While only small amounts of octacosanol are ingested in the diet, many health benefits have surfaced, in part due to researchers developing octacosanol in a supplement form. Most studies to date have used a wheat germ oil extract or policosanol, a natural mixture of primary alcohols isolated from sugar cane wax, of which octacosanol is the primary component. Octacosanol has the potential to benefit human health in many areas, in particular exercise performance, platelet aggregation, and plasma cholesterol levels. Of the potential health benefits associated with octa-cosanol, its ergogenic properties and cholesterol-lowering effects have been the most studied.
Ergogenic aids, substances that enhance athletic performance and increase stamina and capability to exercise, are believed to improve performance by either renewing or increasing energy stores in the body, which facilitates biochemical reactions contributing to fatigue, or by maintaining optimal body weight.5 Because the U.S. Food and Drug Administration does not require nutritional supplements to be proven safe or effective, many athletes take such supplements without realizing potential side effects. Likewise, nutritional supplements are not covered by the U.K. Medicines Act, and therefore no regulations for manufacture, quality, or usage exist, making them subject to abuse.6 Additionally, it is often difficult to fully determine whether an improvement in performance or muscle size is due to a nutritional supplement or to other factors, such as improved training techniques or diet.
Octacosanol is one such ergogenic supplement proposed to enhance performance and delay fatigue. Thomas Cureton was the first to report that wheat germ oil had ergogenic effects. During his career, Cureton performed approximately 42 studies that addressed the ergogenic potential of wheat germ oil.2 In 1963, Cureton published a study involving 30 trainees in the U.S. Navy. The subjects received either 3.7 ml (10 capsules containing 0.37 ml each) of octacosanol in cottonseed oil, cottonseed oil (used as the placebo), or whole-wheat germ oil daily for 6 weeks. While the octacosanol-supplemented group had higher mean exercise performance, they did not differ significantly from that of the placebo group.2
In 1986, Saint-John and McNaughton investigated human subjects taking octacosanol supplements in relationship to chest strength, stamina, grip, cardiovascular function, and reaction time. Specifically, 1000 ^g of octacosanol was administered to healthy human subjects daily. Grip strength and reaction time significantly improved in response to a visual stimulus. The researchers concluded octacosanol was an "active energy releasing factor" and improved performance when compared with the placebo.7 This research led others to hypothesize that octacosanol might exhibit properties affecting the nervous system because reaction time was able to change according to nerve impulses throughout the body. A study was conducted in 1998 on a group of patients with coronary heart disease taking a policosanol supplement that improved their response to exercise angina and significantly increased maximum oxygen uptake.8 Animal studies have also exhibited ergogenic properties of octacosanol. Exercised-trained octacosanol-supplemented Sprague-Dawley rats ran 46% longer and had significantly higher plasma ammonia and lactate concentrations than control rats. While the exercised-trained octacosanol-supple-mented rats ran significantly longer until exhausted, their plasma glucose level and gastronecmius muscle gycogen concentrations were not different from those of the control rats. These results suggest that octacosanol supplementation allows for muscle glycogen sparing and an increase in the oxidative capacity of the muscle.9 On the other hand, Bucci reported a failure of other researchers to significantly substantiate the ergogenic benefit of octacosanol.10
If octacosanol truly does possess ergogenic properties, the mechanism of action is not fully understood at this point. Kabir and Kimura attempted to address this phenomenon using rats. The researchers set out to investigate the biodistribution of radioactive (14C) octacosanol in response to exercise.11 They found the amount of voluntary exercise to be significantly higher in octacosanol-fed rats than in control rats. Additionally, the amount of radioactive octacosanol in the muscle of exercised animals was significantly higher. The muscle seemed to be able to store a considerable amount of octacosanol in response to exercise. While the exact mechanism behind this increase in physical activity caused by octacosanol is unclear, it is quite possible that octacosanol has the ability to increase the mobilization of free fatty acids from fat cells within the muscle. The results from this study indicate that octacosanol possesses an adipolinetic activity that could potentially affect lipolysis in muscle.11
All in all, the studies assessing octacosanol as an ergogenic aid are nonspecific. The trials up to this point appear to have many confounding factors. It is essential in clinical trials, especially when athletic performance is measured, to eliminate the placebo effect as much as possible. Many of the studies presented here, which are considered the most reliable to date, lack consistency. This lack of congruency makes it difficult to compare studies. Furthermore, completely randomized, double-blinded studies comparing athletes participating in similar exercise regimens are warranted.
Platelet aggregation occurs when blood is converted from a thin consistency to a thicker form or even a clot, which can cause a deep-vein thrombosis or stroke. Exogenous factors such as arachidonic acid, collagen, and adenosine diphosphate can cause aggregation. Platelet aggregation is an important factor in coronary artery disease and vascular arterial disease. Patients at risk for one of these diseases have an increased risk for the other.12 Arruzazabala and colleagues found that 5 to 20 mg/kg of policosanol given to rats resulted in antiaggregatory effects.8 These researchers suggested the action was due to the inhibition of arachidonic acid metabolism. The same group of researchers found that when 50 to 200 mg/kg of policosanol was administered, a significant inhibition of platelet aggregation was observed.12 This study emphasized the need for a large dose to allow policosanol to exhibit antiaggregatory effects.
In 1997, the same research group investigated the effects of policosanol and aspirin on platelet aggregation.13 Aspirin is commonly used to prevent thrombosis and cerebral ischemia, but can cause gastric irritation. Policosanol works by inhibiting thromboxane A2 (TxA2) synthesis instead of prostaglandin synthesis; therefore, fewer side effects such as gastric irritation occur. A daily dose of 20 mg of policosanol caused a significant reduction in platelet aggregation, establishing that policosanol was just as effective as 100 mg/day of aspirin.
Researchers noticed that during exercise endurance experiments on mice, octa-cosanol had the ability to alter hepatic and serum lipid concentrations.14 This led them to begin focusing on octacosanol as a cholesterol-lowering agent. In 1992, Hernandez et al. investigated the effects on healthy individuals with normal cholesterol levels given 10 or 20 mg of policosanol or a placebo.15 The policosanol-supplemented group had a significant decrease in serum cholesterol levels. The group taking 20 mg of policosanol also demonstrated an increase in high-density lipopro-tein (HDL) levels. Aside from the cholesterol-lowering effect, this study revealed a good tolerance in all subjects taking the policosanol supplement.
Kato and colleagues set out to test the effect of octacosanol on lipid metabolism through rats fed a high-fat diet supplemented with octacosanol.16 The addition of 10 g octacosanol/kg to a high-fat diet led to a significant reduction in the perirenal adipose tissue weight without causing a decrease in cell number. This suggests that octacosanol may suppress lipid accumulation in this tissue. Furthermore, octacosanol supplementation decreased the serum triacylglycerol concentration, most likely through the inhibition of hepatic phosphatidate phosphohydrolase. High amounts of lipoprotein lipase in the perirenal adipose tissue and an increase in the total oxidation rate of fatty acid in the muscle were also observed. Lipid absorption, however, was unaffected by octacosanol supplementation. This study suggests that the dietary incorporation of octacosanol affects some aspects of lipid metabolism. The action of octacosanol may depend on specific dietary conditions, such as fat content, as suggested by this study.
While statin drugs (drugs currently used to reduce blood cholesterol levels) inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase in the cholesterol synthesis pathway, policosanol inhibits the same pathway but a step earlier. Policosanol could, therefore, prove to be a useful alternative to statin drugs.
In 1999, a study examined just that — the effects of policosanol and pravastatin (a statin drug) on the lipid profile of hypercholesterolemic patients.17 The researchers demonstrated that policosanol was more effective than pravastatin in lowering low-density lipoprotein (LDL), as well as improving the ratios of LDL to HDL and total cholesterol to HDL. As seen in previous studies, policosanol also increased HDL.15,16 It is important to note that both drugs in this study were well tolerated with little or no side effects reported.
A similar study examined the effects of policosanol and fluvastatin, another commonly used statin drug, on hypercholesterolemic patients.18 Policosanol exhibited LDL-lowering and HDL-raising effects. Again, policosanol was well tolerated by the hypercholesterolemic patients. As in the studies discussed here, many others have also investigated the effects of policosanol on hypercholesterolemia, and in all cases the results were similar: LDL cholesterol decreased and HDL cholesterol increased.17-21
From these studies we can conclude that octacosanol/policosanol appears to be a promising lipid-lowering agent that is well tolerated with fewer reported side effects than its statin counterpart. Additionally, the cost of octacosanol/policosanol supplementation is only a fraction of statin drugs, which would make it more available to lower-income hypercholesterolemic patients. It is important to note that most of the studies examined here are considered short term (<1 year long). Larger trials extending over longer periods of time are needed to assess the longer-term effects of octacosanol.
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