Policosanol: a multi-faceted nutrient

 

Policosanol is isolated from sugar cane wax (and interestingly enough lowers blood glucose!) and its main component is octacosanol.  Policosanol “has been shown to lower cholesterol in animal models, healthy volunteers, and patients with type II hypercholesterolemia” (Gouni-Berthold I, Berthold HK. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002 Feb;143(2):356-65).  It is best known for its effects on cholesterol, however this versatile nutrient has many other beneficial effects, such as:

 

*  Raises HDL (the good cholesterol) by 8% to 15% (Gouni-Berthold I, Berthold HK. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002 Feb;143(2):356-65). 

*  Reduces smooth muscle cell proliferation (initial

    step in atherosclerosis) (Gouni-Berthold)

*  Reduces platelet aggregation (Gouni-Berthold)

*  Reduces LDL oxidation (Gouni-Berthold)

*  May enhance LDL catabolism (Gouni-Berthold)

*  Super safe profile

*  Increases efficacy of fish oil and reduces CVD    

     risk factors, especially when combined with other

     co-factors

*  Reduces liver enzymes such as CPK and AST (Castano G et al. Comparison of the Efficacy and Tolerability of Policosanol with Atorvastatin in Elderly Patients with Type II Hypercholesterolaemia Drugs Aging 2003;20(2):153-63).

*  Reduces glucose (Castano et al.)

*  Reduces endothelial damage (Janikula M. Policosanol: a new treatment for cardiovascular disease? Altern Med Rev 2002 Jun;7(3):203-17)

*  Decreases progression and increases regression of cardiovascular disease and decreases    

     symptoms of cardiovascular disease (Janikula)

*  Actually reversed atherosclerotic lesions when studied in monkeys! (Rodriguez-Echenique C,  Effects of policosanol chronically administered in male monkeys (Macaca arctoides).  Food Chem Toxicol 1994 Jun;32(6):565-75)

*  Shows a protective effect on myocardial necrosis and delayed myocardial infarction in monkeys (Rodriguez)

*  Doesn’t deplete Co-Q 10 (Lipitor does; Co-Q 10 depletion causes heart/circulatory problems)

 

**  Note that while it is believed that oxidation of cholesterol is the real problem, a raised cholesterol level indicates more opportunity for oxidation.  Policosanol has been shown to reduce this LDL oxidation process! (Gouni-Berthold I, Berthold HK. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002 Feb;143(2):356-65). 

Policosanol – safe and effective

 

In Castano’s study, policosanol clearly had a safer profile than Lipitor  (Castano G et al. Comparison of the Efficacy and Tolerability of Policosanol with Atorvastatin in Elderly Patients with Type II Hypercholesterolaemia Drugs Aging 2003;20(2):153-63).  Three atorvastatin (Lipitor) but no policosanol patients withdrew from the study because of adverse events: muscle cramps (1 patient), gastritis (1 patient) and uncontrolled hypertension, abdominal pain and myalgia (1 patient). Overall, no policosanol and seven atorvastatin patients (18.9%) reported a total of nine mild or moderate adverse events during the study (p < 0.01).  In the study by Pons et al. on the successive doses, policosanol was very well tolerated, and no disturbances of clinical or blood biochemistry variables attributable to treatment were observed (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). “At dosages of up to 20 mg per day, policosanol is safe and well tolerated, as studies of greater than 3 years of therapy indicate” (Gouni-Berthold I, Berthold HK. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002 Feb;143(2):356-65). 

       “Furthermore, in animal toxicity studies doses up to 1500 times normal human doses (on the basis of body weight) have shown no negative effects on carcinogenesis, reproduction, growth, and development” (Altern Med Rev 2002 Jun;7(3):203-17  Policosanol: a new treatment for cardiovascular disease? Janikula M.) Rat studies have shown that policosanol was well-tolerated and “does not affect the reproductive performance or fetal/neonatal development” (Rodriguez MD, Garcia H. Evaluation of peri- and post-natal toxicity of Policosanol in rats. Teratog Carcinog Mutagen 1998;18:1-7). 

                                                                                                                                                                                                                                                                                                                                          

Policosanol goes up against the statins:

 

Policosanol went up against the statins in clinical trials, and lowered LDL cholesterol AS MUCH as simvastatin or pravastatin (Gouni-Berthold I, Berthold HK. Policosanol: clinical pharmacology and therapeutic significance of a new lipid-lowering agent. Am Heart J 2002 Feb;143(2):356-65).  Another trial reported that policosanol “performed equal to or better than simvastatin, pravastatin, lovastatin, probucol, or acipimox with fewer side effects in patients with type II hypercholesterolemia” (Janikula M. Policosanol: a new treatment for cardiovascular disease? Altern Med Rev 2002 Jun;7(3):203-17).

     In a clinical trial against Lipitor (atorvastatin), both Lipitor and policosanol significantly reduced cholesterol, but policosanol raised HDL significantly, had a better safety and tolerability profile, and didn’t raise liver enzymes like Lipitor did.  In fact policosanol significantly decreased AST, glucose, AND creatine phosphokinase (CPK) levels, while Lipitor significantly increased CPK and creatinine (Castano G et al. Comparison of the Efficacy and Tolerability of Policosanol with Atorvastatin in Elderly Patients with Type II Hypercholesterolaemia Drugs Aging 2003;20(2):153-63).  In this study, policosanol and Lipitor similarly and significantly reduced atherogenic ratios and serum triglycerides! 

      One of the most important things to remember about this study is that policosanol raised HDL significantly (5.3%). HDL is the good cholesterol that works as a reverse transport for LDL, and balances the risk ratio for heart disease.  Also, policosanol was administered at 10 mg a day, a small dose considering that the Lipitor was also administered at 10 mg a day.  

       Another study reported that “In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day” (Crespo N  et al.  Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. Int J Clin Pharmacol Res 1999;19(4):117-27).”  Other studies have found significant results with reduced cholesterol utilizing policosanol supplements at a dosage of 10 mg a day, such as a randomized, double-blind, placebo-controlled crossover study that was performed in 67 patients of both sexes aged 20 to 78 years with moderate hypercholesterolemia (Tedeschi-Reiner E, et al. A randomized, double-blind, placebo-controlled study of the antilipemic efficacy and tolerability of food supplement policosanol in patients with moderate hypercholesterolemia. Lijec Vjesn. 2005 Nov-Dec;127(11-12):273-9.)  Additionally, a study on type 2 diabetics showed favorable results with policosanol supplementation (Torres et al.  Treatment of hypercholesteroaemia in NIDDM with policosanol.  Diabet Care 1995; 18:393-396).

Researchers make a case for policosanol offering many health benefits:

Researchers argue that the “wide-ranging health benefits conferred by statin therapy are mediated, not by reductions in LDL cholesterol (by inhibiting the cholesterol enzyme HMG C0-A Reductase), but rather by inhibition of isoprenylation reactions essential to the activation of Rho family GTPases” – they then continue to suggest that because of the “potential for dangerous side effects that mandates regular physician follow-up” related to the statins, as well as the significant expense, that policosanol might be considered as a better choice for accomplishing basically the same thing, since policosanol works by a similar, but safer mechanism (McCarty MF. Policosanol safely down-regulates HMG-CoA reductase - potential as a component of the Esselstyn regimen. Med Hypotheses 2002 Sep;59(3):268-79).  

       “However, policosanol, a mixture of long-chain aliphatic alcohols extractable from sugar cane wax, has shown cholesterol-lowering potency comparable to that of statins, and yet appears to be devoid of toxic risk. Recent evidence indicates that policosanol down-regulates cellular expression of HMG-CoA reductase, and thus has the potential to suppress isoprenylation reactions much like statins do. Consistent with this possibility, the results of certain clinical and animal studies demonstrate that policosanol has many effects analogous to those of statins that are not likely explained by reductions of LDL cholesterol. However, unlike statins, policosanol does not directly inhibit HMG-CoA reductase, and even in high concentrations it fails to down-regulate this enzyme by more than 50% - thus likely accounting for the safety of this nutraceutical. In light of the fact that policosanol is quite inexpensive and is available as a non-prescription dietary supplement, it may represent a practical resource that could enable the general public to enjoy health benefits comparable to those conferred by statins.”  MF McCarty continues to report that in a long-term clinical study enrolling patients with significant symptomatic coronary disease, Esselstyn demonstrated that a low-fat, whole-food diet, coupled with cholesterol reduction, “can stop the progression of coronary disease and virtually eliminate further risk for heart attack. A comparable regimen, in which policosanol is used in place of statins, may represent a practical strategy whereby nearly everyone willing to commit to health-protective eating can either prevent coronary disease, or prevent pre-existing coronary disease from progressing to a life-threatening event” (McCarty, et al, ibid)

Policosanol and Claudication:  “It is concluded that policosanol (10 mg bid) can be as effective as ticlopidine (250 mg bid) for improving walking distances of claudicant patients, and it could be advantageous for the global risk of these individuals owing to its cholesterol-lowering effects” (Castano G et al. Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. Angiology. 2004 Jul-Aug;55(4):361-71.)  The antiplatelet effects of policosanol were studied in twenty-eight patients who were randomized to policosanol 10 mg or lovastatin 20 mg tablets once daily. Policosanol but not lovastatin, significantly increased distance on the treadmill and the ankle/arm index, and reduced fibrinogen levels.  Additionally, the frequency of patients reporting improvement on quality of life was greater in the policosanol group.  One lovastatin patient withdrew from the study because of a nonfatal myocardial infarction. Five lovastatin patients, but none from the policosanol group, experienced six adverse events. “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” (Castano G, et al. Effects of policosanol and lovastatin in patients with intermittent claudication: a double-blind comparative pilot study. Angiology. 2003 Jan;54(1):25-38.)Does Policosanol have a role in MS Protocols?

 

This inhibition of isoprenylation reactions, mentioned on the previous page, is a mechanism that may be a causal link in the amelioration of autoimmune diseases such as MS. The statins are currently being studied for their role in the treatment of MS (Farrell R, Heaney D, Giovannoni G. Emerging therapies in multiple sclerosis. Expert Opin Emerg Drugs. 2005 Nov;10(4):797-816; Bradbury J. Atorvastatin and glatiramer acetate: new hope in MS? Lancet Neurol. 2006 May;5(5):386-7) and have already proven to be effective in the animal model of MS, preventing and even reversing MS in this model, both in combination therapy and alone (Stuve O, Youssef S, Weber MS, Nessler S, von Budingen HC, Hemmer B, Prod'homme T, Sobel RA, Steinman L, Zamvil SS. Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity. J Clin Invest. 2006 Apr;116(4):1037-44; Neuhaus et. Al, cited below)  

 

 

 

 The following study describes statins as “a future treatment option for MS--either in an add-on therapy regimen or alone--as they have been shown to exhibit potent immunomodulatory effects. Several recent reports have demonstrated that HMG-CoA reductase inhibitors prevent and reverse chronic and relapsing experimental autoimmune encephalomyelitis, an animal model of MS. Furthermore, in vitro experiments with human immune cells have shown an immunomodulatory mode of action of HMG-CoA reductase inhibitors that is comparable to that of interferon-beta, an established treatment for MS. An open-label clinical trial assessing simvastatin treatment in patients with MS revealed a significant decrease in the number and volume of new lesions, as assessed using magnetic resonance imaging, and a favorable safety profile. A large multicentre, placebo-controlled phase II clinical trial assessing atorvastatin (Lipitor) in patients with a clinically isolated syndrome (i.e. a single clinical event that is indicative of demyelination, and that predisposes to the development MS) has recently been initiated” (Neuhaus O, Stuve O, Zamvil SS, Hartung HP. Evaluation of HMG-CoA reductase inhibitors for multiple sclerosis: opportunities and obstacles. CNS Drugs. 2005;19(10):833-41.)         Another study looking at lovastatin and the animal model of MS (EAE) “demonstrated the restoration of remyelination in the spinal cord of lovastatin-treated EAE animals…. Together, these data demonstrate that lovastatin has the potential to augment remyelination in MS lesions and other neuroinflammatory diseases (Paintlia AS, et al. HMG-CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis. FASEB J. 2005 Sep;19(11):1407-21.)

OTHER NUTRIENTS FOR CHOLESTEROL

 

Beta Glucan reduces cholesterol absorption and thus has a cholesterol-lowering effect without affecting plasma concentrations of lipid-soluble antioxidants (Naumann E, et al. Beta-glucan incorporated into a fruit drink effectively lowers serum LDL-cholesterol concentrations. Am J Clin Nutr. 2006 Mar;83(3):601-5.)  An 8-week single blind, controlled study in 89 people with high cholesterol demonstrated that beta glucan significantly lowered total-cholesterol and after-meal concentrations of glucose and insulin (Biorklund M, et al. Changes in serum lipids and postprandial glucose and insulin concentrations after consumption of beverages with beta-glucans from oats or barley: a randomised dose-controlled trial. Eur J Clin Nutr. 2005 Nov;59(11):1272-81.)  Animal studies have shown “anti-hyperglycemic, anti-hypertriglyceridemic, anti-hypercholesterolemic, and anti-arteriosclerotic activity indicating overall anti-diabetic activity” (Kim YW, et al., Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnol Lett. 2005 Apr;27(7):483-7.)

 

Beta-sitosterol “is a plant sterol which is free of side effects and can lower total cholesterol by 10% to 15% and LDL cholesterol by 19% by itself” (Richter, Werner O., et al, Treatment of Severe Hypercholesterolemia With a Combination of Beta-Sitosterol and Lovastatin, Current Therapeutic Research, July, 1996;57(7):497-505.)  Plant sterols are minor lipid components of plants, “which may have potential health benefits, mainly based in their cholesterol-lowering effect” (Jimenez-Escrig A, Common sources and estimated intake of plant sterols in the Spanish diet. J Agric Food Chem. 2006 May 3;54(9):3462-71.)

 

Cordyceps was found to significantly increase endurance capacity of mice with a lessening of fatigue. When given to rats, cordyceps prevented the weight changes of the adrenal gland, spleen, thymus, and thyroid, (factors indicating stress) and also significantly inhibited an increase in total cholesterol (Koh JH, Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis. Biol Pharm Bull. 2003 May;26(5):691-4.)

Policosanol increases the efficacy of fish oil

 

The Cardiovascular Journal of South Africa (vol 17, #2, Mar/Apl 2006) reports on the combination of “policosanol, omega 3 fatty acids and vitamin B-6, which offer synergistic contributions to lowering cholesterol levels, and reducing platelet aggregation, inflammation and endothelium damage”.  The mechanism of action for policosanol in based not only on the inhibition of cholesterol, but on its action in the omega 3 fatty acid production pathway as well (Menedez R. et al. Br J Nutr 1997;77:923-932).  Policosanol has been found in animal studies to stimulate the enzyme responsible for one of the production pathways of DHA (β-oxidase), thereby increasing the pool of omega 3’s in the body and increasing the anti-inflammatory potential. Octacosanol production from policosanol is also linked to the fatty acid pathway by beta-oxidation (Menendez R, In vitro and in vivo study of octacosanol metabolism. Arch Med Res. 2005 Mar-Apr;36(2):113-9.”

     Vitamin B-6 is an important co-factor in this metabolic pathway and encourages the anti-inflammatory cascade of EPA and DHA production.  Additionally, other B vitamins boost the pathway as well.  In fact, B vitamins in addition to fish oil and policosanol result in an improved omega 3 fatty acid index (Harris WS & von Schacky C.  The omega 3 index: A new risk factor for sudden cardiac death.  Prev Med 2004;39:212-220).  Nutrients such as reduced glutathione, selenium, magnesium, alpha lipoic acid and co-enzyme Q 10 are known to be helpful for reducing risk factors beyond cholesterol, and they can be combined synergistically with policosanol, fish oil, and B vitamins to improve the outcome for a healthy life.

 

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