Supplementation With Whey Peptide Rich in β-Lactolin Improves Cognitive Performance in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Epidemiological reports showed that consumptions of fermented dairy products are beneficial for cognitive decline in elderly. Our previous preclinical studies have demonstrated that intakes of whey peptide rich in the β-lactolin [β-lactopeptide of glycine-thereonine-tryptophan-tyrosine (GTWY)] improve memory and attention by regulating monoamine system, and clinical study using neuropsychological test suggested that consumptions with GTWY-rich whey peptide enhance cognitive performance associated with the frontal cortex activity. However, corresponding interventional studies in humans are limited. Objectives: to evaluate the effects of the whey peptide on cognitive functions in healthy older adults using a randomized, double-blinded, placebo-controlled trial design. 114 healthy subjects aged 50–75 were supplemented with the whey peptide or placebo for 12 weeks, and changes in cognitive function were assessed using neuropsychological tests at weeks 0, 6, and 12 of the intervention. Neuropsychological tests included assessments for memory functions (subtests from Wechsler memory scale-revised, standard verbal paired-associate learning test, and recognition memory test for faces), assessments for attention (cancelation and detection tests), and assessments for general cognitive functions (repeatable battery for assessments of neuropsychological status). Cerebral blood flow was also assessed using near-infrared spectroscopy (NIRS) after 6 weeks of intervention. This study was registered on the 19 November, 2017 in the database of the University Hospital Medical Information Network (UMIN) prior to enrollment of subjects (Registration No. UMIN000030461: https://www.umin.ac.jp/ctr/index-j.htm ). In the whey peptide group, visual paired-associates I and visual cancelation tests were significantly improved compared with those in the placebo group at weeks 6 and 12 of the intervention, respectively. Visuospatial and constructional scores of the repeatable battery for assessments of neuropsychological status and standard verbal paired-associate learning tests (S-PA) also tended to be improved by the intervention at week 12. Daily intakes of GTWY-rich whey peptide show beneficial effects on cognitive performance, especially associative learning memory and control of attention, in healthy older adults and might prevent age-related cognitive declines.

β-Lactolin, a Whey-Derived Lacto-Tetrapeptide, Prevents Alzheimer’s Disease Pathologies and Cognitive Decline

“…Accumulating studies indicate that fermented dairy products rich in ␤-lactolin improve cogni- tive performance and dementia [15,17]. However, the effects of ␤-lactolin on AD pathologies and cognitive decline have not been investigated.…”

“…Accumulating evidence [16,17] indicates that supplementation with whey digestion rich in ␤-lactolin improves memory retrieval and attention. However, the effects of ␤-lactolin on brain inflammation in AD have not been investigated.…”

“…␤-Lactolin has been shown to increase monoamine levels in the frontal cortex and hippocampus and improve spatial working memory and attention in pharmacologically induced amnesia mice. Our previous studies showed that supplementation with ␤-lactolin-rich whey peptides improved memory retrieval, attention, and executive function in healthy adults [16,17], and the findings suggest that consumption of ␤-lactolin-rich whey peptides is associated with activation of the frontal cortex, especially the dorsolateral prefrontal cortex regulating memory retrieval and executive function. However, the effects of ␤lactolin on dementia and cognitive decline remain unclear.…”

Tyr-Trp administration facilitates brain norepinephrine metabolism and ameliorates a short-term memory deficit in a mouse model of Alzheimer’s disease

“…Recent studies have identified regulatory activities of various oligopeptides generated from food proteins in functions of peripheral tissues [25,26,27]. Clinical studies have demonstrated that the peptides generated from food proteins exert a beneficial effect on the central nervous system and improves cognitive function [28,29].…”

Antidepressant-Like Effect of β-Lactolin, a Glycine-Threonine-Tryptophan-Tyrosine Peptide

“…b-Lactolin (GTWY peptide; purity: 98%) was purchased from Bachem (Bubendorf, Switzerland). Whey digestion containing 1.6 mg GTWY peptide per 1 g was prepared by Kirin Holdings Company (Tokyo, Japan) (16).…”