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. 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 ß-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.

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. 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.

Matured hop bitter acids improve spatial working and object recognition memory via nicotinic acetylcholine receptors.

RATIONALE: Cognitive decline and dementia are major concerns in today's aging society. As limited treatments are available, measures to prevent cognitive decline and dementia are needed. We previously demonstrated that matured hop bitter acids (MHBA), bitter components of beer, increase norepinephrine in the hippocampus and improve memory in amnesia model mice induced by scopolamine (SCP), an antagonist of muscarinic receptor. However, other neurotransmitters involved in the effects of MHBA on memory improvement remain unknown. OBJECTIVES: This study aimed to assess the role of acetylcholine receptors (AChR) in the effects of MHBA on memory. METHOD: The involvement of AChR on the effects of MHBA (10 mg/kg) on cognitive function was evaluated using AChR antagonists, SCP, mecamylamine hydrochloride (MEC), a non-competitive antagonist of nicotinic-AChR (nAChR), and methyllycaconitine citrate (MLA), an α7nAChR antagonist, for the Y-maze test and the novel object recognition test (NORT). A separate population of mice, which underwent vagotomy or sham operation, was subjected to NORT to elucidate further mechanism. In addition, the effect of MHBA on acetylcholinesterase (AChE) activity was measured in vitro. RESULTS: In accordance with previous reports, MHBA improved spontaneous alternations of the Y-maze test in SCP-induced amnesia mice and increased discrimination index evaluated by the NORT in normal mice. On the other hand, treatment with MEC or MLA attenuated the effects of MHBA on memory improvement in the Y-maze test and the NORT. Vagotomized mice also showed attenuated memory enhancement by MHBA in the NORT. In addition, MHBA did not alter AChE activity in vitro. CONCLUSIONS: The results support the involvement of nAChRs in memory improvement in mice by MHBA. MHBA is thus thought to activate the vagal nerve and enhance hippocampus-dependent memory via nAChRs.