Submitted:
12 February 2026
Posted:
14 February 2026
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Abstract
Background: As the prevention of dementia onset and the slowing of its progression become a global challenge, nutritional interventions focusing on the gut-brain axis are garnering attention. This study examined the effects of a complex functional food containing Clostridium butyricum, 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) derived from fermented rice bran, and salmon milt-derived DNA on cognitive function and bowel habits in middle-aged and older adults. Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted on 80 men and women aged 55–79 years with subjective memory complaints and an MMSE-J score of 24 or higher (UMIN ID: UMIN000057405). Participants ingested either the Test food (containing 1.4 × 10⁷ CFU of C. butyricum, 11.5 mg of HMPA, and 45 mg of salmon milt-derived DNA) or a Placebo once daily for 12 weeks. The primary outcome was cognitive function assessed by Cognitrax. Secondary outcomes included subjective cognition, mood state, bowel habits, blood biochemical parameters, and safety. A subgroup analysis was performed for participants aged ≥65 years with MMSE-J scores of 24–27. Results: In the overall analysis, no significant difference was observed in Composite Memory between groups; however, the number of correct responses in the Symbol Digit Coding (SDC) test, which is related to attention and processing speed, significantly improved in the Test food group. In the subgroup analysis, significant improvements in verbal memory-related indices were observed in the Test food group. Bowel habit indices showed no consistent between-group differences. Exploratory evaluations showed significant improvements in metabolic markers such as fasting plasma glucose, HbA1c, γ-GT, and uric acid in the Test food group. No serious adverse events occurred, and adherence to intake was high. Conclusions: Twelve-week intake of this complex functional food improved indices of attention and processing speed in the overall population, improved verbal memory indices in the high-risk subgroup, and positively affected metabolic markers. However, no clear effects on bowel habits were confirmed. Larger-scale and longer-term verification is needed in the future.
