Efficacy and Safety of Cuban Policosanol on Cognitive Function and Antioxidant Status in Adults with Subjective Memory Decline: A 12-Week Randomized, Double-Blinded, Placebo-Controlled Multicenter Trial

Objectives: Early non-pharmacological interventions for people with subjective memory decline (SMD) are increasingly advocated in preventing age-related cognitive decline and potentially delaying progression to mild cognitive impairment or dementia. In this multicenter clinical trial (RAYDELP1), we evaluated the efficacy and safety of sugarcane-derived Cuban policosanol (PCO) on cognitive function, superoxide dismutase (SOD) activity, inflammatory markers, and metabolic panels in adults aged 55–85 years with subjective cognitive complaints. Methods: A 12-week, randomized, double-blinded, placebo-controlled trial was conducted at Gachon University Gil Medical Center and Seoul Veterans Hospital in adults with SMD complaints. Individuals were randomized equally into three groups: placebo, PCO 20 mg group, or PCO 40 mg group. Assessment of cognitive function was performed using the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 11) and the Korean Mini-Mental State Examination (K-MMSE). All measurements, including SOD activity, inflammatory markers, and metabolic parameters, were analyzed in blood samples at baseline and after 12 weeks. For an exploratory subgroup analysis, participants receiving statins and those with potential ceiling effects or greater cognitive impairment based on K-MMSE scores were excluded. The K-MMSE range of 18–26 was used as an exploratory criterion to reduce heterogeneity in baseline cognitive scores, resulting in a refined analysis population of 56 participants. Results: In the refined SMD population, SOD activity increased significantly in the PCO 40 mg group after 12 weeks (mean change, +0.16 ± 0.25 U/mL; p = 0.0109) with increasing HDL-C, whereas changes in the placebo groups were not statistically significant (+0.08 ± 0.24 U/mL, p = 0.1873) with decreasing HDL-C. HDL-C levels increased in a dose-dependent manner in both the PCO 20 mg (+0.78 ± 5.1 mg/dL) and PCO 40 mg (+2.2 ± 6.7 mg/dL) groups within and between the groups. Both PCO groups showed significant differences compared with placebo in the between-group analysis and baseline-adjusted ANCOVA (p = 0.0124 and p = 0.0142, respectively). K-MMSE place-orientation scores improved significantly from baseline within both PCO groups (20 mg: 0.94 ± 0.87, p = 0.0003; 40 mg: 0.47 ± 0.77, p = 0.0155), whereas no significant within-group change was observed in the placebo group. Similarly, ADAS-Cog 11 language scores improved significantly within both PCO groups (20 mg: −1.17 ± 1.92, p = 0.0194; 40 mg: −0.95 ± 1.58, p = 0.0176). The 20 mg PCO group also showed a significant within-group decrease in Visual CPT false-alarm errors (−3.83 ± 7.13, p = 0.0357). However, between-group comparisons and baseline-adjusted ANCOVA did not demonstrate statistically significant differences in the selected cognitive outcomes. Conclusions: In the analyzed study population, HDL-C levels increased numerically in both PCO groups in a dose-dependent manner. The PCO 40 mg group showed a significant within-group increase in serum SOD activity, while improvements in selected cognitive domains were observed within both 20 mg and 40 mg PCO groups. However, no significant differences were found in between-group or ANCOVA analyses. PCO was well tolerated, and further clinical studies are warranted to confirm these exploratory findings and clarify its potential effects on cognitive function and enhancement of HDL quantity and quality.