Effect of non-alcoholic beer containing matured hop bitter acids on mood states in healthy adults: A single-arm pilot study.
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ABSTRACT:
SUBMITTER: Fukuda T
PROVIDER: S-EPMC9300118 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPrevention 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.ObjectiveWe investigated the effects of MHBA supplementation on cognitive function and mood state in healthy older adults with perceived subjective cognitive decline.MethodsUsing 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.ResultsSymbol 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.ConclusionThis study suggested that MHBA intake improves cognitive function, attention, and mood state in older adults.
| S-EPMC7369117 | biostudies-literature
Project description:Improving and maintaining memory function is effective in preventing cognitive decline and dementia. Previously, we demonstrated that iso-?-acids, the hop-derived bitter components in beer, prevent cognitive impairment in an Alzheimer's disease mouse model. In this report, we investigated the effects of matured hop bitter acids (MHBA) containing components of oxides derived from ?- and ?-acids, and structurally similar to iso-?-acids, on cognitive function using behavioral pharmacological procedures. MHBA and the representative components of MHBA, 4'-hydroxyallohumulinone (HAH) and 4'-hydroxy-cis-alloisohumulone (HAIH) improved spatial working memory in scopolamine-induced amnesia mice. MHBA also enhanced episodic memory in the novel object recognition test (NORT). The administration of MHBA increased the amount of norepinephrine (NE) and NE release into cerebrospinal fluid (CSF) in hippocampus. The MHBA activity in improving memory function was attenuated by treatment with a ?-adrenergic receptor inhibitor. In addition, vagotomized mice did not display the memory improvement induced by MHBA. Together, our results suggest that MHBA improves memory function via stimulation of the vagus nerve and enhancement of NE release in the hippocampus. Vagus nerve activation by the intake of food materials including MHBA may be a safe and effective approach for improving cognitive function.
| S-EPMC6194057 | biostudies-literature
Project description:With the aging population rapidly increasing worldwide, preventive measures and treatments for age-related cognitive decline and dementia are of utmost importance. We have previously demonstrated that the consumption of iso-α-acids (IAA), which are hop-derived bitter compounds in beer, prevents the formation of disease pathology in a transgenic mouse model of Alzheimer's disease (AD). However, the effect of IAA consumption on age-related cognitive decline is unknown. In the present study, we examined the effect of long-term and short-term dietary consumption of IAA, on age-related memory impairments and inflammation in the hippocampus of aged mice. When compared with young mice, aged mice showed impairment in spatial working memory during the Y-maze spontaneous alternation test, impairment in object recognition memory during the novel object recognition test (NORT), a pro-inflammatory hippocampal microglial phenotype with increased CD86 expression and inflammatory cytokine production, increased levels of glutamate and amyloid β1-42, and decreased levels of dopamine (DA). In aged mice fed IAA for 3 months, the age-related alterations in memory, microglial inflammation, and glutamate, amyloid β1-42, and DA levels were all significantly attenuated. Additionally, the oral administration of IAA for 7 days in aged mice with memory impairment, also improved spatial and object recognition memory. These results suggest that IAA consumption prevents inflammation in the hippocampus and ameliorates age-related cognitive decline.
| S-EPMC6369178 | biostudies-literature
Project description: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-?-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. However, the underlying mechanisms have not been entirely elucidated. We aimed to investigate the effects of MHBAs and the common ?-tricarbonyl moiety on memory impairment induced by the activation of microglia and the loss of the noradrenergic system. MHBAs and a model compound with ?-tricarbonyl moiety were administered to LPS-inoculated mice and 5?×?FAD Alzheimer's disease (AD) model mice, following the evaluation in behavioral tests and microglial activation. To evaluate the association of noradrenaline with MHBAs effects, mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin that selectively damages noradrenergic projections from the locus coeruleus, were subjected to the behavioral evaluation. MHBAs reduced brain inflammation and improved LPS-induced memory impairment. A model compound possessing the ?-tricarbonyl moiety improved the LPS-induced memory impairment and neuronal loss via the vagus nerve. Additionally, the protective effects of MHBAs on memory impairment were attenuated by noradrenaline depletion using DSP-4. MHBAs suppressed the activation of microglia and improved the memory impairment in 5?×?FAD mice, which was also attenuated by noradrenaline depletion. Treatment with MHBAs increased cholecystokinin production from the intestinal cells. Generally, cholecystokinin activates the vagal nerve, which stimulate the noradrenergic neuron in the locus ceruleus. Taken together, our results reveal that food ingredients such as hop bitter acids with a ?-tricarbonyl moiety suppress microglial activation and improve memory impairment induced by inflammation or AD pathology via the activation of the gut-brain axis and noradrenergic system. Supplements with hop bitter acids, including MHBAs, might be a novel approach for the prevention of cognitive decline and dementia.
| S-EPMC7674441 | biostudies-literature
Project description: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-?-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. This study was conducted under the Impulsing Paradigm Change through Disruptive Technologies Program (ImPACT) study launched by the Cabinet office of Japan.Method: This study employed an open-labeled, single-arm, before and after design. Healthy middle-aged to older adults consumed a beverage containing IAAs (3 mg/190 mL) for 4 weeks.Recently developed magnetic resonance imaging-based brain health indicators were used to evaluate the following brain conditions: the Brain Healthcare Quotient (BHQ) based on gray matter volume (GM-BHQ) and white matter fractional anisotropy (FA-BHQ).Results: In total, 25 subjects were recruited, and GM-BHQ and FA-BHQ were measured before and after intervention. In all subjects, no significant differences in GM-BHQ and FA-BHQ were observed. In subjects aged ? 60 years (mean 54.5; standard deviation 3.9) (n = 8), GM-BHQ was significantly increased 4 weeks after intervention compared with that before intervention.Conclusion: Intake of beverages containing IAAs might affect brain aging, particularly in healthy older adults, which may prevent the development of neurological disorders. Future studies employing more robust designs can elucidate the effects of IAAs on GM-BHQ and cognitive functions.
| S-EPMC7292307 | biostudies-literature
Project description: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. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.
| S-EPMC7766517 | biostudies-literature
Project description:Iso-α-acids (IAAs) are hop-derived bitter acids of beer. Epidemiologic studies suggest that moderate alcohol consumption is beneficial for cognitive function, but they do not show the ingredients in alcoholic beverages. Previously, we reported that long-term consumption of IAAs prevents inflammation and Alzheimer pathologies in mice, but their effects on cognitive function have not been evaluated. In the present study, we demonstrated that the consumption of IAAs improves spatial and object recognition memory functions not only in normal Crl:CD1(ICR) male mice but also in mice with pharmacologically induced amnesia. IAA consumption increased the total and extracellular levels of dopamine in the hippocampus of mice and Sprague-Dawley male rats, respectively. Dopamine D1 receptor antagonist treatment and knockdown of dopamine D1 receptor expression in the hippocampus attenuated IAA-induced spatial memory improvement. Furthermore, vagotomy attenuated the effects of IAAs in improving spatial and object recognition memory functions and increasing the total level of dopamine in the hippocampus. These results suggest that the consumption of IAAs activates dopamine D1 receptor-signaling in the hippocampus in a vagus nerve-dependent manner and, consequently, improves spatial and object recognition memory functions. Vagal activation with food components including IAAs may be an easy and safe approach to improve cognitive functions.-Ano, Y., Hoshi, A., Ayabe, T., Ohya, R., Uchida, S., Yamada, K., Kondo, K., Kitaoka, S., Furuyashiki, T. Iso-α-acids, the bitter components of beer, improve hippocampus-dependent memory through vagus nerve activation.
| S-EPMC6436653 | biostudies-literature
Project description:The viable but non-culturable (VBNC) state has been studied in detail in bacteria. However, it has received much less attention in eukaryotic cells. The induction of a VBNC beer-spoilage yeast (Brettanomyces bruxellensis) by hop bitter acids with different concentrations and its recovery were studied in this work. B. bruxellensis cells were completely induced into the VBNC state by treatment of 250 mg/L hop bitter acids for 2 h. The addition of catalase at a concentration of 2,000 U/plate on YPD agars enabled these VBNC cells to recover their culturability within 2 days. Moreover, the transcriptome profiling revealed that 267 and 197 genes were significantly changed upon VBNC state entry and resuscitation, respectively. The differentially expressed genes involved in the peroxisome activities, ABC transporter, organic acid metabolism, and TCA cycle were mainly downregulated in the VBNC cells. In contrast, the amino acid and carbohydrate metabolism, cell division, and DNA replication were promoted. This study supplies a theoretical basis for microbial risk assessment in the brewing industry.
| S-EPMC9189414 | biostudies-literature
Project description:Beer is a popular beverage and some beneficial effects have been attributed to its moderate consumption. We carried out a pilot study to test if beer and non-alcoholic beer consumption modify the levels of a panel of 53 cardiometabolic microRNAs in plasma and macrophages. Seven non-smoker men aged 30-65 with high cardiovascular risk were recruited for a non-randomised cross-over intervention consisting of the ingestion of 500 mL/day of beer or non-alcoholic beer for 14 days with a 7-day washout period between interventions. Plasma and urine isoxanthohumol were measured to assess compliance with interventions. Monocytes were isolated and differentiated into macrophages, and plasma and macrophage microRNAs were analysed by quantitative real-time PCR. Anthropometric, biochemistry and dietary parameters were also measured. We found an increase in plasma miR-155-5p, miR-328-3p, and miR-92a-3p after beer and a decrease after non-alcoholic beer consumption. Plasma miR-320a-3p levels decreased with both beers. Circulating miR-320a-3p levels correlated with LDL-cholesterol. We found that miR-17-5p, miR-20a-5p, miR-145-5p, miR-26b-5p, and miR-223-3p macrophage levels increased after beer and decreased after non-alcoholic beer consumption. Functional analyses suggested that modulated microRNAs were involved in catabolism, nutrient sensing, Toll-like receptors signalling and inflammation. We concluded that beer and non-alcoholic beer intake modulated differentially plasma and macrophage microRNAs. Specifically, microRNAs related to inflammation increased after beer consumption and decreased after non-alcoholic beer consumption.
| S-EPMC7823561 | biostudies-literature
Project description:Prior work suggests humans can differentiate between bitter stimuli in water. Here, we describe three experiments that test whether beer consumers can discriminate between different bitterants in beer. In Experiment 1 (n = 51), stimuli were intensity matched; Experiments 2 and 3 were a difference from control (DFC)/check-all-that-apply (CATA) test (n = 62), and an affective test (n = 81). All used a commercial non-alcoholic beer spiked with Isolone (a hop extract), quinine sulfate dihydrate, and sucrose octaacetate (SOA). In Experiment 1, participants rated intensities on general labeled magnitude scales (gLMS), which were analyzed via ANOVA. In Experiment 2, participants rated how different samples were from a reference of Isolone on a 7-point DFC scale, and endorsed 13 attributes in a CATA task. DFC data were analyzed via ANOVA with Dunnett's test to compare differences relative to a blind reference, and CATA data were analyzed via Cochran's Q test. In Experiment 3, liking was assessed on labeled affective magnitude scales, and samples were also ranked. Liking was analyzed via ANOVA and rankings were analyzed with a Cochran-Mantel-Haenszel test. Experiment 1 confirmed that samples were isointense. In Experiment 2, despite being isointense, both quinine (p = 0.04) and SOA (p = 0.03) were different from Isolone, but no significant effects were found for CATA descriptors (all p values > 0.16). In Experiment 3, neither liking (p = 0.16) or ranking (p = 0.49) differed. Collectively, these data confirm that individuals can discriminate perceptually distinct bitter stimuli in beer, as shown previously in water, but these differences cannot be described semantically, and they do not seem to influence hedonic assessments.
| S-EPMC7352581 | biostudies-literature