Background: Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a lacto-tetrapeptide Gly–Thr–Trp–Tyr rich in fermented dairy products that improves memory retrieval, attention, and executive function in older adults with subjective cognitive decline and prevents the pathology of Alzheimer’s disease in rodents. There has been no study on the effects of β-lactolin on neural activity in humans. Objective: We investigated the effects of β-lactolin on neural activity and cognitive function in healthy adults. Methods: In this randomized, double-blind, placebo-controlled study, 30 participants (45–64 years old) consumed β-lactolin or placebo for 6 weeks. Neural activity during auditory and language tasks was measured through 64-channel electroencephalography. Moreover, verbal fluency tests were performed at baseline and after 6 weeks. Results: The β-lactolin group had a significantly higher P300 amplitude at the Cp2 site (a part of the parietal lobe near the center of brain, p = 0.008), and C4 site (the area between the frontal and parietal lobe, p = 0.021) during the auditory tasks after 6 weeks than the placebo group. Thus, β-lactolin supplementation promoted neural activity in the parietal area, which increases attention during auditory cognitive tasks. Compared with the placebo group, the β-lactolin group also showed significant changes in the scores of verbal fluency test after 6 weeks (p = 0.03). Conclusion: Our findings provide insight into the mechanisms underlying the effects of β-lactolin on attention in healthy adults.

In mammals, daily physiological events are regulated by the circadian rhythm, which comprises two types of internal clocks: the central clock and peripheral clocks. Circadian rhythm plays an important role in maintaining physiological functions including the sleep-wake cycle, body temperature, metabolism and organ functions. Circadian rhythm disorder, which is caused, for example, by an irregular lifestyle or long-haul travel, increases the risk of developing disease; therefore, it is important to properly maintain the rhythm of the circadian clock. Food and the circadian clock system are known to be closely linked. Studies on rodents suggest that ingesting specific food ingredients, such as the flavonoid nobiletin, fish oil, the polyphenol resveratrol and the amino acid L-ornithine affects the circadian clock. However, there are few reports on the foods that affect these circadian clocks in humans. In this study, therefore, we examined whether L-ornithine affects the human central clock in a crossover design placebo-controlled human trial. In total, 28 healthy adults (i.e. ≥20 years) were randomly divided into two groups and completed the study protocol. In the 1st intake period, participants were asked to take either L-ornithine (400 mg) capsules or placebo capsules for 7 days. After 7 days' interval, they then took the alternative test capsules for 7 days in the 2nd intake period. On the final day of each intake period, saliva was sampled at various time points in the dim light condition, and the concentration of melatonin was quantified to evaluate the phase of the central clock. The results revealed that dim light melatonin onset, a recognized marker of central circadian phase, was delayed by 15 min after ingestion of L-ornithine. Not only is this finding an indication that L-ornithine affects the human central clock, but it also demonstrates that the human central clock can be regulated by food ingredients.

Context Epidemiological studies have shown that consumption of dairy products reduces the risk of dementia and cognitive decline in older individuals. Tryptophan-tyrosine-related β-lactopeptides and their representative β-lactolin of glycine-threonine-tryptophan-tyrosine tetra-peptide have been identified as agents in dairy products, which improve cognitive function as well as memory function via the activation of the dopaminergic system in a mouse model of amnesia. Previous clinical trials have shown that supplementation with β-lactolin improves memory retrieval in healthy older adults. Specifically, β-lactolin improved the scores in some neuropsychological tests. However, the effects of β-lactolin on memory function have not been clarified. Objectives The aim of this study was to evaluate the effect of β-lactolin on memory function using statistical methods. Data Sources We searched the Web of Science, Cochrane Library, and JDream III until November 2021 to identify relevant randomized controlled trials for integrated analysis. Data Synthesis Three randomized controlled trials evaluating the effect of β-lactolin on memory in healthy adults were selected for the integrated analysis. The results showed that the score of cued recall among the neuropsychological tests in the β-lactolin group was significantly higher than that in the placebo group (g=0.33; 95% CI: 0.10, 0.55). In addition, the total memory score was higher but this difference was not significant (g=0.17; 95% CI: −0.09, 0.43). Conclusions Taken together, these results suggest that supplementation with β-lactolin improves cued recall in healthy older adults.

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