Lack of Effect of Sugar Cane and Sunflower Seed Policosanols on Plasma Cholesterol in Rabbits

Objective: To evaluate the potential for a mixture of policosanol extracted from sunflower oil (SFP) to lower blood cholesterol levels in comparison to sugar cane policosanol (SCP) in rabbits.

Design: Twenty three Semi-lop rabbits were blocked into three groups matched on fasting plasma cholesterol levels then randomly assigned to one of three parallel treatment arms: Control (Vehicle 28.6% sunflower oil/70% water/1.4% emulsifier) n = 7; SFP, 100 mg/kg in vehicle, n = 8; SCP, 100 mg/kg in vehicle, n = 8. Rabbits were gavaged once every two days for four weeks. Blood was collected and analysed for plasma lipids.

Results: Total cholesterol, non-HDL and HDL cholesterol increased significantly following SCP supplementation relative to the control. SFP supplementation had no effect. Triglyceride levels decreased significantly following all dietary treatments (P < 0.05), possibly due to the emulsifier.

Conclusion: Dietary supplementation of normocholesterolemic rabbits with policosanol from sunflower oil does not appear to have any cholesterol lowering effect. A similar lack of efficacy observed with the commercial SCP product which we evaluated raises doubts about the purported cholesterol-lowering efficacy of these products, as reflected in the current literature.     

Characterization and Compatibility Studies between Policosanol,a New Hypocholesterolemic Drug,and Tablet Excipients Using Differential Scanning Calorimetry (DSC)

Characterisation of policosanol, a new active principle composed of 8 high molecular weight fatty alcohols, viz. 1-tetracosanol, 1-hexacosanol, 1-heptacosanol, 1-octacosanol, 1-nonacosanol, 1-triacontanol, 1-dotriacontanol, and 1-tetratriacontanol, shows it have a very stable, well defined composition which is reproducible from batch to batch. Compatibility studies by differential scanning calorimetry (DSC) and thermogravimetry (TG) gave very useful physicochemical information and reveal the characteristic transitions, as well as the thermal stability of this drug. DSC facilitated compatibility studies between policosanol and several tablet excipients generally used for the manufacture of this pharmaceutical dosage form. It is seen that the combination of policosanol with each excipient in every one of the ratios used did not produce any changes in the melting point of policosanol or those of the excipients mixed with it. Also, no new peaks were observed in the policosanol/excipient mixtures. It can be concluded from these results that no dissolution of policosanol in the excipients occurs, and also that no physicochemical interactions take place between them.     

Therapeutic Effects of Policosanol and Atorvastatin against Global Brain Ischaemia-Reperfusion Injury in Gerbils

Stroke is the third cause of death and the first of permanent adult disability. Pretreatment with policosanol and atorvastatin has been effective in experimental models of cerebral ischaemia in rodents. The objective was to compare the therapeutic effects of policosanol and atorvastatin in a model of global cerebral ischaemia in gerbils. Gerbils were distributed into seven groups, a negative control and six with ischaemia-reperfusion-induced global cerebral ischemia (one vehicle positive control, two policosanol (100 and 200 mg/kg), two atorvastatin (10 and 20 mg/kg) and one aspirin (60 mg/kg) group). Treatments were given 4 h after ischaemia induction. Effects on ischemia-reperfusion-induced symptoms, hyperlocomotion, damage of pyramidal hipoccampal neurons and increased plasma oxidative markers were investigated. Positive, not negative controls, exhibited clinical symptoms, hyperlocomotion, neuronal damage and increased plasma oxidative markers. Policosanol (100 and 200 mg/kg) reduced significantly ischemia-reperfusion-induced symptoms, the frequency of symptomatic animals, histological scores of neuronal damage and plasma oxidative markers as compared with the positive control group. Atorvastatin (10 and 20 mg/kg) decreased significantly the symptoms and histological scores, but unchanged the frequency of symptomatic gerbils and oxidative variables. Only the highest dose of policosanol (200 mg/kg) and atorvastatin (20 mg/kg) reduced significantly ischemia reperfusion-induced hyperlocomotion, policosanol being the most effective. Aspirin 60 mg/kg lowered significantly symptom score, the rate of symptomatic gerbils and hyperlocomotion versus the positive controls, but failed to modify oxidative parameters. In conclusion, postreperfusion treatment with policosanol and atorvastatin was effective for ameliorating symptoms, hyperlocomotion and neurological damage of hippocampal CA1 neurons in gerbils with ischemia-reperfusion-induced global cerebral ischemia, but only policosanol reduced increased plasma oxidative variables.     

Effects of policosanol on borderline to mildly elevated serum total cholesterol levels: a prospective, double-blind, placebo-controlled, parallel-group, comparative study

Background

Hypercholesterolemia is a major risk factor for coronary heart disease. Clinical studies have shown that lowering elevated serum cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is beneficial for patients with borderline to mildly elevated serum total cholesterol (TC) levels (5.0-6.0 mmol/L). Policosanol is a cholesterol-lowering drug made from purified sugar cane wax. The therapeutic range of policosanol is 5 to 20 mg/d.

Objective

This study investigated the efficacy and tolerability of policosanol 5 mg/d in patients with borderline to mildly elevated serum TC levels.

Methods

This 14-week, single-center, prospective, double-blind, placebo-controlled, parallel-group, comparative study was conducted in men and women aged 25 to 75 years with a serum TC level ≥4.8 to <6.0 mmol/L. After a 6-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular a cholesterol-lowering diet, patients were randomly assigned to receive policosanol 5-mg tablets or placebo tablets once daily with the evening meal for 8 weeks, and the diet was continued throughout the study. Lipid profile variables, safety indicators, adverse events (AEs), and compliance with study medications were assessed.

Results

One hundred patients (71 women, 29 men; mean [SD] age, 52 [10] years) entered the study after the dietary run-in period. After 8 weeks of treatment, the mean (SD) serum LDL-C level decreased significantly in the policosanol group (P<0.001 vs baseline and placebo) from 3.57 (0.30) mmol/L to 2.86 (0.41) mmol/L (change, −19.9%). Significantly more patients in the policosanol group (42 patients [84%]) achieved a ≥15% decrease in serum LDL-C than in the placebo group (2 patients [4%]) (P<0.001). Also in the policosanol group, the mean (SD) serum TC level decreased significantly, from 5.20 (0.22) mmol/L to 4.56 (0.44) mmol/L (P<0.001 vs baseline and placebo) (change, −12.3%); the mean (SD) triglyceride (TG) level decreased significantly, from 1.59 (0.57) mmol/L to 1.48 (0.57) mmol/L (P<0.01 vs baseline; P<0.05 vs placebo) (change, −6.9%); and the mean (SD) high-density lipoprotein cholesterol (HDL-C) level increased significantly from 1.05 (0.18) mmol/L to 1.16 (0.21) mmol/L (P<0.001 vs baseline and placebo) (change, +10.5%). The percentage changes were significantly different between the policosanol and placebo groups for serum LDL-C, TC, and HDL-C levels (P<0.001, P<0.001, and P<0.05, respectively), but not for TG. In the placebo group, changes in lipid profile variables from baseline were not significant. Policosanol did not significantly impair any safety indicator and was well tolerated. Three patients (3%) (1 patient [2%] in the policosanol group; 2 patients [4%] in the placebo group) withdrew from the trial, none because of AEs. Two patients (1 patient [2%] each in the policosanol and placebo groups) withdrew from the study because of an unwillingness to return for follow-up; 1 patient (2%) in the placebo group had a change of address and could not be followed up. Overall, 4 patients (4%) (1 patient [2%] in the policosanol group; 3 [6%], placebo) reported AEs; all were mild. Of the patients who received placebo and reported AEs, all 3 (6%) experienced heartburn, and 1 (2%) also experienced dry skin, while the policosanol-treated patient (2%) who reported an AE experienced headache.

Conclusions

In this study of patients with borderline to mildly elevated serum TC levels, based on the criterion that ≥70% of policosanol-treated patients reached the LDL-C goal of a decrease ≥15% from baseline whenever this proportion was different with respect to placebo, 8 weeks of treatment with policosanol 5 mg/d was effective. The decreased LDL-C, TC, and TG levels, increased HDL-C level, and good tolerability found with this treatment support its use in such patients.     

多廿烷醇与普伐他汀治疗高脂血症的疗效和安全性

目的评价多廿烷醇治疗高脂血症,特别是高胆固醇血症的疗效和安全性。方法多甘烷醇组(试验组,多廿烷醇10mg·d~(-1))和普伐他汀组(对照组,普伐他汀10 mg·d~(-1))各119例。进行随机、双盲、双模拟、阳性药物平行对照试验。观察2组降脂疗效和不良反应发生情况。结果经过12 wk治疗,多廿烷醇组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、TC-高密度脂蛋白胆固醇(HDL-C)/ HDL-C、载脂蛋白B_(100)(Apo B_(100))、脂蛋白(Lpa)治疗前分别为(6.6±s0.7)、(4.0±0.6)、(0.10±0.03)、(3.3±0.5)mmol·L~(-1)、(260±184)mg·L~(-1),治疗后分别为(6.0±1.3)、(3.5±0.8)、(O.09±0.04)、(2.7±0.8)mmol·L~(-1)、(130±130)mg·L~(-1),治疗后各指标较治疗前均有非常显著差异(P<0.01)。普伐他汀组TC、LDL-C、TC-HDL-C/HDL-C、Apo B_(100)、Lpa治疗前分别为(6.7±0.8)、(4.1±0.7)、(0.10±0.03)、(3.4±0.5)mmol·L~(-1)、(279±240)mg·L~(-1),治疗后分别为(6.0±1.3)、(3.5±0.9)、(0.09±0.03)、(2.8±0.8)mmol·L~(-1)、(182±213)mg·L~(-1),治疗后各指标较治疗前均有非常显著差异(P<0.01)。但2组相比较,调脂作用相似,无显著差异(P>0.05)。不良反应方面,多廿烷醇组(9.2%)明显少于普伐他汀组(18.5%),2组有显著差异(P<0.05)。不良反应大多较轻微,不需停药能自行缓解。结论多廿烷醇10 mg·d~(-1)降脂效果与普伐他汀10 mg·d~(-1)的疗效相当,均能明显降低TC、LDL-C、TC-HDL-C/ HDL-C、Apo B_(100)、Lpa。多廿烷醇的安全性优于普伐他汀,不良反应轻微,耐受性好。     

Antiplatelet effects of policosanol (20 and 40 mg/day) in healthy volunteers and dyslipidaemic patients

1. The present study was undertaken to compare the effects of a higher dose of policosanol, a cholesterol-lowering drug, (40 mg/day) with the effects of 20 mg/day policosanol on platelet aggregation in healthy volunteers and type II hypercholesterolaemic patients. 2. Study subjects were randomized to receive, under double-blind conditions, placebo or policosanol (20 or 40 mg/day) for 30 days once a day. Blood sampling was performed at baseline and after 30 days on therapy. 3. Platelet aggregation was induced with three aggregating agents: arachidonic acid (AA), collagen and low doses of ADP. 4. Policosanol (20 and 40 mg/day) moderately yet significantly reduced platelet aggregation, but no differences were observed in the effects produced by either dose of policosanol. In healthy volunteers, policosanol at 20 and 40 mg/day inhibited aggregation induced by 2 mmol/L AA (28.2 and 24.9%, respectively), 1 micro g/mL collagen (21.1 and 20.2%) and 1 micro mol/L ADP (30.9 and 29.1%). Changes that occurred following the administration of placebo were not significant, although an upward trend for collagen- and ADP-induced aggregation occurred in normal and hypercholesterolaemic subjects, respectively, thus partially masking the effects of policosanol on these responses. 5. The antiplatelet effects of policosanol at 20 and 40 mg/day in hypercholesterolaemic patients were also similar, so that both doses inhibited aggregation induced by 1.5 mmol/L AA (20.1 and 33.0%, respectively), 0.5 micro g/mL collagen (22.7 and 21.1%) and 1 micro mol/L ADP (40.5 and 34.7%). 6. In addition, after 30 days of therapy, 20 and 40 mg/day policosanol significantly (P < 0.01) reduced low-density lipoprotein-cholesterol (15.9 and 17.0%, respectively) and total cholesterol (12.4 and 12.3%, respectively; P < 0.05), yet increased high-density lipoprotein-cholesterol values by 5% in both groups (P < 0.05). 7. Triglycerides were decreased compared with baseline, but not with respect to the placebo. 8. We conclude that the antiplatelet effects induced by 40 mg/day policosanol administered for 30 days to healthy volunteers and to hypercholesterolaemic patients were similar to the effects induced by 20 mg/day policosanol. Thus, no enhancement of the response was achieved with the use of a higher dose of policosanol in study patients.     

多廿烷醇联合他汀治疗老年不稳定型心绞痛的临床研究

目的：研究多廿烷醇联合他汀治疗老年不稳定型心绞痛的疗效和安全性。方法：90例正服用瑞舒伐他汀（10 mg·d^-1）的老年不稳定型心绞痛患者随机分为2组，一组加用多廿烷醇（20 mg·d^-1），另一组继续瑞舒伐他汀单药治疗，比较2组的降脂效果、主要心血管事件和药物相关不良事件。结果：服药24周时观察组总胆固醇、LDL-C水平低于对照组，LDL-C达标率高于对照组，差异均具有统计学意义（P<0.05）；服药24周时观察组血小板聚集率低于对照组，差异具有显著性（P<0.05）；24周内观察组不稳定心绞痛、心肌梗死的事件少于对照组；24周内2组药物相关不良事件差异不显著。结论：多廿烷醇+常规剂量他汀能平稳有效地控制血脂达标，并可安全应用于老年冠心病患者。     

Antidiabetic Effects of a Standardized Egyptian Rice Bran Extract

An extract was prepared from Egyptian stabilized rice bran and standardized to contain 2% γ‐oryzanol in addition to its content of other bioactives, notably tocotrienol and policosanol. The standardized extract was found to have a concentration‐dependent effect on insulin release in vitro, which, however, is not mediated by γ‐tocotrienol in rice bran (detected by HPLC) as could have been expected. Policosanol and γ‐oryzanol have insulinotropic effects. The in vitro data of rice bran directly translate into in vivo data of rats by using a glucose tolerance test (increase in plasma insulin). Tocotrienols are well known for their apoptotic effect on tumor cells; nevertheless, an attempt was made to study glucose uptake in HEP‐G2 cells, which needs to induce an insulin‐resistant state by TNF‐α. The Egyptian rice bran extract has an antidiabetic effect. γ‐Oryzanol, which is a possible precursor of the insulinotropic compound ferulic acid, is a candidate for this effect. Therefore, it is reasonable to assume that the prevalence of diabetes or at least a prediabetic (type 2) situation can be ameliorated by the investigated rice bran extract. The potential usefulness of the extract as a nutraceutical is currently undergoing more thorough investigations. Copyright © 2012 John Wiley & Sons, Ltd.     

多廿烷醇抗动脉粥样硬化的分子机制研究

目的:探讨多廿烷醇抗动脉粥样硬化的分子机制?方法:采用腹腔注射维生素D3+高脂饮食喂养12周,建立大鼠动脉粥样硬化模型,同时使用多廿烷醇对其进行预干预?将40只SD 大鼠随机平分成4组,为正常组?动脉粥样硬化组?阿托伐他汀组及多廿烷醇组?酶法(终点法/CHO-PAP Method)检测血清血脂水平,ELISA法检测血清炎症因子超敏C反应蛋白(hs-CRP),取大鼠腹主动脉行电镜检查,采用Western blot法检测动脉粥样硬化斑块p38MAPK磷酸化的表达水平?结果:正常组可见完整内皮,动脉粥样硬化组大鼠腹主动脉有明显动脉粥样硬化形成,多廿烷醇组动脉粥样硬化程度较轻,大鼠血脂?血清hs-CRP炎症因子及大鼠腹主动脉p38MAPK磷酸化表达量均在正常组最低,动脉粥样硬化组最高,多廿烷醇组居中(P < 0.05)?结论:多廿烷醇除了具有调脂作用外,可对动脉粥样硬化大鼠血清炎症因子hs-CRP和 p38MAPK磷酸化有一定抑制作用,p38MAPK磷酸化通路可能参与多廿烷醇抗动脉粥样硬化机制?     

多廿烷醇与阿托伐他汀治疗高脂血症的疗效对比

目的评价多廿烷醇治疗高脂血症的疗效。方法比较多廿烷醇组（试验组42例,多廿烷醇10mg/d）和阿托伐他汀组（对照组49例,阿托伐他汀10mg/d）的降脂疗效和不良反应发生情况。结果经过16周治疗,两组总胆固醇（TC）、低密度脂蛋白胆固醇（LDL）、高密度脂蛋白胆固醇（HDL-C）较治疗前均有统计学差异（P〈0.05）。两组调脂疗效在TC、LDL-C降低方面无明显差异（P〉0.05）,在降低甘油三酯（TG）方面阿托伐他汀组优于多廿烷醇组。不良反应方面多廿烷醇组（4.7%）明显少于阿托伐他汀组（17.5%）。两组不良反应较轻微,不需停药。结论多廿烷醇10mg/d的降脂效果与阿托伐他汀10mg/d的疗效相当,均能明显降低TC、LDL-C及升高HDL-C。多廿烷醇的安全性优于阿托伐他汀,不良反应轻微,耐受性好。