Octacosanol

Scientific Name(s):1-octacosanol, n-octacosanol, octacosyl alcohol

Common Name(s):24 to 36 carbon alcohols isolated from wheat germ oil or other plants.

Uses

Octacosanol is being investigated as a herpes antiviral and as a treatment for inflammatory diseases of the skin. It may be helpful with Parkinson disease and ALS, but more studies are needed. Octacosanol administration also has conferred enhanced physical endurance in some studies.

Dosing

Octacosanol (policosanol) has been studied at doses from 10 to 20 mg daily in cholesterol reduction and heart disease. 1 , 2 , 3

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

There have been no reported side effects with the use of octacosanol except for a suggestion of interaction with levodopa/carbidopa in Parkinson disease patients.

Toxicology

There are no data on the long-term toxicity of products containing octacosanol. 4

History

Studies in the 1930s and 1940s suggested that athletes who were given daily or weekly doses of raw, unrefined wheat germ oil outperformed subjects who received only vitamin E supplements. The biologic value of wheat germ was reconfirmed in a 1951 study in which college students received wheat germ oil for 18 weeks. Treated subjects improved their “all-out” bicycle riding times by 47%, while the untreated controls increased their average riding times by only 4%. All of these studies suggested that some component of unrefined wheat germ oil increased physical endurance, and that vitamin E was not entirely responsible. Further investigations culminated in a patent for the combination of “physiologically active” components of raw wheat germ oil. 5 No published scientific studies were provided that evaluated the physiologic activity of these “active constituents.” 4

Chemistry

Octacosanol is a constituent of vegetable waxes and has been isolated from wax on green blades of wheat. 6 The name octacosanol specifically pertains to a 28-carbon alcohol, but it is commonly used to denote a mixture of 24-, 26-, 28-, and 30-36-carbon alcohols, that are believed to possess most of the physiologic activity of wheat germ oil. These compounds are present as alcohols or acetates and can also be isolated from plants other than wheat. 4 A number of reports are available, isolating octacosanol as one of many components in certain plants. A brief listing follows, with references listed for those interested in these specific species: octacosanol from leaves of Pithecolobium dulce V., 7 Cymbopogon citratus (Dc.) Stapf (Poaceae); 8 whole plant of Euphorbia myrsinitis L., 9 Euphorbia tinctoria boiss, 10 Daemia extensa R. Br.; 11 stem bark of Acacia modesta ; 12 Heart wood of Cassia javanica ; 13 fruits of Serenoa repens Bartram, 14 Poinsettia pulcherrima , 15 Citrullus colocynthus ; 16 roots of Talinum paniculatum Gaertner, 17 Acanthus illicifolius ; 18 crude drug “jungle pepper” Vitex pubescens ; 19 and octacosanol from Eupolyphaga sinensis Walker. 20

Uses and Pharmacology

Specific biologic activity has been described for triacontanol (30-C alcohol); its application to seedlings and growing plants increases growth rate and fruit yield. 21 It is being investigated in humans for use as an antiviral for herpes and for the treatment of inflammatory skin diseases. The biologic activity of tetracosanol (24-C) and hexacosanol (26-C) are poorly understood.

Physical endurance/vigor

The cited patent proposes that octacosanol improves stamina and vigor by improving oxygen utilization during anaerobic glycolysis. At the onset of exercise, when the circulation is increasing to meet muscle oxygen demand, a period of relative oxygen deficiency exists, and blood lactate levels rise. It is believed that octacosanol and related compounds may aid in the removal of lactic acid by increasing the efficiency of the tricarboxylic acid cycle, which operates through reactions connecting to the oxygen supply. This may also result in an increased oxygen uptake or a decreased oxygen requirement. However, no data exist to confirm this mechanism of action.

Animal data

To understand mechanisms such as increased physical exercise and improved motor endurance by octacosanol, its pharmacokinetic characteristics were evaluated. Octacosanol was found to distribute mainly to adipose tissue when administered orally in rats. 22 After ingestion of octacosanol in rats that were exercised, however, results showed significantly higher distribution to muscle tissue, supporting a theory of octacosanol muscle storage in response to exercise. A similar report by the same authors evaluates muscle storage of serially administered (orally through stomach tubs) radioactive octacosanol. At first, highest concentration is in the liver, but rapidly disappears (even when doses are increased). The muscle was able to store a considerable amount of octacosanol, which may help to explain increased muscle endurance in exercise. 23

Also proposed is the possibility that octacosanol increases mobilization of free fatty acids from fat cells in the muscle, having “adipokinetic” activity affecting the muscle's lipolysis process. 24 In another report, lipid metabolism was evaluated in rats receiving octacosanol and a high-fat diet. Results suggest octacosanol to suppress lipid accumulation in adipose tissue. Additionally, it decreased serum triacylglycerol concentration and enhanced serum fatty acid concentration. 25

Absorption of octacosanol was found to be low, with excretion mainly via feces. Metabolites of the alcohol were found to be present in urine. 22

Orally administered combinations of octacosanol compounds were shown to produce a physiologic response characteristic of androgenic activity in the chick-comb test. 1-Octacosanol increased the size of the testes and seminal vesicles in rats, compared to those fed a cottonseed oil control diet. Further, guinea pigs fed a diet containing 2.2 mg/kg octacosanol for 28 days had a better swimming performance than animals fed rations without the alcohol. Animals that were fed a 2% wheat germ oil diet also swam longer than those fed the control diet. 4

Clinical data

US Patent 3,031,376 provided limited evidence that daily doses ranging from 0.05 to 150 mg of these compounds are well tolerated by humans; it indicated that the usual “maintenance dose” is 40 to 80 mg total alcohols daily. 4

In one single-blind study, 12 men received 1-octacosanol daily in cottonseed oil (dose not specified) and 10 received placebo. Both treatment groups were tested before the study and again at a later, unspecified interval, for ECG R-wave changes, the mile run, 466-yard swim, push-ups and six other athletic events. Significant ( P < 0.05) improvements were noted for all test parameters in the octacosanol-treated group; however, statistically significant improvement was also noted in the placebo group for the mile run, 466-yard swim and step-up test. The maximum percent mean improvement for any test was 18%, and this was observed in both test groups. In another test using four matched groups of boys (population size not specified), subjects given an unspecified quantity of octacosanol for 8 weeks completed the 600-yard run an average of 10% faster than before starting the supplement. Boys who received wheat germ oil improved their times by 9%, those receiving wheat germ by 6% and those receiving placebo by 4%. 4

A recent review article discusses efficacy of nutritional supplementation by athletes. Octacosanol is mentioned to have ergogenic qualities, but with little or no scientific evidence supporting this. 26

Parkinson disease/ALS
Animal data

Research reveals no animal data regarding the use of octacosanol for treatment of Parkinson disease or ALS.

Clinical data

A small study suggests that octacosanol benefits patients with Parkinsonism. In a double-blind, placebo controlled trial, 10 patients received six weeks of treatment with 5 mg octacosanol in wheat germ oil or placebo, three times daily with meals. Three of the patients showed significant symptomatic improvement during the octacosanol phase of treatment. None of the patients showed worsening of their conditions during octacosanol treatment. Overall, the treated group showed a slight improvement in performance of activities of daily living. 27

The promising results in Parkinson patients led to a double-blind, crossover study involving 11 patients with amyotrophic lateral sclerosis. Patients received either 40 mg/day of each of the 28-C, 30-C, and 30-36-C alcohols or a placebo for 3 months. Although 3 patients in the drug phase and 3 in the placebo phase reported subjective improvement, neurological evaluations showed progression of the disease in all cases. Some patients showed some improvement in certain test scores, but there was no significant difference between the octacosanol and placebo groups. 28 , 29

Dosage

Octacosanol (policosanol) has been studied at doses from 10 to 20 mg daily in cholesterol reduction and heart disease. 1 , 2 , 3

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

In the Parkinson disease study, side effects were infrequent but included position-related nonrotational dizziness, mild increase in nervous tension, and worsening of carbidopa/levodopa-related dyskinesias. These effects suggested an interaction with levodopa. 28 , 29

Toxicology

There are no data on the long-term toxicity of products containing octacosanol. 4

Bibliography

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2. Nikitin IuP, Slepchenko NV, Gratsianskii NA, Nechaev AS, Syrkin AL, Poltavskaia MG, et al. [Results of the multicenter controlled study of the hypolipidemic drug polycosanol in Russia] Ter Arkh . 2000;72(12):7-10. Russian.
3. Stusser R, Batista J, Padron R, Sosa F, Pereztol O. Long-term therapy with policosanol improves treadmill exercise-ECG testing performance of coronary heart disease patients. Int J Cin Pharmacol Ther . 1998;36(9):469-73.
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5. US Pat 3,031,376;24 Apr 1962.
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