695 ISSN 0326-2383 KEY WORDS: Antioxidant, Beeswax alcohols, D-002, Lipid peroxidation, Total hydroxyperoxides. PALABRAS CLAVE: Alcoholes de cera de abejas, Antioxidante, D-002, Hidroxiperóxidos totales, Peroxidación lipídica. * Author to whom correspondence should be addressed. E-mail: vivian.molina@cnic.edu.cu Latin American Journal of Pharmacy (formerly Acta Farmacéutica Bonaerense) Lat. Am. J. Pharm. 27 (5): 695-703 (2008) Original Article Received: June 14, 2008 Accepted: July 12, 2008 Effects of D-002 (Beeswax Alcohols) on Lipid Peroxidation in Middle-aged and Older Subjects Ernesto LÓPEZ 1 , José ILLNAIT 1 , Vivian MOLINA 2 *, Ambar OYÁRZABAL 2 , Lilia FERNÁNDEZ 2 , Yohani PÉREZ 2 , Rosa MAS 2 , Meylis MESA 1 , Julio FERNÁNDEZ 2 , Sarahí MENDOZA 2 , Mainel GÓMEZ 3 , Sonia JIMÉNEZ 2 & Dalmer RUIZ 3 1 Centro de Investigaciones Médico Quirúrgicas, 2 Centro de Productos Naturales, 3 Grupo de Software y bases de datos, Centro Nacional de Investigaciones Científicas, Ave. 25 y 158, P.O. 6880, Cubanacán, Ciudad Habana, Cuba SUMMARY. D-002 is a mixture of higher aliphatic alcohols (tetracosanol, hexacosanol, octacosanol, tria- contanol, dotriacontanol, tetratriacontanol) purified from beeswax with antioxidant effects, whose effects on plasma total hydroxyperoxides (TOHP) had not been investigated. This randomised, double-blinded, placebo-controlled study investigated the effects of D-002 (50 mg/day) on plasma TOHP and other oxida- tive variables in 56 subjects who received placebo or D-002 for 12 weeks. D-002, not placebo, reduced sig- nificantly plasma malondialdehyde (MDA) (22.6%) and TOHP (23.8%), and increased plasma total an- tioxidant status (TAS) (19.7%) versus baseline and placebo. D-002 did not affect safety indicators. There were 6 withdrawals (4 placebo, 2 D-002), only one (placebo) due to adverse experiences (AE). Six subjects (5 placebo, 1 D-002) referred some AE. Concluding, D-002 (50 mg/day) reduced significantly plasma TOHP and MDA, increased TAS, and was well tolerated by study subjects, which expands previous knowledge on its antioxidant effects in humans. RESUMEN. “Efectos del D-002 (Alcoholes de la Cera de Abejas) sobre la Peroxidación Lipídica en Sujetos de Edad Media y Avanzada”. El D-002 es una mezcla de alcoholes alifáticos primarios superiores (tetracosanol, he- xacosanol, octacosanol, triacontanol, dotriacontanol, tetratriacontanol) purificada de la cera de abejas con efectos antioxidantes, cuyos efectos sobre los niveles plasmáticos de hidroperóxidos totales (OHPT) no habían sido in- vestigados. Este estudio aleatorizado, doble ciego y controlado con placebo investigó los efectos del D-002 (50 mg/día) sobre los valores plasmáticos de OHPT y otras variables oxidativas en 56 sujetos que recibieron aleato- riamente placebo ó D-002 durante 12 semanas. D-002, no el placebo, redujo significativamente los niveles plas- máticos de malondialdehido (MDA) (22,6%) y OHPT (23,8%), y aumentó el estado antioxidante total del plasma (EAOTP) (19,7%) versus los basales y del placebo. El D-002 no afectó los indicadores de seguridad. Hubo 6 ba- jas (4 placebo, 2 D-002), sólo una (placebo) debida a experiencias adversas (EA). Seis sujetos (5 placebo, 1 D- 002) refirieron alguna EA. Concluyendo, el D-002 (50 mg/día) redujo significativamente los niveles plasmáticos de OHPT y MDA, aumentó el EAOTP y fue bien tolerado por los sujetos de estudio, lo que expande el conoci- miento previo sobre sus efectos antioxidantes en humanos. INTRODUCTION D-002 (beeswax alcohols) is a reproducible mixture of 6 higher aliphatic alcohols (tetra- cosanol, hexacosanol, octacosanol, triacontanol, dotriacontanol and tetratriacontanol) purified from beeswax. D-002 has proven to produce an- tioxidant effects in experimental and clinical studies 1-6 , while triacontanol, the most abun- dant component of D-002, has shown to inhibit both enzymatic and non-enzymatic lipid peroxi- dation (LP) in vitro 7 . Oral treatment with D-002 has demonstrated to reduce iron, CCl 4 and toluene-induced LP in rat plasma, liver, brain and stomachs 2,3 and to increase the activity of antioxidant defensive en- zymes in rats 4 . Clinical trials have shown that D-002 (50 mg/day) for 12 weeks significantly delayed the formation of conjugated dienes in whole plasma, increased the plasma total an- tioxidant status (TAS) and reduced plasma mal- ondialdehyde (MDA) levels in healthy volun- teers and older subjects, without change super-