International Journal of Pharmaceutical Sciences Review and Research Available online at www.globalresearchonline.net © Copyright protected. Unauthorised republication, reproduction, distribution, dissemination and copying of this document in whole or in part is strictly prohibited. © Copyright protected. Unauthorised republication, reproduction, distribution, 7 Ceballos, Sarahí Mendoza, Rosa Mas, José Illnait, Julio Fernández, Lilia Fernández, Meilis Mesa, Rafael Gámez, Yadira Cruz, Dalmer Ruiz. Surgical Medical Research Centre, Havana, Cuba. Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba. Software and Database Group, National Centre for Scientific Research, Havana, Cuba. *Corresponding author’s E-mail: sarahi.mendoza@cnic.edu.cu

Stroke is a major health problem worldwide. Its pharmacological management includes thrombolytic therapy for the acute phase and antiplatelet drugs for stroke recovery and prevention. Statins can help in the acute phase and in preventing stroke in secondary prevention patients. Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects, with protective effects in stroke models. This observational study investigated the effects of policosanol (20 mg/day) administered during the acute phase and for 5 years later on the neurological recovery of patients with ischemic stroke treated with antiplatelets and vitamins. After hospital discharge, patients were followed up every 3 (first year) and 6 (thereafter) months. Neurological improvement was assessed with the modified Canadian Neurological Scale. Adverse events were recorded. Fifty patients were included; all completed the study. Neurological score improved throughout the study. No patient died, and most [40 (80.0%)] did not experience new vascular events; only one (2.0%) suffered a new stroke, and two (4.0%) suffered more than one transient ischemic attack. The time to the first recurrent event was 46.2 months. Policosanol persistently lowered serum total cholesterol, with such reduction correlating with the neurological improvement (R = 0.995253301). Triglycerides were unchanged. Treatment was well tolerated. Policosanol administered to patients suffering ischemic stroke treated with aspirin and vitamins showed good results on neurological outcomes and recurrent events. This study, however, has limitations, since it was open and uncontrolled, and patients also consumed aspirin and vitamins. New randomized, controlled studies are needed to assess the usefulness of policosanol in stroke management.

Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated for treatment of rheumatoid arthritis and osteoarthritis, but often induce gastric adverse experiences (AE), including gastric ulcers and complications. Inhibitors of proton pump and H(2) antagonists are very effective for duodenal ulcer; meanwhile, cytoprotective drugs are more effective for gastric ulcer. D-002 is a mixture of higher aliphatic alcohols obtained from beeswax, wherein triacontanol is the most abundant. D-002 induces anti-ulcer effects through a cytoprotective mechanism, being more effective in protecting against ethanol- and NSAID-induced ulcers. The present double-blind, placebo-controlled clinical study was undertaken to investigate the effects of D-002 on gastric symptoms associated to piroxicam use on patients suffering osteoarthritis. Fifty-nine patients, all taking piroxicam, 20 mg/day, were randomized to placebo or D-002 (40 or 100 mg/day) for 14 days. The primary efficacy variable was the reduction on the frequency of patients with gastric AE compared with placebo. Pain evolution was investigated to discard any influence on D-002 on the analgesic effect of piroxicam. The frequency of patients treated with D-002, 40 and 100 mg/day, reporting acidity [0 of 18 (0%) and 1 of 21 (4.8%), respectively] was lower (P < .05) than in placebo [6 of 20 (30%)]. Also, the frequency of patients treated with 100 mg/day reporting some gastric AE [5 of 21 (23.8%)] was lower (P < .05) than in placebo [13 of 20 (65.0%)]. The analgesic effect of piroxicam was unaffected with D-002. Treatment was well tolerated. Two patients discontinued from the study because of gastrointestinal AE: one in the placebo group and the other treated with D-002, 40 mg/day. Other three patients discontinued because of other AE: mildly uncontrolled hypertension (one in the placebo group, one treated with D-002, 40 mg/day) and headache (one treated with D-200, 100 mg/day). It is concluded that D-002 could be useful for controlling gastric AE of patients treated with NSAIDs, although further studies with a larger sample size and longer follow-up are needed for definitive conclusions.

D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugar cane wax with antiplatelet and cholesterol-lowering effects. Previous studies showed that D-003 (10-20 mg/day) administered for a short time inhibits platelet aggregation, 14 days being the longest duration investigated. This study was conducted to investigate the effects of D-003 (5 and 10 mg/day) for 30 days on platelet aggregation in normocholesterolemic subjects. This report shows the effects of D-003 on platelet aggregation to arachidonic acid (AA) (1.5 mM), collagen (2 microg/ml) and adenosine 5'-diphosphate ADP (2 microM) assessed at baseline and at treatment completion. Fifty-four subjects were randomized to placebo or D-003 (5 or 10 mg/day) for 30 days. Platelet aggregation to AA, collagen and ADP were assessed. D-003 at the lowest dose (5 mg/day) significantly but modestly inhibited (p < 0.01) platelet aggregation to AA (5.0%) and (p < 0.01) to collagen (7.5%). D-003 at 10 mg/day inhibited (p < 0.001) platelet aggregation to AA and collagen (p < 0.01) by 20.3% and 14.7%, respectively. ADP-induced aggregation, however, was unchanged. D-003 at 10 mg/day, but not at 5 mg/day, lowered (p < 0.01) plasma fibrinogen. D-003 (5 and 10 mg/day) reduced low-density lipoprotein cholesterol (LDL-C) by 17.7% and 26.4%, respectively, and total cholesterol (TC) by 14.5% and 18.5%, while at 10 mg/day, but not at 5 mg/day, it increased high-density lipoprotein cholesterol (HDL-C) by 9.6%. Triglycerides, however, were unchanged with D-003. No disturbances in safety indicators were induced with D-003. One subject (D-003 5 mg/day) discontinued the study and four patients (three taking D-003 and one taking placebo) reported adverse effects (AE) (headache in two patients taking D-003 and one patient taking placebo, and polyphagia in one patient taking D-003). In conclusion, D-003 (5-10 mg/day) for 30 days inhibited platelet aggregation to AA and collagen but not to ADP Therefore, the antiplatelet effect was present with the longer treatment, even at a dose of 5 mg/day. The cholesterol-lowering effects of D-003 were consistent with those expected for such a short treatment. In addition, D-003 at 10 mg/day significantly lowered plasma fibrinogen. The treatment was well tolerated.

Biphosphonates, which are antiresorptive agents used to treat osteoporosis, inhibit the mevalonate pathway, preventing protein prenylation and inhibiting osteoclast activity. Statins decrease cholesterol biosynthesis by blocking the mevalonate pathway and have been reported to have beneficial effects on bone. D-003 is a mixture of high molecular weight acids purified from sugarcane wax that inhibits cholesterol biosynthesis before mevalonate production. D-003 prevents bone loss and resorption in rats with osteoporosis induced with ovariectomy or corticoids. Biochemical markers of bone turnover are used to monitor the short-term efficacy of antiosteoporotic therapy. This randomized, double-blind, placebo-controlled study was undertaken to investigate the short-term effects of D-003 (10 mg/day) on biochemical markers of bone turnover in postmenopausal women with low bone mineral density (BMD). After 4 weeks on a low-fat diet, 34 women were randomized to D-003 (10 mg/day) or placebo for 6 months. Pre- and post-treatment samples were analyzed for urinary excretion of deoxypyridinoline (DPD)/creatinine (Cr), a marker of bone resorption, and serum bone specific alkaline phosphatase (BSAP), a marker of bone formation. The effects on lipid profile and safety indicators, as well as adverse events (AE), were investigated. D-003 (10 mg/day) lowered urinary excretion of tDPD/Cr versus baseline (20.6%) (p < 0.001) and placebo (33.7%) (p < 0.01), but did not modify serum BSAP. D-003 decreased low-density lipoprotein-cholesterol (LDL-C) (32.8%), total cholesterol (TC) (16.4%) and the TC/high-density lipoprotein-cholesterol (HDL-C) ratio (34.7%), increased HDL-C (30.3%) (p < 0.001) and did not modify triglycerides. The effects on these variables were significant as early as 3 months after treatment initiation. D-003 was well tolerated. Three patients (one in the placebo group and two in the D-003 group) withdrew from the study. Two of these withdrawals were due to AE: abdominal pain (placebo) and heartburn (D-003). Five patients (four in the placebo group [22.2%] and one in the D-003 group [6.3%]) reported mild AE. In conclusion, D-003 (10 mg/day) reduced urinary excretion of tDPD/Cr, a bone resorption marker and did not change serum BSAP, a bone formation marker, while it lowered cholesterol in study patients. These preliminary results suggest that D-003 could be useful in treating postmenopausal women with low BMD. However, the potential value of D-003 in treating or preventing osteoporosis deserves further clinical investigation.

The main goal of hypercholesterolemia management for coronary prevention is to reduce serum low-density lipoprotein cholesterol (LDL-C) levels. D-003 is a mixture of high molecular weight aliphatic acids purified from sugarcane wax, while policosanol is a cholesterol-lowering drug purified from the same source, consisting in a mixture of higher aliphatic alcohols. No previous comparative study of both drugs in humans has been reported. This randomized, double-blind study compares the efficacy and tolerability of D-003 and policosanol (5 and 10 mg/day) in patients with type II hypercholesterolemia. After a baseline period, 100 patients were randomized to D-003 or policosanol both at 5 mg/day and 10 mg/day, for 8 weeks. D-003 and policosanol 5 mg/day reduced (p < 0.0001) LDL-C by 26.9% and 20.9%, respectively. These reductions increased with 10 mg/day (35.1% for D-003, 25.1% for policosanol. The reductions of LDL-C achieved with D-003 5 mg/day and 10 mg/day were greater (p < 0.05 and p < 0.001, respectively) than with policosanol. The frequency of patients treated with D-003 (5 mg/day) reaching LDL-C reductions > or = 15% (22/25, 88%) was greater (p < 0.01) than with policosanol (5 mg/day) (19/25, 76%), and the same was true for D-003 10 mg/day (25/25, 100%) and policosanol (22/25, 88%; p < 0.01). D-003 and policosanol (5 mg/day) also lowered (p < 0.001) total cholesterol (TC) (16.2% and 13.5%, respectively), and increased high-density lipoprotein cholesterol (HDL-C) by 15.3% (D-003) and 6.7% (policosanol). At 10 mg/day, D-003 and policosanol reduced (p < 0.001) TC (21.3% and 16.0%, respectively), while HDL-C was increased by 17.3% and 9.8%, respectively, D-003 being more effective than policosanol. Treatments did not affect triglycerides. Both drugs were well tolerated, with D-003 tolerated as well as policosanol. Three patients discontinued the study, none due to adverse events (AEs). Seven patients (three from the D-003 group and four from the policosanol group) experienced mild AEs. In conclusion, D-003 (5 and 10 mg/day) administered to patients with type II hypercholesterolemia was more effective than policosanol in lowering LDL-C and TC, and in increasing HDL-C. D-003 could be useful for treating type II hypercholesterolemia, but this subject deserves further clinical research.

Background: Policosanol is a mixture of higher aliphatic primary alcohols purified from sugar-cane wax. The mixture has cholesterol-lowering efficacy, its specific effects being to reduce serum total (TC) and low-density lipoprotein cholesterol (LDL-C), and to increase high-density lipoprotein cholesterol (HDL-C). The effects of policosanol on triglycerides (TG) are modest and inconsistent. Omega-3 fatty acids (FA) from fish oil protect against coronary disease, mainly through antiarrhythmic and antiplatelet effects. Omega-3 FA also have lipid-modifying effects, mostly relating to TG reduction. Thus, potential benefits could be expected from combined therapy with omega-3 FA and policosanol.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. It is safe and well tolerated, even in populations with high consumption of concomitant drugs. These data suggest that adverse events (AE) due to drug-to-drug interactions (DDI) with policosanol are not relevant. Experimental data indicate that potential DDI between policosanol and drugs metabolized through the cytochrome P450 hepatic system are not expected, but pharmacodynamic DDI cannot be excluded. Several clinical studies have shown that policosanol decreased arterial pressure compared with placebo, and a pharmacological interaction with beta-blockers was experimentally proven. Therefore, clinical DDI between policosanol and beta-blockers can be expected. This study investigated whether policosanol reinforces the antihypertensive effects of beta-blockers and/or whether this combination impairs some safety indicators or induces specific AE in older patients. After 5 weeks on a diet-only baseline period, 205 older hypercholesterolemic patients taking beta-blockers were randomized to policosanol 5 mg/day or placebo for 3 years. After 1 year on therapy, policosanol significantly reduced (p < 0.00001 versus placebo) low-density lipoprotein-cholesterol (LDL-C) (20.9%), total cholesterol (TC) (19.3%) and triglycerides (TG) (25.7%), whereas it increased (p < 0.01 and p < 0.001 versus placebo) high-density lipoprotein-cholesterol (HDL-C) levels (4.1%). Treatment effects did not to wear off during the 3-year follow-up. At study completion, policosanol lowered (p < 0.00001 versus placebo) LDL-C (34.3%), TC (23.2%) and TG (21.2%) and raised (p < 0.00001 versus placebo) HDL-C (12.3%). Thirty-one patients (15.1%) discontinued the study, 22 in the placebo group (20.6%) and nine in the policosanol group (9.2%). Of these, 20 patients (16 in the placebo group and four in the policosanol group) withdrew from the study due to AE. The frequency of serious adverse events (SAE), mostly vascular, in policosanol patients (3/98, 3.1%) was lower than in the placebo group (15/107, 14.0%). No impairment of safety indicators was observed. Nevertheless, reductions in systolic and diastolic blood pressure were observed in policosanol patients compared with those in the placebo group. The frequency of policosanol patients reporting mild or moderate AE (18/98, 18.4%) was also lower than in the placebo group (30/107, 28.0%). In conclusion, policosanol was well tolerated in elderly patients taking beta-block- ers and did not increase AE. Additional reduction of blood pressure and a lower frequency of SAE were observed in policosanol patients compared with those taking placebo. The cholesterol-lowering efficacy of policosanol was that expected. These results provide support that policosanol therapy added to hypercholesterolemic elderly individuals taking beta-blockers could provide additional benefits in lowering blood pressure; SAE were not more frequent in the policosanol group than in the placebo group and there was no increase in AE.

Nitric Oxide (NO) plays a key role in many physiological processes and is synthesized by the enzyme Nitric Oxide Synthase (NOS). There is increasing evidence that NO produced in human airways is involved in pathological events, such as asthma. This work investigated the effect of various antioxidants on NO production and on iNOS and SOD expression and activity in stimulated epithelial lung cells, as a model for asthma. L-2 cells were stimulated with combinations of TNFα, INFγ and LPS for 24h, followed by incubation with increasing concentrations of N-acetyl-lcystein (NAC), resveratrol, Genistein, Quercetin, soy saponin 2, 3-dihydro-2, 5-dihydroxy-6-methyl-4H-pyran-4-one (DDMPl) and with an olive leaf polyphenol extract. NO production was determined by measuring nitrate and nitrite concentrations using the Griess reaction. Expression of iNOS and SOD were detected using western blot analysis. SOD activity was measured by an ingel activity assay. cGMP was also detected using radioimmunoassay kit. In stimulated cells, the concentration of nitrites in the medium increased 4 fold compared to control cells. Resveratrol and the olive leaf extract reduced nitrite levels in the medium by 37% and 41% respectively. Quercetin and genistein reduced nitrite levels by approximately 50%. However, NAC increased levels by 48% and DDMP had no effect. Significant reductions in iNOS expression were measured following treatment with polyphenol extract and resveratrol. SOD expression was higher in stimulated cells when compared to controls and significant increases were detected by olive leaf extract, quercetin and genistein. Total SOD activity, as well as cGMP levels were not affected by cytokine stimulation or by any treatment. The presence of resveratrol as well as a polyphenol extract in a cellular model of asthma significantly reduced iNOS expression and medium nitrite concentrations. These compounds presumably act by different mechanisms. The polyphenol extraction affects the antioxidant enzyme MnSOD while resveratrol does not. These results indicate that treatment with these active compounds may be beneficial in inflammatory lung diseases.

The present article focuses on the prevalence and risk factors for varicose veins and the severe stage of chronic venous insufficiency (CVI). The evaluation was made by reviewing the results of specific well-designed studies performed on the general population (case-control studies, cross-sectional studies, and large case series). Data from the literature were compared with the results of a recent multicenter cross-sectional study in Poland, in which 40,095 indi viduals from 803 registers of primary care physicians were clinically examined and assigned a clinical CEAP class. Analysis of the associations between varicose veins or severe CVI preva lence and factors that are usually considered as representing a risk for the development of CVI was performed. In Poland, a prevalence of varicose veins and severe CVI (skin changes, leg ulcer) similar to that observed in the other developed countries was reported. It was more common in women, but female sex was not found to be a strong risk factor. Among the risk factors most closely associated with CVI were age, family history of varicose veins, and consti pation, whatever the sex. This is in keeping with findings from recent epidemiologic studies. Obesity and lack of physical activity were strongly associated with CVI in women, more so than in men. The number of pregnancies (more than 2 pregnancies) significantly distinguished between women with and without CVI. Regarding these latter risk factors, the Polish results do not contradict the commonly held beliefs that are found in the literature. A modest asso ciation was found with female sex, previous injury in legs (DVT), and remaining in the standing position for a long time, although these parameters are usually among those mostly agreed as being risk factors. The role of the prolonged sitting position was not established. The Polish epidemiologic survey provided updated figures on the prevalence of and risk factors for varicose veins and severe CVI, using clear and globally accepted clinical definitions for the venous disease based on the CEAP classification.

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 greater than or equal to4.8 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 greater than or equal to15% 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 greater than or equal to70% of policosanol-treated patients reached the LDL-C goal of a decrease greater than or equal to15% 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.

Background: Atherosclerosis begins in childhood and is influenced by risk factors for coronary heart disease (CHD), of which hypercholesterolemia is crucial. The rationale for treating hypercholesterolemia. in childhood is to limit atherosclerosis development, for which adherence to a cholesterol-lowering diet is the first-choice therapy. Nevertheless, pharmacological intervention with bile acid-binding resins may be prescribed for patients older than 10 years, mainly those with family history of CHD, multiple risk factors, and/or severe hypercholesterolemia. Resins are effective and tolerable in this population, but their clinical use has been limited because of poor compliance due to unpalatability; other effective cholesterol-lowering drugs have not been recommended in this population because of the potential impact of drug-related adverse effects such as increases in transaminases, myopathies, and gastrointestinal disturbances. Thus, the need for safer, easy-to-take, and effective cholesterol-lowering agents for this population continues. Policosanol is a mixture of higher primary aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects proven in patients with type 11 hypercholesterolemia and dyslipidemia due to type 2 diabetes mellitus. Policosanol shows good safety and tolerability profiles, with no evidence of drug-related adverse events (AEs) to date. This background supports the idea that policosanol could be a good candidate for treating hypercholesterolemia in children and adolescents, but it requires clinical demonstration.Objective: This 12-week study was undertaken to investigate the cholesterol-lowering effects and tolerability of policosanol in hypercholesterolemic patients aged 11 to 19 years.Methods: In this randomized, double-blind, placebo-controlled study, after 4 weeks of dietary stabilization, adolescents with type II hypercholesterolemia were randomly assigned (1:1 ratio) to receive placebo or policosanol 5-mg tablets once daily for 12 weeks. Physical examinations were performed, and lipid profiles and blood samples were obtained at baseline and after 6 and 12 weeks of therapy. The treatment was considered effective if mean reductions of low-density lipoprotein cholesterol (LDL-C) were >15%. In addition, the percentages of patients reaching final values of LDL-C <3.4 mmol/L and optimal values of <2.8 mmol/L were also evaluated. The doses were doubled if LDL-C values were greater than or equal to3.4 mmol/L after 6 weeks of therapy. The incidence of AEs and compliance with study medications were also evaluated after 6 and 12 weeks of treatment.Results: Fifty-five patients were enrolled in the study (28 policosanol, 27 placebo). Twenty-three patients (17 placebo, 6 policosanol) required dose titration at 6 weeks. After 12 weeks of therapy, policosanol significantly decreased LDL-C with respect to baseline and placebo (both P < 0.001), showing a mean reduction of 32.6%. Total cholesterol (TC) and TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were reduced by 21.9%, 27.8%, and 37.2%, respectively, in the policosanol group (P < 0.001, compared with baseline and placebo). HDL-C rose 10.1% (P < 0.001), compared with baseline and placebo. Triglycerides were unaffected by policosanol. LDL-C, TC, and both atherogenic ratios were reduced significantly in the policosanol group (P < 0.001), and significant increases in HDL-C values were observed at the 6-week interim checkup (P < 0.001 vs baseline, P < 0.01 vs placebo). Twenty-five (89.3%) of 28 patients in the policosanol group showed LDL-C reductions >15% compared with 2 (7.4%) of 27 patients in the placebo group (P < 0.001). In addition, 26 (92.8%) of 28 policosanol patients reached LDL-C values <3.4 mmol/L compared with 4 (14.8%) of 27 patients in the placebo group (P < 0.001). Likewise, the response rate for achievement of optimal values (LDL-C <2.8 mmol/L) was also larger in the policosanol group (20/28; 71.4%) than in the placebo group (0/27; 0.0%) (P < 0.001). Policosanol was well tolerated, with no drug-related effects found on physical examination. Blood biochemistry determinations revealed significantly lower alanine aminotransferase levels in the policosanol group after 6 weeks of therapy compared with placebo (P < 0.05), as well as significant reductions in aspartate aminotransferase levels at 6 weeks (P < 0.01) and 12 weeks (P < 0.05) compared with baseline. No patients withdrew from the study, and only 3 patients (2 placebo, I policosanol) experienced mild AEs during the study; the placebo patients reported abdominal pain and constipation (1 each), and the policosanol patient reported polyphagia.Conclusions: Policosanol 5 mg/d appears to be well tolerated and effective as short-term treatment of hypercholesterolemia in adolescents.

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol and Octa-60 in patients with type II hypercholesterolemia. After 4 weeks on a diet, 110 patients were randomized to policosanol or Octa-60 5 mg tablets once a day for 5 weeks. The dose was then doubled to 10 mg/day for the next 5 weeks. Policosanol 5 and 10 mg/day significantly lowered low-density lipoprotein-cholesterol (LDL-C) (p<0.0001 and p<0.00001), the main efficacy variable, by 18.6% and 30.2%, while Octa-60 significantly reduced (p<0.05) LDL-C by 10.0% at study completion only. The frequency of policosanol patients reaching reductions of LDL-C > or = 15% after 5 mg/day (37/55; 67.3%) and 10 mg/day (47/55; 88.7%) was greater (p<0.01 and p<0.01) than in the Octa-60 group, which was 5/55 (9.1%) and 20/55 (36.4%). Likewise, the frequency of patients reaching LDL-C values of <3.4 mmol/l at study completion was greater (p<0.001) in the policosanol group (39/55, 70.9%) than in the Octa-60 group (6/55, 10.9%). Policosanol 5 and 10 mg/day significantly lowered (p<0.00001) total cholesterol (TC) (13.4% and 20.4%), LDL-C/high-density lipoprotein-cholesterol (HDL-C) (22.1% and 37.0%) and TC/HDL-C (17.2% and 28.2%). Octa-60 at 10 mg/day lowered (p<0.05) TC (8.7%), LDL-C/HDL-C (12.6%) and TC/HDL-C (9.4%). HDL-C was increased (p<0.001 and 0.0001) by policosanol 5 and 10 mg/day (5.6% and 12.5%) but was unchanged by Octa-60. In both groups, triglycerides remained unchanged. Both treatments were safe and well tolerated. Octa-60, but not policosanol, significantly increased glucose and alanine aminotransferase, but individual values were within the normal range. Four patients (two from each group) discontinued the trial, but only one (in the Octa-60 group) did so because of an adverse event (AE) (skin rash). Overall, three patients (all from the Octa-60 group) reported AEs. In conclusion, original policosanol at 5 and 10 mg/day, but not Octa 60, was effective in patients with type II hypercholesterolemia. Thus, policosanol reached the efficacy criterion for LDL-C reduction in both steps, while Octa-60 failed to reach this goal. In addition, policosanol was better tolerated than Octa-60.

Policosanol is a well defined mixture of higher aliphatic primary alcohols isolated from sugar cane wax with cholesterol-lowering effects proven for a dose range from 5-20 mg/day in patients with type II hypercholesterolemia and dyslipidemia associated with noninsulin dependent diabetes mellitus. This randomized, double-blind study investigated the cholesterol-lowering efficacy and tolerability of policosanol 20 mg/day compared with 40 mg/day. Changes in low-density lipoprotein (LDL)-cholesterol levels were predefined as the primary efficacy endpoint. Patients with type II hypercholesterolemia were enrolled in the study and instructed to continue a step I cholesterol-lowering diet for 6 weeks and those eligible to be included (89) were randomly allocated to receive under double-blind conditions placebo (n = 30), policosanol 20 mg/day (n = 29) or 40 mg/day (n = 30). After 24 weeks, policosanol at 20 and 40 mg/day significantly (p < 0.00001) lowered LDL-cholesterol by 27.4% and 28.1%, total cholesterol (p < 0.00001) by 15.6% and 17.3%, and the LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 37.2% and 36.5%, respectively The ratio of total cholesterol/HDL-cholesterol was lowered by 27.1% and 27.5%, while HDL-cholesterol levels increased (p < 0.001) by 17.6% and 17.0%, respectively. Compared with baseline, policosanol 20 mg/day lowered triglycerides (p < 0.05) by 12.7%, while they were lowered (p < 0.01) by 15.6% at a dose of policosanol 40 mg/day All the above-mentioned significant differences were also different from placebo and no significant changes occurred in any lipid profile parameters in the placebo group. Based on the mean values of LDL-cholesterol levels at study completion, the mean percent reductions from baseline were 27.4% and 28.1% for the 20 and 40 mg/day groups, respectively. Thus, the effects of both policosanol doses on the main efficacy variable were practically identical. Consistent with the data obtained for LDL-cholesterol, both doses were similarly effective in changing all the other lipid profile parameters. No unexpected adverse effects were observed and there were no significant between-group differences regarding safety indicator values or reported adverse effects. In conclusion, although the tolerability profile remains excellent, according to the present results policosanol at a dose of 40 mg/day does not offer significant additional cholesterol-lowering efficacy over the 20 mg/day dose.

Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or poli cosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10°, temperature 25°C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.0 1) the initial claudication distance from 125.9 ±8.7 m to 201.1 ±24.8 m and the absolute claudication distance from 219.5 ± 14.1 m to 380.7 ±50.2 m. Both variables remained unchanged in the placebo group (p<0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 ±28.6 m (initial claudication distance) and 648.9 ±54.1 m (absolute claudication distance); both significantly greater (p<0.0001) than those obtained in the placebo group, which showed values of 137.9 ±21.8 m (initial claudication distance) and 237.7 ±28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improve ment of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p<0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.

D-002 is a mixture of higher aliphatic alcohols isolated from beeswax that inhibits rat microsomal lipid peroxidation in vitro and in vivo. This study was undertaken to investigate whether D-002 also inhibits lipid peroxidation in older subjects. The free radical theory of aging suggests that progressive defects in the protection against free radical reactions leads to progressive deleterious effects of free radicals on cells and tissues. This free radical damage has been implicated in several pathophysiological processes associated with the chronic degenerative diseases that occur with aging. Forty-eight older subjects were randomly assigned, in a double-blind fashion, to receive placebo or D-002 tablets (50 mg/day) once daily. At baseline, D-002 and placebo groups were well matched regarding several variables. D-002 significantly reduced the susceptibility of nonfractionated plasma samples to copper-mediated lipid peroxidation. It also significantly increased the length of the lag phase (P <.001) and the total antiioxidant status (P <.05) compared with baseline and placebo. In addition, D-002 significantly decreased malondialdehyde levels (expressed in terms of thiobarbituric acid reactive substances (TBARS, P <.001) compared with baseline, but not with placebo. No significant changes on lipid peroxidation parameters were observed in the placebo group. We conclude that D-002 treatment may be useful to prevent or manage certain pathophysiological conditions in the elderly.

Background: D-002 is a mixture of higher primary aliphatic alcohols purified from beeswax with antioxidant effects demonstrated in experimental models and humans. In addition, antiulcer effects of D-002 related to a cytoprotective mechanism have been experimentally proven.Objective: This randomized, double-blind, placebo-controlled study was conducted to investigate the effects of D-002 on duodenal ulcer healing and symptoms.Methods: Ninety-two eligible patients with duodenal ulcers entered the study and were randomized into 3 groups: placebo (n = 31), D-002 100 mg/d (n = 30), and D-002 200 mg/d (n = 31). Endoscopic examinations were performed at baseline and after 4 weeks of treatment. Safety was assessed by determining hematologic and blood chemistry indicators at baseline and after 4 weeks of therapy. Adverse events were assessed by physical examination, laboratory analysis, and reports by patients.Results: At study completion, the mean healing score of patients who received D-002 200 mg/d (1.11 +/- 0.96) was significantly lower (P < 0.05) than that of patients who received placebo (1.90 +/- 1.26); the mean healing score of patients who received D-002 100 mg/d (1.32 +/- 1.49) was not significantly different from that of the placebo group. Healing rates in the intent-to-treat population were significantly higher in the D-002 200 mg/d (71.0%) and D-002 100 mg/d groups (43.3%) compared with placebo (16.1%; P < 0.001 and P < 0.05, respectively). After 4 weeks, the combined rate of partial and complete symptom relief was 87.1% (27/31) in the D-002 200 mg/d group, 76.7% (23/30) in the D-002 100 mg/d group, and 25.8% (8/31) in the placebo group. The rates were significantly higher in the 2 treatment groups compared with that in the placebo group (P < 0.001). D-002 was well tolerated in this study. Twenty patients discontinued the study, none because of adverse events. No treatment-related disturbances in clinical, hematologic, or blood biochemistry safety indicators were seen. Two patients receiving D-002 100 mg/d experienced mild side effects headache and diarrhea, 1 each).Conclusions: D-002 200 mg/d was effective in healing and relieving symptoms of duodenal ulcers, although the degree of healing was lower than that reported with first-line antiulcer therapy. Given that D-002 may act through a cytoprotective mechanism, further studies investigating the possible effects of D-002 on the healing and/or relapse of gastric ulcer are warranted.