Effect of Regular Exercise and Functional Beverages on Changes in Body Weight and Waist Circumference in Healthy Japanese Subjects.

Background and objectives: The effects on anthropometry of several lipid-related foods for specified health uses (FOSHU) approved in Japan are not well known. We examined the effects of regular exercise and lipid-related FOSHU beverages on changes in body weight (BW) and waist circumference (WC) among factory and office workers. Materials and Methods: A total of 3002 subjects aged 20 years or older (2497 men and 505 women) received health check-ups in 2015 and 2016 and completed a lifestyle questionnaire. The association between regular exercise or lipid-related FOSHU beverage intake and changes in BW or WC were evaluated using trend test and linear regression analysis. Results: Regular exercise (≥1/week) was reported by 774 subjects (25.8%), and regular consumption of lipid-related FOSHU beverages (≥1/week) was reported by 1168 subjects (38.9%). The significant association between lipid-related FOSHU beverage intake and changes in BW was only observed among subjects with regular exercise (p for trend = 0.042). In the multivariable analysis, sex, older age, baseline weight, baseline body mass index (BMI), and regular exercise behavior were significantly associated with smaller changes in BW (p < 0.05). In WC, only the baseline values of WC and BMI were associated with one-year changes of WC. Conclusions: The combination of regular exercise and lipid-related FOSHU may be effective in maintaining BW.

Effects of Tea Catechins on Alzheimer's Disease: Recent Updates and Perspectives.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders worldwide. Its incidence is gradually increasing because of an aging demographic. Therefore, AD prevention and modification is important to improve the health status of older adults. Oxidative stress is a component of the pathological mechanisms underlying AD. It is caused by a disruption of the balance between reactive oxygen species and antioxidant molecules. This imbalance also causes neuroinflammation. Catechins, which are bioactive components of tea, have antioxidative and anti-inflammatory effects. Moreover, other potential properties related to AD prevention and modification have been reported in in vitro and in vivo studies. Several clinical studies have also been conducted to date. The current review summarizes recent updates and perspectives of the effects of catechins on AD based on the molecular mechanisms and related clinical studies.

Effect of Tea Catechins on Influenza Infection and the Common Cold with a Focus on Epidemiological/Clinical Studies.

Influenza and the common cold are acute infectious diseases of the respiratory tract. Influenza is a severe disease that is highly infectious and can progress to life-threating diseases such as pneumonia or encephalitis when aggravated. Due to the fact that influenza infections and common colds spread easily via droplets and contact, public prevention measures, such as hand washing and facial masks, are recommended for influenza prophylaxis. Experimental studies have reported that tea catechins inhibited influenza viral adsorption and suppressed replication and neuraminidase activity. They were also effective against some cold viruses. In addition, tea catechins enhance immunity against viral infection. Although the antiviral activity of tea catechins has been demonstrated, the clinical evidence to support their utility remains inconclusive. Since the late 1990s, several epidemiological studies have suggested that the regular consumption of green tea decreases influenza infection rates and some cold symptoms, and that gargling with tea catechin may protect against the development of influenza infection. This review briefly summarizes the effect of tea catechins on influenza infection and the common cold with a focus on epidemiological/clinical studies, and clarifies the need for further studies to confirm their clinical efficacy.

Behaviors of consumers, physicians and pharmacists in response to adverse events associated with dietary supplement use.

BACKGROUND: The prevalence of dietary supplements has increased in Japan, and, as a consequence, the adverse events associated with dietary supplement use have become more prominent. Severe adverse events must be reported to the Japanese government via public health centers. However, the number of cases reported to the Japanese government is limited. To clarify this discrepancy, we conducted an internet questionnaire, and surveyed how consumers, physicians and pharmacists acted when they or their patients developed adverse events due to dietary supplement use. METHODS: This study was completed by 2732 consumers, 515 physicians, and 515 pharmacist via internet surveillance on November 2015. RESULTS: Although 8.8% of consumers developed adverse events including diarrhea, constipation, stomachache, headache, and nausea and vomiting, most of them did not report their adverse events to public health centers. However, some consumers went to hospitals because of adverse events. We also surveyed how physicians and pharmacists acted when their patients developed adverse events due to dietary supplement use. Most physicians and pharmacists did not report these cases to public health centers because they were unable to definitively prove the cause-and-effect relationship of these adverse events. Furthermore, some physicians and pharmacists did not know how or where to report these adverse events. CONCLUSIONS: We clarified the reasons for the limited number of reports of adverse events to the Japanese government in this survey. It is important to encourage not only consumers, but also physicians and pharmacists to report adverse events to public health centers. In addition, an analyzing tool of cause-and-effect relationships might be helpful for physicians and pharmacists.

Effects of Green Tea Gargling on the Prevention of Influenza Infection: An Analysis Using Bayesian Approaches.

OBJECTIVES: The aim of this study is to analyze the data obtained from a randomized trial on the prevention of influenza by gargling with green tea, which gave nonsignificant results based on frequentist approaches, by using Bayesian approaches. METHODS: The posterior proportion, with 95% credible interval (CrI), of influenza in each group was calculated. The Bayesian index θ is the probability that a hypothesis is true. In this case, θ is the probability that the hypothesis that green tea gargling reduced influenza compared with water gargling is true. Univariate and multivariate logistic regression analyses were also performed by using the Markov chain Monte Carlo method. RESULTS: The full analysis set included 747 participants. During the study period, influenza occurred in 44 participants (5.9%). The difference between the two independent binominal proportions was -0.019 (95% CrI, -0.054 to 0.015; θ = 0.87). The partial regression coefficients in the univariate analysis were -0.35 (95% CrI, -1.00 to 0.24) with use of a uniform prior and -0.34 (95% CrI, -0.96 to 0.27) with use of a Jeffreys prior. In the multivariate analysis, the values were -0.37 (95% CrI, -0.96 to 0.30) and -0.36 (95% CrI, -1.03 to 0.21), respectively. CONCLUSIONS: The difference between the two independent binominal proportions was less than 0, and θ was greater than 0.85. Therefore, green tea gargling may slightly reduce influenza compared with water gargling. This analysis suggests that green tea gargling can be an additional preventive measure for use with other pharmaceutical and nonpharmaceutical measures and indicates the need for additional studies to confirm the effect of green tea gargling.

Reporting of adverse events related to dietary supplements to a public health center by medical staff: a survey of clinics and pharmacies.

BACKGROUND: Dietary supplements are used by >50% of the adult population in Japan, and adverse events related to these products have been reported with their increased use. Thus, an efficient system to gather and report data on these adverse events is essential. To date, however, reporting has been limited. The aim of this study was to address this deficiency by exploring the routine reporting practices of the medical staff employed at clinics or pharmacies in Japan. METHODS: We conducted a survey of the procedures used by the medical staff to report adverse events related to dietary supplement intake to public health centers in Japan. The survey was conducted in Japan between November 2015 and January 2016. Based on a sample size calculation, questionnaires were administered to 1,700 potential respondents (850 pharmacists and 850 physicians). The questionnaire inquired about the sociodemographic characteristics and dietary supplement-related adverse event-reporting practices. RESULTS: The response rate was 34.7%, including 286 pharmacists and 304 physicians. Although >30% of the pharmacists and physicians had prior experience dealing with such adverse events, <5% had reported these to a public health center. The survey identified several barriers to reporting, such as "difficulty judging the relationship between an adverse event and the dietary supplement" and "lack of clarity regarding the severity of an adverse event". CONCLUSION: This is the first study to explore the routine reporting practices of physicians and pharmacists in terms of adverse events related to dietary supplements. Further studies are required to elucidate the severity of these adverse events. Moreover, standard reporting criteria ought to be introduced to improve public health.

Influences of yokukansankachimpihange on aggressive behavior of zinc-deficient mice and actions of the ingredients on excessive neural exocytosis in the hippocampus of zinc-deficient rats.

We examined the effect of Yokukansankachimpihange (YKSCH), a form of Yokukansan containing parts of two herbaceous plants, Citrus Unshiu Peel (Chimpi) and Pinellia Tuber (Hange), on aggressive behavior of mice housed individually. Mice were fed a zinc-deficient diet for 2 weeks. In a resident-intruder test, the cumulative duration of aggressive behavior was decreased in zinc-deficient mice administrated drinking water containing YKSCH (approximately 300 mg/kg body weight/day) for 2 weeks. We tested mice for geissoschizine methyl ether (GM), which is contained in Uncaria Hook, and 18ß-glycyrrhetinic acid (GA), a major metabolite of glycyrrhizin contained in Glycyrrhiza, which were contained in YKS and YKSCH. In hippocampal slices from zinc-deficient rats, excess exocytosis at mossy fiber boutons induced with 60 mM KCl was attenuated in the presence of GA (100-500 µM) or GM (100 µM). The intracellular Ca2+ level, which showed an increase induced by 60 mM KCl, was also attenuated in the presence of GA (100-500 µM) or GM (100 µM). These results suggest that GA and GM ameliorate excess glutamate release from mossy fiber boutons by suppressing the increase in intracellular Ca2+ signaling. These ameliorative actions may contribute to decreasing the aggressiveness of mice individually housed under zinc deficiency, potentially by suppressing excess glutamatergic neuron activity in the hippocampus.

Effects of green tea consumption on cognitive dysfunction in an elderly population: a randomized placebo-controlled study.

BACKGROUND: Green tea is a beverage with potential effects on cognitive dysfunction, as indicated by results of experimental studies. However, its effects in humans, especially at real-world (typical) consumption levels, are unclear. METHODS: A double-blind, randomized controlled study was conducted to assess the effects of green tea consumption on cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score <28) in Japan. Participants were randomly allocated to the green tea or placebo group, and consumed either 2 g/day of green tea powder (containing 220.2 mg of catechins) or placebo powder (containing 0.0 mg of catechins), respectively, for 12 months. Cognitive function assessments were performed every 3 months using the MMSE-J and laboratory tests. RESULTS: Thirty-three nursing home residents with cognitive dysfunction were enrolled (four men, 29 women; mean age ± SD, 84.8 ± 9.3; mean MMSE-J score ± SD, 15.8 ± 5.4), of whom 27 completed the study. Changes of MMSE-J score after 1 year of green tea consumption were not significantly different compared with that of the placebo group (-0.61 [-2.97, 1.74], least square mean (LSM) difference [95 % CI]; P = 0.59). However, levels of malondialdehyde-modified low-density lipoprotein (U/L), a marker of oxidative stress, was significantly lower in the green tea group (-22.93 [-44.13, -1.73], LSM difference [95 % CI]; P = 0.04). CONCLUSIONS: Our results suggest that 12 months green tea consumption may not significantly affect cognitive function assessed by MMSE-J, but prevent an increase of oxidative stress in the elderly population. Additional long-term controlled studies are needed to clarify the effects. TRIAL REGISTRATION: UMIN000011668.

Effect of gargling with tea and ingredients of tea on the prevention of influenza infection: a meta-analysis.

BACKGROUND: Influenza viruses can spread easily from person to person, and annual influenza epidemics are serious public health issues worldwide. Non-pharmaceutical public health interventions could potentially be effective for combatting influenza epidemics, but combined interventions and/or interventions with greater effectiveness are needed. Experimental studies have reported that tea and its ingredients (especially catechins) have antiviral activities. Although several clinical studies have investigated the use of tea or its ingredients to prevent influenza infections, the effect of gargling these substances has remained uncertain. METHODS: We conducted a meta-analysis of randomized controlled studies and prospective cohort studies to assess the effect of gargling with tea and its ingredients on the prevention of influenza infection. The published literature was searched using the Cochrane Library, PubMed/MEDLINE (1966 to September 2015), Web of Science (1981 to September 2015), and Ichu-shi Web (1983 to September 2015). The extracted studies were read by two reviewers independently, and their overall scientific quality was evaluated. Studies meeting our inclusion criteria were pooled using the Mantel-Haenszel method in a fixed effects model and were also analyzed in a random effects model. The qualities of the model fits were assessed using the Akaike information criterion (AIC) and Bayesian information criterion (BIC). RESULTS: The literature search and review identified 5 studies that met the inclusion criteria for the meta-analysis (total number of participants, 1890; mean age range, 16-83 years). The participants who gargled with tea or its ingredients showed a lower risk of influenza infection than did participants who gargled with placebo/water or who did not gargle (fixed effects model, Mantel-Haenszel method: relative risk [RR] = 0.70, 95 % confidence interval [CI] = 0.54-0.89; random effects model: RR = 0.71, 95 % CI = 0.56-0.91). The fixed effects model had a better quality of fit than the random effects model (fixed effects model: AIC = 6.04, BIC = 5.65; random effects model: AIC = 8.74, BIC = 7.52). CONCLUSIONS: Gargling with tea and its ingredients may have a preventative effect for influenza infection. However, additional large-scale studies in different populations and a pooled analysis of these studies are needed to confirm the effect.

Methods for estimating causal relationships of adverse events with dietary supplements.

OBJECTIVE: Dietary supplement use has increased over past decades, resulting in reports of potentially serious adverse events. The aim of this study was to develop optimised methods to evaluate the causal relationships between adverse events and dietary supplements, and to test these methods using case reports. DESIGN: Causal relationship assessment using prospectively collected data. SETTING AND PARTICIPANTS: 4 dietary supplement experts, 4 pharmacists and 11 registered dietitians (5 men and 14 women) examined 200 case reports of suspected adverse events using the modified Naranjo scale and the modified Food and Drug Administration (FDA) algorithm. PRIMARY OUTCOME MEASURES: The distribution of evaluation results was analysed and inter-rater reliability was evaluated for the two modified methods employed using intraclass correlation coefficients (ICC) and Fleiss' κ. RESULTS: Using these two methods, most of the 200 case reports were categorised as 'lack of information' or 'possible' adverse events. Inter-rater reliability among entire assessors ratings for the two modified methods, based on ICC and Fleiss' κ, were classified as more than substantial (modified Naranjo scale: ICC (95% CI) 0.873 (0.850 to 0.895); Fleiss' κ (95% CI) 0.615 (0.615 to 0.615). Modified FDA algorithm: Fleiss' κ (95% CI) 0.622 (0.622 to 0.622). CONCLUSIONS: These methods may help to assess the causal relationships between adverse events and dietary supplements. By conducting additional studies of these methods in different populations, researchers can expand the possibilities for the application of our methods.

Green tea consumption affects cognitive dysfunction in the elderly: a pilot study.

Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants' MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.

Effects of green tea gargling on the prevention of influenza infection in high school students: a randomized controlled study.

BACKGROUND: The anti-influenza virus activity of green tea catechins has been demonstrated in experimental studies, but clinical evidence has been inconclusive. School-aged children play an important role in the infection and spread of influenza in the form of school-based outbreaks. Preventing influenza infection among students is essential for reducing the frequency of epidemics and pandemics. As a non-pharmaceutical intervention against infection, gargling is also commonly performed in Asian countries but has not yet been extensively studied. METHODS AND FINDINGS: A randomized, open label, 2-group parallel study of 757 high school students (15 to 17 years of age) was conducted for 90 days during the influenza epidemic season from December 1st, 2011 to February 28th, 2012, in 6 high schools in Shizuoka Prefecture, Japan. The green tea gargling group gargled 3 times a day with bottled green tea, and the water gargling group did the same with tap water. The water group was restricted from gargling with green tea. The primary outcome measure was the incidence of laboratory-confirmed influenza using immunochromatographic assay for antigen detection. 757 participants were enrolled and 747 participants completed the study (384 in the green tea group and 363 in the water group). Multivariate logistic regression indicated no significant difference in the incidence of laboratory-confirmed influenza between the green tea group (19 participants; 4.9%) and the water group (25 participants; 6.9%) (adjusted OR, 0.69; 95%CI, 0.37 to 1.28; P = 0.24). The main limitation of the study is the adherence rate among high school students was lower than expected. CONCLUSIONS: Among high school students, gargling with green tea three times a day was not significantly more efficacious than gargling with water for the prevention of influenza infection. In order to adequately assess the effectiveness of such gargling, additional large-scale randomized studies are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT01225770.

Therapeutic effect of Yokukansan on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice.

In patients with dementia including Alzheimer's disease, hallucinations, agitation/aggression and irritability are known to frequently occur and as distressing behavioral and psychological symptoms of dementia (BPSD). On the basis of the evidence on clinical efficacy and safety of Yokukansan, a traditional Japanese herbal medicine, on BPSD, in the present study, Yokukansan was examined in the therapeutic effects on social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice. Yokukansan was p.o. administered for 7 days as a drinking water to isolated mice fed a zinc-deficient diet for 10 days, which exhibited aggressive behavior, and isolated pair-fed mice fed a control diet of the amount consumed by zinc-deficient mice for 10 days, which exhibited aggressive behavior. Aggressive behavior was evaluated by the resident-intruder test. Yokukansan (312 mg/kg/day) attenuated both aggressive behaviors of zinc-deficient and pair-fed mice. Because Yokukansan can suppress abnormal glutamatergic neuron activity, MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, and aminooxyacetic acid (AOAA), a γ-amino butyric acid (GABA) transaminase blocker, were also examined in the effects on social isolation-induced aggressive behavior. MK-801 (0.1 mg/kg) or AOAA (23 mg/kg) was i.p. injected into isolated aggressive mice. Thirty minutes later, the resident-intruder test was performed to evaluate the effect of the drugs. Both drugs attenuated aggressive behavior of zinc deficient mice, but not that of pair-fed mice. These results suggest that Yokukansan ameliorates social isolation-induced aggressive behavior of zinc-deficient and pair-fed mice through the action against glutamatergic neurotransmitter system and other neurotransmitter systems.

Oral administration of highly oligomeric procyanidins of Jatoba reduces the severity of collagen-induced arthritis.

We have previously reported that highly oligomeric procyanidins (HOPC) purified from Jatoba, a South American herb, ameliorated experimental autoimmune encephalomyelitis (EAE) in mice. In this present study, we report that symptoms of arthritis were also significantly reduced by administering the Jatoba extract, when compared with the vehicle-alone-treated control. Interferon-gamma (IFN-gamma) production by the splenocytes from mice injected with procyanidins was also dramatically decreased. The oral administration of purified HOPC was significantly more effective in disease prevention than the ethanol (EtOH) extract of Jatoba. Green tea polyphenol administration, however, surprisingly facilitated disease development. Observation of the joint histopathology on whole paws derived from the HOPC-treated mice showed complete abrogation of collagen induced arthritis (CIA), a characteristic of chronic inflammation in the synovial tissue. These results demonstrate that HOPC administration had an inhibitory effect on both chronic arthritis and EAE and that the oral administration of HOPC exerted its effect after the induction of secondary immunity.

Highly oligomeric procyanidins ameliorate experimental autoimmune encephalomyelitis via suppression of Th1 immunity.

Extracts of Jatoba, a South American herb, when injected i.p. into a mouse model of experimental autoimmune encephalomyelitis (EAE), inhibited the aggravation of clinical symptoms. At the same time, production of myelin oligodendrocyte glycoprotein Ag-specific IFN-gamma and TNF-alpha by spleen cells was markedly suppressed. After administration of Jatoba there was minimal evidence of the demyelination that is characteristic of the EAE model. Decreases in clinical scores were observed when Jatoba extracts were injected just before Ag. The purified active compounds are likely to be polyphenols that are absorbable to polyvinylpolypyrrolidone. The active compounds were polymerized polyphenol polymers (procyanidins) and at least five degrees of polymerization were necessary for activity. In addition, extracts of other plant materials containing such procyanidins had similar activity. After administration of highly polymerized procyanidins, there was a decrease in both dendritic and CD4(+) T cells. Although macrophages were increased in number, the expression of CD80 and MHC class II molecules was depressed indicating that the macrophages were immature. The results indicate that the suppression of development of EAE by the highly polymerized procyanidins resulted from an inhibition of Th1 and the effects might be associated with depression of Ag-presenting capability.