Th-P16:325 A comparison of the effects of D-003 and policosanol (5 and 10 mg/d) in patients with type II hypercholesterolemia: A randomized, double-blinded study

Castaño, Gladys; R, Más; Fernandez, Luisa; Illnait, José; Mendoza, Sarahí; Gámez, Rafael; Fernández, Javier; Mesa, Meilis

doi:10.1016/s1567-5688(06)82283-x

Cited by 9 publications

(11 citation statements)

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“…Policosanol reduces LDLcholesterol by 20 to 30% and increases hepatic LDL-receptor expression (Menendez et al, 1997), both of which are consistent with down-regulation of hepatic cholesterologenesis. Numerous clinical studies have documented the ability of policosanol to reduce serum cholesterol in both normocholesterolemic and hypercholesterolemic patients (for review, see Gouni-Berthold and Berthold, 2002;Varady et al, 2003; see also Castano et al, 2005;Wright et al, 2005), although a very recent clinical study was unable to find a significant cholesterol-lowering effect (Berthold et al, 2006).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…This could be due to the short duration of treatment. One hundred patients with type ɪɪ hypercholesterolemia were randomized, in a double-blind manner, to D-003 or policosanol [38]. Both preparations were tested at doses of 5 mg/day and 10 mg/day.…”

Section: Evidence From Clinical Studiesmentioning

confidence: 99%

D-003 (Saccharum officinarum): The forgotten lipid-lowering agent

Awad

Penson

Banach

2016

Pharmacological Research

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ABSTRACT:Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk.D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies.

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“…The active component(s) has not been established, but it has been shown that very long-chain alcohols can undergo oxidation to fatty acids with subsequent peroxisomal -oxidation, which also yields chain-shortened metabolites (Singh et al, 1987). D-003, a mixture of very long-chain saturated fatty acids, also purified from sugarcane, similarly lowers LDL and total cholesterol in normocholesterolemic patients (Castano et al, 2005) and in normocholesterolemic and casein-induced hypercholesterolemic rabbits, and a more rapid onset of effects suggests that oxidation of policosanols to very long-chain fatty acids may be necessary for their hypocholesterolemic actions (Menendez et al, 2001;Menendez et al, 2004). Several studies have demonstrated that policosanol inhibits cholesterol synthesis in laboratory animals and cultured cells, and it is thought that this is the principal mechanism by which it lowers blood cholesterol levels.…”

Section: Decrease In Cholesterol Level By Policosanolmentioning

confidence: 99%

Cholesterol: Biosynthesis, Functional Diversity, Homeostasis and Regulation by Natural Products

Thomas¹,

Shentu²,

Singh³

2012

Biochemistry

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Th-P16:325 A comparison of the effects of D-003 and policosanol (5 and 10 mg/d) in patients with type II hypercholesterolemia: A randomized, double-blinded study

Cited by 9 publications

References 0 publications

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

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

D-003 (Saccharum officinarum): The forgotten lipid-lowering agent

Cholesterol: Biosynthesis, Functional Diversity, Homeostasis and Regulation by Natural Products

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