%, LDLP cholesterol fell by
18%, triglycerides by 15% in group 1 (polycosanol) and decrease by 8, 11 and 6% in group 2 (besafibrate). The side
effects in group 1 (polycosanol) were mild. They consequently concluded that the hypolipidemic effect of polycosanol
in a daily dose of 10 mg is superior to that of besafibrate in a daily dose of 400 mg. [31]

In 2001, the Cuban researdhers considered that 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase
controlled the cholesterol synthesis. Consequently, they transferred fibroblast to a lipid-depleted medium (LDM) to
up-regulate the enzyme level and accelerate cholesterol sysnthesis. They found, addition of polycosanol retarded the
cholesterol synthesis in a dose-dependent manner. They concluded that polycosanol (policosanol)exerted its effect
on HMG-CoA reductase. [27]

During their studies, other researchers conducted clinical trials on polycosanol (policosanol) and demonstrated
polycosanol (policosanol) is an effective cholesterol-lowering agent in most cases. McCarty MF, NutriGuard Research,
CA, even combined a tablet of polycosanol (policosanol) and ezetimibe to reduce LDL cholesterol by about 40%,
without side effects. [28

THE IMPORTANCE OF THE SOURCE OF POLICOSANOL [POLYCOSANOL]
One research group from Unilever Health Institute, The Netherlands,  has reported that wheat germ polycosanol /
polyicosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations.

THE IMPORTANCE OF THE COMPOSITION OF POLICOSANOL
Their wheat polycosanol extract contains much more long chain alcohols:

                        Patent **                 Wheat Polycosanol*
1-tetracosanol          0.5-1%                     
1-hexacosanol        5.5-8.5%                                    8%
1-heptacosanol         2-3.5%
1-octacosanol           60-70%                                  67%
1-nonacosanol         0.4-1.2%
1-triacontanol               2-3.5%                                 12%
1-dotriacontanol             4-6%          
1-tetratriacontanol       0.4-2%
Other long-chain alchohols                                     13%

*Lin Y et al, Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to midly elevated cholesterol
concentrations. Metabolism. 2004 oct;53(10):1309-14.
**Claim of Patent [# 5663156] filed by the Cuban researchers.
__________________________________________________________
WHAT IS POLICOSANOL?
Polycosanol (policosanol) is a cholesterol-lowering agent* purified from sugarcane wax. Polycosanol (policosanol) has
been shown to decrease the risk of atheroma formation in animals, lower total cholesterol level by 13-23%, lower
low-density lipoprotein (LDL) cholesterol levels by 19-31%, and increase high-density lipoprotein (HDL) cholesterol
from 8 to 29%. Their cholesterol-lowering ability is thought by reducing hepatic cholesterol biosynthesis while
enhancing LDL clearance.

Compared to statins, polycosanol (policosanol) exhibits comparable cholesterol-lowering effects and it is well
tolerated in animals. Researchers suggested that policosanols could be a promising resource in the prevention and
therapy of cardiovascular disease (CVD). Other researchers ran ran a pilot biostudy using patients with dyslipidemia
and type 2 diabetes mellitus to compare the effects of polycosanol (policosanol) and lovastatin on lipid profile and
lipid peroxidation. They found polycosanol (policosanol)(10 mg/day) was even slightly more effective than lovastatin
(20 mg/day) in reducing the LDL-C/HDL-C and total cholesterol/HDL-C ratios, in increasing HDL-C levels and in
preventing LDL oxidation.

ERGOGENIC PROPERTIES OF POLICOSANOL
Kim H, et al evaluated the effects of polycosanol on running performance and related biochemical parameters in
exercise-trained rats run to exhaustion on a treadmill. They found that polycosanol-supplemented group ran
significantly longer until exhausted, their plasma glucose level and gastronecmius muscle glycogen concentration
were not significantly different from those of exercise-trained control group rats. They concluded that the ergogenic
properties of polycosanol include the sparing of muscle glycogen stores and increases in the oxidative capacity in the
muscle of exercise-trained rats. [29]

Bai S et al, found that polycosanol elevated the weight of thymus, improved biomechanical properties of the femur
and improved membrane fluidity of red blood cell from a study using rats. [30]
_________________________________________________________________________
EXTRACTION METHOD OF POLICOSANOL  IS  IMPORTANT
Beside the origin of the raw material, the method of extraction is also important to the polycosanol or policosanol
composition. Here is one example**** that the Cuban researchers used to extract the alochols (i.e. polycosanol or
policosanol) from the sugar cane:

1. Melt 1000 g of refined wax from sugar cane at 100-200C.
2. Dissolve 200 g of potassium hydroxide in 150 g water.
3. Add the KOH solution to the wax; stir the mist. for 5 h.
4. Extract the MHPAA*** from the solid obtained in the process for 12 h in a solid-liquid extraction system using
heptane.
5. Cool the extract obtained at room temperature.
6. Recrystalize the MHPAA in methylethylketone.
You should obtain about 285 g of polycosanol. The purity is about 94.7% and the melting point for this polycosanol is
about 81.5C.

***mixture of higher aliphatic alcohols from 24 to 34 carbon atoms.
****Example 1 of Patent 5663156.

Different extraction method will also lead to different ratios of  alcohols which may determine the result of a clinical
study.

_________________________________________________________________________

. 1. Aleman CL, et al Carcinogenicity of policosanol in mice: an 18-month study. Food Chem Toxicol. 1995 Jul;33(7):573-8. 2.
Aleman CL, Carcinogenicity of policosanol in Sprague Dawley rats: a 24 month study. Teratog Carcinog Mutagen.
1994;14(5):239-49. 3. A 12-month study of policosanol oral toxicity in Sprague Dawley rats. Toxicol Lett. 1994 Jan;70(1):77-87.4.
Mesa AR et al, Toxicity of policosanol in beagle dogs: one-year study. Toxicol Lett. 1994 Aug;73(2):81-90. 5. Rodriguez-Echenique
C, Effects of policosanol chronically administered in male monkeys (Macaca arctoides). Food Chem Toxicol. 1994 Jun;32(6):565-75.
6 Rodriguez MD et al, Teratogenic and reproductive studies of policosanol in the rat and rabbit. Teratog Carcinog Mutagen.
1994;14(3):107-13. [7] Effect of policosanol on platelet aggregation in healthy volunteers, Int J Clin Pharmacol Res.
1996;16(2-3):67-72. [8] Fernandez S, A pharmacological surveillance study of the tolerability of policosanol in the elderly
population. Am J Geriatr Pharmacother. 2004 Dec;2(4):219-29.[9] Chen JT et al, Meta-analysis of natural therapies for
hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy. 2005 Feb;25(2):171-83. [10] A two-year study on
the efficacy and tolerability of policosanol patients with type II hyperlipoproteinaemia, Int J Clin Pharmacol Res.
1995;15(4):159-65].[11] Nikitin IuP et al Results of the multicenter controlled study of the hypolipidemic drug polycosanol in
Russia Ter Arkh. 2000;72(12):7-10.[12] An ezetimibe-policosanol combination has the potential to be an OTC agent that could
dramatically lower LDL cholesterol without side effects. Med Hypotheses. 2005,64(3):636-45. 13  Policosanol S ide Effects Chinese-
school netfirms.com online publication. June 2005 14 Femandez L et al. Policosanol;results of a postmarketing surveillance control
on 27,879 patients. Curr Ther Res. 1998;59:717-722.
[15] Arruzazabalab ML. Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers.  [16]
Pharmacol Res. 1996;34:181-185, [17] Arruzazabala ML et al. Comparative study of policosanol, aspirin and the combination
therapy policosanol-aspirin on platelet aggregation in healthy volunteers. [18] Pharmacol Res. 1997;36:293-297. [19] Carbajal D et
al. Effect of policosanol on platelet aggregation and serum levels of arachidonic acid metabolites in healthy volunteers.
Prostaglandins leukot Essent Fatty Acids 1998;58:61-64. [20]
Fraga V et al, Arch Med Res. 1997 Autumn; 28 (3): 355-60]. [21] Fukuda, Effect of sugar cane wax on serum liver lipids on rats;
Chemical Abstracts, 106, 17, 137413p and Sho H. et al, Effects of Okinawan sugar cane wax and fatty alcohols on serum and liver
lipids in the rates, J. Nutri. Vitaminol 30 (6) 553-559.[22] Shimura S. et al, Studies on the effect of octacosanol on the motor
endurance in mice; Nutrition Reports Int. 198736, 1029-1038.[23]  Hagiwara Y. Antilipaemic agents containing hexacosanol used to
treat hypertension, arteriosclerosis, diabetes mellitus, heart disease and obesity 1987. JP A 62 099323.[24] Mixture of higher
primary aliphatic alcohols, its obtention from sugar cane wax and its pharmaceutical uses, patent# 5663156. Patent # 5856316
[Biol Res. 1994;27(3-4):199-203] [25] [Biol Res. 1996;29(2):253-7] [26] Composition for reducing serum cholesterol levels,
Patents # 5952393 and 6197832. [27] [Arch Med Res. 2001 Jan-Feb;32(1):8-12][28]Med Hypotheses. 2005;64(3):636-45][29]
Octacosanol supplementation increases running endurance time and improves biochemical parameters after exhaustion in trained
rats., J Med Food. 2003 Winter;6(4):345-51.[30]Space Med Med Eng (Beijing). 1997 Dec;10(6):450-2..[31] Results of the
multicenter controlled study of the hypolipidemic drug polycosanol in Russia Ter Arkh. 2000;72(12):7-10.
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