Policosanol might be the most sensible first choice for high cholesterol, if Cuban research is true.  Unfortunately, all of the positive research to date comes from the same group in Havana, Cuba. They have published at least seven double-blind studies, including three long-term studies, showing excellent results with no side-effects.  Policosanol costs only $3-7 per month vs. $50-200 per month for statin medications.  

Policosanol is a type of sugar cane wax, easily produced and not patentable.  While it has not been as well studied the statins, the three long-term trials have shown markedly fewer adverse heart and circulatory events with policosanol compared to placebo, including fewer heart attacks and deaths.  

Unfortunately, one poor-quality human replication study using wheat policosanol failed to replicate Cuban findings.  Also, a rabbit study from Australia using both sunflower policosanol and sugar cane policosanol was unable to replicate Cuban findings of decreased cholesterol in normal rabbits.

I sure hope that the Cuban research is accurate.  It is fairly extensive, which suggests that either it is accurate or the Cubans are being dishonest.  The Cuban medical establishment has long had an excellent reputation in Latin America predating Castro.  It is very unlikely that the Cuban research is dishonest, but stranger things have happened.

While the most common size is 10 mg tablets, 5 mg once a day appears to work just as well.  The tablets are easily broken in half.  I am also eager to learn if policosanol decreases depression in patients with high cholesterol as two research studies suggest this may occur with the statins.  Since it is so inexpensive and harmless, I have started recommending it to patients, but am watching for urgently needed replication studies outside of Cuba.  The Cuban research cannot be ignored forever.

Policosanol Helped High Cholesterol Hypertensives on Beta-Blockers in 3-Year Study: Policosanol is safe and well tolerated, even in populations with high consumption of other medications. Studies have shown that it also decreases blood pressure compared with placebo. In a 3-year DB PC study of 205 older hypercholesterolemic patients taking beta-blockers, policosanol lowered LDL-C (34%), total cholesterol (23%) and triglycerides (21%) and raised HDL-C (12%)(p < 0.00001). Serious adverse events, mostly vascular, in policosanol patients (3%) were lower than in the placebo group (14%). No impairment of safety indicators was observed. Blood pressure was reduced in more policosanol patients. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). Concomitant use of policosanol and beta-blockers in older patients. Castano G, Mas R, et al. Havana City, Cuba. Int J Clin Pharmacol Res. 2004;24(2-3):65-77

Policosanol Helped Obese with High Cholesterol in 3-Year Study: In a 3-year DB PC study of 129 obese patients with Type II hypercholesterolemia, changes with placebo were not significant. Treatment effects of policosanol 5 mg/day were persistent, even slightly enhanced, during the following two years. At completion, policosanol had lowered (p < 0.00001) LDL-C (31.8 %) and TC (20.1 %), while markedly raised (p < 0.00001) HDL-C (24.6 %). Twelve had (9 placebo, 3 policosanol) serious adverse events (SAE), mostly vascular. Policosanol did not show any drug effect on body weight. Long-term effects of policosanol on obese patients with Type II Hypercholesterolemia. Mas R, Castano G, Fernandez J, Gamez R, Illnait J, Fernandez L, Lopez E, Mesa M, Alvarez E, Mendoza S. Havana, Cuba. Asia Pac J Clin Nutr. 2004;13(Suppl):S102

Policosanol Reported to Decrease Serious Vascular Effects in High Cholesterol Diabetics in 2-Year Study: In a 2-year DB PC study of 239 Type 2 diabetics with high cholesterol, those on policosanol 5 mg/day lowered LDL-C (29.5 %), TC (21.9 %), TG (16.9 %) and raised HDL-C (12.4 %). No significant changes occurred with placebo. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (6/119, 5.0 %) was much lower than in placebo (26/120, 43.3 %). Five patients, all placebo, died during the study, four due to myocardial infarction. No drug-related impairment of safety indicators, particularly on glycemic control, was observed. A reduction of systolic and diastolic blood pressure was observed with policosanol. Long- term effects of policosanol on older patients with Type 2 diabetes. Mas R, Castano G, Fernandez J, Gamez RR, Illnait J, Fernandez L, Lopez E, Mesa M, Alvarez E, Mendoza S, Cuba. Asia Pac J Clin Nutr. 2004;13(Suppl):S101

Policosanol Helps Lower LDL, Raise HDL; Side-Effects 0% vs. 19% for Atorvastatin (Lipitor): Policosanol is mixture of 8 aliphatics alcohols (waxes) from sugar cane. In animal toxicity studies doses up to 1500 times normal human doses (on the basis of body weight) have shown no negative effects. Policosanol has performed equal to or better than simvastatin, pravastatin, lovastatin, probucol, or acipimox with fewer side effects in type II hypercholesterolemia. Policosanol decreases other risk factors of cardiovascular disease by decreasing LDL oxidation, platelet aggregation, endothelial damage, and smooth muscle cell proliferation. Policosanol decreases progression and increases regression of cardiovascular disease assessed by scintigraphy and ultrasound, and decreases symptoms of cardiovascular disease. In 75 patients ages 60-80 year with type II hypercholesterolemia in a DB PC trial of policosanol or atorvastatin 10 mg/day each for 8 weeks, at 4 and 8 weeks, policosanol 10 mg/day significantly lowered serum LDL-C levels by 17.5 and 23.1%; vs. atorvastatin 28.4% and 29.8%. Policosanol  reduced total cholesterol (TC) (16.4%), LDL-C/HDL-C ratio (25.5%) and TC/HDL-C ratio (19.3%), and triglycerides (15.4%). Atorvastatin 10 mg/day decreased TC (22.6%), LDL-C/HDL-C (26.2%) and TC/HDL-C (19.8%) ratios, and triglyceride levels (15.5%). Atorvastatin was significantly more effective than policosanol in reducing LDL-C and TC, but similar in reducing both atherogenic ratios and triglyceride levels. Policosanol, but not atorvastatin, significantly increased serum HDL-C levels by 5.3%. Atorvastatin mildly increased (bad) creatine phosphokinase (CPK) and creatinine, whereas policosanol significantly reduced liver AST and glucose and muscle CPK levels, which is good. Three atorvastatin (8%) withdrew from the study because of muscle cramps (1), gastritis (1) and uncontrolled hypertension, abdominal pain and myalgia (1). No policosanol and seven atorvastatin patients (19%) reported mild or moderate adverse events. Comparison of the Efficacy and Tolerability of Policosanol with Atorvastatin in Elderly Patients with Type II Hypercholesterolaemia. Castano G, Mas R, Fernandez L, Illnait J, Mesa M, Alvarez E, Lezcay M. Drugs Aging 2003;20(2):153-63. Cuba

Policosanol Slightly Better Than Lovastatin (Mevacor): DB PC 36 patient study of policosanol 10 mg vs. lovastatin 20 mg/day. Slightly lower LDL, higher HDL, and less LDL oxidation with policosanol. 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. Cuba, Int J Clin Pharmacol Res. 2002;22(3-4):89-99

Wheat Germ Policosanol Didn't Help Normals: Sugar cane policosanol is a mixture of long-chain primary alcohols (67% as octacosanol). In a short 4-week DB PC study of wheat germ policosanol (WGP) 20 mg/d on plasma lipid profiles in 58 adults with normal to mildly elevated plasma cholesterol, neither the WGP nor the control significantly changed plasma total cholesterol, LDL- and HDL-cholesterol, or triacylglycerol. WGP consists of 8% hexacosanol, 67% octacosanol, 12% triacosanol, and 13% other long-chain alcohols, which is similar to the composition of sugar cane policosanol. Lin Y, Rudrum M, Van Der Wielen RP, Trautwein EA, McNeill G, Sierksma A, Meijer GW. Metabolism. 2004 Oct;53(10):1309-14. Ed: It would have been better to use sugar cane policosanol for 10 weeks with adults with truly elevated cholesterols as in previous studies. Still, the results are of concern. Someone needs to replicate the policosanol studies outside of Cuba. 

Policosanol Decreases HBP, Heart Disease in 1-Year Study: 589 patients were randomized to policosanol (5 mg) or placebo tablets, to be taken once daily for 12 months. The dosage was doubled to 10 mg/day if total cholesterol values were > 6.1 mmol/L after 6 months of therapy. Policosanol (p < 0.00001) lowered LDL (Bad)-Cholesterol by 20.5%, total cholesterol (TC) 15.4%, triglycerides 11.9%, LDL-C/high-density lipoprotein-cholesterol (HDL-C) ratio 22.2% and TC/HDL-C ratio 20.1%, and increased (p < 0.0001) HDL-C 12.7%. The frequency of vascular and all-cause serious adverse events (SAEs) was lower (p < 0.05) in the policosanol recipients (two vascular SAEs, 0.7%; five all-cause SAEs, 1.7%) than in the placebo recipients (six vascular SAEs, 2.0%; 12 all-cause SAEs, 4.1%). Three placebo recipients and no policosanol recipents died during the study as a result of myocardial infarction (two patients) and sudden cardiac arrest (one). Policosanol was well tolerated, and no drug-related disturbances in safety indicators were found. Policosanol significantly decreased systolic blood pressure (BP). Cuba. Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia. Castano G, Mas R, Fernandez JC, Fernandez L, Illnait J, Lopez E. Drugs R D 2002;3(3):159-72; 

Policosanol as Good as or Better than Statins in Two Short Studies: The protective effect of policosanol against neointima formation in this experimental model was slightly better than that of lovastatin. Pharmacol Res 2001 Jan;43(1):31-7; The effects of policosanol (10 mg/day) on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk are more favorable than those induced by the same doses of pravastatin in a DB 8-week study. Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients. Castano G, Mas R, Arruzazabala ML, Noa M, Illnait J, Fernandez JC, Molina V, Menendez A. Cuba. Int J Clin Pharmacol Res 1999;19(4):105-1 

Other Policosanol Benefits

Policosanol vs. Aspirin on Platelet Aggregation: In a DB 7- day study of 43 normal adults, 20 mg policosanol vs. 100 mg of aspirin vs. the combination were compared. Three measures of platelet aggregation were used. 3 patients had side-effects on aspirin: headache, stomachache, and nose bleed; 1 on the combination: gum bleed. Both were similar in their decrease in aggregation. Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers. Arruzazabala ML, Valdes S, Mas R, Carbajal D, Fernandez L.

Policosanol 10mg > 5mg: In a DB study for 4 weeks, there was a 13% vs. 20% reduction in total cholesterol with 10 mg/d doing better. HDL increased by 6% and 12%. 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. Int J Clin Pharmacol Res 2002;22(2):55-66; Cuba; 40 mg was no better than 20 mg/d. 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. Clin Exp Pharmacol Physiol 2002 Oct;29(10):891-7

Intermittent Claudication

Policosanol Helped Intermittent Claudication in Small Study: Policosanol also has an antiplatelet effect. In a 28-patient, 20-week DB PC study after a 4-week baseline, those on policosanol 10 mg or ticlopidine 250 mg tablets twice daily did equally well. Walking distances in a treadmill, policosanol significantly increased the initial claudication distance from 162.1 to 273.2 m and the absolute (ACD) from 255.8 to 401.0 m. Ticlopidine also raised ICD (166.2 to 266.3 m) and ACD (252.9 to 386.4 m). Policosanol, but not ticlopidine, (p < 0.05) modestly increased the ankle/arm pressure ratio. Policosanol lowered (p < 0.001) LDL-C (30.2%), TC (16.9%), and TC/HDL-C (33.9%), increased HDL-C (+31.7%), and left triglycerides unchanged. Ticlopidine did not affect the lipid profile. Policosanol induced modest reductions (p < 0.01) of fibrinogen levels compared with baseline and ticlopidine. Three ticlopidine patients (21.4%) withdrew, only 1 owing to a serious adverse event (unstable angina). Effects of policosanol and ticlopidine in patients with intermittent claudication: a double-blinded pilot comparative study. Castano G, Mas R, Gamez R, Fernandez L, Illnait J. Havana City, Cuba. Angiology. 2004 Jul-Aug;55(4):361-71

Policosanol Better than Lovastatin (Mevacor) for Intermittent Claudication: In a DB 20-week study, researchers found increased exercise distance with policosanol but not lovastatin. Side-effects with five on lovastatin but none of policosanol. 31% decreased LDL. 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. Cuba. Angiology. 2003 Jan;54(1):25-38. Ed: I was able to buy policosanol for less than $5 for a month's supply at www.asnutrition.com when I placed a large order. 40mg/day was no better than 20 mg/day. Int J Clin Pharmacol Res. 2001;21(1):43-57

Policosanol Helped Intermittent Claudication: In a DB 6 month study of 56 patients, there was a 150% increase in distance walked with policosanol, both in initial and absolute claudication distances. Side-effects worse with placebo with no serious adverse events on med. A long-term study of policosanol in the treatment of intermittent claudication. Castano G, Mas Ferreiro R, Fernandez L, Gamez R, Illnait J, Fernandez C. Angiology 2001 Feb;52(2):115-25 

Animal Research

Policosanol Decreases Bone Loss in Rats: Mevalonate is required for producing lipoids that are important in osteoclast activity and thus drugs affecting mevalonate production can prevent bone loss in rodents. Policosanol is a cholesterol-lowering drug isolated from sugar cane wax that inhibits cholesterol biosynthesis through an indirect regulation of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity. Estradiol and policosanol prevented these effects compared with ovariectomized controls. Both treatments also prevented an increase in the number and area of osteoclasts. Estradiol, but not policosanol, significantly prevented an increase of osteoblast surface area compared with ovariectomized controls. Policosanol prevents bone loss in ovariectomized rats. Noa M, Mas R, Mendoza S, Gamez R, Mendoza N, Gonzalez J. Havana City, Cuba. Drugs Exp Clin Res. 2004;30(3):117-23. Ed: Statins decrease bone loss in humans. Maybe policosanol does as well.

Policosanols Didn't Work in Rabbit Replication Study: Normocholesterolemic rabbits were given either a plain sunflower oil emulsion, 100 mg/kg sugar cane policosanol (SCP), or 100 mg/kg sunflower policosanol (SFP) for 4 weeks. There was no treatment effect of either policosanol, even though a lower dose of SCP than used here (5 mg /day) has been reported to lower cholesterol in rabbits. Lack of effect of sugar cane and sunflower seed policosanols on plasma cholesterol in rabbits. Murphy KJ, Saint DA, Howe PR. University of South Australia. Asia Pac J Clin Nutr. 2004: Aug;13(Suppl):S69 

Policosanol Helped Cerebral Ischemia in Gerbils: Ischemia, a shortage of blood flow, was induced by tying off the carotid artery. Brain swelling in those not on policosanol occurred. It may be of value for cerebral vascular disease. Effect of policosanol on cerebral ischemia in Mongolian gerbils. Cuba. Molina V, Arruzazabala ML, Carbajal D, Valdes S, Noa M, Mas R, Fraga V, Menendez R. Braz J Med Biol Res 1999 Oct;32(10):1269-76

Policosanol No Effect on Mouse Longevity, Cancer: Also no effect on weight gain. Cuba. Carcinogenicity of policosanol in mice: an 18-month study. Aleman CL, Puig MN, Elias EC, Ortega CH, Guerra IR, Ferreiro RM, Brinis F. Food Chem Toxicol 1995 Jul;33(7):573-8