RESUMEN

BACKGROUND: Aging is associated with increased lipid peroxidation (LP). D-003, a mixture of long-chain aliphatic primary acids purified from sugar cane wax, has been found to inhibit LP in experimental models and in healthy subjects. OBJECTIVES: The aim of this study was to assess the effects of D-003 on LP markers and the lipid profile of older individuals. METHODS: This randomized, double-blind, placebo-controlled study was conducted at the Plaza Veterans' House, Havana City, Cuba. Male and female patients aged ≥60 years with total cholesterol values of <6.1 mmol/L were eligible for inclusion in the study. After a 3-week lead-in and baseline assessment period, patients were randomized to receive PO D-003 5 mg/d, D-003 10 mg/d, or placebo for 8 weeks. The effect on copper-induced LP of low-density lipoprotein (LDL) particles was the primary variable, and the effects on plasma total antioxidant status (TAS), plasma malondialdehyde (MDA) concentration, plasma antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities, and the lipid profile were secondary variables. A clinical examination was performed at each visit (baseline, weeks 4 and 8). A clinical examination, LP, and blood tests (lipid profile, hematologic, and blood biochemistry safety indicators) were performed at baseline and after 8 weeks of treatment. Compliance and adverse events (AEs) were assessed at weeks 4 and 8. A 2-tailed P < 0.05 was considered statistically significant for comparisons of both continuous and categoric variables. RESULTS: Fifty-four patients aged ≥60 years were assessed for inclusion in the study, and 51 patients (40 women, 11 men; mean [SD] age, 67 [6] years) were included in the study. The lag phase of conjugated diene formation increased significantly and in a dose-dependent manner in the group treated with D-003 5 mg (24.7%; P < 0.01) and in the group treated with D-003 10 mg (29.3%; P < 0.01) compared with placebo. The maximal rate of conjugated diene propagation decreased significantly in the D-003 5- and 10-mg groups -22.7% and -25.8%, respectively; both, P < 0.05) compared with placebo. TAS increased significantly (17.7% and 23.0%, respectively; both, P < 0.01) in both active treatment groups compared with placebo. Plasma MDA concentration decreased significantly in the D-003 10-mg group (-28.6%; P < 0.05) but not in the D-003 5-mg group, compared with placebo. These changes were also significant compared with baseline. Antioxidant enzyme activities did not change in the active treatment groups compared with placebo or baseline. In the D-003 5- and 10-mg groups, significant decreases were found in LDL cholesterol concentration (-15.8% and -23.8%, respectively; both, P < 0.001) and total cholesterol concentration (-13.0% and -16.8%, both, P < 0.05) compared with placebo. High-density lipoprotein cholesterol concentration increased significantly in the D-003 5-mg group (5.7%; P < 0.05) and the D-003 10-mg group (18.2%; P < 0.001) compared with placebo. Changes in the lipid profile were also significant compared with baseline. In the placebo group, no variable changed significantly compared with baseline. D-003 was well tolerated at both dose levels, and no patient withdrew from the study. There were a total of 3 AEs reported: insomnia and acidity in 2 patients receiving placebo; and heartburn in 1 patient receiving D-003 5 mg. CONCLUSIONS: D-003 5 and 10 mg/d administered to these older individuals (aged ≥60 years) for 8 weeks inhibited LP of LDL and increased TAS in a dose-dependent manner, while plasma MDA concentration decreased in the patients receiving D-003 10 mg/d only. D-003 was well tolerated at both doses.