Effects of whey-derived lactopeptide β-lactolin on cognitive performance in mild cognitive impairment: a randomized, double-blind, placebo-controlled trial.

Objective: This study aimed to investigate the effects of a long-term intervention with β-lactolin, a tetrapeptide (sequence: glycine-threonine-tryptophan-tyrosine) derived from milk, on cognitive performance in individuals with mild cognitive impairment (MCI).

Methods: A randomized, double-blind, placebo-controlled trial was conducted. We recruited 48 participants aged 50 years or older with the Japanese version of the Mini-Mental State Examination (MMSE-J) score of 24-28 and a Clinical Dementia Rating (CDR) score of 0.5. Participants were administered β-lactolin (1.8 mg daily) or placebo for 24 weeks. The primary outcomes were the MMSE-J and the Japanese version of the Montreal Cognitive Assessment (MoCA-J) scores for cognitive function.

Results: A total of 422 individuals were screened, 48 of whom were included in this study. The MMSE-J and MoCA-J scores showed no significant differences between the groups. In the intra-group comparison of the MoCA-J delayed recall score, a significant difference was observed in the β-lactolin group after 12 and 24 weeks of intervention ( = 0.0256,  = 0.0175, respectively). Furthermore, the subgroup analysis stratified for females only showed a significant difference in MoCA-J total score in the β-lactolin group after 24 weeks of intervention ( = 0.0253).

Conclusion: β-lactolin intake does not significantly improve cognitive function in MCI in an inter-group comparison; nevertheless, the MoCA-J delayed recall score was significantly improved in the β-lactolin group. The number of participants was lower than planned, limiting the confirmation of the effectiveness of β-lactolin on MCI. This report demonstrated the effect size of β-lactolin intervention in MCI, contributing insights for future research.