Policosanol

Policosanol is a mixture of oils from Cuban Cane Sugar; touted as a cholesterol lowering agent, it shows potency at this claim in several studies released from Cuba. Other studies undermine the quality of these, however, and it remains controversial.

This page features 109 unique references to scientific papers.

Confused about supplements?


Free 5 day supplement course

Summary

All Essential Benefits/Effects/Facts & Information

Policosanol is a term used to refer to a mixture of lipophilic (fat-soluble) compounds derived from the waxy coating of Cuban Cane Sugar. It has been used frequently to treat high cholesterol levels, and several studies claim that it does so with a potency rivaling statin therapy. The studies in question all appear to originate from Cuba, and when all studies are looked at collectively yet exclude Cuba the 100% success rate in Cuba declines to approximately 14% success rates in human trials. Due to this significant schism in the literature coupled with Policosanol being derived from a Cuban export, it is plausible that the scientific literature is suffering from publication bias.

The studies conducted outside of Cuba and those conducted in Cuba use similar participant pools, similar dosing, and at times have used the same sources of Cuban Cane Sugar specifically. The only difference is in the dietary protocol given, but some evidence suggests that this is a plausible explanation for the differences seen.

At this moment in time, publication bias and dietary intervention lead-in period are both plausible explanations for the observed differences. Which is disconcerting, as the latter would mean that policosanol can be as effective as statin therapy whereas the former means it is merely a placebo; a black and white issue with little grey area.

Regardless of source of the study or context, however, policosanol usage appears to be very safe; no side-effects have been reported in human interventions from Cuba or elsewhere and blatant overdoses in research animals fail to exert toxicity.

Confused about supplements?

Free 5 day supplement course

Things To Know

Also Known As

Cane Sugar Extract

Do Not Confuse With

Octacosanol (major constituent)

Things to Note

  • Studies may suffer from publication bias, but this is not ascertained

Goes Well With

  • Aspirin (in regards to anti-platelet actions)

  • Fish Oil (complimentary benefits on lipid parameters)

Caution Notice

May Interact adversely with Warfarin, especially in the form of D-003

Examine.com Medical Disclaimer

How to Take

Recommended dosage, active amounts, other details

The standard supplemental dosage of policosanol is 5-10mg taken twice daily (for a daily total of 10-20mg), although due to the state of the research on this supplement it is not sure if it is bioactive in this range.

Confused about supplements?

Free 5 day supplement course

Editors' Thoughts on Policosanol

In regards to heart disease, there are two plausible hypothesis' here and I cannot discredit either of them right now. Either there is some Cuban export conspiracy going on in the scientific literature, or replication in other locations has been poorly conducted due to lack of dietary lead in and control. Hard to determine what is the cause right now...

At least it doesn't harm you, at all


Kurtis Frank

Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects policosanol has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
HDL-C Minor Moderate See all 12 studies
Unlikely to be potent, either small or no increases in HDL-C are likely to occur after policosanol ingestion. A good deal of the literature is based upon some highly suspicious past research from Cuba
LDL-C Minor Moderate See all 13 studies
It is possible that policosanol is either effective or totally ineffective due to older Cuban studies being remarkably different than more recent replications; high probability of publicity bias
Total Cholesterol Minor Moderate See all 12 studies
There may be some limited efficacy of policosanol on cholesterol (when excluding the studies from cuba, which are highly suspicious, there is still some scattered but unreliable evidence) whereas it does not appear to be potent in any way.
Triglycerides - Moderate See all 5 studies
When excluding older cuban studies (which are highly suspicious) there is no evidence to support a reduction of triglycerides.
Blood Pressure Minor - See study
Possibly a small effect in persons with high blood pressure.
Oxidation of LDL Minor Moderate See 2 studies
Mixed evidence, possibly an effect but needs to be replicated
Reaction Time Minor - See study
Reductions in reaction time were not overly significant.
Symptoms of Intermittent Claudation Minor Very High See 2 studies
Possible benefits to intermittent claudition, 'notable' rating is being held until it is replicated outside of Cuba
Blood Flow - - See study
No significant influence detected on blood flow

Studies Excluded from Consideration

  • Excluded studies due to being confounded with Berberine and Red Yeast Extract[1][2][3][4]

  • Confounded with other nutrients, such as tomato extract and grape seed extract[5]

  • Confounded with Fish Oil[6]

  • Combined with Red Yeast Extract[7]


Disagree? Join the Policosanol Discussion

Scientific Research

Table of Contents:

  1. 1 Sources and Structure
    1. 1.1 Sources
    2. 1.2 Structure
    3. 1.3 Stability
  2. 2 Pharmacology
    1. 2.1 Absorption
    2. 2.2 Serum
    3. 2.3 Distribution
    4. 2.4 Metabolism
  3. 3 Cardiac Health and Cholesterol
    1. 3.1 Mechanisms
    2. 3.2 Interventions
  4. 4 Interactions with Neurology
    1. 4.1 Cognition
    2. 4.2 Neuromuscular junction
  5. 5 Interactions with Bone
    1. 5.1 Osteroporosis
  6. 6 Nutrient-Nutrient Interactions
    1. 6.1 Warfarin
    2. 6.2 Aspirin
    3. 6.3 Fish Oil
    4. 6.4 CoQ10
    5. 6.5 Red Yeast Extract
  7. 7 Safety and Toxicity
    1. 7.1 Human Intervention Overview
    2. 7.2 Toxicology Studies

Don't Miss an Update!

Your e-mail is safe with us. We don’t share personal data.


1Sources and Structure

1.1. Sources

Policosanol is a term that refers to a mixture of fatty acid alcohols, and is sometimes referred to as 'Cane Sugar Extract' or 'Cane Sugar Wax' due to its first discovered source being Cuban Cane Sugar. It can also be extracted from Rice Bran, Wheat Germ, and Beeswax by solvent extraction and saponification.[1][2]

Policosanol can also be found in:

  • Perilla Seeds (Perilla frutescens), alongside Rosmarinic Acid and the gamma forms of Vitamin E[3] in approximately the same ratios as in Cane Sugar[4] In Perilla oil, the content is 427.83mg/kg oil (10mg Policosanol per 23.4g oil)[5]

  • Wheat and Wheat Germ[6]

  • Peanuts[7]

  • Rice (Orzya species only such as Gamma Oryzanol)[8] and Rice Bran Oil[5] at 171.17mg/kg oil (10mg Policosanol per 58.4g oil)

  • Pomegranate seeds[9]

  • Grape seed oil, at 245.15mg/kg oil (10mg Policosanol per 40.8g oil)[5]

  • Corn, Sesame, and Soybean oil in minute quantities[5]

  • Switchgrass (Panicum virgatum)[10]

  • Guduchi (Tinospora cordifolia)[11]

Found mostly in seeds and the waxy coating of Cane Sugar, but is seen in a variety of unique sources

1.2. Structure

As 'Policosanol' is a term used to refer to a mixture of fatty acid alcohols, there are several molecules and structures associated with the term. The Fatty Acid alcohols in question are all long-chained, with the most prominent fatty acid alcohols being between 26-32 carbons in length and all fatty acid alcohols being between 20-34 in length.

The fatty acid alcohols in question (with their carbon length designated as Cxx), and their approximate quantities, are:

  • C20, Eicosanol at less than 0.1%[12]

  • C22, Docosanol at less than 0.1%[12]

  • C23, Tricosanol at less than 1%[12]

  • C24, Tetracosanol at approximately 2%[12]

  • C26, Hexacosanol at approximately 6%[12] but standardized to the 3-10% range

  • C27, Heptacosanol at less than 1%[12]

  • C28, Octacosanol at approximately 66%[12] but standardized to the 60-70% range

  • C29, Nonacosanol at less than 0.1%[12]

  • C30, Triacontanol at approximately 17%[12] and standardized to the 10-15% range usually

  • C32, Dotriacontanol at approximately 5%[12] and standardized to the 5-10% range at times

  • C34, Tetratriacontanol at less than 1%[12]

The bolded terms are those that are in highest amounts. Octacosanol is seen as the primary bioactive fatty alcohol whereas Triacontanol is seen as a significant source of bioactivity as well; the others should be noted as their bioactivity may be relevant.

For all intents and purposes, 'Policosanol' is a term used to refer to a collection of fatty acid alcohols

1.3. Stability

In two studies on 5-10mg capsules of Policosanol, it was found that the product was stable for up to 9 months under ambient storage conditions; some degradation was noted into fatty acid esters from the alcohol form of the molecules, such as octacosanol to octacosanoyl ester.[13][14]


2Pharmacology

2.1. Absorption

Using cane sugar policosanols in a CaCo-2 cell line, up to 86% of the octosanol was absorbed after 48 hours of incubation yet was not detected on the basolateral (post-absorptive) side of the membrane, theoretically due to oxidation.[15] Octosanol did not appear to change into other fatty acid alcohol in these tests.[15] When comparing the absorption of policosanols derived from 'authentic' Cuban Cane Sugar against an assortment of alternative sources that were matched for octacosanol content, it was found that no significant difference existed.[16]

Policosanol appeared to enhance cholesterol ester and free fatty acid uptake into intestinal cells, without affecting triglyceride or phospholipid uptake; cholesterol ester retention in these cells was enhanced, while free fatty acids could not be determined.[15] However, when tested in hypercholesterolemic individuals cholesterol absorption rates do not appear to be significantly affected.[17] The omega-6 content of the intestinal cells appeared to increase relative to control.[15]

Interestingly, it was found that 1.14ug/mL Policosanol inhibited growth of the CaCo-2 cells, whereas half the concentration (0.57ug/mL) had no effect.[15]

Absorbed fairly well and in vitro is rapidly metabolized, does not appear to prevent a large deal of cholesterol uptake

2.2. Serum

After intra-gastric administration of 60mg/kg policosanol in water, hepatic (liver) levels were a Cmax of 68.4ng/g Octacosanol (used as biomarker) and 331.6ng/g Octacosanoic Acid, the fatty acid metabolite of Octacosanol; both of these Cmax values were attained at the Tmax of 30 minutes.[18] The levels in circulation were lower, with the Cmax of octacosanol still occurring at 30 minutes but at 30.4ng/mL (44.4% of the liver value) and octacosanoic acid not reaching Tmax during the 100 minute testing period, instead gradually increasing concentration in the blood until 19.51ng/mL was recorded at 90 minutes, the time where Octacosanoic Acid's ascending curve passed Octacosanol's descending curve.[18]

Similar results were seen in Macaca arctoides monkeys fed 10mg/kg bodyweight Policosanol, with the Tmax of Octacosanol at 1 hour (when fed via a banana) with a Cmax of approximately 500ng/mL, and Octacosanoic Acid reaching a similar Cmax at the Tmax of 2 hours.[18]

2.3. Distribution

After oral administration of carbon-labelled octacosanol, it was found that 9.5% of the oral dose accumulated in the liver while 8.2% and 3.5% accumulated in the intestinal organs and the skeletal muscle; respectively.[19]

2.4. Metabolism

In vitro studies suggest that Octacosanol (main fatty alcohol of Policosanol) can be metabolized into Octacosanolic Acid, its fatty acid, in a time-dependent manner in cultures.[18] Another undetermined metabolite of Octacosanol was noted in cellular medium.

Octacosanoic acid may be able to be partially metabolized for energy similar to other fatty acids, as one study using carbon labelling on Octacosanol noted that some carbon left as breath carbon dioxide.[20]


3Cardiac Health and Cholesterol

3.1. Mechanisms

Policosanol has been reported to activate AMPK in liver cells by 2-2.5 fold after intragastric dosing and after incubation (15-25ug/mL), respectively, in rats. The increases seen in vitro were comparable to the active controls of Metformin and AICAR.[12] Oral doses of 10 and 100mg/kg bodyweight failed to influence AMPK and HMG-CoA, while doses of 25 and 50mg/kg were successful.[12] This activation may be downstream of other kinases, in particular CAMKKβ[12][21] and possibly LKB1 (although the study investigating policosanol's influence on this did not reach statistical significance).[12]

This inhibition of AMPK may reduce cholesterol synthesis, and in isolated rat cells has been shown to reduce synthesis by up to 30%.[22] This phosphorylation occurs at Thr172.[22][23] Policosanol has also been demonstrated to influence (inhibit) HMG-CoA Reductase, the regulatory step in cholesterol synthesis.[12] Policosanol does not directly modify this enzyme expression or content,[22] but seems to be secondary to the influences of AMPK[22] and it has been noted before that higher AMPK activation in liver cells phosphorylates HMG-CoA at Ser872[24][25] and in vitro complete phosphorylation inhibits 70-80% of cholesterol synthesis.[26] The suppression of cholesterol seems to be most related to the fatty acid triacontanol.[22] The discrepancy between policosanol's cholesterol inhibition (30% or so) and the aforementioned 70-80% may be due to policosanol being inable to activate AMPK in intestinal cells, which can account for up to 25% of circulating cholesterol levels.[12]

All the previous mechanisms have been replicated in vitro in human fibroblasts.[27][28] When tested in vivo, suppression of cholesterol synthesis has been noted twice with rats[29] and rabbits[30] and has not been demonstrated in two studies using hamsters.[31][32]

The mechanisms appear to exist for policosanol to reduce cholesterol synthesis, via AMPK acting as the main lever but the true activation probably occurring more upstream of that. Ultimately, it is an indirect inhibition of HMG-CoA (rate limiting step of cholesterol synthesis) which is credited

Interestingly, policosanol fatty acid alcohols appear to work mostly through their metabolites; the fatty acids. Elimination of peroxisomal metabolism (converting alcohols to acids) eliminates influence on HMG-CoA and halves the influence on AMPK, but coincubation with acetate preserved this.[12] Interestingly, despite similar in vitro potencies between policosanol and Metformin, Metformin was not influenced by peroxisomal elimination.[12]

Possible lifestyle interactions here, where the liver must be 'burning fat' in order for conversion to the active molecules to occur

3.2. Interventions

At least in regards to literature on policosanol, there appears to be a schism of sorts when it comes to studies conducted in Cuba on the efficacy of Policosanol compounds. Studies that are conducted in Cuba are listed here, and those that show benefit[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] significantly outweigh those that show negative or null effects, of which none can be found.

Going on the assumption that the above studies are valid, the range of improvement in blood lipids tends to be quite reliably in the range of 20+/-5% reductions in LDL cholesterol, 10+/-5% reductions in total cholesterol, and 15+/-10% increases in HDL cholesterol (numbers approximations). Studies range from 6-12 weeks[38][41] to 12[33] to 24 months[37] and tend to have similar overall reductions. Doses used tend to be 5-20mg taken in two divided doses daily, and studies investigating varying dosages usually find no significant differences between lower and higher doses.[34]

The only study originating from Cuba painting Policosanols in a bad light is a comparative study that was testing out a product called D-003, which is a purified form of Policosanols.[49] However, if these studies are true then 5-20mg of Policosanol daily is about as effective as statin therapy in reducing cholesterol levels

For studies conducted outside of cuba, ones that show benefit are conducted in Chile,[50] and Mexico,[51] with a study from Croatia showing mixed benefits[52]; studies from Italy,[53][54], the Netherlands,[55] Germany,[56] South Africa,[57] Canada,[58][17] and the USA[59][60][61][62] note no effects on circulating cholesterol or triglyceride levels, and some studies do make note that they use 'authentic' Cuban Cane Sugars.[58][54] When assessing non-Cuban studies for possible conflicts of interest, none are reported and only 3 studies report external funding; all from companies not directly involved with statin or pharmaceutical distribution.[56][61][57]

These possible publication bias shows in studies on LDL oxidation, where a Cuban study reported benefit[63] while a study conducted in Montreal, Canada reported no such effect.[64] It is possible that studies on blood flow are also subject to this, as although there is a multitude of research originating from Cuba showing benefits on platelet aggregation[65][66][67][68][69][70] physical performance secondary to blood flow (intermittent claudation or heart disease)[71][72] and adverse effects reduction related to heart disease.[33] Counter-evidence to this point is minimal, but the only study conducted outside Cuba on blood clotting (Croatia) noted no effects[73] and an Australian study noted no interactions with Warfarin efficacy (a blood thinner).[74]

Not to sound all conspiracy theorist like, but the chances of the above occurring by pure chance are next to nothing and 'true' Policosanols are derived from Cuban Cane Sugar; this discord in the evidence undermines a lot of the beneficial studies on the subject matter, and despite the large body of evidence there really is not much quality evidence if we assume the Cuban studies are undermined
A 100% success rate is seen with studies conducted in Cuba while the success rate for every other location combined is 2 out of 14 (14.2%). The possibility that Policosanol is ineffective in treating cholesterol levels but suffers from a large degree of publication bias cannot be ruled out

When looking at studies that are both conducted within Cuba and those that find benefit, some are seen using the step I NCEP (National Cholesterol Education Program) diet found here.[75] and these studies include the following.[76][34][33][40] Other studies specified a lipid-lowering diet,[43][35][42] while some a cholesterol-lowering diet.[45][38][44] and some unspecified but present.[36][47][46] Several studies using diets do include a 2-6 week 'run-in' period where diet is adapted to and made routine before the intervention is conducted.

Two studies have been conducted in Cuba on persons who do not appear to respond to dietary interventions,[37][41] neither study specified whether dietary control was continued, but both studies found non-responsiveness to the NCEP dietary intervention as well as improvements with policosanol. The one study noted that did not have dietary interventions was a retrospective cohort study of the elderly population and policosanol.[48]

When looking at studies conducted outside of Cuba that found positive effects of policosanol, all three studies used a modified diet but not the specified NCEP diet.[50][51][52]

When looking at the studies that found no effects of policosanol on blood lipids (all conducted outside of Cuba), one used controlled cholesterol lowering diets such as 55/15/20 carbohydrate/protein/fat with under 300mg cholesterol[57] and another used the NCEP diet;[56] most of the others used no controlled dietary intervention (just measuring intake post-intervention to see if any significant differences existed).[17][62][61][55][58] Beyond that, one study measured food intake via questionnaire to see if any changes that could have influenced results existed,[59] and another controlled for calories but permitted standard lifestyle food intake.[53] One study specifically investigated persons who, using an NCEP intervention prior to the study, failed to have any reduction of cholesterol by the diet; they were instructed to continue with their current lifestyle diets but were controlled for calories.[54]

Of those, two studies used the dietary 'lead-in' period of accustomizing persons to a lifestyle change diet before introducing policosanol intervention. A study from Croatia[8] can back with a reduction of total cholesterol (down to 94% of baseline) and no significant influence on LDL-C or HDL-C between groups and a study from Germany[56] found no significant effects and no patients reporting more than a 10% drop in LDL-C regardless of statistical significance.

The notion that policosanol's efficacy is reliant on a controlled diet is a plausible counter-hypothesis that has not yet been ruled out, and may play some importance given the 2011 in vitro study suggesting fatty acid metabolism is mandatory for fatty acid alcohols to become effective. This is the only significant difference between Cuban studies and non-Cuban studies that persists, and the differences can be explained currently by either location or dietary intervention


4Interactions with Neurology

4.1. Cognition

One study in karate athletes found that Fish Oil at 2.25g daily paired with 10mg policosanol found that after 21 days of supplementation that the combination was able to reduce reaction time and increase mood, with the increased mood persisting 21 days after cessation of supplementation while reaction time returned to normal.[77] These effects have been seen with isolated policosanol compounds at 3.6mg daily in as short as a week[78] Both studies were carried out on otherwise healthy and youthful persons, although the degree of improved speed is minor; the study in athletes noted decreased reaction time from approximately 860milliseconds (ms) to 840ms (data extracted from graphs, approximately a 2% decrease)[77] whereas in healthy sedentary persons the decreases range from 90% of baseline values to 94% of baseline depending on the manner of testing.[78]

May increase reaction time in humans after ingestion, but aside from being relatively understudied the effects do not seem overly potent. Kava or Vinpocetine may be better options

4.2. Neuromuscular junction

A single rat study on policosanol noted that it had a small effect on enhancing the apparent acetylcholine release, possibly through interaction with acetylcholinesterase.[79]


5Interactions with Bone

5.1. Osteroporosis

A study in rats noted that policosanol at 50 and 200mg/kg bodyweight was able to preserve some bone mass during a model of menopausal bone loss, theoretically via the same mechanisms that reduce cholesterol.[80] With indirect inhibition of HMG-CoA comes decreased production of Mevalonate, which is a cholesterol precursor that can influence production of osteoclasts that may act as pro-osteoporotic.[81]


6Nutrient-Nutrient Interactions

6.1. Warfarin

Warfarin is a blood thinning pharmaceutical, and adverse reactions with nutraceuticals and Warfarin can cause excessive blood thinning resulting in death in some persons using Warfarin.

When policosanol and Warfarin were investigated alongside each other, Policosanol dosed at 10mg and taken twice daily did not influence the effects of Warfarin (25mg) and was deemed safe in this preliminary investigation; study conducted in otherwise healthy subjects.[74]

A study in rats using D-003 (the fatty acids of policosanol) did note synergism, however, and suggests that the combination may confer much greater anti-platelet activity than Warfarin and D-003 in isolation.[82]

May interact adversely with Warfarin, possibly mediated through the active metabolites

6.2. Aspirin

The formulation of D-003, which is the fatty acids of policosanol rather than the fatty alcohols, appears to be synergistic with Aspirin in both positive and negative manners; the combination of D-003 (50mg/kg) and Aspirin (3mg/kg) synergistically enhanced bleeding time from preventing platelet aggregation (negative) but the combination enhanced a 33% survival rate seen with the isolated treatments in response to a blood clotting stimuli to 88% survival with combination therapy.[83]

May work synergistically with Aspirin

6.3. Fish Oil

Policosanol has been investigated with Fish Oil, as Policosanol has evidence for benefitting lipoproteins with minimal influence on triglycerides while fish oil can reduce triglycerides while possible raising LDL-C. One Cuban trial done into this combination in hypercholesterolemic patients[76] found that combination therapy led to LDL-C decreases of 21.1-26.2% at 5-10mg daily, although the fish oil only group had a decrease of 2.1% (possibly due to following a NCEP cholesterol reduction diet); Triglycerides decreased by 13% in the fish oil group at 2g daily (44% EPA, 37% DHA), and the addition of policosanol did not significantly influence the triglyceride reduction.[76]

Preliminary evidence that they can nicely compliment each other, although no synergism has been demonstrated

6.4. CoQ10

CoQ10 is a vitamin-like compound that becomes important to ingest or supplement when using statin drugs, as endogenous synthesis of CoQ10 is reduced when the HMG-CoA enzyme is inhibited; synthesis normally occurs to sustain CoQ10 levels and mitochondrial function, and the decrease may lead to myopathies and increased fatigue.

As the mechanisms of policosanol are ultimately mediated via HMG-CoA, a long-term deficiency of CoQ10 could be suspect. This has not been reported in chronic studies with Policosanol currently (1-2 years) when dosed at 10-20mg, but has not been ruled out either.

Possible interaction with these two based on the mechanisms of Policosanol, under the assumption that it works

6.5. Red Yeast Extract

Red yeast extract is an extract from rice that has been fermented by the bacteria Monascus purpureus, and appears to have additive effects when paired with policosanols in reducing cholesterol levels (according to one study conducted in rabbits).[84]


7Safety and Toxicity

7.1. Human Intervention Overview

No significant adverse events have been reported with policosanol in the dosage range of 5-20mg daily in all currently conducted trials, regardless of region of origin, up to 2 years of usage. And the opposite of this (high dose, small time frame) has demonstrated that doses up to 80mg daily for 12 weeks have been tested with no adverse events reported.[56] 40mg for 6 months also appears to be well tolerated[34] and over the short term does not adversely affect platelet function.[67]

7.2. Toxicology Studies

A 1 year study of the toxicological effects of policosanol in beagle dogs with doses ranging between 30 or 180mg/kg bodyweight, with no toxicity reported in either group.[67] The latter dose is approximately 620 times higher than the recommended dose of 20mg daily.[67] Doses of 50mg/kg bodyweight in rats[85] (172.4 fold higher than the recommended dose), 500mg/kg in rats[86][87][85] (1,724 fold higher) and 5,000mg/kg in rats[88] (17,240 fold higher) also appeared to be free of side-effects, with the latter study being conducted over a period of 6 months[88] and the former study being conducted starting 15 days after pregnancy onset and continuing during pregnancy to after lactation.[87] This study on maternal supplementation has been replicated with 1,000mg/kg and in two species (rats and rabbits) with the same null results.[89]

A study in monkeys, the most repesentative animal model to humans, was found to be safe and not affect any measured parameter adversely at doses of 35mg/kg bodyweight for just over 1 year of supplementation.[90]

No differences between groups have been noted in rats fed 500mg/kg in regards to tumor growth, suggesting policosanol may not influence cancer metabolism.[85] This study was replicated and extended 6 months (from 18 to 24) and a lack of effects was again noted.[91]

Independent of whether it works or not, Policosanol appears to be quite a safe supplement to ingest and has not been linked to side-effects currently

Scientific Support & Reference Citations

References

  1. Afinisha Deepam LS, Arumughan C Effect of saponification on composition of unsaponifiable matter in rice bran oil . J Oleo Sci. (2012)
  2. Luciani GB, Swilley S, Starnes VA Pulmonary atresia, intact ventricular septum, and major aortopulmonary collaterals: morphogenetic and surgical implications . J Thorac Cardiovasc Surg. (1995)
  3. Kim JK, et al Metabolite profiling based on lipophilic compounds for quality assessment of perilla (Perilla frutescens) cultivars . J Agric Food Chem. (2012)
  4. Adhikari P, et al Policosanol content and composition in perilla seeds . J Agric Food Chem. (2006)
  5. Jung DM, et al A gas chromatography-tandem quadrupole mass spectrometric analysis of policosanols in commercial vegetable oils . J Food Sci. (2011)
  6. Irmak S, Dunford NT Policosanol contents and compositions of wheat varieties . J Agric Food Chem. (2005)
  7. Cherif AO, et al Comparison of the Concentrations of Long-Chain Alcohols (Policosanol) in Three Tunisian Peanut Varieties ( Arachis hypogaea L.) . J Agric Food Chem. (2010)
  8. Reiner Z, Tedeschi-Reiner E, Romić Z Effects of rice policosanol on serum lipoproteins, homocysteine, fibrinogen and C-reactive protein in hypercholesterolaemic patients . Clin Drug Investig. (2005)
  9. Caligiani A, et al Characterization of a potential nutraceutical ingredient: pomegranate (Punica granatum L.) seed oil unsaponifiable fraction . Plant Foods Hum Nutr. (2010)
  10. Ravindranath SV, et al Policosanol, alpha-tocopherol, and moisture content as a function of timing of harvest of Switchgrass (Panicum virgatum L.) . J Agric Food Chem. (2009)
  11. Thippeswamy G, Sheela ML, Salimath BP Octacosanol isolated from Tinospora cordifolia downregulates VEGF gene expression by inhibiting nuclear translocation of NF-<kappa>B and its DNA binding activity . Eur J Pharmacol. (2008)
  12. Banerjee S, Ghoshal S, Porter TD Activation of AMP-kinase by policosanol requires peroxisomal metabolism . Lipids. (2011)
  13. Cabrera L, et al Study of the stability of tablets containing 10 mg of policosanol as active principle . Boll Chim Farm. (2002)
  14. Cabrera L, et al Stability studies of tablets containing 5 mg of policosanol . Boll Chim Farm. (2003)
  15. Li Q, Thomson AB, Clandinin MT Cholesterol ester and free fatty acids are modulated by policosanol in CaCo-2 intestinal cells . J Am Coll Nutr. (2011)
  16. Marinangeli CP, et al Comparison of composition and absorption of sugarcane policosanols . Br J Nutr. (2007)
  17. Kassis AN, Jones PJ Changes in cholesterol kinetics following sugar cane policosanol supplementation: a randomized control trial . Lipids Health Dis. (2008)
  18. Menéndez R, et al In vitro and in vivo study of octacosanol metabolism . Arch Med Res. (2005)
  19. Kabir Y, Kimura S Tissue distribution of (8-14C)-octacosanol in liver and muscle of rats after serial administration . Ann Nutr Metab. (1995)
  20. Kabir Y, Kimura S Biodistribution and metabolism of orally administered octacosanol in rats . Ann Nutr Metab. (1993)
  21. Carling D, Sanders MJ, Woods A The regulation of AMP-activated protein kinase by upstream kinases . Int J Obes (Lond). (2008)
  22. Singh DK, Li L, Porter TD Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase . J Pharmacol Exp Ther. (2006)
  23. Oliaro-Bosso S, et al Regulation of HMGCoA reductase activity by policosanol and octacosadienol, a new synthetic analogue of octacosanol . Lipids. (2009)
  24. Clarke PR, Hardie DG Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver . EMBO J. (1990)
  25. Ferrer A, et al Activation of rat liver cytosolic 3-hydroxy-3-methylglutaryl coenzyme A reductase kinase by adenosine 5'-monophosphate . Biochem Biophys Res Commun. (1985)
  26. Beg ZH, Stonik JA, Brewer HB Jr 3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation . Proc Natl Acad Sci U S A. (1978)
  27. Menendez R, et al Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts . Biol Res. (1994)
  28. Menéndez R, et al Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts . Arch Med Res. (2001)
  29. Menendez R, et al Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats . Biol Res. (1996)
  30. Menéndez R, et al Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet . Br J Nutr. (1997)
  31. Wang Y, et al Very long chain fatty acids (policosanols) and phytosterols affect plasma lipid levels and cholesterol biosynthesis in hamsters . Metabolism. (2005)
  32. Wang YW, et al Effects of policosanols and phytosterols on lipid levels and cholesterol biosynthesis in hamsters . Lipids. (2003)
  33. Castaño G, et al Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia . Drugs R D. (2002)
  34. Castaño G, et al Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study . Int J Clin Pharmacol Res. (2001)
  35. Castaño G, et al Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk . J Gerontol A Biol Sci Med Sci. (2001)
  36. 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)
  37. 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)
  38. Torres O, et al Treatment of hypercholesterolemia in NIDDM with policosanol . Diabetes Care. (1995)
  39. 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)
  40. Más R, et al Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors . Clin Pharmacol Ther. (1999)
  41. Castaño G, et al Effects of policosanol on postmenopausal women with type II hypercholesterolemia . Gynecol Endocrinol. (2000)
  42. Castaño G, et al Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients . Int J Clin Pharmacol Res. (1999)
  43. 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)
  44. Castaño G, et al Effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia associated with type 2 diabetes mellitus . Int J Clin Pharmacol Res. (2002)
  45. Castaño G, et al Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia . Drugs Aging. (2003)
  46. Castaño G, et al Comparison of the efficacy, safety and tolerability of original policosanol versus other mixtures of higher aliphatic primary alcohols in patients with type II hypercholesterolemia . Int J Clin Pharmacol Res. (2002)
  47. Castaño G, et al Concomitant use of policosanol and beta-blockers in older patients . Int J Clin Pharmacol Res. (2004)
  48. Fernández S, et al A pharmacological surveillance study of the tolerability of policosanol in the elderly population . Am J Geriatr Pharmacother. (2004)
  49. Castaño G, et al A comparison of the effects of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia: a randomized, double-blinded study . Drugs Exp Clin Res. (2005)
  50. Prat H, Román O, Pino E Comparative effects of policosanol and two HMG-CoA reductase inhibitors on type II hypercholesterolemia . Rev Med Chil. (1999)
  51. Alcocer L, et al A comparative study of policosanol Versus acipimox in patients with type II hypercholesterolemia . Int J Tissue React. (1999)
  52. 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)
  53. Francini-Pesenti F, et al Effect of sugar cane policosanol on lipid profile in primary hypercholesterolemia . Phytother Res. (2008)
  54. Francini-Pesenti F, et al Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study . Complement Ther Med. (2008)
  55. Lin Y, et al Wheat germ policosanol failed to lower plasma cholesterol in subjects with normal to mildly elevated cholesterol concentrations . Metabolism. (2004)
  56. Berthold HK, et al Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial . JAMA. (2006)
  57. Greyling A, et al Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolaemic and heterozygous familial hypercholesterolaemic subjects . Br J Nutr. (2006)
  58. Kassis AN, Jones PJ Lack of cholesterol-lowering efficacy of Cuban sugar cane policosanols in hypercholesterolemic persons . Am J Clin Nutr. (2006)
  59. Dulin MF, et al Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial . Am J Clin Nutr. (2006)
  60. Cubeddu LX, et al Comparative lipid-lowering effects of policosanol and atorvastatin: a randomized, parallel, double-blind, placebo-controlled trial . Am Heart J. (2006)
  61. Backes JM, et al Modified-policosanol does not reduce plasma lipoproteins in hyperlipidemic patients when used alone or in combination with statin therapy . Lipids. (2011)
  62. Swanson B, et al Policosanol for managing human immunodeficiency virus-related dyslipidemia in a medically underserved population: a randomized, controlled clinical trial . Altern Ther Health Med. (2011)
  63. Menéndez R, et al Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro . Br J Clin Pharmacol. (2000)
  64. Kassis AN, Kubow S, Jones PJ Sugar cane policosanols do not reduce LDL oxidation in hypercholesterolemic individuals . Lipids. (2009)
  65. Arruzazabala ML, et al Antiplatelet effects of policosanol (20 and 40 mg/day) in healthy volunteers and dyslipidaemic patients . Clin Exp Pharmacol Physiol. (2002)
  66. Valdes S, et al Effect of policosanol on platelet aggregation in healthy volunteers . Int J Clin Pharmacol Res. (1996)
  67. Arruzazabala ML, et al Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers . Pharmacol Res. (1996)
  68. Arruzazabala ML, et al Comparative study of policosanol, aspirin and the combination therapy policosanol-aspirin on platelet aggregation in healthy volunteers . Pharmacol Res. (1997)
  69. 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)
  70. Arruzazabala ML, et al Effect of policosanol on platelet aggregation in type II hypercholesterolemic patients . Int J Tissue React. (1998)
  71. Stüsser R, et al Long-term therapy with policosanol improves treadmill exercise-ECG testing performance of coronary heart disease patients . Int J Clin Pharmacol Ther. (1998)
  72. Castaño G, et al A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication . Angiology. (1999)
  73. Reiner Z, Tedeschi-Reiner E Rice policosanol does not have any effects on blood coagulation factors in hypercholesterolemic patients . Coll Antropol. (2007)
  74. Abdul MI, et al Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects . Br J Clin Pharmacol. (2010)
  75. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) . JAMA. (2001)
  76. Castaño G, et al Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia . Drugs R D. (2005)
  77. Fontani G, et al Effect of omega-3 and policosanol supplementation on attention and reactivity in athletes . J Am Coll Nutr. (2009)
  78. Fontani G, Maffei D, Lodi L Policosanol, reaction time and event-related potentials . Neuropsychobiology. (2000)
  79. Re L, et al Effects of some natural extracts on the acetylcholine release at the mouse neuromuscular junction . Pharmacol Res. (1999)
  80. Noa M, et al Policosanol prevents bone loss in ovariectomized rats . Drugs Exp Clin Res. (2004)
  81. Fisher JE, Rodan GA, Reszka AA In vivo effects of bisphosphonates on the osteoclast mevalonate pathway . Endocrinology. (2000)
  82. Arruzazabala ML, et al D-003 and warfarin interaction on the bleeding time and venous thrombosis experimentally induced in rats . J Med Food. (2004)
  83. Molina V, et al Synergistic effect of D-003 and aspirin on experimental thrombosis models . Prostaglandins Leukot Essent Fatty Acids. (2003)
  84. Setnikar I, Senin P, Rovati LC Antiatherosclerotic efficacy of policosanol, red yeast rice extract and astaxanthin in the rabbit . Arzneimittelforschung. (2005)
  85. Alemán CL, et al Carcinogenicity of policosanol in mice: an 18-month study . Food Chem Toxicol. (1995)
  86. Alemán CL, et al A 12-month study of policosanol oral toxicity in Sprague Dawley rats . Toxicol Lett. (1994)
  87. Rodríguez MD, Garcia H Evaluation of peri- and post-natal toxicity of Policosanol in rats . Teratog Carcinog Mutagen. (1998)
  88. Gámez R, et al A 6-Month Study on the Toxicity of High Doses of Policosanol Orally Administered to Sprague-Dawley Rats . J Med Food. (2001)
  89. Rodríguez MD, García H Teratogenic and reproductive studies of policosanol in the rat and rabbit . Teratog Carcinog Mutagen. (1994)
  90. Rodríguez-Echenique C, et al Effects of policosanol chronically administered in male monkeys (Macaca arctoides) . Food Chem Toxicol. (1994)
  91. Alemán CL, et al Carcinogenicity of policosanol in Sprague Dawley rats: a 24 month study . Teratog Carcinog Mutagen. (1994)
  92. Fontani G, Maffei D, Lodi L Policosanol, reaction time and event-related potentials . Neuropsychobiology. (2000)
  93. Francini-Pesenti F, et al Sugar cane policosanol failed to lower plasma cholesterol in primitive, diet-resistant hypercholesterolaemia: a double blind, controlled study . Complement Ther Med. (2008)
  94. Cubeddu LX, et al Comparative lipid-lowering effects of policosanol and atorvastatin: a randomized, parallel, double-blind, placebo-controlled trial . Am Heart J. (2006)
  95. Kassis AN, Jones PJ Lack of cholesterol-lowering efficacy of Cuban sugar cane policosanols in hypercholesterolemic persons . Am J Clin Nutr. (2006)
  96. Dulin MF, et al Policosanol is ineffective in the treatment of hypercholesterolemia: a randomized controlled trial . Am J Clin Nutr. (2006)
  97. Francini-Pesenti F, et al Effect of sugar cane policosanol on lipid profile in primary hypercholesterolemia . Phytother Res. (2008)
  98. Reiner Z, Tedeschi-Reiner E Rice policosanol does not have any effects on blood coagulation factors in hypercholesterolemic patients . Coll Antropol. (2007)
  99. Illnait J, et al Effects of policosanol (10 mg/d) versus aspirin (100 mg/d) in patients with intermittent claudication: a 10-week, randomized, comparative study . Angiology. (2008)
  100. Kassis AN, Jones PJ Changes in cholesterol kinetics following sugar cane policosanol supplementation: a randomized control trial . Lipids Health Dis. (2008)
  101. Kassis AN, Kubow S, Jones PJ Sugar cane policosanols do not reduce LDL oxidation in hypercholesterolemic individuals . Lipids. (2009)
  102. Swanson B, et al Policosanol for managing human immunodeficiency virus-related dyslipidemia in a medically underserved population: a randomized, controlled clinical trial . Altern Ther Health Med. (2011)
  103. Backes JM, et al Modified-policosanol does not reduce plasma lipoproteins in hyperlipidemic patients when used alone or in combination with statin therapy . Lipids. (2011)
  104. Castaño G, et al Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia . Drugs R D. (2002)
  105. Castaño G, et al Effects of policosanol 20 versus 40 mg/day in the treatment of patients with type II hypercholesterolemia: a 6-month double-blind study . Int J Clin Pharmacol Res. (2001)
  106. Mirkin A, et al Efficacy and tolerability of policosanol in hypercholesterolemic postmenopausal women . Int J Clin Pharmacol Res. (2001)
  107. Castaño G, et al Effects of policosanol in older patients with type II hypercholesterolemia and high coronary risk . J Gerontol A Biol Sci Med Sci. (2001)
  108. Castaño G, et al A long-term study of policosanol in the treatment of intermittent claudication . Angiology. (2001)
  109. Menéndez R, et al Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro . Br J Clin Pharmacol. (2000)

(Common misspellings for Policosanol include policsanl, policsanol, policosonal)