Policosanol


Clinical Studies
References


Policosanol can be extracted from sugar cane and beeswax. The Policosanol used in Total Balance is a high potency form from sugar cane. It does not increase blood sugar levels. It is used orally for treating hypercholesterolemia and intermittent claudication. Policosanol significantly decreases total cholesterol and low-density lipoprotein (LDL) cholesterol, as well as increasing high-density lipoprotein (HDL) cholesterol. Policosanol lowers cholesterol levels by inhibiting hepatic cholesterol synthesis and seems to increase the degradation of low-density lipoprotein (LDL) cholesterol.

Policosanol also decreases arachidonic acid and collagen-induced platelet aggregation. Policosanol at 10mg per day reduces platelet aggregation about as much as aspirin at 50mg per day, but it does not seem to significantly affect coagulation time.

Policosanol is used for improving strength, stamina and reaction times, for herpes infections, treating inflammatory skin diseases, Parkinson's disease, amyotrophic lateral sclerosis (ALS), hyperlipidemia and for atherosclerosis. It may also suppress lipid accumulation in fat tissue and increases the use of fat in muscles.

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Published Clinical Studies
Policosanol


IGF-I activity may be a key determinant of stroke risk--a cautionary lesson for vegans.

McCarty MF.

Pantox Laboratories, San Diego, California 92109, USA.

IGF-I acts on vascular endothelium to activate nitric oxide synthase, thereby promoting vascular health; there is reason to believe that this protection is especially crucial to the cerebral vasculature, helping to ward off thrombotic strokes. IGF-I may also promote the structural integrity of cerebral arteries, thereby offering protection from hemorrhagic stroke. These considerations may help to explain why tallness is associated with low stroke risk, whereas growth hormone deficiency increases stroke risk--and why age-adjusted stroke mortality has been exceptionally high in rural Asians eating quasi-vegan diets, but has been declining steadily in Asia as diets have become progressively higher in animal products. There is good reason to suspect that low-fat vegan diets tend to down-regulate systemic IGF-I activity; this effect would be expected to increase stroke risk in vegans. Furthermore, epidemiology suggests that low serum cholesterol, and possibly also a low dietary intake of saturated fat--both characteristic of those adopting low-fat vegan diets--may also increase stroke risk. Vegans are thus well advised to adopt practical countermeasures to minimize stroke risk--the most definitive of which may be salt restriction. A high potassium intake, aerobic exercise training, whole grains, moderate alcohol consumption, low-dose aspirin, statin or policosanol therapy, green tea, and supplementation with fish oil, taurine, arginine, and B vitamins--as well as pharmacotherapy of hypertension if warranted--are other practical measures for lowering stroke risk. Although low-fat vegan diets may markedly reduce risk for coronary disease, diabetes, and many common types of cancer, an increased risk for stroke may represent an 'Achilles heel'. Nonetheless, vegans have the potential to achieve a truly exceptional 'healthspan' if they face this problem forthrightly by restricting salt intake and taking other practical measures that promote cerebrovascular health.

PMID: 12944100 [PubMed - in process]


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Antiplatelet effects of policosanol (20 and 40 mg/day) in healthy volunteers and dyslipidaemic patients.

Arruzazabala ML, Molina V, Mas R, Fernandez L, Carbajal D, Valdes S, Castano G.

Center of Natural Products, National Center for Scientific Research Cubanacan, Havana City, Cuba.

  1. The present study was undertaken to compare the effects of a higher dose of policosanol, a cholesterol-lowering drug, (40 mg/day) with the effects of 20 mg/day policosanol on platelet aggregation in healthy volunteers and type II hypercholesterolaemic patients.
  2. Study subjects were randomized to receive, under double-blind conditions, placebo or policosanol (20 or 40 mg/day) for 30 days once a day. Blood sampling was performed at baseline and after 30 days on therapy.
  3. Platelet aggregation was induced with three aggregating agents: arachidonic acid (AA), collagen and low doses of ADP.
  4. Policosanol (20 and 40 mg/day) moderately yet significantly reduced platelet aggregation, but no differences were observed in the effects produced by either dose of policosanol. In healthy volunteers, policosanol at 20 and 40 mg/day inhibited aggregation induced by 2 mmol/L AA (28.2 and 24.9%, respectively), 1 micro g/mL collagen (21.1 and 20.2%) and 1 micro mol/L ADP (30.9 and 29.1%). Changes that occurred following the administration of placebo were not significant, although an upward trend for collagen- and ADP-induced aggregation occurred in normal and hypercholesterolaemic subjects, respectively, thus partially masking the effects of policosanol on these responses.
  5. The antiplatelet effects of policosanol at 20 and 40 mg/day in hypercholesterolaemic patients were also similar, so that both doses inhibited aggregation induced by 1.5 mmol/L AA (20.1 and 33.0%, respectively), 0.5 micro g/mL collagen (22.7 and 21.1%) and 1 micro mol/L ADP (40.5 and 34.7%).
  6. In addition, after 30 days of therapy, 20 and 40 mg/day policosanol significantly (P < 0.01) reduced low-density lipoprotein-cholesterol (15.9 and 17.0%, respectively) and total cholesterol (12.4 and 12.3%, respectively; P < 0.05), yet increased high-density lipoprotein-cholesterol values by 5% in both groups (P < 0.05).
  7. Triglycerides were decreased compared with baseline, but not with respect to the placebo.
  8. We conclude that the antiplatelet effects induced by 40 mg/day policosanol administered for 30 days to healthy volunteers and to hypercholesterolaemic patients were similar to the effects induced by 20 mg/day policosanol. Thus, no enhancement of the response was achieved with the use of a higher dose of policosanol in study patients.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial



PMID: 12207568 [PubMed - indexed for MEDLINE]

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Effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia associated with type 2 diabetes mellitus.

Castano G, Menendez R, Mas R, Amor A, Fernandez JL, Gonzalez RL, Lezcay M, Alvarez E.

Medical Surgical Research Center, Havana City, Cuba.

In this pilot, randomized, double-blind study, we compared the effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia and type 2 diabetes mellitus. After 4 weeks on a cholesterol-lowering diet, 36 patients were randomized to policosanol (10 mg/day) or lovastatin (20 mg/day) tablets o.i.d. for 8 weeks. Policosanol significantly (p < 0.001) lowered serum low-density lipoprotein-cholesterol (LDL-C) (29.9%), total cholesterol (21.1%), triglycerides (13.6%) and the LDL-C/high-density lipoprotein-cholesterol (HDL-C) (36.7%) and total cholesterol/HDL-C (28.9%) ratios and significantly (p < 0.01) increased HDL-C (12.5%). Lovastatin significantly (p < 0.001) lowered LDL-C (25%), total cholesterol (18%), triglycerides (10.9%) and the LDL-C/HDL-C (30.4%) and total cholesterol/HDL-C ratios (23.9%) and significantly (p < 0.01) raised HDL-C (8.3%). Policosanol was more effective (p < 0.05) than lovastatin in reducing both ratios and in increasing (p < 0.05) HDL-C. Policosanol, but not lovastatin, significantly raised the lag time (20.9%) of Cu+2-induced LDL peroxidation and total plasma antioxidant activity (24.2%) (p < 0.05). Both policosanol and lovastatin significantly decreased the propagation rate (41.9% and 41.6% respectively, p < 0.001), maximal diene production (8.3% and 5.7%) and plasma levels of thiobarbituric acid reactive substances (9.7% and 11.5%, p < 0.001). Both treatments were well tolerated. Only one patient in the lovastatin group withdrew from the trial due to adverse events. In conclusion, policosanol and lovastatin administered short term to patients with dyslipidemia secondary to type 2 diabetes were effective in lowering cholesterol and in inhibiting the extent of lipid peroxidation. Policosanol (10 mg/day) was 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. Nevertheless, since this was a pilot study, further clinical studies performed in larger sample sizes of diabetic patients are needed for definitive conclusions.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial


PMID: 12837046 [PubMed - indexed for MEDLINE]

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Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study.

Castano G, Mas R, Fernandez L, Gamez R, Illnait J.

Medical Surgical Research Center, Havana City, Cuba.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. The present study was undertaken to compare the effects of policosanol and lovastatin on patients with moderately severe intermittent claudication. The study had a 4-week baseline step, followed by a 20-week double blinded, randomized treatment period. Twenty-eight patients who met study entry criteria were randomized to policosanol 10 mg or lovastatin 20 mg tablets once daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees, temperature 25 degrees C) were assessed before and after 20 weeks of treatment. Both groups were similar at randomization. Compared with baseline, policosanol increased significantly (p < 0.01) the initial claudication distance (ICD) from 160.39 +/- 15.82 m to 211.31 +/- 21.48 m (+33.7%) and the absolute claudication distance (ACD) (p < 0.001) from 236.39 +/- 25.44 m to 288.09 +/- 28.47 m (+24.3%); meanwhile both variables remained unchanged after lovastatin therapy. Changes in ICD and ACD were significantly larger in the policosanol than in the lovastatin group (p < 0.01). Policosanol, but not lovastatin, significantly increased (p < 0.05) the ankle/arm index, although between-group differences were not significant. The frequency of patients reporting improvement on quality of life domains was greater in the policosanol than in the lovastatin group. Policosanol significantly (p < 0.001) lowered total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) by 17.5% and 31.0%, respectively, and meanwhile increased (p < 0.01) high-density lipoprotein-cholesterol (HDL-C) levels by 31.5%. Lovastatin reduced (p < 0.01) TC (18.0%), LDL-C (22.6%), and (p < 0.05) triglycerides (9.8%). In addition, policosanol, but not lovastatin, moderately, but significantly, reduced (p < 0.05) fibrinogen levels, so that final values and percent changes in both groups were different (p < 0.01). Treatments were well tolerated. Only 1 lovastatin patient withdrew from the study because of a nonfatal myocardial infarction. Five lovastatin patients, but none from the policosanol group, experienced 6 adverse events (AE) (p < 0.01). The present results indicate that policosanol, but not lovastatin, is a suitable alternative to manage patients with intermittent claudication because of pleiotropic properties beyond its cholesterol-lowering effects.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial


PMID: 12593493 [PubMed - indexed for MEDLINE]

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Effect of policosanol on carbon tetrachloride-induced acute liver damage in Sprague-Dawley rats.

Noa M, Mendoza S, Mas R, Mendoza N.

Center of Natural Products from the National Center for Scientific Research, Havana City, Cuba. clinica@enet.cu

BACKGROUND: Policosanol is a cholesterol-lowering drug purified from sugarcane (Saccharum officinarum, L.) wax. Beneficial pleiotropic effects of policosanol, such as inhibition of the susceptibility of low density lipoprotein to lipid peroxidation, have been shown. Policosanol has a good safety profile and well tolerated and, to date, no drug-related adverse effects have been demonstrated. Specifically, policosanol has not been shown to affect liver function or to increase liver enzyme levels in experimental or clinical studies.AIM: This study was conducted to determine whether policosanol prevents liver damage induced by carbon tetrachloride (CCl4) in rats, since this model has been associated with an increased rate of lipid peroxidation.METHODS: Male Sprague-Dawley rats were randomised to four experimental groups: negative controls (no CCl4 or policosanol, group 1); positive controls (CCl4 but no policosanol, group 2); policosanol 25 mg/kg (group 3) and policosanol 100 mg/kg (group 4). Acute liver injury was induced in groups 2, 3 and 4 by CCl4 suspended in olive oil and administered at a dose of 1590 mg/kg via intraperitoneal injection. Eighteen hours after CCl4 dosing, the rats were anaesthetised and their livers removed for histopathological studies.RESULTS: Policosanol 25 and 100 mg/kg dose dependently and significantly (p < 0.01) decreased the percentage of ballooned cells and hepatocytes with lipid inclusions and increased the percentage of normal hepatocytes compared with positive controls. The percentage inhibition of the occurrence of ballooned cells and hepatocytes with lipids was marked, reaching 71 and 49%, respectively, with the higher dose (100 mg/kg). The percentage of swollen hepatocytes was unchanged by policosanol compared with positive controls. No histological alterations in liver sections were found in the negative control group. Necrotic areas and inflammatory infiltrates were observed in the liver of seven of eight (87.5%) animals in the positive control group. However, only one of eight (12.5%) animals treated with policosanol 25 mg/kg and none (0%) treated with the higher dose (100 mg/kg) showed such a pattern. CONCLUSIONS: Policosanol protected against the histological changes characteristic of CCl(4)-induced hepatic injury in rats, a model of hepatotoxicity in which the process of lipid peroxidation plays a role. Further studies aimed at demonstrating the connection between such hepatoprotective and antioxidant effects of policosanol must be initiated.

PMID: 12568632 [PubMed - indexed for MEDLINE]

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Comparison of the efficacy, safety and tolerability of original policosanol versus other mixtures of higher aliphatic primary alcohols in patients with type II hypercholesterolemia.

Castano G, Fernandez L, Mas R, Illnait J, Fernandez J, Mesa M, Alvarez E, Lezcay M.

Medical and Surgical Research Center, National Center for Scientific Research, Havana, Cuba.

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol and Octa-60 in patients with type II hypercholesterolemia. After 4 weeks on a diet, 110 patients were randomized to policosanol or Octa-60 5 mg tablets once a day for 5 weeks. The dose was then doubled to 10 mg/day for the next 5 weeks. Policosanol 5 and 10 mg/day significantly lowered low-density lipoprotein-cholesterol (LDL-C) (p<0.0001 and p<0.00001), the main efficacy variable, by 18.6% and 30.2%, while Octa-60 significantly reduced (p<0.05) LDL-C by 10.0% at study completion only. The frequency of policosanol patients reaching reductions of LDL-C > or = 15% after 5 mg/day (37/55; 67.3%) and 10 mg/day (47/55; 88.7%) was greater (p<0.01 and p<0.01) than in the Octa-60 group, which was 5/55 (9.1%) and 20/55 (36.4%). Likewise, the frequency of patients reaching LDL-C values of <3.4 mmol/l at study completion was greater (p<0.001) in the policosanol group (39/55, 70.9%) than in the Octa-60 group (6/55, 10.9%). Policosanol 5 and 10 mg/day significantly lowered (p<0.00001) total cholesterol (TC) (13.4% and 20.4%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) (22.1% and 37.0%) and TC/HDL-C (17.2% and 28.2%). Octa-60 at 10 mg/day lowered (p<0.05) TC (8.7%), LDL-C/HDL-C (12.6%) and TC/HDL-C (9.4%). HDL-C was increased (p<0.001 and 0.0001) by policosanol 5 and 10 mg/day (5.6% and 12.5%) but was unchanged by Octa-60. In both groups, triglycerides remained unchanged. Both treatments were safe and well tolerated. Octa-60, but not policosanol, significantly increased glucose and alanine aminotransferase, but individual values were within the normal range. Four patients (two from each group) discontinued the trial, but only one (in the Octa-60 group) did so because of an adverse event (AE) (skin rash). Overall, three patients (all from the Octa-60 group) reported AEs. In conclusion, original policosanol at 5 and 10 mg/day, but not Octa 60, was effective in patients with type II hypercholesterolemia. Thus, policosanol reached the efficacy criterion for LDL-C reduction in both steps, while Octa-60 failed to reach this goal. In addition, policosanol was better tolerated than Octa-60.

Publication Types:

  • Clinical Trial
  • Randomized Controlled Trial


PMID: 12503776 [PubMed - indexed for MEDLINE]

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References

  1. Castano G, et al. Effects of policosanol in hypertensive patients with type II hypercholesterolemia. Curr Ther Res, 1996; 57(9): 691-5.
  2. Fernandez JC, Mas R, Castano G, et al. Comparison of the efficacy, safety and tolerability of policosanol versus fluvastatin in elderly hypercholesterolaemic women. Clin Drug Invest. 2001;21:103–13.
  3. Torres O, et al. Treatment of hypercholesterolemia in NIDDM with policosanol. Diabetes Care, 1995; 18(3): 393-7.
  4. Batista J, et al. Effect of policosanol on hyperlipidemia and coronary heart disease in middle-aged patients. A 14-month pilot study. Int J Clin Pharmacol Ther 1996;34(3):134-7.
  5. Valdes S, Arruzazabala ML, Fernandez L. Effect of policosanol on platelet aggregation in healthy volunteers. Int J Clin Pharmacol Res, 1996; 16(2-3): 67-72.
  6. Arruzazabala ML, et al. Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Pharmacol Res, 1997; 36(4): 293-7.
  7. 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(1): 61-4.
  8. Arruzazabala ML, et al. Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers. Pharmacol Res, 1996; 34(5-6): 181-5.
  9. Menendez R, et al. Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet. Br J Nutr 1997;77:923-32.
  10. Arruzazabala ML, et al. Effect of policosanol on platelet aggregation in type II hypercholesterolemic patients. Int J Tissue React, 1998; 20(4): 119-24.
  11. Castano G, et al. Efficacy and tolerability of policosanol in elderly patients with type II hypercholesterolemia: A 12-month study. Curr Ther Res, 1995; 56(8): 819-23.
  12. Merck Index, 12th ed. Whitehouse Station: Merck Research Laboratories, 1996.
  13. Pons P, et al. Effects of successive dose increases of policosanol on the lipid profile of patients with type II hypercholesterolaemia and tolerability to treatment. Int J Clin Pharmacol Res, 1994; 14(1): 27-33.
  14. Canetti M, et al. A two-year study on the efficacy and tolerability of policosanol in patients with type II hyperlipoproteinaemia. Int J Clin Pharmacol Res, 1995; 15(4): 159-65.
  15. VI Sourcing. www.gvisourcing.com/pharmaceuticals/ppg/default.html (Accessed 16 July 1999).
  16. Parker SP. ed. McGaw Hill Dictionary of Chemistry. New York: McGraw-Hill Book Company 1984.
  17. Neal H. Dictionary of Chemical Names and Synonyms. Chelsea: Lewis Publishers, 1992.
  18. Castano G, et al. A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication. Angiology, 1999; 50(2): 123-30.
  19. Menendez R, et al. Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts. Biol Res, 1994; 27(3-4): 199-203.
  20. GVI Sourcing Website: URL: www.gvisourcing.com/pharmaceuticals/ppg/specs.html (Accessed 16 July 1999).