Toxicity of policosanol in beagle dogs: one-year study

Mesa, Alba; Más, Rosa; Noa, Miríam; Hernández, Caridad; Rodeiro, Idania; Gámez, Rafael; García, M. A.; Capote, Amelia; Alemán, Celia

doi:10.1016/0378-4274(94)90098-1

Cited by 52 publications

(17 citation statements)

References 8 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: 56%

“…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: 56%

Section: Introductionmentioning

confidence: 99%

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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“…As in previous studies, [24][25][26][27][28][29][30][31] policosanol was suspended in an acacia gum/water vehicle (10 mg/ml) recommended for poorly soluble substances. 33 The suspensions were prepared weekly, and the concentration of policosanol in each one was calculated, taking into account the mean body weight value of each group to ensure adequate dosage according to body weight increase.…”

Section: Administration and Dosagementioning

confidence: 99%

“…20 Excellent safety and tolerability, compared with other lipid-lowering drugs, have been demonstrated in clinical studies. [21][22][23] Because cholesterol-lowering drugs must be used as long-term therapy, extensive experimental toxicology studies have been conducted to demonstrate any potential oral toxicity of policosanol, [24][25][26][27][28][29][30][31] but all of them have failed to demonstrate any drug-related toxicity. Studies on oral acute toxicity of policosanol performed in rodents and nonrodents have shown that the median lethal dose (LD 50 ) in rats, mice, rabbits, and dogs is greater than 5,000 mg/kg.…”

Section: Introductionmentioning

confidence: 99%

A 6-Month Study on the Toxicity of High Doses of Policosanol Orally Administered to Sprague-Dawley Rats

Gámez

Alemán

Más

et al. 2001

Journal of Medicinal Food

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Policosanol is a cholesterol-lowering drug purified from sugar cane. Previous toxicological studies have not demonstrated any policosanol-related toxicity, even with long-term oral administration at 500 mg/kg, a dose 1,724 times larger than the maximal therapeutic dose (20 mg/day) recommended to date. The present study was undertaken to investigate the oral toxicity of policosanol administered for 6 months in doses up to 5,000 mg/kg to Sprague-Dawley rats. Animals were randomly distributed in five groups (15 animals per dose per sex): a control and four groups given oral policosanol (50, 500, 2,500, or 5,000 mg/kg). Eight treated rats (6 males, 2 females) died during the study, five of them (4 males, 1 female) from among those receiving the highest dose (5,000 mg/kg). According to necropsy, all deaths were related to gavage manipulation of higher doses. Although the differences were not significant, body weight gain and food consumption in the groups receiving 2,500 or 5,000 mg/kg tended to be lower than in the control group. Nevertheless, no drug-related toxicity symptoms were detected. Analysis of blood biochemistry, hematology, organ weight ratios, and histopathological findings did not show significant differences compared with controls, nor any tendency with the dose. Therefore, the present study did not show any new evidence of oral toxicity of policosanol, and the findings observed were a consequence of long-term administration by gastric gavage of the highly concentrated suspensions needed to reach the higher doses. It is concluded that policosanol chronically administered by the oral route is safe and that no drug-related toxicity was demonstrated.

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“…Twelve tri-color Beagle dogs were used, six males and six females, aged 3 to 4 months, in accordance with the literature (Mesa et al, 1994;Guzman et al, 2000). The animals were kept in animal facilities, separated by gender and fed with all the standard pet food and water ad libitum.…”

Section: Animalsmentioning

confidence: 99%

Toxicological evaluation of the João da Costa e Associações® on Beagle dogs

Magri¹,

Neves²,

Kaneshima³

et al. 2012

Rev. bras. farmacogn.

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A toxicological study was performed in Beagle dogs treated for 180 days with the product João da Costa e Associações. Were used six males and six females distributed in control and treated groups (n=3). We used a dose of 566 mg/kg of the product according to preclinical study in rodents. The animals were weighed and evaluated by clinical and laboratory aspects. The product did not cause mortality or alter the normal behavior of animals, but interfered with the weight gain on males in the middle phase of the treatment. The group treated had a lower incidence of clinical abnormalities compared to control, checked by veterinary consultations. Laboratory data showed elevated blood glucose levels perhaps due to the high amount of sucrose present in the product; about the histopathological data no significant change was found. We conclude that the product Joao da Costa and Associações, at the dose tested, has low toxicity in Beagle dogs treated chronically.

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Toxicity of policosanol in beagle dogs: one-year study

Cited by 52 publications

References 8 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

A 6-Month Study on the Toxicity of High Doses of Policosanol Orally Administered to Sprague-Dawley Rats

Toxicological evaluation of the João da Costa e Associações® on Beagle dogs

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