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Osteonecrosis (ON) is characterized through the impairment of osseous blood flow that leads to the collapse of femur head. Corticoid-induced ON in rats and lipopolysaccharide (LPS)-induced in rabbits are useful models to assess the efficacy of potential treatments on this disease. D-003 inhibits the mevalonate pathway, lipid peroxidation and prevents osteoporosis in rats through increasing the osteoclast apoptosis. This study investigated the effects of D-003 on corticoid- and LPS-induced ON in rats and rabbits. Corticoid-induced ON: Rats were randomized into five groups. A negative control and four groups treated with prednisolone 6 mg/Kg: a positive control and three treated with D-003 (5, 25 and 200 mg/Kg) for 80 days. All positive controls presented ON areas. D-003 significantly reduced the numbers and proportions of ON lesions, as compared to the positive control group. LPS-induced ON in rabbits: Rabbits were randomized into five groups: a negative control and four injected with a single intra-venous injection of LPS (10 μg/Kg) including a positive control and three with D-003 (5, 25 and 200 mg/Kg) for 30 days. ON was seen in all positive controls. The incidence of ON and the number of ON lesions in the groups treated with D-003 (25 and 200 mg/Kg) was significantly lower compared to the positive controls. LPS injection significantly increased the size of bone marrow fat cells in positive controls and such increase was significantly decreased by D-003. In conclusion, D-003 reduced ON lesions in corticoidand LPS-induced ON and also the size of bone marrow fat cells in rabbits with LPS. [ABSTRACT FROM AUTHOR]

Stroke is one of the three leading causes of disability and death worldwide. Transient ischemic attacks (TIA) pose an increased risk of subsequent ischaemic stroke. Antiplatelet therapy, mainly aspirin, remains as first-line therapy to prevent recurrent TIA and/or ischemic strokes, and antihypertensives and cholesterol-lowering agents play also a key role in this strategy. Policosanol, with cholesterol-lowering drug and concomitant antiplatelet effects, has shown protective effects on stroke models. Policosanol 20 mg/d added to aspirin during the acute phase of ischemic stroke and thereafter provided good results on neurological outcomes and recurrent events. This study assessed the benefits of policosanol 20 mg/d administered from hospital discharge up to 60 months thereafter in 55 patients of both sexes with ischaemic stroke who had previously suffered TIA. At each visit, clinical and neurological examination with the modified Canadian Neurological Scale, request on adverse experiences and laboratory tests were done. All new events were recorded. In addition to the previous TIA, the most frequent personal risk factors at baseline were hypertension (98.2 %), hypercholesterolemia (81.8 %), smoking (32.7 %) and coronary disease (29.1 %). All patients completed the study. Neurological score improved significantly and progressively during the first year , and such improvement persisted to study completion. Only five patients (9.1 %) suffer a new event: one new stroke, four new TIA. After three months, serum cholesterol significantly lowered (21. 3 %) compared with baseline, and this effect did not wear off, but improved after long-term therapy. The improvement of the neurological outcome correlated with TC reduction (r = 0.987). Treatment unchanged safety indicators. Then, treatment with policosanol 20 mg/d + aspirin 125 mg/d after hospital discharge produced good results in the neurological recovery, recurrence of events and cholesterol control in patients with ischemic stroke and a previous TIA, but these benefits should be confirmed in randomized, double-blind, controlled studies. [ABSTRACT FROM AUTHOR]

Context • Nonsteroidal, anti-inflammatory drugs effectively relieve osteoarthritis (OA) symptoms but also induce adverse effects (AEs) that limit their long-term use, which drives a search for safer treatments. D-002, a mixture of beeswax alcohols, and D-003, a mixture of sugarcane wax acids, have been effective in experimental and clinical studies for patients with OA. Objective • The study intended to investigate the effects on OA symptoms of a combined therapy using D-002 and D-003 (D-002/D-003), which were administered for 6 wk. Design • The study was a randomized, double-blind, placebo-controlled trial. Setting • The study was conducted at the Surgical Medical Research Center in Havana, Cuba. Participants • Participants were patients with mild-to-moderate OA. Intervention • Participants were randomly assigned to 1 of 4 groups—(1) a control group, which received a placebo; (2) the D-002 group (intervention group), which received 50 mg/d of D-002; (3) the D-003 group (intervention group), which received 10 mg/d of D-003; or (4) the D-002/D-003 group (intervention group), which received a combined therapy of 50 mg/d of D-002 plus 10 mg/d of D-003. The control group received tablets that were indistinguishable in appearance from the D-002 and D-003 tablets and had a similar composition, except that the active ingredients were replaced by lactose. The groups took the medications once per day for 6 wk. Outcome Measures • Symptoms were assessed using the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and a visual analogue scale (VAS). The primary outcome was the reduction in the total WOMAC score. The subscale scores on the WOMAC for pain, stiffness, and physical function, the VAS scores, and the use of rescue medications were secondary outcomes. Results • Of the 120 enrolled participants, 116 completed the study. The treatments with D-002, D-003, and D-002/D-003 reduced the mean total WOMAC scores significantly from baseline to postintervention, by 75.1%, 72.8%, and 91.2%, respectively. Compared with the placebo, the treatments decreased the mean WOMAC scores for pain, joint stiffness, and physical function significantly. The VAS scores significantly decreased, showing a 71.4%, a 66.9%, and an 84.7% reduction for the D-002, D-003, and D-002/D-003 groups, respectively. All the reductions were significant from the first week and were enhanced during the trial. The D-002/D-003 treatment was more effective in improving all of the scores than either monotherapy. With respect to rescue medications, 3/30, 2/30, and 2/30 used the medications in the D-002, D-003, and D-002/D-003 groups, respectively, vs 17/30 in the control group. The treatments were well tolerated. Conclusions • Administered for 6 wk, 50 mg/d of D-002 and 10 mg/d of D-003 ameliorated OA symptoms, but the combined therapy, D-002/D-003, was more effective than either monotherapy. All treatments were well tolerated. [ABSTRACT FROM AUTHOR]

The reduction of serum levels of low-density lipoprotein (LDL-C) and total cholesterol (TC) has been shown to reduce coronary morbidity and mortality, even in subjects with normal or borderline values of serum TC. High-molecular weight sugarcane wax alcohols (SCWA) have been shown to reduce serum LDL-C and TC, and to increase high-density lipoprotein-cholesterol (HDL-C) levels, without substantial changes on triglycerides (TG), in both normocholesterolemic and hypercholesterolemic subjects. Nevertheless, the data supporting the effects of the dose of 10 mg/d in individuals with normal or borderline serum TC levels are relatively scarce. The aim of this randomised, double-blinded and placebo- controlled study was to confirm the efficacy and safety of SCWA (10 mg/d) in subjects with serum TC = 5.9 mmol/L . Fifty five men and women (mean age: 63 years) were randomised to receive placebo or SCWA for 12 weeks. The treatment significantly reduced LDL-C (22.1 %, p < 0.000 01) and TC (11.7 %, p < 0 000 01), and increased HDL-C (9.6 %, p < 0.05) values compared with baseline and placebo. Safety indicators were not affected by therapy. Only one subject (placebo) discontinued prematurely the trial, but not because of adverse effects AE, and two subjects (one treated, one placebo) referred some AE (arthralgia) during the trial. This study confirms that SCWA (10 mg/d ) administered for 12 weeks was effective for lowering LDL-C, TC, LDL-C/HDL-C ratio and for increasing HDL-C, being safe and well tolerated in subjects with normal or borderline serum TC levels [ABSTRACT FROM AUTHOR]

Beeswax alcohols (BWA) (Abexol®) (formerly D-002, a mixture of six high molecular weight aliphatic alcohols purified from beeswax), has been shown gastroprotective effects in experimental and clinical studies. Experimental studies have proven that BWA reduces the gastric damage through a multifactorial cytroprotective effect that involves antioxidant effects on rat gastric mucosa and the increase of the quantity of soluble gastric mucus and its content of total proteins, neutral glycoproteins and sulphated macromolecules, relevant defensive factors of the gastric mucosa. Previous clinical studies have demonstrated that Abexol® is effective for reducing common gastrointestinal complaints in general population, subjects consuming non-steroidal anti-inflammatory drugs (NSAIDs) and patients with duodenal ulcers, but none of them had used an internationally validated symptom scale. This randomized, double-blinded, placebo-controlled study investigated the effects of Abexol® on the gastrointestinal symptoms of 60 middle-aged subjects of both sexes, otherwise healthy, using the validated Gastrointestinal Symptom Rating Scale (GSRS). Subjects were randomised to receive Abexol® (BWA - 50 mg) or placebo tablets twice a day for 8 weeks. After complete 4 weeks on treatment, the dose was titrated to three tablets/d in those subjects who did not experience symptom improvement. Both groups were well matched at baseline. After 8 weeks on treatment Abexol reduced significantly (p < 0.000 1) the total score of the GSRS compared with baseline and placebo (40.8 % versus placebo) after 4 weeks on treatment and that did not wear off at study completion, reduction that was significant from the first 2 weeks on treatment. The frequency of subjects titrated to three tablets a day (lunch, dinner and bedtime) in Abexol®-treated group (4/30, 13.3 %) was lower (p < 0.01) than in placebo (16/30, 53.3 %). Compared with placebo, treatment with Abexol® also decreased significantly the following symptoms: acidity/heartburn, regurgitation, bloating, sensation of stomach emptiness & flatulence. Abexol did not affect any physical or blood safety indicator. There were seven study withdrawals (five placebo, two Abexol®), but only one (placebo) was due to an adverse experience (AE) (transient increase of arterial blood pressure). Concluding, Abexol® (100 - 150 mg/d) given for 8 weeks improved the whole score of the validated GSRS scale, which reflects the overall gastrointestinal symptoms, and specifically improved the several symptoms characteristics of acid-peptic ailments in middle-aged and older subjects. Abexol® was safe and well tolerated. These results are consistent with those of previous clinical studies and support the usefulness of taking Abexol® for middle-aged and older subjects who experience gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Benign prostate hyperplasia (BPH), very frequent in men = 50 years, is a non malignant prostate enlargement that leads to experience lower urinary tract symptoms. D-004, a lipid extract of the royal palm (Roystonea regia) fruits, has shown to inhibit prostate 5 α-reductase, to prevent prostate hyperplasia induced with testosterone in rodents, and to antagonize α1-adrenoreceptors-mediated responses. D-004, however, does not exhibit treatment-related toxicity, and therefore, it shows a promising profile to manage BPH. This randomized, double-blind, placebo-controlled Phase I study researched the tolerability to single and repeated oral doses of D-004 (320-960 mg/d), and the reversibility of the possible effects. The study included two steps. Step I researched the effects of single dosing (320-960 mg) assessed throughout a further period of 14 d, and step II assessed the effects of doses (320-960 mg/d) repeated for 21 d, with interim controls every 7 d, followed by a period of treatment withdrawal (washout) of other 14 d . Forty eligible healthy males were randomized to four groups. one placebo, three treated with D-004 (320, 640 and 960 mg). Baseline characteristics were similar among the groups. No patient withdrew from the trial. In both steps, the treatment did not produce significant differences or trend versus placebo, including on their sexual activity. Also, individual values were within normal ranges. The adverse experiences (AE) occurred, all gastrointestinal, were mild. Concluding, D-004 as single (320-960 mg) or repeated doses for 21 d was well tolerated by study subjects, without producing AE characteristic of this therapeutic class, like postural hypotension or changes on serum prostate antigen, testosterone or estradiol levels. [ABSTRACT FROM AUTHOR]

Background: D-003 is a mixture of long-chain aliphatic primary acids purified from sugar cane wax with cholesterol-lowering and preventive effects on lipoprotein lipid peroxidation (LP) proven in experimental and clinical studies. Objectives: To investigate if D-003 favourably modifies LP markers on older individuals. Methods: This double-blinded, randomized, placebo-controlled study investigated the effects of D-003 (5 and 10 mg/d) administered for 8 weeks on serum LP markers of older individuals. We assessed the effects of D-003 on LP of LDL as primary variable, while effects on plasma total antioxidant status (TAS), malondialdehyde (MDA) levels and plasma antioxidant enzyme activities were also investigated. We investigated the effects on lipid profile. Fifty-one older individuals (40 women, 11 men) were randomized to placebo or D-003 (5 or 10 mg/d), tablets being taken once a day with evening meal for 8 weeks. Laboratory tests and physical examination were performed at baseline and after 4 and 8 weeks on therapy, whereas compliance and adverse experiences (AE) were assessed at weeks 4 and 8. Results: D-003 (5 and 10 mg/d) significantly increased (p < 0.05 and p < 0.01) lag phase by 24.7 % and 29.3 %, respectively, while decreased propagation rate (p< 0.05) by 22.7 % (5 mg/d) and 25.8 % (10 mg/d). D-003 (5 and 10 mg/d) increased (p < 0.01) TAS by 17.7% and 23.0%, respectively, but only the changes achieved with 10 mg/d were different from placebo (p < 0.05). D-003 at 10 mg/d, not at 5 mg/d, significantly lowered (p < 0.05) plasma levels of thiobarbituric acid reactive substances (TBARS). D-003 (5 or 10 mg/d) did not modify superoxide dismutase (SOD) and GPX (glutathione peroxidase) activities. Also, D-003 (5 and 10 mg/d) reduced significantly low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and increased high-density lipoprotein-cholesterol (HDL-C). D-003 (10 mg/d) also reduced modestly, but significantly triglycerides. No significant changes of LP or lipid profile occurred in placebo. Treatment was well tolerated. D-003 did not impair safety indicators. No subject withdrew from the study. Only 3 subjects (2 placebo, 1 D-003 5 mg/d) reported AE: the two placebo patients reported insomnia and acidity, respectively, while that treated with D-003 referred acidity. Conclusions: D-003 (5 and 10 mg/d) administered for 8 weeks to older subjects effectively prevented LP in older and favourable modified lipid profile parameters. The present results add new data on the antioxidant effects of D-003, including demonstration on a new population subset. However, this aspect deserves further investigation including studies with larger sample sizes, doses and treatment duration. [ABSTRACT FROM AUTHOR]

Background/aims: Osteoarthritis (OA), the commonest joint disorder, is a leading cause of disability. Symptomatic slow-acting drugs for OA (SYSADOA), particularly glucosamine plus chondroitin sulphate (GS/CS), are effective for symptom relief, protect joint cartilage and delay OA progression, with a good safety profile. D-002, a mixture of beeswax alcohols that inhibits both cyclooxygenase and 5-lipoxygenase activities, has been effective in experimental and clinical OA studies, showing also a chondroprotective effect., Objectives: To compare the effects of D-002 and GS/SC administered for 12 weeks on OA symptoms., Methods: Participants were randomized to GS/CS (375/300 mg) or 50 mg D-002 once daily for 12 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the Visual Analogy Scale (VAS) scores. The primary outcome was the reduction of the total WOMAC score. Secondary outcomes included WOMAC pain, stiffness and function scores, VAS score and rescue medication consumption., Results: Of 60 randomized patients, 59 completed the study. D-002 and GS/SC reduced significantly total WOMAC score (72.1% and 78.5%, respectively), and pain, joint stiffness and physical function scores versus baseline. VAS scores decreased significantly with D-002 (76.6%) and GS/SC (76.8%). The reductions, significant from the second week, were enhanced over the trial. Rescue medications were consumed by 3/30 D-002 and 4/30 GS/SC patients. No differences between groups were found. Treatments were well tolerated., Conclusions: D-002 (50 mg/day) administered for 12 weeks was safe and comparable to GS/SC for alleviating OA symptoms (pain, stiffness, and functional limitation) (RPCEC00000180).