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Background: Previous epidemiological and clinical studies have shown that dairy products have beneficial effects on cognitive decline and dementia. Enzymatic digestion of whey protein produces a whey peptide rich in tryptophan-tyrosine-related peptides which improve cognitive performance in mice. We evaluated the effects of whey peptides on cognitive functions in healthy adults in a randomized, double-blind, placebo-controlled design. Methods: 101 healthy adults (45 to 64 years), with a self-awareness of cognitive decline received either whey peptide or placebo supplements for 12 weeks. Changes in cognitive function were assessed using neuropsychological tests at 6 and 12 weeks after the start of supplementation. Results: Verbal fluency test (VFT) score changes tended to be higher in the whey peptide group compared with the placebo at 12 weeks. Subgroup analysis classified by the degree of subjective fatigue showed that changes in the VFT as well as the Stroop and subjective memory function tests between baseline and 6 weeks of intervention were significantly better in subjects with high-level fatigue from the whey peptide group as compared to the placebo group. Conclusions: Intake of whey peptide might improve cognitive function in healthy middle- and older-aged adults with high subjective fatigue levels. Further studies will elucidate the relationship among cognitive improvement, whey peptides, and psychological fatigue.

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.

The present study aimed to investigate the effects of matured hop bitter acids (MHBAs) on human cognition, mental fatigue, and mood state. In this randomized double-blind placebo-controlled study, 60 healthy adults (age 45−64 years) with self-awareness of cognitive decline were randomly divided into 2 groups and received either orally administered MHBAs (35 mg/day) or placebo for 12 weeks. Cognitive functions and mental states were assessed using neuropsychological tests or questionnaires at baseline and weeks 6 and 12 of the intervention. The change in verbal fluency score at week 6 compared with that at baseline was significantly higher in the MHBAs-treated group compared with that in the placebo group (P = 0.034), and Stroop test score at week 12 was significantly lower in the MHBAs-treated group compared with the placebo group (P = 0.019). Furthermore, subjective fatigue and anxiety at week 12 were significantly improved in the MHBAs-treated group (P = 0.008 and 0.043, respectively) compared with the placebo group. This is the first study to evaluate the effects of bitter ingredients in beer on cognition, subjective mood, and mental fatigue in a clinical trial. Our findings suggest that hop-derived bitter acids might be beneficial for cognition and mood state.

Background: Prevention of age-related cognitive decline and depression is becoming urgent because of rapid growing aging populations. Effects of vagal nerve activation on brain function by food ingredients are inadequately investigated; matured hop bitter acid (MHBA) administration reportedly improves cognitive function and depression via vagal nerve activation in model mice. Objective: We investigated the effects of MHBA supplementation on cognitive function and mood state in healthy older adults with perceived subjective cognitive decline. Methods: Using a randomized double-blind placebo-controlled trial design, 100 subjects (aged 45–69 years) were randomly assigned into placebo ( n = 50) and MHBA ( n = 50) groups, and received placebo or MHBA capsules daily for 12 weeks. Results: Symbol Digit Modalities Test (SDMT) score assessing divided attention at week 12 was significantly higher ( p = 0.045) and β-endorphin at week 12 was significantly lower ( p = 0.043) in the subjects receiving MHBA. Transthyretin in serum, a putative mild cognitive impairment marker, was significantly higher at week 12 in the MHBA group than in the placebo group ( p = 0.048). Subgroup analysis classified by the subjective cognitive decline questionnaire revealed that in addition to improved SDMT scores, memory retrieval assessed using the standard verbal paired-associate learning tests and the Ray Verbal Learning Test at week 12 had significantly improved in the subgroup with perceived subjective cognitive decline and without requirement for medical assistance in the MHBA group compared with that in the placebo group. Conclusion: This study suggested that MHBA intake improves cognitive function, attention, and mood state in older adults.