Effects of whey-derived lactopeptide β-lactolin on cognitive performance in mild cognitive impairment: a randomized, double-blind, placebo-controlled trial.

Objective: This study aimed to investigate the effects of a long-term intervention with β-lactolin, a tetrapeptide (sequence: glycine-threonine-tryptophan-tyrosine) derived from milk, on cognitive performance in individuals with mild cognitive impairment (MCI).

Methods: A randomized, double-blind, placebo-controlled trial was conducted. We recruited 48 participants aged 50 years or older with the Japanese version of the Mini-Mental State Examination (MMSE-J) score of 24-28 and a Clinical Dementia Rating (CDR) score of 0.

[Hop Bitter Acids Activate the Brain-Gut Axis: Vagal Stimulus via Food Ingredients].

Maintenance and improvement of cognitive function and mood is important in an aging society. Preventive approaches, including diets used in daily life have received increasing attention in recent times. Clinical trials and preclinical studies have shown that hop bitter acids, which represent the bitter ingredients in beer, activate the bitter taste receptors and the brain-gut axis, which was shown to improve cognitive function and mood.

Tryptophan-tyrosine dipeptide improves tau-related symptoms in tauopathy mice.

Neurodegenerative diseases involving pathological tau protein aggregation are collectively known as tauopathies and include Alzheimer's disease and Pick's disease. Recent studies show that the intake of tryptophan-tyrosine (Trp-Tyr)-related β-lactopeptides, including β-lactolin, attenuates cognitive decline in the elderly and prevents the amyloid pathology in mouse models of Alzheimer's disease. However, the effects of Trp-Tyr-related β-lactopeptides on tau-related pathology have not been investigated.

β-Lactolin improves mitochondrial function in Aβ-treated mouse hippocampal neuronal cell line and a human iPSC-derived neuronal cell model of Alzheimer's disease.

Mitochondrial dysfunctions are a key hallmark of Alzheimer's disease (AD). β-Lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine tetrapeptide, has been previously reported to prevent AD-like pathologies in an AD mouse model via regulation of microglial functions. However, the direct effect of β-lactolin on neuronal cells and neuronal mitochondrial functions remains unknown.

Effect of non-alcoholic beer containing matured hop bitter acids on mood states in healthy adults: A single-arm pilot study.

This study aimed to investigate the effect of non-alcoholic beer containing matured hop bitter acids on mood states among healthy adults older than 20 years. This study was an open-label longitudinal intervention design in which each participant served as their control. For 3 weeks, we evaluated the effect of non-alcoholic beer containing 35 mg of matured hop bitter acids on mood, sleep quality, and work performance.

β-Lactolin Reduces Age-Related Inflammation and Cognitive Decline.

With the rapid increase in aging populations worldwide, there has been an increase in demand for preventive and therapeutic measures for age-related cognitive decline and dementia. Epidemiological studies show that consumption of dairy products reduces the risk for cognitive decline and dementia in the elderly. We have previously demonstrated in randomized trials that the consumption of β-lactolin, a whey-derived Gly-Thr-Trp-Tyr lactotetrapeptide, improves cognitive function in older adults.

Deposition of Phosphorylated α-Synuclein and Activation of GSK-3β and PP2A in the PS19 Mouse Model of Tauopathy.

The simultaneous accumulation of multiple pathological proteins, such as hyperphosphorylated tau (hp-tau) and phosphorylated α-synuclein (p-αSyn), has been reported in the brains of patients with various neurodegenerative diseases. We previously demonstrated that hp-tau-dependent p-αSyn accumulation was associated with the activation of GSK-3β in the brains of P301L tau transgenic mice. To confirm the effects of another mutant tau on p-αSyn accumulation in vivo, we herein examined the brains of PS19 mice that overexpress human P301S mutant tau.

β-Lactolin Enhances Neural Activity, Indicated by Event-Related P300 Amplitude, in Healthy Adults: A Randomized Controlled Trial.

Background: Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a Gly-Thr-Trp-Tyr lacto-tetrapeptide 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.

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.

Epidemiological studies have reported that consumption of dairy products rich in β-lactolin is beneficial for cognitive decline among elderly individuals. Although previous studies have shown that β-lactolin supplementation improves memory function and attention in healthy adults, the mechanism through which β-lactolin affects human brain function has yet to be elucidated. This placebo-controlled randomized double-blind study therefore examined the effects of β-lactolin on human regional cerebral blood flow (rCBF) using near-infrared spectroscopy (NIRS) according to the Consolidated Standards of Reporting Trials guidelines.

Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress.

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown.

Hop bitter acids containing a β-carbonyl moiety prevent inflammation-induced cognitive decline via the vagus nerve and noradrenergic system.

The prevention of age-related cognitive decline and dementia is becoming a high priority because of the rapid growth of aging populations. We have previously shown that hop bitter acids such as iso-α-acids (IAAs) and matured hop bitter acids (MHBAs) activate the vagus nerve and improve memory impairment. Moreover, supplements with MHBAs were shown to improve memory retrieval in older adults.

Bitter taste receptor activation by hop-derived bitter components induces gastrointestinal hormone production in enteroendocrine cells.

Matured hop bitter acids (MHBA) are bitter acid oxides derived from hops, widely consumed as food ingredients to add bitterness and flavor in beers. Previous studies have suggested a potential gut-brain mechanism in which MHBA simulates enteroendocrine cells to produce cholecystokinin (CCK), a gastrointestinal hormone which activates autonomic nerves, resulting in body fat reduction and cognitive improvement; however, the MHBA recognition site on enteroendocrine cells has not been fully elucidated. In this study, we report that MHBA is recognized by specific human and mouse bitter taste receptors (human TAS2R1, 8, 10 and mouse Tas2r119, 130, 105) using a heterologous receptor expression system in human embryonic kidney 293T cells.

β-lactolin increases cerebral blood flow in dorsolateral prefrontal cortex in healthy adults: a randomized controlled trial.

The number of elderly individuals with age-related cognitive decline or dementia is rapidly increasing. Dairy product consumption, including β-lactolin, is beneficial for their cognitive function. The underlying mechanism of β-lactolin's effects on human brain activity is yet to be investigated.

Phosphorylation and oligomerization of α-synuclein associated with GSK-3β activation in the rTg4510 mouse model of tauopathy.

Neurodegenerative diseases are characterized by the accumulation of specific phosphorylated protein aggregates in the brain, such as hyperphosphorylated tau (hp-tau) in tauopathies and phosphorylated α-synuclein (p-αSyn) in α-synucleinopathies. The simultaneous accumulation of different proteins is a common event in many neurodegenerative diseases. We herein describe the detection of the phosphorylation and dimerization of αSyn and activation of GSK-3β, a major kinase known to phosphorylate tau and αSyn, in the brains of rTg4510 mice that overexpress human P301L mutant tau.

Supplementation with Matured Hop Bitter Acids Improves Cognitive Performance and Mood State in Healthy Older Adults with Subjective Cognitive Decline.

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.

Distillation remnants of shochu, a traditional Japanese liquor, improve pork meat quality by reducing stress.

Distillation remnants of Shochu, a traditional Japanese liquorare fed to livestock, but their effects on livestock health have not been investigated. Here, we investigated the effects of these remnants on pig stress and pork quality (N = 6/group). The remnants reduced plasma cortisol (17.

Amyloid β-induced Mesenteric Inflammation in an Alzheimer's Disease Transgenic Mouse Model.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder histopathologically characterized by the accumulation of amyloid β (Aβ) peptides and inflammation associated with activated microglia. These features are well investigated in the central nervous system using AD-model mice; however, peripheral inflammation in these mice has not been investigated well.

Objective: We evaluated the inflammatory responses, especially myeloid dendritic cells (mDCs), in peripheral lymphoid tissues in AD-model mice to determine their association with Aβ deposition.

Improving Effects of Hop-Derived Bitter Acids in Beer on Cognitive Functions: A New Strategy for Vagus Nerve Stimulation.

Dementia and cognitive decline are global public health problems. Moderate consumption of alcoholic beverages reduces the risk of dementia and cognitive decline. For instance, resveratrol, a polyphenolic compound found in red wine, has been well studied and reported to prevent dementia and cognitive decline.

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

The prevention of age-related memory decline and dementia has been becoming a high priority because of the rapid growth in aging populations. Accumulating epidemiological and clinical studies indicate that intake of fermented dairy products rich in β-lactolin improves memory retrieval and executive function and attenuates cognitive decline in the elderly. However, the effects of long-term consumption of β-lactolin on Alzheimer's disease (AD) pathologies have not been investigated.

β-lactolin, a whey-derived glycine-threonine-tryptophan-tyrosine lactotetrapeptide, improves prefrontal cortex-associated reversal learning in mice.

Dementia and cognitive decline have become worldwide public health problems. We have previously reported that a whey-derived glycine-threonine-tryptophan-tyrosine peptide, β-lactolin, improves hippocampus-dependent memory functions in mice. The supplementation with a whey digest rich in β-lactolin improves memory retrieval and executive function in a clinical trial, but the effect of β-lactolin on prefrontal cortex (PFC)-associated cognitive function was unclear.

Effects of Hop Bitter Acids, Bitter Components in Beer, on Cognition in Healthy Adults: A Randomized Controlled Trial.

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.

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

The number of patients with mental illnesses, including depression, is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. Consequently, corrective measures, such as diet-based treatment for diseases, are receiving great attention. We previously showed that β-lactolin, a β-lactopeptide of glycine-threonine-tryptophan-tyrosine peptide, inhibits monoamine oxidase and improves memory impairment in mice, but the effects on depression have not been investigated.

The Lacto-Tetrapeptide Gly-Thr-Trp-Tyr, β-Lactolin, Improves Spatial Memory Functions via Dopamine Release and D1 Receptor Activation in the Hippocampus.

Scope: Peptides containing tryptophan-tyrosine sequences, including the lacto-tetrapeptide glycine-threonine-tryptophan-tyrosine (GTWY) and β-lactolin, from β-lactoglobulin in whey enzymatic digestion, enhance hippocampus-dependent memory functions, which are blocked by the systemic administration of dopamine D1-like antagonist. In this study, we investigated the role of the hippocampal dopaminergic system in the memory-enhancing effect of β-lactolin.

Methods And Results: The results of in vivo microdialysis revealed that oral administration of β-lactolin increased the extracellular concentration of dopamine in the hippocampus and enhanced both spatial working memory, as measured in the Y-maze test, and spatial reference memory, as measured in the novel object location test.

Effects of iso-α-acids, the hop-derived bitter components in beer, on the MRI-based Brain Healthcare Quotient in healthy middle-aged to older adults.

Aim: Neurological disorders are a major public health issue worldwide and are often associated with structural changes in the brain. We have previously demonstrated that iso-α-acids (IAAs), the hop-derived bitter components in beer, improve memory impairment in aged and Alzheimer's disease mouse models. In this study, we evaluated the effects of IAA intake on the brain structure in healthy middle-aged to older adults.