Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease

José Illnait,Iván Rodríguez,Sarahí Mendoza,Yolanda Fernández,Rosa Mas,Mirtha Miranda,Jesús Piñera,Julio César Fernández,Meilis Mesa,Lilia Fernández,Daisy Carbajal,Rafael Gámez 대한내과학회 2013 The Korean Journal of Internal Medicine Vol.28 No.4

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is intimately related to insulin resistance and ranges from a benign course to liver fibrosis and cirrhosis. NAFLD management mainly involves dietary modification and weight loss. Although no fully successful pharmacological intervention is available, alternative therapies to treat NAFLD have shown promising results. Experimental studies have shown that D-002, a mixture of beeswax alcohols with antioxidant effects, is hepatoprotective. The aim of this study was to investigate the efficacy and safety of D-002 in patients with NALFD. Methods: Fifty patients with NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks. The primary endpoint was a significant ultrasonography-detected reduction of liver fat infiltration versus a placebo. Secondary endpoints were decreases in the homeostatic model assessment (HOMA) index,insulin levels, serum liver enzymes, increases in plasma total antioxidant status (TAS) and improved clinical symptoms versus the placebo recipients. Results: At randomization, all indicators were comparable in both groups. At study completion, seven (28.0%) D-002-patients, but none of the placebo recipients,exhibited a normal liver echo pattern on ultrasonography (p < 0.01). Also,D-002 significantly reduced (p < 0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased the TAS, but did not affect other parameters. The proportion of D-002-patients (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three patients in each group withdrew from the study. Conclusions: D-002 (100 mg/day) improved ultrasonographic findings, indicators of insulin resistance, plasma TAS and clinical evolution on NAFLD patients. Further studies, however, are needed to confirm these results.

Evaluation of the effect of D-002, a mixture of beeswax alcohols, on osteoarthritis symptoms

Roberto Puente,José Illnait,Rosa Mas,Daisy Carbajal,Sarahí Mendoza,Julio César Fernández,Meilis Mesa,Rafael Gámez,Pablo Reyes 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.2

Background/Aims: Nonsteroidal anti-inflammatory drugs relieve osteoarthritis(OA) symptoms but cause adverse effects. D-002, a mixture of beeswax alcohols,is effective against experimental OA. A pilot study found that D-002 (50 mg/day)for 8 weeks improves OA symptoms. The aim of this study was to investigate theeffects of D-002 (50 to 100 mg/day) administered for 6 weeks on OA symptoms. Methods: Patients with OA symptoms were double-blindly randomized to D-002(50 mg) or placebo for 6 weeks. Symptoms were assessed by the Western Ontarioand McMaster Individual Osteoarthritis Index (WOMAC) and the visual analogscale (VAS) scores. Patients without symptom improvement at week 3 were titratedto two daily tablets. The primary outcome was the total WOMAC score. WOMACpain, joint stiffness and physical function scores, VAS score, and use of rescuemedications were secondary outcomes. Results: All randomized patients (n = 60) completed the study, and 23 experienceddose titration (two in the D-002 and 21 in the placebo groups). At study completion,D-002 reduced total WOMAC (65.4%), pain (54.9%), joint stiffness (76.8%), andphysical function (66.9%) WOMAC scores, and the VAS score (46.8%) versusplacebo. These reductions were significant beginning in the second week, andbecame enhanced during the trial. The use of rescue medication by the D-002(6/30) group was lower than that in the placebo (17/30) group. The treatment waswell tolerated. Seven patients (two in the D-002 and five in the placebo group)reported adverse events. Conclusions: These results indicate that D-002 (50 to 100 mg/day) for 6 weeksameliorated arthritic symptoms and was well tolerated.

Lack of Protective Effect of D-003, a Mixture of High-Molecular-Weight Primary Acids from Sugar Cane Wax, on Liver Damage Induced by Galactosamine in Rats

Miriam Noa,Sarah Mendoza,Rosa Mas,Nilda Mendoza 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.3

D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar cane wax, whereinoctacosanoic acid is the most abundant. Experimental and clinical studies have shown that D-003 lowers cholesterol and pre-vents plasma lipoprotein peroxidation (LP). D-003 has protected against the histological changes characteristic of CCl4- andparacetamol-induced hepatic injury in rats, in which LP plays a pivotal role for explaining the resulting hepatotoxicity. Galac-tosamine induces hepatotoxicity associated with depressed RNA and protein synthesis, not with LP. The aim of this studywas to evaluate whether D-003 could prevent hepatoxicity induced by mechanisms others than increased LP. We investigatedthe effects on galactosamine hepatotoxicity in rats distributed into five groups: a negative control group, a positive controlgroup, and three groups treated with galactosamine and D-003 (5, 25, and 100 mg/kg). To induce liver damage, galactosamine(800 mg/kg) was injected intraperitoneally 30 minutes after dosing with vehicle or D-003. Twenty-four hours later, rats weresacrificed, and livers were immediately removed for histopathological studies. Livers from positive controls showed the char-acteristic pattern of galactosamine-induced damage. Galactosamine significantly reduced the percentage of normal hepato-cytes, increasing both necrotic or lipid-rich hepatocytes compared with negative controls. D-003, however, did not increasethe percentage of normal hepatocytes compared with positive controls, indicating that treatment was not effective for pre-venting the hepatic injury induced with galactosamine. Likewise, D-003 failed to change the content of necrotic and lipid-rich hepatocytes relative to positive controls. It is concluded that D-003 did not protect against the histological changes ofgalactosamine-induced hepatotoxicity.

Effect of D-003 on Intimal Thickening and Circulating Endothelial Cells in Rabbit Cuffed Carotid Artery

Miriam Noa,Sarah? Mendoza,Rosa M?s 한국식품영양과학회 2005 Journal of medicinal food Vol.8 No.2

D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar-cane (Saccha-rum officinarumL.) wax, in which octacosanoic acid is the most abundant component. Previous experimental studies haveshown that D-003 not only shows cholesterol-lowering and anti-platelet effects, but also reduces thromboxane B2 and in-creases prostacyclin levels. It acts by inhibiting cholesterol biosynthesis. The positioning of a non-occlusive silicone collararound the rabbit carotid artery results in the formation of a neointima. Collars were placed around the left carotid for 15 days.The contralateral artery was sham-operated. We included three experimental groups: A control group received vehicle, andtwo others received D-003 at 5 and 25 mg/kg until sacrificed. Samples of arteries were examined by light microscopy. Toevaluate intimal thickening the cross-sectional areas of intima and media were measured. Neointima was significantly reducedin D-003-treated animals compared with controls. Furthermore, the circulating endothelial cell has been studied in this ex-perimental model with endothelium damage. The results demonstrate the protective effect of D-003 on vascular endotheliumof the studied rabbits. It is concluded that the protective effect of D-003 against neointima formation and circulating endothelialcells in this experimental model could represent potential beneficial pleiotropic effects in the anti-atherogenic profile of thissubstance, beyond its cholesterol-lowering and anti-platelet effects independently demonstrated.

Effect of D-003 on Isoproterenol-Induced Myocardial Necrosis in Rats

Daisy Carbajal,Miriam Noa,Vivian Molina,Maria Lourdes Arruzazabala,Rosa M?,Sarah?Mendoza,Jorge Gonz?ez 한국식품영양과학회 2003 Journal of medicinal food Vol.6 No.1

D-003 is a mixture of high-molecular-weigh t aliphatic primary acids purified from sugar canewax with antiplatelet and cholesterol-lowering effects. Cardiac lesions induced by isopro-terenol (ISO) are characterized by myocardial necrosis and exudative infiltration. The objec-tive of this study was to determine whether D-003 shows protective effects against ISO-in-duced myocardial necrosis in rats. Effects of orally administered single doses of D-003 (25 40mg/kg) and acetylsalicylic acid (ASA, 30 mg/kg), as well as repeated doses of D-003 (5 20mg/kg), on characteristic markers of ISO-induced myocardial necrosis in rats were investi-gated. D-003 administered as single doses dose-dependen tly decreased necrosis area, percentof infarct area, and the presence of polymorphonuclear cells (PMNs) in myocardial tissue, butonly the reductions induced by 200 and 400 mg/kg were significant. Oral acute treatment withASA also decreased necrosis area and percent of infarct area, but the occurrence of PMNs wasunchanged. D-003 administered repeatedly for 10 days also decreased all myocardial necro-sis indicators in a dose-dependen t maner, with results effective from 25 mg/kg to the high-est dose tested, indicating that the repeated dose scheme was more effective to prevent thedamage. It is concluded that D-003 shows a protective effect on the myocardial necrosis in-duced by ISO in rats.13