Effects of policosanol chronically administered in male monkeys (Macaca arctoides)

Rodríguez-Echenique, C.; Mesa, Rosario; Más, Rosa; Noa, Miríam; Menéndez, Roberto; González, Rafael de Miguel; Amor, Ana María; Fraga, V.; Sotolongo, V.; Laguna, Abilio

doi:10.1016/0278-6915(94)90115-5

Cited by 58 publications

(29 citation statements)

References 19 publications

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“…These results are in contrast with previous research conducted on the Dalmer mixture that demonstrates reductions in total cholesterol and LDL-cholesterol of more than 13% (Varady et al, 2003). Studies conducted on rabbits, dogs and monkeys agree with the conclusion that policosanols reduce levels of LDL-C and TC significantly at dosages ranging from 5 mg-500 mg/kg body weight/day (Arruzazabala et al, 1994;Mesa et al, 1994;Rodriguez-Echenique et al, 1994;Menendez et al, 1996;Menendez et al, 1997). The hamster model used in the present study is considered to be one of the most suitable models for studying lipid lowering mechanisms (Kris-Etherton & Dietschy, 1997) and has shown to resemble humans with regard to regulation of LDL-C metabolism (Spady & Dietschy, 1988).…”

Section: Discussioncontrasting

confidence: 83%

“…Furthermore, no changes in serum lipid levels were noted. The original researchers have demonstrated cholesterol-lowering efficacy of PC using a genetically diverse range of models including humans (Aneiros et al, 1995), monkeys (Rodriguez-Echenique et al, 1994), rabbits (Arruzazabala et al, 1994;Menendez et al, 1997), dogs , and rats (Menendez et al, 1996). Hence, it is unlikely that our observations are due to the hamster model utilized in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Various animal models including rats (Menendez et al, 1996), rabbits (Arruzazabala et al, 1994;Menendez et al, 1997;Arruzazabala et al, 2000), dogs and monkeys Rodriguez-Echenique et al, 1994) were given doses ranging from 5 mg/kg/day to 500 mg/kg/day of SCP, all of which incurred substantial reductions in total cholesterol (TC) and LDL-C levels. A 20% reduction in TC which was recorded at week 8 was maintained throughout study periods of up to 54 weeks RodriguezEchenique et al, 1994).…”

Section: Animal Studies Investigating Policosanol Efficacymentioning

confidence: 99%

“…Cuban SCP, derived from the waxy coating of stems and leaves of sugar cane and other plant materials, has been shown to exert beneficial effects on lipid profiles in animals and humans in numerous studies conducted by a single laboratory and using an SCP product manufactured by Dalmer laboratories (La Havana, Cuba) (Mas, 2000). Animal trials testing the alcohols within experimental models including rats, rabbits, dogs and monkeys, have demonstrated reductions in circulating total cholesterol (TC) levels consistently greater than 13% (Arruzazabala et al, 1994;Mesa et al, 1994;Rodriguez-Echenique et al, 1994;Menendez et al, 1996;Menendez et al, 1997). Similarly, human policosanol feeding trials (Menendez et al, 2000c;Castano et al, 2001b;Mirkin et al, 2001;Castaño et al, 2002) have shown reductions of up to 20% and 30% in TC and low-density-lipoprotein cholesterol (LDL-C) levels respectively, depending on dose and duration of SCP treatment.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of cholesterol-lowering and antioxidant properties of sugar cane policosanols in hamsters and humans

Kassis

2008

Appl. Physiol. Nutr. Metab.

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Atherosclerosis prevention is now a major focus of the scientific community and the pharmaceutical industry. Sugar cane policosanols (SCP) have gained increasing popularity over the last decade as a result of numerous studies conducted in Cuba considering SCP as the natural alternative to statin drugs. However, independent research on policosanols was not able to replicate cholesterol reductions reported by Cuban laboratories. No independent study to date has examined the cholesterol-lowering effect and antioxidant capacity of original SCP in humans. In addition, since independent research was criticized because of the use of alternative policosanol formulations, the source and composition of policosanol mixtures are now at the core of the policosanol controversy.The aim of the present thesis project was first to compare the composition and cholesterol-lowering effects of different SCP preparations in hamsters, and secondly to test the cholesterol-lowering efficacy, mechanism of action and antioxidant capacity of the original Cuban SCP in hypercholesterolemic humans.Study 1: Forty-eight male hamsters were randomly assigned to 4 groups for a period of 4 weeks (i) non-cholesterol control, (ii) cholesterol control, (iii) original SCP and (iv) alternative SCP. Hamsters were sacrificed and blood was collected at the end of the feeding period for lipid measurements.Study 2: Twenty-one hypercholesterolemic volunteers consumed 10 mg/day of SCP or a placebo for a period of 28 days in a crossover trial. Plasma lipid levels and LDL oxidation were measured at the start and end of supplementation phases. Cholesterol absorption and synthesis were assessed using single isotope single tracer technique and deuterium incorporation respectively.There was no significant difference in cholesterol-lowering efficacy between hamsters in the original and alternative SCP groups relative to control. Similarly, in hypercholesterolemic humans, original SCP supplementation did not significantly improve lipid parameters and no change in cholesterol absorption or synthesis was observed relative to control. In vivo assessment of LDL oxidation showed no significant changes in oxidized LDL concentration relative to baseline and control.

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Section: Discussioncontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Animal Studies Investigating Policosanol Efficacymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of cholesterol-lowering and antioxidant properties of sugar cane policosanols in hamsters and humans

Kassis

2008

Appl. Physiol. Nutr. Metab.

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“…In normocholesterolemic patients, policosanol caused a small and generally insignificant increase in high-density lipoprotein-cholesterol, whereas in seven clinical studies of dyslipidemic patients high-density lipoprotein-cholesterol was increased by an average of 17%. Policosanol is also effective in rabbits and monkeys, where it lowers blood cholesterol and reduces the development of atherosclerotic plaques (Arruzazabala et al, 1994;Rodriguez-Echenique et al, 1994;Menendez et al, 1997), but it was found not to be effective in hamsters .…”

mentioning

confidence: 99%

Policosanol Inhibits Cholesterol Synthesis in Hepatoma Cells by Activation of AMP-Kinase

Singh

Li²,

Porter³

2006

J Pharmacol Exp Ther

146

126

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Policosanol is a mixture of long-chain primary alcohols that has been shown to decrease serum cholesterol in animals and in humans. The hypocholesterolemic effect results from a decrease in cholesterol synthesis by suppression of HMG-CoA reductase activity, but the mechanism of this suppression and the active components of policosanol have not been established. In the present study, we investigated the ability of policosanol and its principal components to inhibit cholesterol synthesis in cultured rat hepatoma cells. Maximal inhibition by policosanol yielded a 30% decrease in [14 C]acetate incorporation without evidence of cellular toxicity. Octacosanol (C28, the major constituent of policosanol), heptacosanol (C27), and hexacosanol (C26) yielded smaller and statistically insignificant decreases in cholesterol synthesis, whereas triacontanol (1-hydroxytriacontane; C30) replicated the inhibition obtained with policosanol. At pharmacological concentrations (Ͻ5 g/ml), policosanol and triacontanol decreased [14 C]acetate incorporation into cholesterol without affecting the incorporation of [ 14 C]mevalonate, indicating that these compounds act at or above HMG-CoA reductase. Policosanol and triacontanol did not directly inhibit HMG-CoA reductase, and incubation of these compounds with hepatoma cells did not affect reductase enzyme levels. However, reductase activity was decreased by up to 55% in lysates prepared from these cells, suggesting that HMG-CoA reductase activity was down-regulated by policosanol treatment. Consistent with this hypothesis, a 3-fold increase in AMP-kinase phosphorylation was noted in policosanoltreated cells. Because AMP-kinase is activated by phosphorylation and is well established to suppress HMG-CoA reductase activity, these results suggest that policosanol or a metabolite decreases HMG-CoA reductase activity by activating AMPkinase.

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Evaluation of peri- and post-natal toxicity of policosanol in rats

Rodríguez

Garcı́a

1998

Teratog. Carcinog. Mutagen.

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The effects of Policosanol, a newly developmented hypocholesterolemic drug administered during the perinatal and postnatal periods, were studied in Sprague‐Dawley rats. This compound was administered orally to female rats at dose levels of 0 (control), 5, 50, and 500 mg/kg/day, from day 15 of pregnancy to day 21 after parturition. The animals were allowed to deliver and their offspring were examined for postnatal growth and development. No signs of toxic effects related to the test material were observed in the dams F0 during pregnancy and lactation. No adverse effects were observed on the postnatal growth, behaviours, or reproductive ability of pups F1. The physical and sensorial development of pups F2 was also normal. These results confirm that Policosanol does not affect the reproductive performance or fetal/neonatal development. Teratogenesis Carcinog. Mutagen. 18:1–7, 1998. © 1998 Wiley‐Liss, Inc.

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Effects of policosanol chronically administered in male monkeys (Macaca arctoides)

Cited by 58 publications

References 19 publications

Evaluation of cholesterol-lowering and antioxidant properties of sugar cane policosanols in hamsters and humans

Evaluation of cholesterol-lowering and antioxidant properties of sugar cane policosanols in hamsters and humans

Policosanol Inhibits Cholesterol Synthesis in Hepatoma Cells by Activation of AMP-Kinase

Evaluation of peri- and post-natal toxicity of policosanol in rats

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