Orally administered scallop-derived plasmalogens improve cognitive function in healthy middle-aged and older adults: a randomized, double-blind, placebo-controlled trial

Background Plasmalogens (Pls) are ether phospholipids enriched in the brain that help maintain synaptic integrity and support cognitive function. However, evidence of their cognitive benefits in otherwise healthy individuals remains limited. This randomized, double-blind, placebo-controlled trial examined whether supplementation with scallop-derived Pls (sPls) improves cognitive performance in cognitively healthy Japanese adults aged ≥40 years with below-average verbal memory at baseline. Methods Of 168 individuals screened, 68 eligible participants were randomly assigned (1:1) to receive either sPls (1 mg/day) or placebo for 12 weeks. Cognitive performance was assessed using the web-based Cognitrax battery (CNS Vital Signs), with the standardized verbal memory score as the primary outcome. Secondary outcomes included other cognitive domains and plasma brain-derived neurotrophic factor (BDNF) levels. Safety was evaluated through adverse event monitoring and clinical assessments. Results Sixty-six participants were included in the analysis. After 12 weeks, standardized verbal memory scores were significantly higher in the sPls group than in the placebo group (estimated marginal mean difference, 10.1; 95% confidence interval, 0.4–19.9; p = 0.042). The sPls group also showed significantly greater improvements in selected attention-related cognitive domains. Plasma BDNF levels increased in both groups, with no significant between-group differences; a modest negative correlation between BDNF levels and cognitive performance was observed in the sPls group at 12 weeks. No adverse events or clinically meaningful safety concerns were reported. Conclusion In cognitively healthy middle-aged and older adults with below-average verbal memory, 12 weeks of sPls supplementation was associated with improved verbal memory compared with placebo. Exploratory analyses also suggested potential improvements in selected attention-related cognitive domains. Dietary sPls may have the potential to support cognitive function in this population; however, further studies are required to confirm these findings and evaluate long-term safety. Clinical trial registration https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000066286 , identifier UMIN000057985.