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Effect of the Casein-Derived Peptide Met-Lys-Pro on Cognitive Function in Community-Dwelling Adults Without Dementia: A Randomized, Double-Blind, Placebo-Controlled Trial

Authors Yuda N, Tanaka M, Yamauchi K, Abe F, Kakiuchi I, Kiyosawa K, Miyasaka M, Sakane N, Nakamura M

Received 11 March 2020

Accepted for publication 7 May 2020

Published 27 May 2020 Volume 2020:15 Pages 743—754


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Richard Walker

Naoki Yuda,1 Miyuki Tanaka,1 Koji Yamauchi,1 Fumiaki Abe,1 Izumi Kakiuchi,2 Kyoko Kiyosawa,2 Mitsunaga Miyasaka,2 Naoki Sakane,3 Masahiko Nakamura4

1Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, Japan; 2Department of Nursing, Matsumoto Junior College, Matsumoto, Nagano, Japan; 3Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; 4Matsumoto City Hospital, Matsumoto, Nagano, Japan

Correspondence: Naoki Yuda
Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., 1-83, 5-Chome, Higashihara, Zama, Kanagawa, Japan
Tel +81 46 252 3051
Fax +81 46 252 3017
Email [email protected]

Background: Preventative measures have recently been taken to reduce the incidence of Alzheimer’s disease worldwide. We previously showed that Met-Lys-Pro (MKP), a casein-derived angiotensin-converting enzyme inhibitory peptide with the potential to cross the blood–brain barrier, attenuated cognitive decline in a mouse model of Alzheimer’s disease. However, the effect of MKP on cognitive function improvement in humans remains unknown. This exploratory study sought to investigate whether MKP intake could improve cognitive function in adults without dementia.
Methods: A total of 268 community-dwelling adults without dementia participated in this 24-week randomized controlled trial. Participants were randomly allocated to the MKP (n = 134) or placebo (n = 134) group. The MKP group received four tablets daily, each containing 50 μg MKP, while the placebo group received four dextrin tablets containing no detectable MKP for 24 weeks. Scores on the Japanese version of the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) were used as the primary outcome to compare cognitive function between the MKP and placebo groups. The study products were also evaluated for safety.
Results: The intention-to-treat analysis showed that there was no significant difference between the groups in terms of the ADAS-cog total score. Orientation, as measured by the respective ADAS-cog subscale, was significantly improved compared to placebo at 24 weeks post-MKP administration (P = 0.022). No serious adverse events due to MKP intake were observed.
Conclusion: To the best of our knowledge, this is the first study to report the effects of MKP on human cognition. These preliminary results suggested the safety of daily MKP intake and its potential to improve orientation in adults without dementia. Further clinical studies are needed to confirm the present findings and the benefits of MKP on cognitive function.

Keywords: humans, MKP, cognition, cognitive dysfunction, orientation, Alzheimer’s disease

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