World First: Research Reveals Milk-derived β-lactopeptides Improve Cerebral Blood Flow in the Middle-aged As Well As Elderly

Background to the research

In Japan’s rapidly-aging society, in which one in four people is elderly,*6 dementia and cognitive decline due to aging are huge social issues. Since dementia is thought to be caused by changes in the brain with aging, attention is being focused on early prevention through actions taken in daily life, such as by improving dietary habits. In recent years, epidemiological research on the Japanese population has found that the consumption of milk and dairy products reduces the risk of dementia and impaired cognitive function.*7

*6 Cabinet Office, Japanese government, White Paper on the Aging Society, FY 2020
*7 Ozawa M, et al, Journal of the American Geriatrics Society, 2014, 62(7): 1224-1230

As a result of Kirin Holdings’ long years of brain research in collaboration with the University of Tokyo and Kyowa Kirin Co., Ltd., Kirin Holdings has discovered that β-lactopeptides abundantly found in fermented dairy products such as camembert cheese, improve cognitive function.*8 Kirin Holdings has also demonstrated, in collaborative clinical trials with Keio University, that GTWY peptide, among other β-lactopeptides, improves memory and attention.*9 Although data suggested the involvement of the brain’s prefrontal cortex in these effects, the exact mechanism remained to be elucidated.

*8 Ano Y, Nakayama H, et al., Neurobiology of Aging, 2018, 72: 23-31
*9 Kita M, Ano Y, et al., Frontiers in Neuroscience, 2019, 13: 399

To elucidate the mechanism, the company focused on CBF. CBF carries oxygen, nutrients, and other energy sources to the brain, and therefore is essential for the normal functioning of the brain. Age-related decline in cognitive function is thought to be caused by a decrease in CBF. The company conducted this research based on the hypothesis that GTWY peptide could increase CBF.

Outline of the research

A randomized, double-blind controlled trial was carried out on 50 middle-aged to elderly healthy participants*10 to verify the effect of supplementation with GTWY peptide on human CBF. The participants’ CBF during loading tasks was measured using a 34CH CBF measurement device (optical topography device). The GTWY peptide intake group showed a significant increase in the magnitude of change in CBF in the dorsolateral prefrontal cortex compared with the placebo group. These results elucidated part of the mechanism by which GTWY peptide enhances memory and concentration.

In a separate clinical trial, 114 middle-aged to elderly healthy participants were included and took a supplement containing GTWY peptide. The results demonstrated that CBF during cognitive tasks, as measured with a 2CH wearable device (Fig. 2), was significantly increased in the GTWY peptide intake group compared with the placebo group. In this trial, the company succeeded for the first time in detecting an improvement in CBF using a wearable device with the abovementioned specification.

*10 A method of testing used in clinical trials in which participants are randomly divided into placebo and active drug groups, and are not told which group they are in until the trial is complete.

Trial methodology

1) A double-blind trial was conducted in which 50 healthy, middle-aged to elderly (between 45 and 64) men and women were randomly assigned to take either GTWY peptide or placebo. The participants’ CBF during cognitive tasks was measured at weeks 0 and 6, using a 34CH optical topography device.

2) A double-blind trial was conducted in which 114 healthy men and women (between 50 and 75) who were aware of forgetfulness (but without dementia) were randomly assigned to take either GTWY peptide or placebo. The participants’ CBF during cognitive tasks was measured at week 6, using a 2CH optical topography device.

Trial results

1) The results of the trial using a 34CH optical topography device demonstrated that the GTWY peptide intake group showed a significantly greater change from week 0 in CBF in the dorsolateral prefrontal cortex during a working memory task at week 6, compared with the placebo group (Fig. 1).

2) The results of the trial using a 2CH optical topography device also demonstrated that after 6 weeks of GTWY peptide intake, CBF in the dorsolateral prefrontal cortex was significantly higher than that in the placebo group (Fig. 2).

The results of these two studies were published in international journals Aging (Albany NY)*11and Journal of Clinical Medicine.*12

*11 Ano Y, et al., β-lactolin increases cerebral blood flow in dorsolateral prefrontal cortex in healthy adults: a randomized controlled trial, Aging (Albany NY). 2020 Sep 29;12(18):18660-18675.
*12 Ano Y, er al., Effects of β-Lactolin on Regional Cerebral Blood Flow within the Dorsolateral Prefrontal Cortex during Working Memory Task in Healthy Adults: A Randomized Controlled Trial, J Clin Med. 2021 Jan 28;10(3):480.

Future developments

Going forward, based on the demonstrated effect of the GTWY peptide on improving CBF and the successful visualization of this effect with a wearable device, Kirin Holdings will advance initiatives to support brain health through collaboration with universities and municipalities.

Comment from Dr. Ryuta Kawashima (co-presenter):

Dr. Ryuta Kawashima summarized the importance of the discovery: “Improving blood flow in the brain is one of the essential factors in maintaining cognitive function. The current clinical trial has revealed part of the mechanism by which β-lactopeptides improve CBF and enhance memory and concentration. In a super-aging society, the role of dietary habits in maintaining cognitive function is expected to increase further.

It is also our great pleasure to see that the CBF-improving effect of β-lactopeptides could be easily visualized by NeU's wearable CBF measurement device. We hope that this initiative will be accelerated to make brain health support more accessible to society.”

Kirin Brain Research

Japan’s average life expectancy has been increasing and the country has entered a super-aged society. Given that an estimated one in five elderly people will suffer from dementia in 2025,*13 healthy life extension is a social issue. The Kirin Group understands that the joys and concerns in a daily life are intimately associated with brain activity, and thus launched KIRIN Brain Research to develop the new solutions mainly in health science to promote brain health and create joy.

Kirin Brain Research based on Kirin’s distinct technology and ways of thinking contributes to promote brain health in an effort to help resolve social issues and will create a society conductive to psychologically prosperous living, where everyone has confidence and ambition and feels free to experience their emotions.

*13 Grants in Aid for Scientific Research, MHLW Special Research Project, Research on Future Trends in the Prevalence of Dementia among Elderly People in Japan, 2014, Report on General & Specialized Research, 2015